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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.

Background: The purpose of this research was to study the effects of exercise on the concentration of plasma orexin A, a peptide regulating several physiological functions., Methods: Blood samples were collected from participants (men, n=10; age: 24.4±2.93 years) 15, 0 min before the start of exercise, and 30, 45, 60 min after a cycle ergometer exercise at 75 W for 15 min. Also heart rate (HR), galvanic skin response (GSR), and rectal temperature were monitored., Results: The exercise induced a significant increase (p<0.01) in plasmatic orexin A with a peak at 30 min after the exercise bout, in association with an increase of the other three monitored variables: HR (p<0.01), GSR (p<0.05), and rectal temperature (p<0.01)., Conclusions: Our findings indicate that plasmatic orexin A is involved in the reaction to physical activity.

Hypocretin/orexin (ORX) are two hypothalamic neuropeptides discovered in 1998. Since their discovery, they have been one of the most studied neuropeptide systems because of their projecting fields innervating various brain areas. The orexinergic system is tied to sleep-wakefulness cycle, and narcolepsy is a consequence of their system hypofunction. Orexinergic system is also involved in many other autonomic functions such as feeding, thermoregulation, cardiovascular and neuroendocrine regulation. The main aim of this mini review article is to investigate the relationship between ORX and thyroid system regulation. Although knowledge about the ORX system is evolving, its putative effects on hypothalamic-pituitary-thyroid (HPT) axis still appear unclear. We analyzed some studies about ORX control of HPT axis to know better the relationship between them. The studies that were analyzed suggest Hypocretin/ORX to modulate the thyroid regulation, but the nature (excitatory or inhibitory) of this possible interaction remains actually unclear and needs to be confirmed.

The high fat diet (HFD) rich in lard induces obesity, inflammation and oxidative stress, and the deregulation of hypothalamic nuclei plays an important role in this mechanism. One important factor involved in the food intake and inflammation is adenosine monophosphate-dependent kinase (AMPK), a serine/threonine kinase activated by phosphorylation. Omega (ω)3-polyunsaturated fatty acids (PUFA) are dietary compounds known to attenuate the obesity-related diseases, although the molecular mechanisms underlying their actions in the hypothalamus are not completely understood. We hypothesized that the beneficial effects of PUFA may be mediated by AMPK in the hypothalamus. To this aim, rats were fed a control diet (CD), or isocaloric HFD containing either fish oil (FD; rich in ω3-PUFA) or lard for 6 weeks, and the activation of AMPK, inflammatory state (IKKβ, TNF-α) and oxidative stress were analyzed in the hypothalamus. In addition, we also studied serum lipid profile, homeostatic model assessment (HOMA) index, and pro-inflammatory parameters. Our results showed, at the hypothalamic level of LD-fed rats, an increase of AMPK activation, inflammation and oxidative stress, while no modifications were detected in FD-fed animals compared to CD. In addition body weight gain, serum lipid profile, pro-inflammatory parameters and insulin resistance were reduced in FD animals compared to LD. In conclusion, our data indicate that the substitution of saturated by unsaturated fatty acids in the diet has beneficial effects on modulation of hypothalamic inflammation and function in obesity, underlying, at hypothalamic level, the interaction among insulin and/or leptin resistance, AMPK activation and hyperphagia.

It is generally accepted that visual illusions affect line bisection in the predicted direction. However, it has been reported an illusionary bias which seems questioning such general view. In a previous study, participants bisected lines flanked at both ends by two pairs of arrows, pointing in the same direction. The medialmost vertices of one pair converged on the line (converging arrows), whereas those of the other pair did not (non-converging arrows). Participants bisected lines toward the base of the arrows, i.e., toward the wider end of the stimulus and in the direction opposite to that predicted by the Baldwin illusion. However, the bisection bias was also directed away from the location of the converging arrows. We investigated what is the main factor affecting line bisection: arrows orientation, as previously suggested, or interference effects related to the location of converging arrows. In experiment 1, participants bisected lines flanked by converging versus non-converging arrows. Results confirmed the presence of a bisection bias directed not only toward the base of the converging arrows but also away from their location. In experiment 2, the arrows were located more internally, so that their medialmost vertices always converged on the line. Results showed that the bisection bias was directed away from the location of the arrows regardless of their orientation. It is suggested that the previously reported bisection bias did not depend on arrows orientation, but rather on interference effects related to converging arrows position. The theoretical implications of the results are discussed.

Background: Visuo-spatial and problem-solving abilities are commonly impaired in patients with Alzheimer's disease (AD). Conversely, subjects with amnestic mild cognitive impairment (aMCI) do not exhibit overt involvement of cognitive domains other than memory. Consequently, a detection of an impairment at the Raven's colored progressive matrices (RCPM) could be useful to discriminate aMCI from AD and to mark the progression from one condition to another., Aim of the Study: To describe the pattern of errors at RCPM in subjects suffering from AD as compared with that of aMCI., Methods: Fifteen patients with AD, 15 subjects with aMCI and 31 Healthy Controls (HC) received the RCPM. The errors were classified as: (1) difference (D); (2) inadequate individuation (II); (3) repetition of the pattern (RP); (4) incomplete correlation (IC)., Results: No difference approached significance between aMCI subjects and HC. AD patients always exhibited a higher number of errors as compared with HC. AD patients showed higher number of errors as compared with aMCI only on RP and IC errors., Conclusions: The results suggest that the visuo-spatial and problem-solving impairment that characterize AD, and probably subtend the progression from aMCI to dementia, do not affect to the same extent all cognitive dimensions explored by RCPM.

Background: The word "stress" describes the status of the body affected by external or internal forces, or "stressors", threatening to alter its dynamic balance or homeostasis. The adaptive changes which occur in reply to stressors are either behavioral or physical. Once a given threshold is surpassed, a systemic reaction takes place involving the "stress system" in the brain together with its peripheral components, the hypothalamic-pituitary-adrenal axis and autonomic sympathetic., Objectives: Stress induces an activation of the sympathetic nervous system (SNS) and the hypothalamic-pituitary-adrenal (HPA) axis. The purpose of this study was to investigate whether the SNS and the HPA axis would show parallel or divergent stress response patterns in a session of first parachute jump., Patients and Methods: Activation of the SNS was evaluated by dosage of salivary alpha-amylase, galvanic skin responses, and heart rate in seven male novice parachutists. Activation of HPA axis was tested by dosage of cortisol. These variables were measured before and 1 minute and 90 minute after the jump., Results: All variables reached a peak at 1 minute post-jump. Salivary alpha-amylase, galvanic skin responses and heart rate did not return to basal value at 90 minutes post-jump, while cortisol returned to basal value at 90 minutes post-jump., Conclusions: This evidence indicates that parachute jumping is accompanied by a dissociation of SNS and HPA response patterns in novice parachutists, showing a slower recovery in sympathetic activity than in cortisol secretion.

The G protein-coupled estrogen receptor (GPR30) is suggested to be involved in non-nuclear estrogen signalling and is expressed in a variety of hormone dependent cancer entities. It is well established that oestrogens are involved in pathological germ cell proliferation including testicular germ cell tumours. This study was performed to further elucidate the role of this receptor and the possible correlation with the estrogen receptor β in human testicular carcinoma in situ (CIS), seminomas and in GC1 and TCam-2 germ cell lines; in addition, a Tissue Micro-Array was built using the most representative areas from 25 cases of human testicular seminomas and 20 cases of CIS. The expression of ERβ and GPR30 were observed by using Western blot analysis in combination with immunocytochemistry and immunofluorescence analyses. Here, we show that down regulation of ERβ associates with GPR30 over-expression both in human testicular CIS and seminomas. In addition, we show that 17β-oestradiol induces the ERK1/2 activation and increases c-Fos expression through GPR30 associated with ERβ down-regulation in TCam-2 cell line. The present results suggest that exposure to oestrogens or oestrogen-mimics, in some as of yet undefined manner, diminishes the ERβ-mediated growth restraint in CIS and in human testicular seminoma, probably due to ERβ down-regulation associated to GPR30 increased expression indicating that GPR30 could be a potential therapeutic target to design specific inhibitors., (© 2014 Wiley Periodicals, Inc.)

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

It is extremely important for the health to understand the regulatory mechanisms of energy expenditure. These regulatory mechanisms play a central role in the pathogenesis of body weight alteration. The hypothalamus integrates nutritional information derived from all peripheral organs. This region of the brain controls hormonal secretions and neural pathways of the brainstem. Orexin-A is a hypothalamic neuropeptide involved in the regulation of feeding behavior, sleep-wakefulness rhythm, and neuroendocrine homeostasis. This neuropeptide is involved in the control of the sympathetic activation, blood pressure, metabolic status, and blood glucose level. This minireview focuses on relationship between the sympathetic nervous system and orexin-A in the control of eating behavior and energy expenditure. The "thermoregulatory hypothesis" of food intake is analyzed, underlining the role played by orexin-A in the control of food intake related to body temperature. Furthermore, the paradoxical eating behavior induced orexin-A is illustrated in this minireview.

Although testicular germ cell tumors (TGCTs) are relatively uncommon, they are particularly important, as they tend to affect children and young men, the most common tumor being in males aged from 20 to 40 years, and the incidence has been increasing in the last years. TGCTs comprise two major histologic groups: seminomas and non-seminomas germ cell tumors (NSGCTs). NSGCTs can be further divided into embryonal, carcinoma, Teratoma, yolk sac tumor, and choriocarcinoma. Seminomas and NSGCTs present significant differences in clinical features, therapy, and prognosis, and both show characteristics of the Primordial Germ Cells (PGCs). For proper diagnosis of the different histological subgroups, immunohistochemistry is required using different molecular markers, such as Aurora B, GPR30, Nek2, HMGA1, HMGA2, and others, and they could represent useful novel molecular targets for antineoplastic strategies. More insight into the pathogenesis of TGCTs is likely to contribute not only to better treatment of these tumors but also to a better understanding of stem cells and oncogenesis.

Background: Non Muscle Invasive Bladder Transitional Cancer (NMIBC) and Muscle Invasive Bladder Transitional Cancer (MIBC)/invasive have different gene profile and clinical course. NMIBC prognosis is not completely predictable, since the relapse rate is higher than 20%, even in the form of MIBC. The aim of this study is to evaluate if UTR expression can discriminate between NMIBC and MIBC and predict the risk of relapses in NMIBCs., Methods: We have investigated upon urotensin-II (UII) receptor (UTR) expression in vivo in 159 patients affected by NMIBC. The biological role of UTR was also investigated in vitro. UTR expression was evaluated in a tissue-micro-array, consisting of normal, NMIBC and invasive bTCC samples., Results: UTR discriminated between NMIBC and MIBC and showed a significant correlation between low UTR expression and shorter disease free survival in NMIBC. The superagonist UPG84 induced growth suppression at nM concentrations on 3/4 cell lines. Bladder cancer cell treatment with the antagonist urantide or the knock-down of UTR with a specific shRNA significantly blocked both the motility and invasion of bladder cancer cells., Conclusions: The evaluation of UTR expression can discriminate between NMIBC at high and low risk of relapse. Moreover, our data suggest that UTR is involved in the regulation of motility, invasion and proliferation of bladder cancer cells. High UTR expression is an independent prognostic factor of good prognosis for NMIBC regulating motility and invasion of bladder cancer cells.

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

Since the first description by Lhermitte (1983), the utilization behavior (UB) still represents an enigma for behavioral neurology and neuropsychology. Recent findings shed some light on new frameworks for interpreting this interesting phenomenon. Functional neuroanatomical basis is still unclear, although recent advances in neuroimaging techniques have contributed to a better understanding of the syndrome. An important and promising step is given by shifting researcher's attention from frontoparietal to intrafrontal mechanisms. From a cognitive standpoint, three models have been proposed. However, a comprehensive account for the UB neurobehavioral complexity is still lacking. Aims of this paper are to briefly review the reported cases of utilization behavior (UB) and to describe the putative neurological mechanisms underlying UB. Furthermore, the cognitive models proposed to interpret UB will be summarized. For clinical purposes, features suitable for distinguishing UB from other neurobehavioral symptoms will be briefly described.

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

Testicular germ cell tumors (TGCTs), the most common malignancy in males between 15 and 34 years of age and the most frequent cause of death from solid tumors in this age group. TGCTs can be subdivided into seminoma and non-seminoma germ cell tumors (NSGCTs), including embryonal cell carcinoma, choriocarcinoma, yolk sac tumor, and teratoma. Seminomas and NSGCTs do not only present distinctive clinical features, but they also show significant differences as far as therapy and prognosis are concerned. Seminomas are highly sensitive to both radiation and chemotherapy, with a good prognosis, non-seminomas are sensitive to platinum-based combination chemotherapy and are less susceptible to radiation, with the exception of teratomas. The different therapeutic outcome might be explained by inherent properties of the cells from which testicular neoplasia originate. The unique treatment sensitivity of TGCTs is unexplained so far, but it is likely to be related to intrinsic molecular characteristics of the PGCs/gonocytes, from which these tumors originate. Many discovered bio-markers including OCT3/4, SOX2, SOX17, HMGA1, HMGA2, PATZ1, GPR30, Aurora B, estrogen receptor β, and others have given further advantages to discriminate between histological subgroups. In addition, therapeutic approaches for the treatment of TGCTs have been proposed: humanized antibodies against receptors/surface molecules on cancer cells, inhibitors of serine-threonine, and tyrosine kinases, and others. The mini-review will be an overview on the molecular alterations identified in TGCTs and on novel targeted antineoplastic strategies that might help to treat chemotherapy resistant TGCTs., (Copyright © 2013 Wiley Periodicals, Inc.)

Menopause is a period of significant physiological changes that may be associated with increased body weight and obesity-related diseases. Many researches were conducted to assess the contribution of factors such as estrogen depletion, REE decline, and aging to weight gain. An increase in orexin-A plasma levels, paralleling lower estrogen levels, was found during menopause. Orexins are hypothalamic neuropeptides recently discovered, involved in the regulation of feeding behaviour, sleep-wakefulness rhythm, and neuroendocrine homeostasis. Orexins might offer the missing link between postmenopausal hypoestrogenism and other manifestations of the menopausal syndrome, including appetite and weight changes and increase in cardiovascular risk.

Previous studies have shown that a flanking distractor produces a spatial bias during line bisection. In the present study, we investigated whether that bias depends on perceptual or motor components. Participants were asked to bisect a horizontal line, or to reach towards a dot, with or without vision of their hand. The line and the target could be flanked by a distractor. Movement trajectories and endpoints were consistently deviated away from the location of the distractor in the bisection task, but not in the reaching task, irrespectively of whether the participants had online visual feedback from their moving hand. It is suggested that flanking distractors influence perceptual localization of the subjective mid-point during line bisection.

Objective: to investigate patterns of anosognosia for memory deficit in subjects with amnestic mild cognitive impairment (MCI) and Alzheimer's disease (AD)., Methods: the study involved twenty-five subjects with MCI, 15 with mild AD and 21 normal controls (NC). Subjective rating of memory functioning was assessed with a six-items questionnaire that was administered before and after memory testing; an informant version from caregivers gave a discrepancy score (SRD). In the Objective Judgement (OJ) task, aiming to evaluate memory-monitoring abilities, subjects were requested three times to predict their memory performance in recalling words from a list of ten. Then they had to recall the words. Prediction accuracy was computed by subtracting the predicted performance from the actual performance., Results: MCI and AD showed reduced awareness of memory difficulties at the SRD and did not change their rating of these difficulties after memory testing. At the OJ task, MCI and AD consistently overestimated their memory performances as compared with NC. The SRD and OJ measures were not correlated with some patients being impaired on only one measure. Only the OJ measure was significantly related to executive functioning., Conclusions: AD and MCI subjects show unawareness for memory deficit and significant memory-monitoring disorder. This confirms that anosognosia is an important symptom of MCI. Similarities of patterns of impaired awareness between AD and MCI supports the view of a continuum of the anosognosia phenomenon in MCI and AD., (Copyright © 2010 John Wiley & Sons, Ltd.)

We examined whether and how deictic gestures and words influence each other when the content of the gesture was congruent or incongruent with that of the simultaneously produced word. Two experiments were carried out. In Experiment 1, the participants read aloud the deictic word 'QUA' ('here') or 'LA" ('there'), printed on a token placed near to or far from their body. Simultaneously, they pointed towards one's own body, when the token was placed near, or at a remote position, when the token was placed far. In this way, participants read 'QUA' ('here') and pointed towards themselves (congruent condition) or a remote position (incongruent condition); or they read 'LA" ('there') and pointed towards a remote position (congruent condition) or themselves (incongruent condition). In a control condition, in which a string of 'X' letters was printed on the token, the participants were silent and only pointed towards themselves (token placed near) or a remote position (token placed far). In Experiment 2, the participants read aloud the deictic word placed in the near or far position without gesturing. The results showed that the congruence/incongruence between the content of the deictic word and that of the gesture affected gesture kinematics and voice spectra. Indeed, the movement was faster in the congruent than in the control and incongruent conditions; and it was slower in the incongruent than in the control condition. As concerns voice spectra, formant 2 (F2) decreased in the incongruent conditions. The results suggest the existence of a bidirectional interaction between speech and gesture production systems.

Under visual guidance normal subjects usually misbisect radial lines farther than the true midpoint (distal bias). We investigated whether this distal bias is constant across the peripersonal space or it varies by varying the distance of the stimulus from the subject. Subjects were asked to bisect radial lines presented below eye level either in the near or far peripersonal space. The results showed an increase of distal bias in the far-space. This finding suggests that the influence of spatial factors on bisection of radial lines is not constant across the peripersonal space. Distal bias increases as a function of the distance of the stimulus from the subject, according to a spatiotopic processing scheme.

In a recent note, Mizuguchi (2006) stated that beats are not directly related to the meaning of the production of speech. We report a number of studies that suggest the existence of a clear relationship between beats and significant parts of co-occurring speech.

Special ability in computing the day of the week from given dates was observed in a 18 years old male, L.E., suffering from autism. Neuropsychological testing revealed severe deficits in all cognitive domains and poor explicit knowledge of calendar structure. The subject scored well above the chance level on dates of the past and future decades. Error rate and response latency increased with temporal remoteness of dates. Most of errors were in indicating the weekday before or after that of date stimulus. The performance and error pattern suggest that L.E. used "encapsulated" computation algorithm(s) for the day of week task.

In the present pilot study, we examined the relationship between gesture and verbal production. Subjects were asked to read a story and then to narrate what they remembered. We analyzed verbal production according to Kintsch's procedure and obtained a list of hierarchically organized propositions that represented the meaning of subject's narration. Propositions were subdivided into High- and Low-level propositions. Further, we analyzed gesture production by identifying hand or arm movement that accompanied subject's narration. Each gesture was associated with the word simultaneously produced, and then with the proposition to which the word belonged. Analysis showed subjects were more likely to produce gestures in association with High- rather than with Low-level propositions. High-level propositions may elicit the production of gestures which, in turn, mark the importance of verbal meaning conveyed simultaneously.

The influence of contextual stimuli on line-bisection performance was investigated. Subjects were required to bisect lines flanked at one end by one pair of solid black rectangles. Bisection was performed along three orthogonal axes (horizontal, radial, vertical). The results showed the presence of a bisection bias in the direction opposite to the location of flanking rectangles. This finding suggests that the presence of rectangles beside one end of a line interfered with representation of the line as a whole and induced the subjects to neglect the flanked part of the line.

In the present study, we explored the influence of a visual distractor on the trajectory of movements made to join two dots. The two dots could be unconnected (D) or connected by a straight (L) or curved line, convex either to the left (LL) or to the right (RL). The connecting line constituted the visual distractor. In Experiment 1, subjects were asked to perform the joining movement as straight as possible. The results showed that hand trajectory moved to the left of the midsagittal axis in LL and to the right in RL, while it was almost straight both in L and D. In Experiment 2, subjects were explicitly required to follow the connecting line during their movements to verify whether, in the previous experiment, they had used curved lines as guide for their movements. An increase of movement time and different hand paths showed that this was not the case. In Experiment 3, subjects were asked to move as straight as possible without vision of their hand. Hand trajectories were shifted to the left in all experimental conditions, but the leftward shift was greater in LL than in all other conditions, and also greater in D and L than in RL. These findings suggest that the visual distractor influenced hand trajectory by attracting subject's attention and competing with target for motor response. It is hypothesized that the attracting influence operated by the distractor was sustained by involuntary attentional mechanisms.

In the present study we investigated whether masking/perceptual factors may influence line bisection performance in normal subjects. We carried out two experiments. In Experiment 1 the stimuli consisted of a line flanked at each end by: (1) parallel arrows, (2) oblique arrows, (3) or oblique geometrical figures. Of the two pairs of labels, one pair converged on the line and appeared to mask the flanked portion of the line. The results showed the presence of a bisection bias in the direction opposite to location of masking labels. In Experiment 2 we examined if orientation factors might have contributed to the observed bisection bias. The stimuli consisted of a line flanked by only one pair of oblique geometrical figures. The results showed that bisection bias was always in the direction opposite to label location, independently of the direction pointed out by oblique figures. These findings suggest that masking/perceptual factors may influence bisection performance in normal subjects.

The attentional field resulting from the presentation of peripheral cues; which were either informative or non informative about the position of the imperative stimulus, was studied. Different time intervals between cue and stimulus (120, 300, 600 ms) were used. The results showed facilitation of the response with the informative cue and inhibition with the non informative cue. This happened for the longest cue-stimulus intervals and when the position of the cue and the position of the stimulus were congruent. Also order of cue presentation (i.e., either informative followed by the non informative cue or vice versa) proved important in producing facilitatory and inhibitory effects.

Periodontics and endodontics share common objectives and common field of interest. Both disciplines treat lesions of the periodontal tissues; in their marginal aspect the first, in the periapical aspect the latter. These relationships have not been well understood for a long time. This article is a review of the literature on the topic aimed at clarifying the anatomic, microbiological, pathogenetic relationship in the periodontal and endodontic lesions.

Kinematics of reaching-grasping movement towards stimuli of three different sizes located at two different distances were studied in one monkey (Macaca nemestrina). Transport and manipulation components were analyzed using the ELITE system. Transport time, peak velocity and deceleration phase of velocity were influenced by stimulus size, whilst acceleration phase remained unmodified. Peak velocity clearly increased with distance, while transport time remained constant (isochrony ). The main parameters of manipulation component were all influenced by stimulus size but they did not vary with distance. A comparison with kinematic data obtained from human subjects was made.

In this study the temporal coupling between transport and manipulation components of prehension movements was tested. For this purpose two experiments were carried out. In Experiment 1 six normal subjects were required to reach and grasp one of three spheres located at three different distances (Blocked trials). In Experiment 2 a visual perturbation paradigm was used in which the location of the object to be reached and grasped could change at onset of arm movement (Perturbed trials). The results of this study exclude a temporal coupling between events of transport and manipulation components. On the contrary they suggest that manipulation component organizes its time course having information about the time required to reach the object.

We investigated whether the errors made by aphasic patients and right brain-damaged (RBD) patients on a word-picture matching test were differently related to the semantic and perceptual difficulties of the task. To this effect, the target picture was presented in one condition along with two semantically similar distractors, in another condition with two perceptually similar distractors, and in a third condition with two distractors that were both semantically and perceptually similar. There were also two control conditions in which part of targets that had been originally shown with semantic distractors were now presented with perceptual distractors and vice versa. The findings were consistent with the hypothesis that aphasics mainly fail when the task involves semantic discrimination and RBD patients when it involves perceptual discrimination. In aphasics the semantic perceptual condition produced the highest number of errors, but this was due, it was argued, to an increase of the semantic demands of the task.