Clinical Benefits of Therapeutic Interventions Targeting Mitochondria in Parkinson’s Disease Patients

Parkinson’s disease is the second most common neurodegenerative disease. Mitochondrial dysfunction has been associated with neurodegeneration in Parkinson’s disease, and several treatments targeting mitochondria have been tested in these patients to delay disease progression and tackle disease symptoms. Herein, we review available data from randomised, double-blind clinical studies that have investigated the role of compounds targeting mitochondria in idiopathic Parkinson’s disease patients, with a view of providing patients and clinicians with a comprehensive and practical paper that can inform therapeutic interventions in this group of people. A total of 9 compounds have been tested in randomized clinical trials, but only exenatide has shown some promising neuroprotective and symptomatic effects. However, whether this evidence can be translated into daily clinical practice still needs to be confirmed. In conclusion, targeting mitochondrial dysfunction in Parkinson’s disease is a promising therapeutic approach, although only one compound has shown a positive effect on Parkinson’s disease progression and symptoms. New compounds have been investigated in animal models, and their efficacy needs to be confirmed in humans through robust, randomised, double-blind clinical trials

Neuroimaging of human motor control in real world scenarios: from lab to urban environment

The main goal of this research programme was to explore the neurophysiological correlates of human motor control in real-world scenarios and define mechanism-specific markers that could eventually be employed as targets of novel neurorehabilitation practice. As a result of recent developments in mobile technologies it is now possible to observe subjects' behaviour and monitor neurophysiological activity whilst they perform natural activities freely. Investigations in real-world scenarios would shed new light on mechanisms of human motor control previously not observed in laboratory settings and how they could be exploited to improve rehabilitative interventions for the neurologically impaired. This research programme was focussed on identifying cortical mechanisms involved in both upper- (i.e. reaching) and lower-limb (i.e. locomotion) motor control. Complementary results were obtained by the simultaneous recordings of kinematic, electromyographic and electrocorticographic signals. To study motor control of the upper-limb, a lab­based setup was developed, and the reaching movement of healthy young individuals was observed in both stable and unstable (i.e. external perturbation) situations. Robot-mediated force-field adaptation has the potential to be employed in rehabilitation practice to promote new skills learning and motor recovery. The muscular (i.e. intermuscular couplings) and neural (i.e. spontaneous oscillations and cortico­muscular couplings) indicators of the undergoing adaptation process were all symbolic of adaptive strategies employed during early stages of adaptation. The medial frontal, premotor and supplementary motor regions appeared to be the principal cortical regions promoting adaptive control and force modulation. To study locomotion control, a mobile setup was developed and daily life human activities (i.e. walking while conversing, walking while texting with a smartphone) were investigated outside the lab. Walking in hazardous environments or when simultaneously performing a secondary task has been demonstrated to be challenging for the neurologically impaired. Healthy young adults showed a reduced motor performance when walking in multitasking conditions, during which whole-brain and task-specific neural correlates were observed. Interestingly, the activity of the left posterior parietal cortex was predictive of the level of gait stability across individuals, suggesting a crucial role of this area in gait control and determination of subject specific motor capabilities. In summary, this research programme provided evidence on different cortical mechanisms operative during two specific scenarios for "real­world" motor behaviour in and outside the laboratory-setting in healthy subjects. The results suggested that identification of neuro-muscular indicators of specific motor control mechanisms could be exploited in future "real-world" rehabilitative practice

Caloric vestibular stimulation reduces pain and somatoparaphrenia in a severe chronic central post-stroke pain patient: a case study

Central post-stroke pain is a neuropathic syndrome characterized by intolerable contralesional pain and, in rare cases, somatic delusions. To date, there is limited evidence for the effective treatments of this disease. Here we used caloric vestibular stimulation to reduce pain and somatoparaphrenia in a 57-year-old woman suffering from central post-stroke pain. Resting-state functional magnetic resonance imaging was used to assess the neurological effects of this treatment. Following vestibular stimulation we observed impressive improvements in motor skills, pain, and somatic delusions. In the functional connectivity study before the vestibular stimulation, we observed differences in the patient's left thalamus functional connectivity, with respect to the thalamus connectivity of a control group (N = 20), in the bilateral cingulate cortex and left insula. After the caloric stimulation, the left thalamus functional connectivity with these regions, which are known to be involved in the cortical response to pain, disappeared as in the control group. The beneficial use of vestibular stimulation in the reduction of pain and somatic delusion in a CPSP patient is now documented by behavioral and imaging data. This evidence can be applied to theoretical models of pain and body delusions

L’« inexpressivité » masculine : des mythes et des faits

Cet article examine la thèse couramment admise selon laquelle les hommes expriment moins leurs émotions que les femmes. Les données de recherche montrent peu de différences à cet effet entre les garçons et les filles avant l'adolescence et la vie adulte où, par ailleurs, les hommes apparaissent moins expressifs que les femmes, sauf pour les émotions reliées aux conduites agressives. Cette expressivité moins grande s'observe toutefois dans le cadre d'interactions intimes, alors que les contextes sociaux où la compétition et le statut social sont en jeu semblent plus propices à l'expression d'émotions chez les hommes. Nous proposons que davantage d'études soient menées à ce sujet, en tenant compte des contextes sociaux d'expression émotive engendrés par la division sexuelle du travail.This article examines the common admission that men express their emotions less than do women. Research data shows little difference between the behaviours of boys and girls before adolescence. During adulthood, however, evidence points to men being less expressive than women except in situations involving aggressive behaviour. Men's diminished expressiveness is apparent in a context of intimate interaction. But in situations where they compete for social status, men seem more likely to express emotions. The authors suggest that more studies take into account the social contexts of emotional expressiveness generated by division of labor based on sex

Left Imaginal Neglect in Heminattention: Experimental Study with the O'Clock Test

Both sensory and imaginal defects have been reported in unilateral neglect, but their assessment based on the description of famous squares can be difficult in a clinical setting. The O'clock Test is an alternative tool for revealing imaginal defects. Our aim was to demonstrate imaginal neglect in patients with left heminattention. Ten patients were studied and a mild unilateral defect in imaginal processes was found with an increase in the defect when the patients were fatigued

Assessment of executive functions in adults: a systematic review and empirical investigation

Abstract available at each chapter

Designing clinical trials for rare diseases: unique challenges and opportunities

Orphan drug development is a rapidly expanding field. Nevertheless, clinical trials for rare diseases can present inherent challenges. Optimal study design and partnerships between academia and industry are therefore required for the successful development, delivery and clinical approval of effective therapies in this group of disorders

The affective and neural correlates of heroin vs. cocaine use in addiction are influenced by environmental setting but in opposite directions

Previous studies have shown that individuals with heroin and cocaine addiction prefer to use these drugs in distinct settings: mostly at home in the case of heroin and mostly outside the home in the case of cocaine. Here we investigated whether the context would modulate the affective and neural responses to these drugs in a similar way. First, we used a novel emotional task to assess the affective state produced by heroin or cocaine in different settings, based on the recollections of male and female drug users. Then we used fMRI to monitor neural activity during drug imagery (recreating the setting of drug use) in male drug users. Consistent with our working hypothesis, the majority of participants reported a shift in the affective valence of heroin from mostly pleasant at home to mostly unpleasant outside the home (p<0.0001). The opposite shift was observed for cocaine, that is, most participants who found cocaine pleasant outside the home found it unpleasant when taken at home (p<0.0014). Furthermore, we found a double dissociation, as a function of drug and setting imagery, in BOLD signal changes in the left prefrontal cortex and caudate, and bilaterally in the cerebellum (all p's<0.01), suggesting that the fronto-striatal-cerebellar network is implicated in the contextualization of drug-induced affect. In summary, we report that the same setting can influence in opposite directions the affective and neural response to psychostimulants versus opiates in humans, adding to growing evidence of distinct substrates for the rewarding effects of these two drug classes

Qualité relationnelle des couples gais et conduites sexuelles à risque

La présente étude teste l'hypothèse suivant laquelle la qualité relationnelle des couples gais est positivement associée à l'adoption de conduites sexuelles à risque réduit, dans les situations de monogamie et de non-monogamie. Des mesures d'ajustement relationnel et de comportements sexuels sont recueillies auprès de 29 couples (58 hommes) homosexuels de la région de Montréal. Conformément à l'hypothèse, la distribution des couples selon un index multifactoriel de risque indique une relation entre la satisfaction de couple et le niveau de risque encouru dans les relations sexuelles à l'intérieur et à l'extérieur du couple. Les résultats sont discutés à la lumière des données existantes sur la relation santé-qualité relationnelle chez les couples hétérosexuels.This study examines the hypothesis by which quality relationships among gay couples is closely related to the adoption of low-risk sexual behaviours, in monogamous and non-monogamous situations. Data was collected from 29 homosexual couples (58 men) of the Montréal area. The survey, which graded sexual conduct as well as adjustments made within the relationship, confirmed the author's hypothesis. Indeed, the distribution of couples according to a multifactorial risk index does in fact establish a connection between the couple's happiness and the level of risk during sexual relations within and outside the couple. These conclusions are discussed in light of existing data pertaining to the link between health and the quality of a relationship among heterosexual couples

Discovery of the grave and identification of the remains of Matteo Maria Boiardo in Saint Mary's church, Scandiano (Reggio Emilia)

According to the documentary information and to the prospectings performed by means of the georadar, beneath the floor of the Church of Santa Maria of Scandiano (RE), it has been possible to locate the sepulchral crypts where the poet Matteo Maria Boiardo and other members of his family, such as his father Giovanni, his grandfather Feltrino and maybe his wife Taddea Gonzaga and one of his sons, Camillo, must have been buried. The exploration of these sepulchral crypts has led to the recovery of the skeletal remains belonging altogether to at least 20 persons (adults and children). Among them, 3 have been discovered into a sepulchral room and the rest into an adjacent tomb. Among the first ones, a person, with the same sex, age of death, sturdiness, height and physical characteristics of the poet Boiardo, has been identified. As confirmation of this probable identity, the genetic profile of this man, got from the nuclear dna sample taken from his body, has come out to be compatible with a possible father/child relationship, this result has been compared to the one gotten from the find found into the adjacent room where the poet's father and grandfather had to be buried. The body of a second person, of female sex and well on in years, with a genetic profile different from the previous ones, could be identified with Boiardo's wife. For what regards the body of the third man, besides it is not possible to exclude that it belongs to Camillo, the poet's son dead when he was very young, it has not been possible yet, to get enough proofs able to confirm this theory