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Vincenzo Monda,1,* Marco La Marra,1,* Raffaella Perrella,2 Giorgio Caviglia,2 Alessandro Iavarone,3 Sergio Chieffi,1 Giovanni Messina,4 Marco Carotenuto,5 Marcellino Monda,1 Antonietta Messina1 1Department of Experimental Medicine, Section of Human Physiology, University of Campania Luigi Vanvitelli, Naples, Italy; 2Neurological and Stroke Unit, CTO Hospital, AORN ‘‘Ospedali dei Colli’’, Naples, Italy; 3Department of Psychology, University of Campania Luigi Vanvitelli, Naples, Italy; 4Department of Clinical and Experimental Medicine, University of Foggia, Foggia, Italy; 5Clinic of Child and Adolescent Neuropsychiatry, Department of Mental Health, Physical and Preventive Medicine, University of Campania Luigi Vanvitelli, Naples, Italy *These authors contributed equally to this work Abstract: Recent findings showed that obesity represents an additional risk factor to developing brain illness such as cognitive impairments and psychopathological disorders. However, some benefits of overweight in the elderly have been identified and an “obesity paradox” has been shown. Currently, it is still unknown how obesity and brain functioning could be linked, and the process by which body fat independently injures cognitive abilities and psychological well-being remains unclear. To establish the independent role of obesity on cognitive abilities and mental health, clarifying the role played by several factors and understanding their interaction is essential. In this review, we discuss the relationship between obesity and brain illness and underline the role played by confounders and other covariates to determine this link. Keywords: obesity, cognitive decline, mood disorders, obesity paradox

The prevalence of obesity is increasing in the industrialized world, so that the World Health Organization considers obesity as a "pandemia" in rich populations. The autonomic nervous system plays a crucial role in the control of energy balance and body weight.This reviewsummarizes our own data and perspectives, emphasizing the influence exerted by autonomic nervous systemon energy expenditure and food intake, which are able to determine the body weight. Activation of the sympathetic discharge causes an increase in energy expenditure and a decrease in food intake, while reduction of food intake and body weight loss determines a reduction of the sympathetic activity. On the other hand, pathophysiological mechanisms of the obesity involve alterations of the sympathetic nervous system in accordance with the "Mona Lisa Hypothesis," an acronym for "most obesities known are low in sympathetic activity." Furthermore, the parasympathetic influences on the energy expenditure are analyzed in this review, showing that an increase in parasympathetic activity can induce a paradoxical enhancement of energy consumption. [ABSTRACT FROM AUTHOR]

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

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., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. The author(s) declared that they were an editorial board member of Frontiers, at the time of submission. This had no impact on the peer review process and the final decision., (Copyright © 2024 Sessa, Polito, Li Rosi, Salerno, Esposito, Pisanelli, Ministeri, Messina, Carotenuto, Chieffi, Messina and Monda.)

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.

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., Competing Interests: The authors declare no conflicts of interest.

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.

Hidradenitis suppurativa (HS) is a chronic inflammatory, immune-mediated, debilitating skin disease, characterized by subcutaneous nodules, with a still not clear pathophysiology. Although the prevalence is rather low (about 1% in Europe), its clinical complications, as well as the disabling symptomatology, make it necessary multidisciplinary therapeutic approaches. Not recently several authors described the involvement of the well-known gut-skin axis in both pathogenesis and progression of dermatological diseases. In particular, a high frequency of intestinal disorders (such as irritable bowel syndrome and inflammatory bowel disease) has been reported in HS patients, leading to speculate the existence of a relationship between such gut and skin diseases. The keystone in this relationship seems to be an impairment of the physiological gut mucosal barrier structure, resulting in the so-called leaky gut. The leaky gut, thus, might be responsible for a dietary compound-caused activation of the local immune system, with consequent trigging of both local and systemic inflammation, resulting in exacerbation of skin symptoms in HS patients. The current literature suggests the use of a low fermentable, oligo-, di, mono-saccharides and polyols (FODMAP) diet as a valid nutritional strategy in leaky gut. In light of this, we want to evaluate and consider the potential use of low-FODMAP diet in HS patient.

When normal individuals are asked to localize and mark the midpoint of a radial line, they tend to bisect it farther than the true center. It has been suggested that radial misbisection depends on the presence of a visual attentional bias directed toward the far space. The aim of the present study was to investigate whether the localization of the center of radial lines was affected by the starting position of the hand. There were two starting positions: one between the body and the radial line ("near"), the other beyond the radial line ("far"). Thirty-four subjects participated in the experiment. The results showed that (i) participants bisected radial lines farther than the true center, measured with reference to their body, in both near and far condition, and (ii) bisection errors in the near condition were greater than those in the far condition. We suggest that hand starting position and direction of ongoing movement influenced radial line misbisection by modulating visual attentional bias directed to far space., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Ricci, Iavarone, Ilardi and Chieffi.)

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.

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.

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., Competing Interests: The authors declare no conflict of interest.

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.

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.

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.

Decreased upper-extremity/visuomotor abilities are frequently encountered in healthy aging. However, few studies have assessed hand movements in the prodromal stage of dementia. The evaluation of visuomotor skills in patients with Mild Cognitive Impairment (PwMCI) may have non-negligible clinical relevance both in diagnostic and prognostic terms, given the strong relationships with executive functioning and functional autonomies. In the present review paper, these issues will be disclosed by describing general pathophysiological and neuropsychological mechanisms responsible for visuomotor deficits, and by reporting the available experimental results on differences in visuomotor functioning between PwMCI, healthy controls and/or patients with dementia. Moreover, the relationships binding visuomotor and executive domains to functional autonomies will be then addressed. Finally, we will propose insights for future research., Competing Interests: The authors declare no conflict of interest., (© 2022 The Author(s). Published by IMR Press.)

Objective: The Frontal Assessment Battery (FAB) is a neuropsychological tool largely used to assess executive functions. Prior studies found a marked ceiling effect for the prehension behavior subtest (PBT) in healthy and clinical populations. Aims of the present study were (i) to examine the psychometric properties of the FAB without the contribution of PBT and (ii) to provide normative data for a revised version of the FAB after exclusion of PBT (FAB15)., Methods: The normative sample included 1,187 healthy participants. PBT had near-zero variance, poor content validity, and no discrimination power. Internal consistency increased when PBT was excluded. We assessed the FAB15 factorial structure, interrater, and test-retest reliabilities. Normative data  for the FAB15 were extracted through a regression-based procedure according to sex, age, and education., Results: The principal component analysis revealed a single "executive factor" or alternatively a bifactorial solution reflecting the different degree of discriminative capability vs. difficulty of the subtests. The FAB15 demonstrated excellent interrater and test-retest reliabilities. Regression analysis showed that sex (lowly educated women < lowly educated men), higher age, and lower education affected FAB15 score. Accordingly, three grids for adjustment of raw scores (men, women, and both) were constructed. The cut-off was fixed at the non-parametric outer tolerance limit on the fifth centile (9.36, 95% CI)., Conclusion: The observation of a ceiling effect in healthy subjects makes PBT not suitable for inclusion in a neuropsychological battery. The FAB15 may successfully replace the conventional FAB as a more severe and valid short screening tool to assess executive functioning., (© 2021. Fondazione Società Italiana di Neurologia.)

In the present review, we discuss the rationale and the clinical implications of assessing visuospatial working memory (VSWM), awareness of memory deficits, and visuomotor control in patients with mild cognitive impairment (MCI). These three domains are related to neural activity in the posteromedial parietal cortex (PMC) whose hypoactivation seems to be a significant predictor of conversion from MCI to Alzheimer's disease (AD) as indicated by recent neuroimaging evidence. A systematic literature search was performed up to May 2021. Forty-eight studies were included: 42 studies provided analytical cross-sectional data and 6 studies longitudinal data on conversion rates. Overall, these studies showed that patients with MCI performed worse than healthy controls in tasks assessing VSWM, awareness of memory deficits, and visuomotor control; in some cases, MCI patients' performance was comparable to that of patients with overt dementia. Deficits in VSWM and metamemory appear to be significant predictors of conversion. No study explored the relationship between visuomotor control and conversion. Nevertheless, it has been speculated that the assessment of visuomotor abilities in subjects at high AD risk might be useful to discriminate patients who are likely to convert from those who are not. Being able to indirectly estimate PMC functioning through quick and easy neuropsychological tasks in outpatient settings may improve diagnostic and prognostic accuracy, and therefore, the quality of the MCI patient's management., (© 2021. The Author(s).)

Background: Early detection of anxiety symptoms in older people is capital as it may be linked to increased physical/functional disabilities, onset and progression of neurodegenerative disorders, and poor cognitive functioning. Nonetheless, there is a paucity of psychometrically validated anxiety measures in the elderly., Aims: This study aimed at assessing the psychometric properties of the State-Trait Anxiety Inventory-Form Y (STAI-Y) and providing the first normative data for the Italian elderly population., Methods: The sample included 361 individuals aged 65-94. All subjects underwent the Mini-Mental State Examination (MMSE), the Geriatric Depression Scale (GDS), and the state (S-Anxiety) and trait anxiety (T-anxiety) scales of the STAI-Y., Results: The S-Anxiety and T-Anxiety scales showed reliable internal consistency and, overall, good item characteristics. Divergent validity was "apparently" threatened, with S-Anxiety scale correlating with MMSE and GDS, and T-Anxiety scale only with GDS. The principal component analysis revealed a three-factor solution for both scales, i.e., presence and absence of state (or trait) anxiety, and performance anxiety. Since no effect of sociodemographic variables was found, unadjusted cutoffs were provided., Conclusions: Although some questions on the psychometric properties of the STAI-Y remain unanswered, this normative study can help clinicians and researchers to monitor anxiety levels in the Italian elderly population., (© 2021. The Author(s), under exclusive licence to Springer Nature Switzerland AG part of Springer Nature.)

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.

Background: This study aimed at assessing how population density (PD), aging index (AI), use of public transport (URPT), and PM10 concentration (PI) modulated the trajectory of the main COVID-19 pandemic outcomes in Italy, also in the recrudescence phase of the epidemic., Study Design: Ecological study., Methods: For each region, we recovered data about cases, deaths, and case fatality rate (CFR) recorded since both the beginning of the epidemic and September 1, 2020. Data about total hospitalizations were included as well., Results: PD correlated with, and was the best predictor of, total and partial cases, total and partial deaths, and total hospitalizations. Moreover, URPT correlated with, and was the best predictor of, total CFR. Besides, PI correlated significantly with total and partial cases, total and partial deaths, and total hospitalizations., Conclusion: PD explains COVID-19 morbidity, mortality, and severity while URPT is the best predictor of disease lethality. These findings should be interpreted with caution due to the ecological fallacy.

Objectives: The present normative study aimed to (1) develop the Italian version of the Starkstein Apathy Scale (SAS-I) and (2) construct a shortened version including only the most sensitive items to "pure apathy" experiences., Methods: The normative sample included 392 healthy subjects. A regression-based procedure was used to explore the effects of sex, age, and education on the raw SAS-I score. A correction grid was designed for adjusting raw scores by adding or subtracting the contribution of any significant variable and net of sociodemographic interindividual differences. Cutoff scores were also calculated and fixed at the external tolerance limit on the ninety-fifth centile. To obtain the shortened version, each SAS-I item was correlated with the Beck's Depression Inventory (BDI) score. The only items showing no correlation with BDI were implemented to bypass the well-known overlap between apathetic and depressive symptoms., Results: The mean raw SAS-I score was 11.27 (SD = 4.42). A significant education effect was observed, with highly educated subjects obtaining lower scores than lowly educated ones. The proposed general cutoff score was 20.68. The SAS-I had fair internal consistency and discriminant validity. Internal consistency increased by removing item 3. The new SAS-6 included items 1, 2, 4, 10, 11, and 13 of the original scale., Conclusion: The SAS-I is a reliable assessment tool to support the diagnosis of apathy. The SAS-6, instead, is a brief questionnaire useful for quickly screening apathetic symptoms in outpatient practice, addressing or not the clinician to further investigations.

Since the beginning of the coronavirus disease 2019 (COVID-19) epidemic in China, elderly and multimorbid subjects showed a higher mortality rate. However, other factors could influence the mortality and spread of contagion, such as population density. Archival research based on the Italian data stratified by region was performed to quantify the association between population density, aging index, number of positive cases, number of deaths, case-fatality rate, and medical equipment (gloves, masks, and ventilators). Results showed a significant positive linear correlation between population density and cases, deaths, and case-fatality rate. No correlation with the aging index was observed. Furthermore, we found a significant positive correlation between the number of medical supplies and population density, cases, and deaths. However, the medical supplies did not show any correlation with the case-fatality rate. Thus, these findings suggest that the population density and the lack of medical equipment are key factors explaining the morbidity and mortality of COVID-19 in Italy.

Background: The clock-drawing test (CDT) is a neuropsychological screening tool largely used to explore cognitive functioning. It requires participants to draw an analog clock face. Many studies have reported a good correlation between the CDT and the Mini-Mental State Examination (MMSE). The CDT has also showed a variable specificity. There are, however, some inconsistencies concerning the effect of sociodemographic variables (sex, age, education) on clock-drawing abilities. The present study aimed at examining these issues in a sample of middle-aged/young-old healthy adults., Method: Participants (n = 97) performed the MMSE and CDT. Clock drawings were assessed by five formal scoring systems (Wolf-Klein, Watson, Freedman, Manos, Shulman). In addition, three naïve raters provided a dichotomous judgment (normal vs. abnormal) for each clock., Results: Sociodemographic variables did not affect CDT performance. Unlike earlier studies, CDT scores did not correlate with MMSE. Moreover, test specificity was appropriate only for Freedman's, Shulman's, and Wolf-Klein's methods. Interestingly, some participants drew clocks with numbers as they appear in digital clocks. By re-running the statistical analyses after removing these atypical clocks, four out of the five formal scores showed a significant correlation with MMSE; furthermore, CDT specificity slightly increased for all scoring systems including naïve ratings., Conclusions: CDT is not affected by sociodemographic variables. The finding of some clocks with digitally represented numbers suggests the need to align neuropsychological assessments with demands from an increasing digitalized environment. Moreover, the occurrence of high false-positives and possible digital contaminations suggest great caution in interpreting the clinical significance of CDT.

Objective: The aims of the present study were: (a) to obtain new normative data of the Italian version of the Mini-Mental Examination State (MMSE) (Measso et al. in Dev Neuropsychol 9:77-85, 1993) by administering the tool to a sample of normal Italian individuals more representative of the current Italian population; (b) to compare the sensitivity of this tool in detecting patients suffering from Alzheimer's disease (AD according to NIA-AA), as compared to the those reported in previous normative Italian studies., Methods: MMSE was administered to 314 normal subjects recruited among individuals (and/or their relatives) attending the Offices of General Practitioners (GP) or Memory Clinics in Campania (Italy) by convenience sampling. A group of 47 patients with AD were included into the study. The effect of demographic variables on the raw MMSE scores of normal subjects was checked by multiple linear regression assuming MMSE scores as dependent variable and age, gender and education as the independent one(s). Therefore, a simultaneous regression model was constructed to correct the raw scores according the sensitive variables. Correction grid and equivalent scores were devised to classify subject's performance., Results: The mean raw MMSE score was 27.78 (SD = 1.80) (range 22-30/30). There was no significant difference between scores achieved by men or women (p = 0.688). Multiple linear regression analysis showed a significant effect of age and years of school attendance on the MMSE raw score, whereas gender did not show any significant effect. The cutoff score, distinguishing between pathological and normal performances, was fixed at the fifth centile corresponding to 24.9/30, higher than the current score of 23.8/30. The new cutoff value was able to identify 44/47 patients with AD, in contrast to 38/47 subjects detected by currently used norms., Conclusions: (1) A more updated and representative population sample; (2) a new cutoff threshold able to distinguish between normal and pathological performances; (3) a correction grid that reduces the risk of false-positive and false-negative values due to the influence of the main demographic factors; (4) greater sensitivity, compared to previous Italian normative studies in identifying people with dementia.

Under visual guidance, healthy subjects usually misbisect radial lines farther than, and vertical lines above the true center. It was suggested that radial and vertical misbisection depended on the presence of an attentional bias toward far/upper space. The aim of the present study was to investigate whether such attentional bias depends on a single mechanism or on separate mechanisms. Ninety participants were asked to bisect lines radially and vertically oriented. The results confirmed the presence of a consistent bisection bias farther than (radial lines), and above (vertical lines) the true center. Furthermore, there was a significant correlation between radial and vertical bisection errors. These findings suggest that a single neural mechanism is involved in producing the attentional bias toward far/upper space., (Copyright © 2019 Académie des sciences. Published by Elsevier Masson SAS. All rights reserved.)

Modafinil (Mo) is increasingly being used as an enhancement drug rather than for its therapeutic effects. The effects of this drug have been examined in attention deficit disorders, depression, mental fatigue, and in enhancing concentration. The drug possesses wakefulness-promoting properties which are mediated through the interaction of orexinergic system with the activated sympathetic nervous system. Mo exerts a synergistic effect on the orexin system, controls energy expenditure and strengthens the ability of the individual to exercise. Some view Mo as a drug that enhances sports performance, since it induces a prolonged wakefulness and decreasing the sense of fatigue. These characteristics being similar to conventional stimulants have allowed Mo to emerge as a novel stimulant requiring medico-legal considerations. However, more studies are needed to better understand the mid and long-term effects of the drug on user/abuser.

Background: Recent investigations have highlighted significant differences in verbal recall between patients with panic disorder (PD) and controls. These studies have highlighted that verbal memory and working memory could be impaired in PD., Objectives: The objective of the present meta-analysis is to confirm this hypothesis, reviewing the studies that have investigated neurocognitive testing in PD., Methods: We performed a systematic literature search for studies published between 1980 and 2015 that reported cognitive measurements in PD patients and controls. Effect size estimates were computed using the restricted maximum likelihood model. Only case-control studies were selected for this meta-analysis. We included studies that made a direct comparison between PD subjects and healthy controls. The diagnostic group consisted of adult patients aged over 18 years diagnosed with PD. We excluded the studies that did not employ a case-control design. All statistical analyses were carried out on R using the "metafor" package version 1.9-8. The effect size for each study neuropsychological test was calculated using the mean and SD of performance results, and p values < 0.05 were considered significant., Results: We identified few studies that tested verbal memory and executive functions in PD patients and controls, and this difference was not significant. On the other hand, there are several studies that have used the emotional Stroop task to assess cognitive functions in PD. There is no robust evidence of impairment of memory function in PD; however, when considering the emotional Stroop task, it was found that PD patients performed slower (p < 0.01) than healthy controls for all three types of stimuli (neutral, negative, positive)., Conclusion: This meta-analysis included a small number of studies, which may have introduced bias into the analysis. However, there is some evidence of impairment of neurocognitive functions in PD when performing the emotional Stroop task. Furthermore, the paucity of studies evaluating neurocognition in PD suggests the need for further research in this field in order to draw meaningful conclusions., (© 2019 S. Karger AG, Basel.)

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.

Objective: Antipsychotics (APs) are associated with metabolic syndrome, with increases in leptin proposed as an underlying mechanism of AP-induced weight gain. Currently available meta-analyses on this topic have limited their populations of interest to those diagnosed with schizophrenia. The purpose of this meta-analysis is to explore the relationship between leptin levels and AP use across multiple psychiatric diagnoses, and also in healthy controls., Method: Systematic electronic searches were conducted using PubMed and OVID: Medline. Longitudinal studies were included if showing leptin levels before and after AP use. We included participants with any psychiatric disorders and mentally healthy participants, if exposed to AP use. The differences in leptin levels were evaluated using Hedges' g with a random effects model., Results: Forty-two studies were found (36 schizophrenia, 2 bipolar disorder, 1 anorexia nervosa, and 3 healthy controls), encompassing 66 study arms and 1,156 participants. The meta-analysis showed that regardless of diagnoses, leptin levels increase with AP use (Hedges' g = 0.811, p ≤ .001)., Conclusion: Leptin increases induced by APs are present across all diagnoses. More comprehensive research is needed to understand the relationship between AP use and leptin levels across multiple diagnoses., (Copyright © 2017 John Wiley & Sons, Ltd.)

Background: Previous studies suggested that movement velocity influence space perception. Aim and Objectives: We examined whether healthy participants used velocity information when they were asked to reproduce a previously performed movement. Two experiments were carried out. Methods: In Experiment 1, blindfolded participants actively performed an arm movement (criterion movement, CM) at a natural velocity, or quickly, or slowly. After a brief delay, participants were asked to reproduce (reproduction movement, RM) CM-amplitude. No velocity constraints were imposed in making RM. In Experiment 2, CM was performed quickly or slowly. After a brief delay, the participants were asked to reproduce not only CM-amplitude but also CM-velocity. Results: Experiment 1: in Natural condition, RM-velocity did not differ from CM-velocity and the participants accurately reproduced CM-amplitude. Conversely, in Fast and Slow condition, RM-velocities differed from CM-velocities and in Slow condition RM-amplitude was greater than CM-amplitude. Experiment 2: both RM-amplitude and -velocity did not differ from CM-amplitude and -velocity. Conclusion: The present study confirms the view that movement velocity influences selectively space perception and suggests that this influence is stronger for slow than fast movements. Furthermore, although velocity information is crucial in accurately reproducing CM-amplitude, it was not used spontaneously when movements were performed at unnatural velocities.

The orexin-A/hypocretin-1 and orexin-B/hypocretin-2 are neuropeptides synthesized by a cluster of neurons in the lateral hypothalamus and perifornical area. Orexin neurons receive a variety of signals related to environmental, physiological and emotional stimuli, and project broadly to the entire CNS. Orexin neurons are "multi-tasking" neurons regulating a set of vital body functions, including sleep/wake states, feeding behavior, energy homeostasis, reward systems, cognition and mood. Furthermore, a dysfunction of orexinergic system may underlie different pathological conditions. A selective loss orexin neurons was found in narcolepsia, supporting the crucial role of orexins in maintaining wakefulness. In animal models, orexin deficiency lead to obesity even if the consume of calories is lower than wildtype counterpart. Reduced physical activity appears the main cause of weight gain in these models resulting in energy imbalance. Orexin signaling promotes obesity resistance via enhanced spontaneous physical activity and energy expenditure regulation and the deficiency/dysfunction in orexins system lead to obesity in animal models despite of lower calories intake than wildtype associated with reduced physical activity. Interestingly, orexinergic neurons show connections to regions involved in cognition and mood regulation, including hippocampus. Orexins enhance hippocampal neurogenesis and improve spatial learning and memory abilities, and mood. Conversely, orexin deficiency results in learning and memory deficits, and depression.

Previous studies suggested that the occipitoparietal stream orients attention toward the near/lower space and is involved in immediate reaching, whereas the occipitotemporal stream orients attention toward the far/upper space and is involved in delayed reaching. In the present study, we investigated the role of the occipitotemporal stream in attention orienting and delayed reaching in a patient (GP) with bilateral damage to the occipitoparietal areas and optic ataxia. GP and healthy controls took part in three experiments. In the experiment 1, the participants bisected lines oriented along radial, vertical, and horizontal axes. GP bisected radial lines farther, and vertical lines more above, than the controls, consistent with an attentional bias toward the far/upper space and near/lower space neglect. The experiment 2 consisted of two tasks: (1) an immediate reaching task, in which GP reached target locations under visual control and (2) a delayed visual reaching task, in which GP and controls were asked to reach remembered target locations visually presented. We measured constant and variable distance and direction errors. In immediate reaching task, GP accurately reached target locations. In delayed reaching task, GP overshot remembered target locations, whereas the controls undershot them. Furthermore, variable errors were greater in GP than in the controls. In the experiment 3, GP and controls performed a delayed proprioceptive reaching task. Constant reaching errors did not differ between GP and the controls. However, variable direction errors were greater in GP than in the controls. We suggest that the occipitoparietal damage, and the relatively intact occipitotemporal region, produced in GP an attentional orienting bias toward the far/upper space (experiment 1). In turns, the attentional bias selectively shifted toward the far space remembered visual (experiment 2), but not proprioceptive (experiment 3), target locations. As a whole, these findings further support the hypothesis of an involvement of the occipitotemporal stream in delayed reaching. Furthermore, the observation that in both delayed reaching tasks the variable errors were greater in GP than in the controls suggested that in optic ataxia is present not only a visuo- but also a proprioceptivo-motor integration deficit.

In the present article, we provide a review of current knowledge regarding the role played by physical activity (PA) in preventing age-related cognitive decline and reducing risk of dementia. The cognitive benefits of PA are highlighted by epidemiological, neuroimaging and behavioral studies. Epidemiological studies identified PA as an influential lifestyle factor in predicting rates of cognitive decline. Individuals physically active from midlife show a reduced later risk of cognitive impairment. Neuroimaging studies documented attenuation of age-related brain atrophy, and also increase of gray matter and white matter of brain areas, including frontal and temporal lobes. These structural changes are often associated with improved cognitive performance. Importantly, the brain regions that benefit from PA are also those regions that are often reported to be severely affected in dementia. Animal model studies provided significant information about biomechanisms that support exercise-enhanced neuroplasticity, such as angiogenesis and upregulation of growth factors. Among the growth factors, the brain-derived neurotrophic factor seems to play a significant role. Another putative factor that might contribute to beneficial effects of exercise is the neuropeptide orexin-A. The beneficial effects of PA may represent an important resource to hinder the cognitive decline associated with aging.

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.

Adipose tissue, defined as white adipose tissue (WAT) and brown adipose tissue (BAT), is a biological caloric reservoir; in response to over-nutrition it expands and, in response to energy deficit, it releases lipids. The WAT primarily stores energy as triglycerides, whereas BAT dissipates chemical energy as heat. In mammals, the BAT is a key site for heat production and an attractive target to promote weight loss. The autonomic nervous system (ANS) exerts a direct control at the cellular and molecular levels in adiposity. The sympathetic nervous system (SNS) provides a complex homeostatic control to specifically coordinate function and crosstalk of both fat pads, as indicated by the increase of the sympathetic outflow to BAT, in response to cold and high-fat diet, but also by the increase or decrease of the sympathetic outflow to selected WAT depots, in response to different lipolytic requirements of these two conditions. More recently, a role has been attributed to the parasympathetic nervous system (PNS) in modulating both adipose tissue insulin-mediated glucose uptake and fatty free acid (FFA) metabolism in an anabolic way and its endocrine function. The regulation of adipose tissue is unlikely to be limited to the autonomic control, since a number of signaling cytokines and neuropeptides play an important role, as well. In this review, we report some experimental evidences about the role played by both the ANS and orexins into different fat pads, related to food intake and energy expenditure, with a special emphasis on body weight status and fat mass (FM) content.

In the present article, we provide a brief review of current knowledge regarding the effects induced by physical exercise on hippocampus. Research involving animals and humans supports the view that physical exercise, enhancing hippocampal neurogenesis and function, improves cognition, and regulates mood. These beneficial effects depend on the contribute of more factors including the enhancement of vascularization and upregulation of growth factors. Among these, the BDNF seems to play a significant role. Another putative factor that might contribute to beneficial effects of exercise is the orexin-A. In support of this hypothesis there are the following observations: (1) orexin-A enhances hippocampal neurogenesis and function and (2) the levels of orexin-A increase with physical exercise. The beneficial effects of exercise may represent an important resource to hinder the cognitive decline associated with the aging-related hippocampal deterioration and ameliorate depressive symptoms.

The basal forebrain (BF) cholinergic system has an important role in attentive functions. The cholinergic system can be activated by different inputs, and in particular, by orexin neurons, whose cell bodies are located within the postero-lateral hypothalamus. Recently the orexin-producing neurons have been proved to promote arousal and attention through their projections to the BF. The aim of this review article is to summarize the evidence showing that the orexin system contributes to attentional processing by an increase in cortical acetylcholine release and in cortical neurons activity.

The human gastrointestinal tract (GIT) is inhabited by a wide cluster of microorganisms that play protective, structural, and metabolic functions for the intestinal mucosa. Gut microbiota is involved in the barrier functions and in the maintenance of its homeostasis. It provides nutrients, participates in the signaling network, regulates the epithelial development, and affects the immune system. Considering the microbiota ability to respond to homeostatic and physiological changes, some researchers proposed that it can be seen as an endocrine organ. Evidence suggests that different factors can determine changes in the gut microbiota. These changes can be both quantitative and qualitative resulting in variations of the composition and metabolic activity of the gut microbiota which, in turn, can affect health and different disease processes. Recent studies suggest that exercise can enhance the number of beneficial microbial species, enrich the microflora diversity, and improve the development of commensal bacteria. All these effects are beneficial for the host, improving its health status. In this paper, we intend to shed some light over the recent knowledge of the role played by exercise as an environmental factor in determining changes in microbial composition and how these effects could provide benefits to health and disease prevention., Competing Interests: The authors declare that they have no competing interests.