Interplay between Peripheral and Central Inflammation in Obesity-Promoted Disorders: The Impact on Synaptic Mitochondrial Functions.

The metabolic dysfunctions induced by high fat diet (HFD) consumption are not limited to organs involved in energy metabolism but cause also a chronic low-grade systemic inflammation that affects the whole body including the central nervous system. The brain has been considered for a long time to be protected from systemic inflammation by the blood-brain barrier, but more recent data indicated an association between obesity and neurodegeneration. Moreover, obesity-related consequences, such as insulin and leptin resistance, mitochondrial dysfunction and reactive oxygen species (ROS) production, may anticipate and accelerate the physiological aging processes characterized by systemic inflammation and higher susceptibility to neurological disorders. Here, we discussed the link between obesity-related metabolic dysfunctions and neuroinflammation, with particular attention to molecules regulating the interplay between energetic impairment and altered synaptic plasticity, for instance AMP-activated protein kinase (AMPK) and Brain-derived neurotrophic factor (BDNF). The effects of HFD-induced neuroinflammation on neuronal plasticity may be mediated by altered brain mitochondrial functions. Since mitochondria play a key role in synaptic areas, providing energy to support synaptic plasticity and controlling ROS production, the negative effects of HFD may be more pronounced in synapses. In conclusion, it will be emphasized how HFD-induced metabolic alterations, systemic inflammation, oxidative stress, neuroinflammation and impaired brain plasticity are tightly interconnected processes, implicated in the pathogenesis of neurological diseases.

Manual asymmetry for temporal and spatial parameters in sensorimotor synchronization.

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.

Evaluation of Orexin-A Salivary Levels and its Correlation with Attention After Non-invasive Brain Stimulation in Female Volleyball Players.

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 Relationship between Executive Functions and Body Weight: Sex as a Moderating Variable.

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.

Functional Characteristics and Coping Strategies among Rugby Athletes: A Cluster Analysis Approach.

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.

Role of Milk Micronutrients in Human Health.

The aim of this review is to provide an overview of different compositions, in terms of main minerals and vitamins, of milk from animal species that represent the most common source of this food for humans, highlighting the uniqueness of nutritional qualities linked to animal species. It is known that milk is an important and valuable food for human nutrition, representing an excellent source of nutrients. Indeed, it contains both macronutrients (proteins, carbohydrates, and fat) that contribute to its nutritive and biological value and micronutrients represented by minerals and vitamins, which play a relevant role in the body's various vital functions. Although their supply is represented by small quantities, vitamins and minerals are important components for a healthy diet. Milk composition in terms of minerals and vitamins differs between various animal species. Micronutrients are important components for human health as their deficiency is causes of malnutrition. Furthermore, we report on the most significant metabolic and beneficial effects of certain micronutrients in the milk, emphasizing the importance of this food for human health and the need for some milk enrichment procedures with the most relevant micronutrients to human health.

Mechanisms of Transmission and Processing of Pain: A Narrative Review.

Knowledge about the mechanisms of transmission and the processing of nociceptive information, both in healthy and pathological states, has greatly expanded in recent years. This rapid progress is due to a multidisciplinary approach involving the simultaneous use of different branches of study, such as systems neurobiology, behavioral analysis, genetics, and cell and molecular techniques. This narrative review aims to clarify the mechanisms of transmission and the processing of pain while also taking into account the characteristics and properties of nociceptors and how the immune system influences pain perception. Moreover, several important aspects of this crucial theme of human life will be discussed. Nociceptor neurons and the immune system play a key role in pain and inflammation. The interactions between the immune system and nociceptors occur within peripheral sites of injury and the central nervous system. The modulation of nociceptor activity or chemical mediators may provide promising novel approaches to the treatment of pain and chronic inflammatory disease. The sensory nervous system is fundamental in the modulation of the host's protective response, and understanding its interactions is pivotal in the process of revealing new strategies for the treatment of pain.

The assessment of executive functions to test the integrity of the nigrostriatal network: A pilot study.

Background: Parkinson's disease (PD) is a chronic neurodegenerative disorder characterized by motor and non-motor symptoms. The latter mainly include affective, sleep, and cognitive deficits. Non-demented PD patients often demonstrate impairments in several executive domains following neuropsychological evaluation. The current pilot study aims at assessing the discriminatory power of the Frontal Assessment Battery-15 (FAB15) in differentiating (i) non-demented PD patients and healthy controls and (ii) PD patients with more and less pronounced motor symptoms. Methods: Thirty-nine non-demented early-stage PD patients in the "on" dopamine state (26 females, mean age = 64.51 years, SD = 6.47, mean disease duration = 5.49 years, SD = 2.28) and 39 healthy participants (24 females, mean age = 62.60 years, SD = 5.51) were included in the study. All participants completed the FAB15. Motor symptoms of PD patients were quantified via the Unified Parkinson's Disease Rating Scale-Part III (UPDRS-Part III) and Hoehn and Yahr staging scale (H&Y). Results: The FAB15 score, adjusted according to normative data for sex, age, and education, proved to be sufficiently able to discriminate PD patients from healthy controls (AUC = 0.69 [95% CI 0.60-0.75], SE = 0.06, p = 0.04, optimal cutoff = 11.29). Conversely, the battery lacked sufficient discriminative capability to differentiate PD patients based on the severity of motor symptoms. Conclusion: The FAB15 may be a valid tool for distinguishing PD patients from healthy controls. However, it might be less sensitive in identifying clinical phenotypes characterized by visuospatial impairments resulting from posteroparietal and/or temporal dysfunctions. In line with previous evidence, the battery demonstrated to be not expendable in the clinical practice for monitoring the severity of PD-related motor symptoms.

Obesity Is Associated with Changes in Laboratory Biomarkers in Chilean Patients Hospitalized with COVID-19.

BACKGROUND AND AIMS: It is reported that patients with obesity are more frequently hospitalized for COVID-19, and evidence exists that obesity is a risk factor, regardless of other comorbidities. The objective of this study was to evaluate the association of obesity with changes in laboratory biomarkers in hospitalized Chilean patients. MATERIALS AND METHODS: A total of 202 hospitalized patients (71 with obesity and 131 without obesity) with a diagnosis of COVID-19 were included in the study. Demographic, clinical, and laboratory (days 1, 3, 7, 15) data were obtained. We performed a statistical analysis, assuming significance with a value of p < 0.05. RESULTS: Significant differences in chronic respiratory pathology are observed between patients with and without obesity. The inflammatory markers CPR, ferritin, NLR, and PLR are elevated during the evaluated period, while changes in leukocyte populations are present on day 1 (eosinophils) and day 3 (lymphocytes). Finally, a persistent elevation of D-dimer level is observed, presenting significant differences on day 7 between patients with and without obesity. Obesity had a positive correlation with admission to the critical patient unit, invasive mechanical ventilation, and length of hospital stay. CONCLUSION: Patients with obesity hospitalized for COVID-19 present marked elevations of inflammatory and hemostasis parameters, with a correlation between obesity, changes in laboratory biomarkers, and the risk of adverse clinical outcomes also observed.

Heart Rate Variability and Sympathetic Activity Is Modulated by Very Low-Calorie Ketogenic Diet.

Obesity is characterized by an energy imbalance and by the accumulation of visceral adipose tissue. The energy balance is controlled by a complex set of balanced physiological systems that provide hunger and satiety signals to the brain and regulate the body's ability to consume energy. The central nervous system controls the metabolic state, influencing the activity of other systems and receiving information from them. Heart rate variability (HRV) is the natural variability of the heart rate in response to several factors. HRV is related to the interaction between the SNS and the parasympathetic. In the light of this evidence, the aim of this study is to investigate the possible effects of the two different dietary regimens such as very low-calorie ketogenic diet (VLCKD) vs. low caloric diet (LCD), on the functions of the nervous system, with particular attention to the autonomous control of heart rate variability (HRV). A total of 26 obese subjects underwent diet therapy in order to reduce body weight; they were also randomly divided into two groups: the VLCKD group and the LCD group. Our results showed that in both groups, there is a reduction in heart rate as an indicator of sympathetic activity; we found a statistically significant variation only in the VLCKD group. Therefore, this study supports the notion that the sympathovagal balance can be modulated by a specific diet, but further studies are needed to clarify the molecular pathway undergoing this modulation.

Physiological Role of Orexinergic System for Health.

Orexins, or hypocretins, are excitatory neuropeptides involved in the regulation of feeding behavior and the sleep and wakefulness states. Since their discovery, several lines of evidence have highlighted that orexin neurons regulate a great range of physiological functions, giving it the definition of a multitasking system. In the present review, we firstly describe the mechanisms underlining the orexin system and their interactions with the central nervous system (CNS). Then, the system's involvement in goal-directed behaviors, sleep/wakefulness state regulation, feeding behavior and energy homeostasis, reward system, and aging and neurodegenerative diseases are described. Advanced evidence suggests that the orexin system is crucial for regulating many physiological functions and could represent a promising target for therapeutical approaches to obesity, drug addiction, and emotional stress.

Obesity as a Risk Factor for Severe COVID-19 in Hospitalized Patients: Epidemiology and Potential Mechanisms.

SARS-CoV-2 infection is a global public health problem, causing significant morbidity and mortality. Evidence shows that obesity is a recognized risk factor for hospitalization, admission to critical care units, and the development of serious complications from COVID-19. This review analyzes the available epidemiological evidence that relates obesity to a higher risk of severity and mortality from COVID-19, examining the possible pathophysiological mechanisms that explain this phenomenon on a cellular and molecular level.

Executive Functions in Overweight and Obese Treatment-Seeking Patients: Cross-Sectional Data and Longitudinal Perspectives.

BACKGROUND: Recent evidence suggests that a higher body weight may be linked to cognitive impairment in different domains involving executive/frontal functioning. However, challenging results are also available. Accordingly, our study was designed to verify whether (i) poor executive functions are related to a higher body weight and (ii) executive functioning could contribute to weight loss in treatment-seeking overweight and obese patients. METHODS: We examined general executive functioning, inhibitory control, verbal fluency, and psychomotor speed in a sample including 104 overweight and obese patients. Forty-eight normal-weight subjects participated in the study as controls. RESULTS: Univariate Analysis of Variance showed that obese patients obtained lower scores than overweight and normal-weight subjects in all executive measures, except for errors in the Stroop test. However, when sociodemographic variables entered the model as covariates, no between-group difference was detected. Furthermore, an adjusted multiple linear regression model highlighted no relationship between weight loss and executive scores at baseline. CONCLUSIONS: Our results provide further evidence for the lack of association between obesity and the executive domains investigated. Conflicting findings from previous literature may likely be due to the unchecked confounding effects exerted by sociodemographic variables and inclusion/exclusion criteria.

The Role of Nutraceutical Supplements, Monacolin K and Astaxanthin, and Diet in Blood Cholesterol Homeostasis in Patients with Myopathy.

Several studies suggest that different combinations of nutraceutical supplements may improve the lipid profile, representing a viable alternative to statins. However, their effects on individuals with myopathy need to be investigated. The aim of our study was to explore the mid- and long-term physiological effects of monacolin k (5 mg) and astaxanthin (0.1 mg) supplements in association with a low-energy/fat diet in a group of subjects with mild myopathy. Eighty subjects (44 women) took part in this observational study. Participants were assigned to the experimental group (EG, n = 40, 24 women) treated with a low-energy/fat diet (1200-1500 Kcal/day and 15-20% lipids) in combination with monacolin k (5 mg) and astaxanthin (0.1 mg) supplementation, and to the control group (CG, n = 40, 20 women) treated only with a low-energy/fat diet (1200-1500 Kcal/day and 15-20% lipids). BMI and biochemical parameters (blood glucose, total cholesterol, HDL, LDL, triglycerides, C-reactive protein (CRP) and creatine phosphokinase-CPK) were collected at baseline (T0), after 12 (T1) and 24 (T2) weeks. A mixed factorial ANOVA was performed to determine if there were significant main effects and/or interactions between time and treatment. Treatment (EG vs. CG) was entered as the between-subjects factor and time (T0 vs. T1 vs. T2) as the within-subject factor. We found a significant improvement in total cholesterol, HDL, LDL, PCR and CPK parameters in EG compared with CG. Our results highlight the efficacy and safety of combined use of monacolin k (5 mg) and astaxanthin (0.1 mg) in combination with a low-energy/fat diet in the treatment of dyslipidemia.

Functional Relationship between Inhibitory Control, Cognitive Flexibility, Psychomotor Speed and Obesity.

In the last decades, it has been proposed that executive functions may be particularly vulnerable to weight-related issues. However, evidence on the matter is mixed, especially when the effects of sociodemographic variables are weighted. Thus, the current study aimed at further examining the relationship between executive functions and obesity. To this aim, we compared treatment-seeking overweight, obese, and morbidly obese patients with normal-weight control participants. We examined general executive functioning (Frontal Assessment Battery−15) and different executive subdomains (e.g., inhibitory control, verbal fluency, and psychomotor speed) in a clinical sample including 208 outpatients with different degrees of BMI (52 overweight, BMI 25−30, M age = 34.38; 76 obese, BMI 30−40, M age = 38.00; 80 morbidly obese, BMI > 40, M age = 36.20). Ninety-six normal-weight subjects served as controls. No difference on executive scores was detected when obese patients were compared with over- or normal-weight subjects. Morbidly obese patients reported lower performance on executive scores than obese, overweight, and normal-weight subjects. Between-group difference emerged also when relevant covariates were taken into account. Our results support the view that morbid obesity is associated with lower executive performance, also considering the critical role exerted by sociodemographic (i.e., sex, age, and education) variables. Our results support the view that executive functioning should be accounted into the management of the obese patient because of non-negligible clinical relevance in diagnostic, therapeutic, and prognostic terms.

Factorial Model of Obese Adolescents: The Role of Body Image Concerns and Selective Depersonalization-A Pilot Study.

BACKGROUND: The relationship binding body weight to psychological well-being is unclear. The present study aims at identifying the contribution, and specificity, of some dimensions (i.e., eating-related symptoms, body image disorders, eating habits, personality traits, and emotional difficulties) characterizing the psychological profile of obese adolescents (749 participants, 325 females; 58.3% normal-weight, 29.9% overweight, and 11.7% obese; mean age = 16.05, SD = 0.82). METHODS: By introducing the scores obtained by standardized self-report tools into a generalized linear model, a factorial reduction design was used to detect the best fitting discriminant functions and the principal components explaining the higher proportion of the variance. RESULTS: We found two discriminant functions correctly classifying 87.1% of normal-weight, 57.2% of overweight, and 68.2% of obese adolescents. Furthermore, two independent factors, explaining 69.68% of the total variance, emerged. CONCLUSIONS: The first factor, "Body Image Concerns", included the drive for thinness, body dissatisfaction, and interpersonal distrust. The second factor, "Selective Depersonalization", included a trend toward depersonalization and dissatisfaction with the torso. The neurophysiological implications of our findings will be discussed.

Higher general executive functions predicts lower body mass index by mitigating avoidance behaviors.

Background: The present study examines the relationship between obesity, executive functions, and body image in a nonclinical population from southern Italy. Methods: General executive functioning (Frontal Assessment Battery-15), and body image disturbances (Body Uneasiness Test) were assessed in a sample including 255 participants (138 females, M age = 43.51 years, SD = 17.94, range = 18-86 years; M body mass index (BMI) = 26.21, SD = 4.32, range = 18.03-38.79). Findings: Multiple Linear Regression Analysis indicated that age, years of education, FAB15 score, body image concerns, and avoidance predicted the variance of BMI. A subsequent mediation analysis highlighted that the indirect effect of FAB15 on BMI through avoidance was statistically significant. Interpretation: Our results suggest that more performing executive functioning predicts a decrease in BMI that is partially due to the mitigation of avoidance behaviors.

Correction: La Torre et al. Role of Vitamin E and the Orexin System in Neuroprotection. Brain Sci. 2021, 11, 1098.

In the original article [...].

The Neglected Factor in the Relationship between Executive Functioning and Obesity: The Role of Motor Control.

BACKGROUND: The association between obesity and executive functions (EFs) is highly controversial. It has been suggested that waist circumference (WC), compared to body mass index (BMI), is a better indicator of fat mass and EFs in obesity. Moreover, according to the viewpoint that the brain's functional architecture meets the need for interactive behavior, we hypothesize that the relationship between EFs and body weight might be mediated by the motor performance. METHODS: General executive functioning (frontal assessment battery-15), additional cognitive subdomains (trail making test and digit span backward), and motor performance (finger tapping task) were assessed in a sample that included 330 volunteers (192 females, M age = 45.98 years, SD = 17.70, range = 18-86 years). RESULTS: Hierarchical multiple regression analysis indicated that the FAB15 score and FTT negatively predicted WC but not BMI. A subsequent mediation analysis highlighted that the indirect effect of FAB15 on WC through finger tapping was statistically significant. CONCLUSIONS: Our results suggest that WC, as compared to BMI, is a more effective measure for studying the association between EFs and body weight. Still, we found that the motor domain partially mediates the dynamics of such a relationship.

Egocentric and allocentric spatial representations in a patient with Bálint-like syndrome: A single-case study.

Previous studies suggested that egocentric and allocentric spatial representations are supported by neural networks in the occipito-parietal (dorsal) and occipito-temporal (ventral) streams, respectively. The present study aimed to explore the integrity of ego- and allo-centric spatial representations in a patient (GP) who presented bilateral occipito-parietal damage consistent with the picture of a Bálint-like syndrome. GP and healthy controls were asked to provide memory-based spatial judgments on triads of objects after a short (1.5sec) or long (5sec) delay. The results showed that GP's performance was selectively impaired in the Ego/1.5sec delay condition. As a whole, our findings suggest that GP's spared ventral stream could generate short- and long-term allocentric representations. Furthermore, the stored perceptual representation processed within the ventral stream might have been used to generate long-term egocentric representation. Conversely, the generation of short-term egocentric representation appeared to be selectively undermined by the damage of the dorsal stream.