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Beska Z Witka,1 Dede J Oktaviani,1 Marcellino Marcellino,1 Melisa I Barliana,2,3 Rizky Abdulah1,3 1Departement of Pharmacology and Clinical Pharmacy, Faculty of Pharmacy, Universitas Padjadjaran, Jatinangor, Indonesia; 2Departement of Biological Pharmacy, Faculty of Pharmacy, Universitas Padjadjaran, Jatinangor, Indonesia; 3Center of Excellence in Higher Education for Pharmaceutical Care Innovation, Universitas Padjadjaran, Jatinangor, IndonesiaCorrespondence: Melisa I BarlianaDepartment of Biological Pharmacy, Faculty of Pharmacy, Universitas Padjadjaran, Jl. Raya Bandung Sumedang KM. 21, Jatinangor 45363, IndonesiaEmail melisa.barliana@unpad.ac.idAbstract: Diabetes is a major cause of mortality worldwide. There are several types of diabetes, with type 2 diabetes mellitus (T2DM) being the most common. Many factors, including environmental and genetic factors, are involved in the etiology of the disease. Numerous studies have reported the role of genetic polymorphisms in the initiation and development of T2DM. While genome-wide association studies have identified around more than 200 susceptibility loci, it remains unclear whether these loci are correlated with the pathophysiology of the disease. The present review aimed to elucidate the potential genetic mechanisms underlying T2DM. We found that some genetic polymorphisms were related to T2DM, either in the form of single-nucleotide polymorphisms or direct amino acid changes in proteins. These polymorphisms are potential predictors for the management of T2DM.Keywords: type 2 diabetes, genetic polymorphisms, susceptibility prediction

Introduction: The aim of this prospective study was to see whether LD-1227, a quality-controlled marine nutraceuticals shown to protect experimental stress-induced hyppocampal degeneration, could beneficially modulate BDNF, as measured in the serum, in otherwise healthy but work-stressed individuals. Materials and Methods: Forty-eight men and women between the ages of 38 and 62 reporting high-demanding work activity but with an overall positive attitude towards their personal life were recruited. Subjects were divided in two group (24 patients each) and blindly supplemented for 2 month with: a) LD-1227 400mg or b) placebo. A third group of healthy non-stressed subjects was used as well. Blood samples were taken before and after the supplementation period. Unstimulated saliva was collected and tested for amylase while serum levels were used to measure BDNF. State Trait Anxiety Inventory (STAI), Pittsburgh Sleep Quality Index (PSQI) and psychological wellbeing assessment (PSWB) were measured too. Patients with Val66Met functional polymorphism of BDNF excluded those given their reported association with an impaired release of BDNF. Results: Results showed that, as compared to healthy, nonstressed individuals, stressed ones has a trend decrease of BDNF and this was significantly increased by LD 12-1227 supplementation and the same inverse phenomenon occurred to salivary amylase (p

Abstract Background The capacity to change attention from one area to another depending on the many environmental circumstances present is a crucial aspect of selective attention and is strictly correlated to reaction time. The cholinergic system of the basal forebrain is crucial for attentive abilities. Several inputs, particularly orexin neurons, whose cell bodies are found in the postero-lateral hypothalamus, can activate the cholinergic system. The aim of this study was to investigate if high frequencies rTMS at dorsolateral prefrontal cortex (DLPFC) in highly trained volleyball players can change Orexin-A levels, attention and reaction time. This study was a double-blinded (participant and evaluator) matched-pair experimental design. Twenty right-handed female volleyball players were recruited for the study (age 24.6 ± 2.7 years; height 177.0 ± 5.5 cm; body mass 67.5 ± 6.5 kg; BMI 21.5 ± 1.2). Results The main finding of this study was that 10 Hz rTMS to the DLPFC seems to increase Orexin-A salivary levels and the percentage of correct answers, while decreasing RT. After rTMS, the athletes show an increase in the percentage of correct answers immediately after the end of stimulation, and also after 15 and 30 min. Moreover, the athletes show decreases in reaction time after the end of stimulation and after 15 and 30 min to the end of stimulation, while no differences were found at the end of stimulation. Finally, the athletes show significant increases in Orexin-A salivary levels after stimulation with a peak after 30’ of the end. Conclusion The results of our study seem to indicate that there is a relationship between salivary Orexin-A levels and RT. These results could provide useful tools for modulating sports training; in fact, if confirmed, they could lead coaches to offer their athletes rTMS sessions appropriately integrated with training. In fact, alternating attention is a mental flexibility that enables people to change their point of focus and switch between tasks requiring various levels of cognition.

The task of preventing suicide in older adults is an important social burden as older adults aged above 65 are exposed to singular psychological aspects that increase suicide risks. Moreover, when an older adult corpse is found, the medico-legal inspection represents a fundamental tool to identify the exact cause of death, classifying or excluding it as suicide. In this scenario, this review aims to explore the neurobiological factors that could be related to suicidal behavior in older adults. A further goal of this review is the exploration of the medico-legal aspects surrounding older adult suicides, clarifying the importance of forensic investigation. Particularly, this review examines issues such as neurotransmitter imbalances, cognitive impairment, neuroinflammation, psychosocial factors related to geriatric suicide, and neurodegenerative diseases. Additionally, medico-legal aspects such as policy considerations, legal frameworks, mental health assessments, ethical implications and forensic investigation were explored. Considering the importance of this phenomenon, especially in western countries, a need has emerged for focused screening tools on suicidal behavior among older adults, in order to contain it. Therefore, this review makes an exhaustive appraisal of the literature giving insights into the delicate interplay between neurobiology as well as mental health in relation to older adult suicide within a medico-legal context. The comprehension of different aspects about this complex phenomenon is fundamental to propose new and more effective interventions, supporting tailored initiatives such as family support and improving healthcare, specifically towards vulnerable ageing societies to reduce older adult suicide risks.

The ketogenic diet (KD) is marked by a substantial decrease in carbohydrate intake and an elevated consumption of fats and proteins, leading to a metabolic state referred to as “ketosis,” where fats become the primary source of energy. Recent research has underscored the potential advantages of the KD in mitigating the risk of various illnesses, including type 2 diabetes, hyperlipidemia, heart disease, and cancer. The macronutrient distribution in the KD typically entails high lipid intake, moderate protein consumption, and low carbohydrate intake. Restricting carbohydrates to below 50 g/day induces a catabolic state, prompting metabolic alterations such as gluconeogenesis and ketogenesis. Ketogenesis diminishes fat and glucose accumulation as energy reserves, stimulating the production of fatty acids. Neurodegenerative diseases, encompassing Alzheimer’s disease, Parkinson’s disease are hallmarked by persistent neuroinflammation. Evolving evidence indicates that immune activation and neuroinflammation play a significant role in the pathogenesis of these diseases. The protective effects of the KD are linked to the generation of ketone bodies (KB), which play a pivotal role in this dietary protocol. Considering these findings, this narrative review seeks to delve into the potential effects of the KD in neuroinflammation by modulating the immune response. Grasping the immunomodulatory effects of the KD on the central nervous system could offer valuable insights into innovative therapeutic approaches for these incapacitating conditions.

Diabetic gastroparesis (DGP) delays gastric emptying in diabetes patients, notably impacting those with type 1 and long-standing type 2 diabetes. Symptoms include early satiety, fullness, appetite loss, bloating, abdominal pain, and vomiting, arising from slow stomach-to-intestine food movement. DGP’s unpredictable nature complicates diagnosis and blood glucose management, leading to severe complications like dehydration, malnutrition, and bezoar formation. Understanding DGP’s mechanisms is crucial for effective management. Vagal dysfunction, disturbances in the interstitial cells of Cajal, reduced neural nitric oxide synthase, and increased oxidative stress contribute to the complex pathophysiology. Accurate diagnosis demands a comprehensive approach, utilizing tools like gastric scintigraphy and the Gastric Emptying Breath Test. Considering the complex relationship between DGP and glycemia, managing blood glucose levels becomes paramount. Nutritional interventions, tailored to each patient, address malnutrition risks, emphasizing smaller, more frequent meals and liquid consistency. DGP’s complex nature necessitates collaborative efforts for enhanced diagnostic strategies, improved pathophysiological understanding, and compassionate management approaches. This comprehensive approach offers hope for a future where individuals with DGP can experience improved well-being and quality of life.

Study purpose. At the end of the twentieth century, the development of highly reliable and painless non-invasive transcranial brain stimulation techniques and devices has aroused great scientific and clinical interest in numerous fields. In neuroscience, since the introduction of innovative and non-invasive devices such as the brain stimulator, the investigation of cortical processes and their neural basis has played a fundamental role. Furthermore, neuroscientists are attracted to therapeutic applications for the treatment of food craving. This narrative review is aimed to explain the growing and constant interest of neuroscientific experimentation in the field of non-invasive transcranial stimulation. Material and methods. After an introduction explaining the historical evolution of NIBS, we will try to provide an overview of the two stimulation techniques (TMS and tDCS); we will describe the different types of stimulation that can be performed using these techniques, the excitatory/inhibitory effects, and the various mechanisms of action at the level of brain activity. Results. We will also provide some elucidations regarding the implications of the facilitative/inhibitory effects, and how these stimulation methods can be used to advance knowledge of the neurofunctional organization of the brain. Conclusion. The results of the study showed the effect of brain neuromodulation on sports and nutrition.

Chronic kidney disease (CKD) represents a significant global health challenge, affecting millions of individuals and leading to substantial morbidity and mortality. This review aims to explore the epidemiology, cardiovascular complications, and management strategies associated with CKD, emphasizing the importance of preventing cardiovascular disease and early intervention. CKD is primarily driven by conditions such as diabetes mellitus, hypertension, and cardiovascular diseases, which often coexist and exacerbate renal impairment. Effective management requires a multifaceted approach, including lifestyle modifications, pharmacological interventions, and regular monitoring. Dietary changes, such as sodium restriction and a controlled intake of phosphorus and potassium, play a vital role in preserving renal function. Pharmacological therapies, particularly angiotensin-converting enzyme (ACE) inhibitors, angiotensin receptor blockers (ARBs), and emerging agents like SGLT2 inhibitors, have shown efficacy in slowing disease progression and improving patient outcomes. Furthermore, patients undergoing dialysis face increased cardiovascular risk, necessitating comprehensive management strategies to address both renal and cardiac health. As the landscape of CKD treatment evolves, ongoing research into novel therapeutic options and personalized medical approaches are essential. This review underscores the urgent need for awareness, education, and effective preventive measures to mitigate the burden of CKD and enhance the quality of life for affected individuals.

This study investigates dietary supplement use among rugby players and their general health, focusing on prevalence and underlying motivations. Involving 92 athletes, it examines the relationship between supplement usage, motivations, and health outcomes using the 36-item Short Form Health Survey and a 24-item ad hoc questionnaire. Findings reveal a high frequency of supplement usage, motivated by desires to enhance performance, appearance, and mood. Significant differences in health-related quality of life are found between users and non-users, particularly in mental health, social functioning, and emotional stability. Motivations like performance enhancement and body shape manipulation were linked to altered health perceptions, indicating the psychosocial impacts of supplementation. This study emphasizes the need to consider the holistic effects of supplements on athlete well-being, advocating for a balanced approach prioritizing both physical and mental health. It calls for increased awareness among athletes, coaches, and sports professionals about the potential risks and benefits of supplement use and the importance of informed decision-making. Additionally, it highlights the need for further research to understand the mechanisms of supplement use and its impact on athlete health, aiming to enhance sports science and promote overall athlete well-being in competitive environments.

Type 2 diabetes mellitus (T2DM) is a prevalent chronic metabolic disorder characterized by insulin resistance and progressive beta cell dysfunction, presenting substantial global health and economic challenges. This review explores recent advancements in diabetes management, emphasizing novel pharmacological therapies and their physiological mechanisms. We highlight the transformative impact of Sodium-Glucose Cotransporter 2 inhibitor (SGLT2i) and Glucagon-Like Peptide 1 Receptor Agonist (GLP-1RA), which target specific physiological pathways to enhance glucose regulation and metabolic health. A key focus of this review is tirzepatide, a dual agonist of the glucose-dependent insulinotropic polypeptide (GIP) and GLP-1 receptors. Tirzepatide illustrates how integrating innovative mechanisms with established physiological pathways can significantly improve glycemic control and support weight management. Additionally, we explore emerging treatments such as glimins and glucokinase activators (GKAs), which offer novel strategies for enhancing insulin secretion and reducing glucose production. We also address future perspectives in diabetes management, including the potential of retatrutide as a triple receptor agonist and evolving guidelines advocating for a comprehensive, multifactorial approach to care. This approach integrates pharmacological advancements with essential lifestyle modifications—such as dietary changes, physical activity, and smoking cessation—to optimize patient outcomes. By focusing on the physiological mechanisms of these new therapies, this review underscores their role in enhancing T2DM management and highlights the importance of personalized care plans to address the complexities of the disease. This holistic perspective aims to improve patient quality of life and long-term health outcomes.

Milk and its derivatives are included in a balanced diet of humans as excellent sources of proteins, vitamins, and essential minerals that are functional nutrients. Knowledge about the nutritional benefits or harms due to milk consumption has been expanding in recent years. We previously explored, in rodent models, the metabolic effects of isoenergetic intake of milk derived from cows, donkeys, or humans, while the impact of goat’s milk intake has remained unexplored. The aim of this work was to investigate, in an animal model, the effects of dietary supplementation with goat’s milk on energy homeostasis and inflammatory state, focusing on the modulation of mitochondrial functions in most metabolically active organs, such as skeletal muscle and the liver. In addition, we highlighted a link between nutrient intake, substrate metabolism, and the orexinergic system. Our results indicate that goat milk improves mitochondrial oxidative capacity and reduces inflammation and oxidative stress in both organs. Notably, goat milk lowers the circulating levels of Orexin-A, a neuropeptide that plays a crucial role in regulating peripheral energy balance and central nervous system mechanisms. These data provide the first evidence that the anti-inflammatory and antioxidant effects of goat milk are mediated by the modulation of mitochondrial functions and orexinergic signaling.

The objective of this study was to examine the effect of a training program utilizing action perception technology (PAD) tools on improving the motor reaction times and neuromuscular capabilities of the upper and lower limbs compared to a traditional training program. Twenty-four female volleyball players competing in the Italian national championship were randomized into two groups of 12 athletes each: an experimental group (EG) and a control group (CG). A preliminary analysis confirmed the absence of significant differences in age and anthropometric characteristics between the groups. All the players underwent an initial battery of tests (pre-test), including Reaction Time simple Upper and Lower Limb (RTsUL and RTsLL) and Tapping Upper and Lower Limb (TUL and TLL). During a 6-week training program, the experimental group used exercises with a technological system of illuminated disks, while the control group followed the traditional training methods without advanced technology. At the end of the program, both groups were subjected to final tests (post-test). The main results show that after 6 weeks, both groups improved their performance compared to the initial tests. However, EG achieved significantly better results than CG in every test, with significant reductions in average times (ip%) of −14.9% in RTsUL (DX = −0.072 s, t = 23.2, p < 0.05, d = 6.7), −14.9% in RTsLL (DX = −0.091 s, t = 44.0, p < 0.05, d = 12.7), −10.6% in TUL (DX = −0.622 s, t = 42.0, p < 0.05, d = 12.1), and −10.7% in TLL (DX = −0.983 s, t = 43.1, p < 0.05, d = 12.4). The use of light-based perception–action technology devices in volleyball training has shown potential for significantly improving movement speed and reaction time. However, further research is needed to determine whether these improvements actually translate into enhanced overall performance in competitive contexts compared to the traditional training methods.

The prevalence of obesity has become a global health concern, with significant impacts on quality of life and mortality rates. Recent research has highlighted the role of ultra-processed foods (UPFs) in driving the obesity epidemic. UPFs undergo extensive processing, often containing high levels of sugars, fats, and additives, while lacking essential nutrients. Studies have linked UPF consumption to obesity and cardiometabolic diseases, underscoring the importance of dietary patterns rich in whole foods. Thus, the aim of this narrative review is to elucidate the correlation between ultra-processed foods and the increased trend of obesity and its related complications. These foods, prevalent in modern diets, contribute to nutritional deficiencies and excessive caloric intake, exacerbating obesity rates. Lifestyle factors such as busy schedules and quick meal management further drive UPF consumption, disrupting hunger regulation and promoting overeating. UPF consumption correlates with adverse health outcomes, including dyslipidemia, hypertension, and insulin resistance. Promoting whole, minimally processed foods and implementing school-based nutrition education programs are crucial steps. Also, numerous challenges exist, including unequal access to healthy foods, the industry’s influence, and behavioral barriers to dietary change. Future research should explore innovative approaches, such as nutrigenomics and digital health technologies, to personalize interventions and evaluate policy effectiveness. Collaboration across disciplines and sectors will be vital to develop comprehensive solutions and improve public health outcomes globally.

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.

Oxidative stress is a critical factor in the pathogenesis and progression of diabetes and its associated complications. The imbalance between reactive oxygen species (ROS) production and the body’s antioxidant defence mechanisms leads to cellular damage and dysfunction. In diabetes, chronic hyperglycaemia and mitochondrial dysfunction contribute to increased ROS production, further exacerbating oxidative stress. This oxidative burden adversely affects various aspects of diabetes, including impaired beta-cell function and insulin resistance, leading to disrupted glucose regulation. Additionally, oxidative stress-induced damage to blood vessels and impaired endothelial function contribute to the development of diabetic vascular complications such as retinopathy, nephropathy, and cardiovascular diseases. Moreover, organs and tissues throughout the body, including the kidneys, nerves, and eyes, are vulnerable to oxidative stress, resulting in diabetic nephropathy, neuropathy, and retinopathy. Strategies to mitigate oxidative stress in diabetes include antioxidant therapy, lifestyle modifications, and effective management of hyperglycaemia. However, further research is necessary to comprehensively understand the underlying mechanisms of oxidative stress in diabetes and to evaluate the efficacy of antioxidant interventions in preventing and treating diabetic complications. By addressing oxidative stress, it might be possible to alleviate the burden of diabetes and improve patient outcomes.

Non-invasive brain stimulation (NIBS) approaches have seen a rise in utilization in both clinical and basic neuroscience in recent years. Here, we concentrate on the two methods that have received the greatest research: transcranial direct current stimulation (tDCS) and repetitive transcranial magnetic stimulation (rTMS). Both approaches have yielded pertinent data regarding the cortical excitability in subjects in good health as well as pertinent advancements in the management of various clinical disorders. NIBS is a helpful method for comprehending the cortical control of the ANS. Previous research has shown that there are notable changes in muscular sympathetic nerve activity when the motor cortex is modulated. Furthermore, in NIBS investigations, the ANS has been employed more frequently as an outcome measure to comprehend the overall impacts of these methods, including their safety profile. Though there is ample proof that brain stimulation has autonomic effects on animals, new research on the connection between NIBS and the ANS has produced contradictory findings. In order to better understand NIBS processes and ANS function, it is crucial to take into account the reciprocal relationship that exists between central modulation and ANS function.

Summary: In the aftermath of the recent financial crisis there has been considerable focus on methods for predicting macroeconomic variables when their behaviour is subject to abrupt changes, associated for example with crisis periods. We propose similarity‐based approaches as a way to handle parameter instability and apply them to macroeconomic forecasting. The rationale is that clusters of past data that match the current economic conditions can be more informative for forecasting than the entire past behaviour of the variable of interest. We apply our methods to predict both simulated data in a set of Monte Carlo experiments, and a broad set of key US macroeconomic indicators. The forecast evaluation exercises indicate that similarity‐based approaches perform well, in general, in comparison with other common time‐varying forecasting methods, and particularly well during crisis episodes. [ABSTRACT FROM AUTHOR]

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.

Background and Aims: The COVID-19 pandemic, caused by the novel coronavirus SARS-CoV-2, has fundamentally reshaped the landscape of global public health, with some people suffering more adverse clinical outcomes than others. The aim of this study is to deepen our understanding of the specific impact of acute kidney injury (AKI) on the in-hospital mortality in octogenarian patients with COVID-19. Methods: This is a prospective observational cohort study, which involved 23 COVID-19 hospital units in the Campania Region, Italy. Exposure variables were collected during hospital admission and at discharge. Only patients aged ≥80 years were deemed eligible for the study. Results: 197 patients were included in the study (median age 83.0 [82.0–87.0] years; 51.5% men), with a median duration of hospitalization of 15.0 [8.0–25.0] days. From the multivariable Cox regression analysis, after the application of Šidák correction, only the respiratory rate (HR 1.09, 95% CI: 1.04 to 1.14; p < 0.001) and AKI development (HR: 3.40, 95% CI: 1.80 to 6.40; p < 0.001) were independently associated with the primary outcome. Moreover, the Kaplan–Meier analysis showed a significantly different risk of in-hospital mortality between patients with and without AKI (log-rank:

IntroductionDNA double-strand breaks are the most toxic lesions repaired through the non-homologous and joining (NHEJ) or the homologous recombination (HR), which is dependent on the generation of single-strand tails, by the DNA end resection mechanism. The resolution of the HR intermediates leads to error-free repair (Gene Conversion) or the mutagenic pathways (Single Strand Annealing and Alternative End-Joining); the regulation of processes leading to the resolution of the HR intermediates is not fully understood.MethodsHere, we used a hydrophilic extract of a new tomato genotype (named DHO) in order to modulate the Camptothecin (CPT) DNA damage response.ResultsWe demonstrated increased phosphorylation of Replication Protein A 32 Serine 4/8 (RPA32 S4/8) protein in HeLa cells treated with the CPT in combination with DHO extract with respect to CPT alone. Moreover, we pointed out a change in HR intermediates resolution from Gene Conversion to Single Strand Annealing through the modified DNA repair protein RAD52 homolog (RAD52), DNA excision repair protein ERCC-1 (ERCC1) chromatin loading in response to DHO extract, and CPT co-treatment, with respect to the vehicle. Finally, we showed an increased sensitivity of HeLa cell lines to DHO extract and CPT co-treatment suggesting a possible mechanism for increasing the efficiency of cancer therapy.DiscussionWe described the potential role of DHO extract in the modulation of DNA repair, in response to Camptothecin treatment (CPT), favoring an increased sensitivity of HeLa cell lines to topoisomerase inhibitor therapy.

Background and aims: Cardiovascular disease (CVD) is the leading cause of early mortality in orthotopic liver transplantation (OLT) patients. The fatty liver index (FLI) is strongly associated with carotid and coronary atherosclerosis, as well as cardiovascular mortality, surpassing traditional risk factors. Given the lack of data on FLI as a predictor of cardiovascular events in OLT recipients, we conducted a retrospective study to examine this topic. Methods and results: We performed a multicenter retrospective analysis of adult OLT recipients who had regular follow-up visits every three to six months (or more frequently if necessary) from January 1995 to December 2020. The minimum follow-up period was two years post-intervention. Anamnestic, clinical, anthropometric and laboratory data were collected, and FLI was calculated for all patients. Clinical trial.gov registration ID NCT05895669. A total of 110 eligible patients (median age 57 years [IQR: 50–62], 72.7% male) were followed for a median duration of 92.3 months (IQR: 45.7–172.4) post-liver transplantation. During this period, 16 patients (14.5%) experienced at least one adverse cardiovascular event (including fatal and non-fatal myocardial infarction and stroke). Receiver Operating Characteristic (ROC) analysis identified a cut-off value of 66.0725 for predicting cardiovascular events after OLT, with 86.7% sensitivity and 63.7% specificity (68% vs. 31%; p = 0.001). Kaplan–Meier analysis showed that patients with FLI > 66 had significantly reduced cardiovascular event-free survival than those with FLI ≤ 66 (log-rank: 0.0008). Furthermore, multivariable Cox regression analysis demonstrated that FLI > 66 and pre-OLT smoking were independently associated with increased cardiovascular risk. Conclusions: Our findings suggest that FLI > 66 and pre-OLT smoking predict cardiovascular risk in adult OLT recipients.

Study purpose. The aim of this study was to verify the effect of three sessions of aerobic training, for a period of 12 weeks, on VO2max and on the distance covered during the test. Materials and Methods. Fifteen sedentary males were recruited in this study. VO2max was investigated using Cooper test. Aerobic intervention lasted for 12 weeks. The exercise the subjects were performing for the first 6 weeks was supervised aerobic training, 3 times per week at 60–75% of heart rate max (HRmax) (The first two weeks at 60–65 % HRmax, third and fourth week at 65–70% HRmax, fifth and sixth week at 70–75% HRmax). Afterwards, the subjects continued supervised aerobic training for 6 weeks until the twelfth week at 70–75% HRmax. Results. After 8 weeks of aerobic training, a significant increase in distance covered during the Cooper test (p

Diazepam (DZP) is a benzodiazepine drug used as an anti-drug and sedative. It is often misused to induce or create euphoria in combination with other drugs (high or fly sensation) or administered alone. So far, screening for DZP abuse with sensitive analytical methods is needed, as its small concentrations make it difficult to detect. Increased sensitivity of the analytical method can be obtained by using a preparation method that selectively separates the analyte from the sample matrix. Molecularly imprinted polymer (MIP) is one of the preparation solutions with good selectivity, specificity, and sensitivity. MIP was made from DZP as a template, itaconic acid, and ethylene glycol dimethacrylate in a composition of 1:4:20. MIP was made by precipitation polymerisation to obtain microsphere polymer type. MIP had a binding capacity value of 0.0557 mg/g and followed the Freundlich isotherm. Application of the microsphere MIP on spiked blood serum resulted in a recovery of 105.63 ± 1.0% for MIP compared to 21.28 ± 0.4% for non-imprinted polymer, with the imprinting factor value reaching 4.96. Hence, MIP DZP with itaconic acid as a functional monomer and propanol as a porogen, fabricated by the precipitation polymerisation method, is a promising sorbent for DZP extraction in biological fluids.

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.

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.

One-third of patients with epilepsy do not respond to antiepileptic drugs and may seek complementary and alternative treatment modalities. Dietary therapies, such as the ketogenic diet (KD), the modified Atkins diet, as well as the medium-chain triglyceride and the low glycaemic index diets, have been successfully implemented with some forms of epilepsy and are growing in utilization. The KD is a high-fat, low-protein, low-carbohydrate diet that has been used for various conditions for over a century. Insights into the mechanism of action of these diets may provide more targeted interventions for patients with epilepsy. Knowledge of these mechanisms is growing and includes neuroprotective effects on oxidative stress, neuroinflammation, potassium channels in the brain, and mitochondrial function. In this review, we explain the role of physical exercise and the ketogenic diet on epilepsy.

Non-alcoholic fatty liver disease (NAFLD) comprises a heterogeneous group of metabolic liver diseases and is characterized by the presence of steatosis in at least 5% of hepatocytes. The aim of our study was to assess the effect of the combination therapy of empagliflozin + metformin vs. metformin monotherapy on NAFLD progression in type 2 diabetic (T2DM) patients. Sixty-three metformin-treated T2DM patients who were SGLT2i-naïve and had an ultrasound diagnosis of NAFLD (aged 60.95 ± 11.14 years; males, 57.1%) were included in the present analysis. Thirty-three started the combination therapy. All patients were observed for 6 months and routinely monitored with anthropometry, blood biochemistry, and FibroScan®/CAP. At the 6-month follow-up, the combination therapy group presented a significant reduction in BMI (30.83 ± 3.5 vs. 28.48 ± 3.25), glycated hemoglobin (8.2 (7.4–8.8)) vs. 7.2 (6.8–7.9), ALT (68.5 (41.5–88.0) vs. 45.00 (38.00, 48.00)), CAP parameter (293.5 (270.0–319.25) vs. 267.00 (259.50, 283.75)) and steatosis degree (p = 0.001) in comparison with the control group, whose parameters remained almost stable over time. In patients affected by T2DM, the combination of empagliflozin + metformin vs. metformin monotherapy ameliorated liver steatosis, ALT levels, body weight, and glycated hemoglobin after a 6-month follow-up.

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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.

Bisphenol A (BPA) is an endocrine disruptor (ED) frequently used in food packaging. BPA is used as a monomer in the manufacture of some food packaging. This study aimed to evaluate the urinary BPA concentration in an Italian pediatric cohort, testing the levels of this ED over a period of 6 months, evaluating the effects of a diet regimen with a reduction of Plastic Food Packaging (PFP). One hundred thirty Italian children were enrolled and divided into two groups “School Canteen” and “No School Canteen.” The first group consumed one meal at school using a plastic-free service for 5 days/weeks, while the other group did not modify their normal meal-time habits. The BPA levels were tested in urine samples at three time points: T0, is the time before the application of the plastic-free regimen diet; T3, 3 months later; and T6, 6 months later. A reduction of urine BPA levels was detected in the “School Canteen” group. In particular, the reduction was significant analyzing both the intra (among the three testing times) group and inter (between “School Canteen” and “No School Canteen”) group variability. Our results show the effects of a diet regimen with a reduction of PFP, demonstrating a connection between urinary BPA levels and food packaging.

Prolonged mastication may induce an asymmetric modification of the local perfusion of the trigeminal principal nucleus. The aim of the present study was to evaluate the possible influence of vitamin C (vit. C) on such effect. Four groups of healthy volunteers underwent arterial spin labeling magnetic resonance imaging (ASL-MRI) to evaluate the local perfusion of the trigeminal nuclei after a vit. C-enriched lunch or a control lunch. Two ASL-MRI scans were acquired, respectively, before and after a 1 h-long masticating exercise or a 1 h long resting period. The results showed (i) an increased global perfusion of the brain in the vit. C-enriched lunch groups, (ii) an increased local perfusion of the right principal trigeminal nucleus (Vp) due to mastication, and (iii) a reduction of the rightward asymmetry of the Vp perfusion, due to mastication, after the vit C-enriched meal compared to the control meal. These results confirmed a long-lasting effect of prolonged mastication on Vp perfusion and also suggest a possible effect of vit. C on cerebral vascular tone regulation. Moreover, the data strongly draw attention on the side-to-side relation in Vp perfusion as a possible physiological parameter to be considered to understand the origin of pathological conditions like migraine.

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.

Exercise represents the most important integrative therapy in metabolic, immunologic and chronic diseases; it represents a valid strategy in the non-pharmacological intervention of lifestyle linked diseases. A large body of evidence indicates physical exercise as an effective measure against chronic non-communicable diseases. The worldwide general evidence for health benefits are both for all ages and skill levels. In a dysregulated lifestyle such as in the obesity, there is an imbalance in the production of different cytokines. In particular, we focused on Adiponectin, an adipokine producted by adipose tissue, and on Orexin-A, a neuropeptide synthesized in the lateral hypothalamus. The production of both Adiponectin and Orexin-A increases following regular and structured physical activity and both these hormones have similar actions. Indeed, they improve energy and glucose metabolism, and also modulate energy expenditure and thermogenesis. In addition, a relevant biological role of Adiponectin and Orexin A has been recently highlighted in the immune system, where they function as immune-suppressor factors. The strong connection between these two cytokines and healthy status is mediated by physical activity and candidates these hormones as potential biomarkers of the beneficial effects induced by physical activity. For these reasons, this review aims to underly the interconnections among Adiponectin, Orexin-A, physical activity and healthy status. Furthermore, it is analyzed the involvement of Adiponectin and Orexin-A in physical activity as physiological factors improving healthy status through physical exercise.

Overweight and obesity are conditions of excessive body fat accumulation. In clinical practice, child and adolescent overweight and obesity are commonly identified by age- and gender-specific body mass index (BMI) percentiles, BMI standard deviation scores, and waist circumference (WC) percentiles relative to a reference population. A recent analysis of population data of children aged five to 19 years estimated that in 2016 obesity was identified in 50 million girls and 74 million boys worldwide. In the USA in 2014, the prevalence of child and adolescent obesity (BMI > 95th centile) was 9.4% (two to five years), 17.4% (six to 11 years), and 20.6% (12 to 19 years). In Europe, obesity prevalence was on average 4.0% in adolescents, with vast differences between countries. Childhood obesity prevalence is increasing in middle- and low-income countries, for example, up to 40% of children in Mexico were living with obesity or overweight, 32% in Lebanon and 28% in Argentina. Health problems are common in children and adolescents with obesity. These include cardiovascular conditions (e.g. hyperlipidaemia, hypertension), endocrinologic conditions (e.g. Type 2 diabetes, metabolic syndrome), gastrointestinal conditions (non-alcoholic fatty liver disease), respiratory conditions (e.g. obstructive sleep apnoea), musculoskeletal disorders, (e.g. slipped capital femoral epiphysis) and psychosocial disorders (e.g. depression, anxiety.

Personality disorders (PDs) are one of the major problems for the organization of public health systems. Deepening the link between personality traits and psychopathological drifts, it seems increasingly essential for the often dramatic repercussions that PDs have on social contexts. Some of these disorders, such as borderline PD, antisocial PD, in their most tragic expression, are the basis of problems related to crime, sexual violence, abuse, and mistreatment of minors. Many authors propose a dimensional classification of personality pathology, which has received empirical support from numerous studies over the last 20 years based on more robust theoretical principles than those applied to current nosography. The present study investigates the nature of the research carried out in the last years on the personality in the clinical field exploring the contents of current research on personality relapses, evaluating, on the one hand, the emerging areas of greatest interest and others, those that they stopped generating sufficient motivations in scholars. This study evaluates text patterns regarding how the terms “personality” and “mental health” are used in titles and abstracts published in PubMed in the last 5 years. We use a topic analysis: Latent Dirichlet Allocation that expresses every report as a probabilistic distribution of latent topics that are represented as a probabilistic distribution of words. A total of 7,572 abstracts (from 2012 to 2017) were retrieved from PubMed for the query on “mental health” and “personality.” The study found 30 topics organized in eight hierarchical clusters that describe the type of current research carried out on personality and its clinical relapse. The hierarchical clusters latent themes were the following: social dimensions, clinical aspects, biological issues, clinical history of PD, internalization and externalization symptoms, impulsive behaviors, comorbidities, criminal behaviors. The results indicate that the concept of personality is associated with a wide range of conditions. The study of personality and mental health still proceeds, mainly, according to a practical-clinical approach; too little moves, however, according to an innovative research approach, but the work shows the common commitment of scholars to a new way of dealing with the study of personality.

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 between neurotransmitters and their specific receptors, 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.

It is widely acknowledged that obesity is a growing public clinical issue involving both physical and psychological well-being. Nevertheless, the relationship between psychological features and weight gain is still unclear. Although emotional eating (EE) and personality traits are considered significant predictors of eating disorders, their role in obesity without eating disorders (OB-wed) is far from proven. The present study aimed at investigating the cumulative effect of EE and personality traits on overeating behavior in a sample of 266 university students (169 female; mean age = 21.85, SD = 2.39) stratified based on their body mass index (BMI; normal weight, overweight, obese). They were enrolled during free screening days promoted by the Human Dietetic and Sport Service of a Southern Italian university. The results show a psychological pattern of increasing overeating behavior and lower Self-Directedness combined with higher Sadness and Anger. However, OB-wed subjects overate regardless of this emotional/personological configuration.

Brain mitochondrial dysfunction is involved in the development of neurological and neurodegenerative diseases. Mitochondria specifically located at synapses play a key role in providing energy to support synaptic functions and plasticity, thus their defects may lead to synaptic failure, which is a common hallmark of neurodegenerative diseases. High-Fat Diet (HFD) consumption increases brain oxidative stress and impairs brain mitochondrial functions, although the underlying mechanisms are not completely understood. The aim of our study is to analyze neuroinflammation and mitochondrial dysfunctions in brain cortex and synaptosomal fraction isolated from a mouse model of diet-induced obesity. Male C57Bl/6 mice were divided into two groups fed a standard diet or HFD for 18 weeks. At the end of the treatment, inflammation (detected by ELISA), antioxidant state (measured by enzymatic activity), mitochondrial functions and efficiency (detected by oxidative capacity and Seahorse analysis), and brain-derived neurotrophic factor (BDNF) pathway (analyzed by western blot) were determined in brain cortex and synaptosomal fraction. In HFD animals, we observed an increase in inflammatory parameters and oxidative stress and a decrease in mitochondrial oxidative capacity both in the brain cortex and synaptosomal fraction. These alterations parallel with modulation of BDNF, a brain key signaling molecule that is linking synaptic plasticity and energy metabolism. Neuroinflammation HFD-dependent negatively affects BDNF pathway and mitochondrial activity in the brain cortex. The effect is even more pronounced in the synaptic region, where the impaired energy supply may have a negative impact on neuronal plasticity.

Milk and dairy products are relevant components of daily diet and are part of dietary recommendation in many countries due to their content of key nutrients. However, the relatively high content of saturated fat of the milk and its extensive usage for every age group raises concerns about its potential negative health effects. Therefore, in the last years, several researchers dedicated their attention to milk production and quality. Milk fatty acids profile depend on cow feeding and in particular on the type of forage and concentrate and forage/concentrate ratio. It was demonstrated that feeding dairy cows with a 70/30 forage/concentrate ratio yields milk with a low ω6:ω3 ratio and high CLA levels. In this work, we demonstrated that the supplementation of rats diet with this high forage milk (HFM) results, in the skeletal muscle of these animals, in a reduced lipid content and inflammation levels, and an improved mitochondrial lipid oxidation, and redox status through modulation of AMPK activity.

Transcranial magnetic stimulation, since its introduction in 1985, has brought important innovations to the study of cortical excitability as it is a non-invasive method and, therefore, can be used both in healthy and sick subjects. Since the introduction of this cortical stimulation technique, it has been possible to deepen the neurophysiological aspects of motor activation and control. In this narrative review, we want to provide a brief overview regarding TMS as a tool to investigate changes in cortex excitability in athletes and highlight how this tool can be used to investigate the acute and chronic responses of the motor cortex in sport science. The parameters that could be used for the evaluation of cortical excitability and the relative relationship with motor coordination and muscle fatigue, will be also analyzed. Repetitive physical training is generally considered as a principal strategy for acquiring a motor skill, and this process can elicit cortical motor representational changes referred to as use-dependent plasticity. In training settings, physical practice combined with the observation of target movements can enhance cortical excitability and facilitate the process of learning. The data to date suggest that TMS is a valid technique to investigate the changes in motor cortex excitability in trained and untrained subjects. Recently, interest in the possible ergogenic effect of non-invasive brain stimulation in sport is growing and therefore in the future it could be useful to conduct new experiments to evaluate the impact on learning and motor performance of these techniques.

Brown-like adipocytes can be induced in white fat depots by a different environmental or drug stimuli, known as “browning” or “beiging”. These brite adipocytes express thermogenin UCP1 protein and show different metabolic advantages, such as the ability to acquire a thermogenic phenotype corresponding to standard brown adipocytes that counteracts obesity. In this research, we evaluated the effects of several browning agents during white adipocyte differentiation of bone marrow-derived mesenchymal stromal cells (MSCs). Our in vitro findings identified two compounds that may warrant further in vivo investigation as possible anti-obesity drugs. We found that rosiglitazone and sildenafil are the most promising drug candidates for a browning treatment of obesity. These drugs are already available on the market for treating diabetes and erectile dysfunction, respectively. Thus, their off-label use may be contemplated, but it must be emphasized that some severe side effects are associated with use of these drugs.

Background and objectives: Coronavirus disease 2019 (COVID-19) is a highly contagious infectious disease, responsible for a global pandemic that began in January 2020. Human/COVID-19 interactions cause different outcomes ranging from minor health consequences to death. Since social interaction is the default mode by which individuals communicate with their surroundings, different modes of contagion can play a role in determining the long-term consequences for mental health and emotional well-being. We examined some basic aspects of human social interaction, emphasizing some particular features of the emotional contagion. Moreover, we analyzed the main report that described brain damage related to the COVID-19 infection. Indeed, the goal of this review is to suggest a possible explanation for the relationships among emotionally impaired people, brain damage, and COVID-19 infection. Results: COVID-19 can cause several significant neurological disorders and the pandemic has been linked to a rise in people reporting mental health problems, such as depression and anxiety. Neurocognitive symptoms associated with COVID-19 include delirium, both acute and chronic attention and memory impairment related to hippocampal and cortical damage, as well as learning deficits in both adults and children. Conclusions: Although our knowledge on the biology and long-term clinical outcomes of the COVID-19 infection is largely limited, approaching the pandemic based on lessons learnt from previous outbreaks of infectious diseases and the biology of other coronaviruses will provide a suitable pathway for developing public mental health strategies, which could be positively translated into therapeutic approaches, attempting to improve stress coping responses, thus contributing to alleviate the burden driven by the pandemic.

Neurodevelopmental disorders (NDDs) include diverse neuropathologies characterized by abnormal brain development leading to impaired cognition, communication and social skills. A common feature of NDDs is defective synaptic plasticity, but the underlying molecular mechanisms are only partially known. Several studies have indicated that people’s lifestyles such as diet pattern and physical exercise have significant influence on synaptic plasticity of the brain. Indeed, it has been reported that a high-fat diet (HFD, with 30–50% fat content), which leads to systemic low-grade inflammation, has also a detrimental effect on synaptic efficiency. Interestingly, metabolic alterations associated with obesity in pregnant woman may represent a risk factor for NDDs in the offspring. In this review, we have discussed the potential molecular mechanisms linking the HFD-induced metabolic dysfunctions to altered synaptic plasticity underlying NDDs, with a special emphasis on the roles played by synaptic protein synthesis and mitochondrial functions.

Functional non-retentive fecal incontinence (FNRFI) is a common problem in pediatric age. FNRFI is defined as unintended loss of stool in a 4-year-old or older child after organic causes have been excluded. FNRFI tends to affects up to 3% of children older than 4 years, with males being affected more frequently than females. Clinically, children affected by FNRFI have normal intestinal movements and stool consistency. Literature data show that children with fecal incontinence have increased levels of separation anxiety, specific phobias, general anxiety, attention-deficit/hyperactivity disorder (ADHD), and oppositional defiant disorder. In terms of possible relationship between incontinence and sleep, disorders of sleep organization have been observed in the pathogenesis of enuresis so generating the hypothesis that the orexinergic system may have a crucial role not only for the sleep organization per se but also for the sphincterial control in general. This study aimed to focus on specific neurophysiological aspects to investigate on the possible relationship between sleep organizational abnormalities and FNRFI. Specifically, we aimed to measure orexin serum levels in children with FNRFI and assess their polysomnographic sleep macrostructure patterns. Two study groups were considered: FNFRI (n = 45) and typically developed (TD) (n = 45) group. In both groups, sleep patterns and respiratory events were assessed by polysomnographic recordings (PSG) during a period of two nights at least, and plasma levels of Orexin-A were measured in each participant. The findings of this initial investigation seem to support a major role of Orexin-A in sleep organization alterations in children with FNFRI. Also, our data suggest that sleep habits evaluation should be considered as screening and complementary tool for the diagnosis of fecal incontinence in children.

Previous studies showed that healthy individuals bisect radial lines oriented along the midsagittal plane farther than the true center (distal bisection bias). It was proposed that the distal bisection bias depended on the presence of an attention bias directed toward far space (distal attention bias) and that this bias is related to the activity of the occipitotemporal visual processing stream. Other studies have also suggested that a similar distal attention bias is linked to the activity of the right hemisphere. In the present experiment we investigated whether distal bisection bias increased when radial lines were placed in the left hemispace. Furthermore, we also examined whether the bisection bias was enhanced by the use of the left hand, as left hand movements are mainly controlled by the right hemisphere. Right-handed participants were asked to bisect radial lines presented below eye level along the midsagittal plane (central lines), or laterally and parallel to the midsagittal plane, in the left or right hemispace (left and right lines, respectively). Participants used their right or left hand. The results showed that participants consistently bisected left and central radial lines farther than (i) the true center and (ii) the subjective midpoint of right radial lines. Conversely, they bisected accurately right radial lines. The hand did not influence bisection error. The present study suggests that the distal bisection bias found in the bisection of left radial lines might depend on the presence of a distal attention bias related to right hemisphere activity. The relative contribution of retinotopic and spatiotopic factors in producing the distal bisection bias is discussed.