Heterogeneity of neuroinflammatory responses in amyotrophic lateral sclerosis: A challenge or an opportunity?

Amyotrophic Lateral Sclerosis (ALS) is a complex pathology: (i) the neurodegeneration is chronic and progressive; it starts focally in specific central nervous system (CNS) areas and spreads to different districts; (ii) multiple cell types further than motor neurons (i.e., glial/immune system cells) are actively involved in the disease; (iii) both neurosupportive and neurotoxic neuroinflammatory responses were identified. Microglia cells (a key player of neuroinflammation in the CNS) attracted great interest as potential target cell population that could be modulated to counteract disease progression, at least in preclinical ALS models. However, the heterogeneous/multifaceted microglia cell responses occurring in different CNS districts during the disease represent a hurdle for clinical translation of single-drug therapies. To address this issue, over the past ten years, several studies attempted to dissect the complexity of microglia responses in ALS. In this review, we shall summarize these results highlighting how the heterogeneous signature displayed by ALS microglia reflects not only the extent of neuronal demise in different regions of the CNS, but also variable engagement in the attempts to cope with the neuronal damage. We shall discuss novel avenues opened by the advent of single-cell and spatial transcriptomics technologies, underlining the potential for discovery of novel therapeutic targets, as well as more specific diagnostic/prognostic not-invasive markers of neuroinflammation

Visuospatial skills in children affected by primary nocturnal enuresis: Rehabilitative proposals

The sphincterial control problems in childhood are very common, with relevant comorbidities (i.e.: difficulty in academic performance, sleep disturbances, minor neurological signs) involved in the complex process of maturation and learning, such as to cause a great deal of discomfort and related disorders in affected subjects. Enuresis is characterized by the involuntary urination in the absence of a physical disorder, socially unacceptable in places and at one stage of life where such control is acquired by the majority of subjects (about 5 years). The present study aims to evaluate the visuospatial skills in children affected by primary monosymptomatic nocturnal enuresis (PMNE). 31 PMNE children (16 males and 15 females) (mean age 10.87, SD ± 1.68) and 61 healthy children (32 males, 29 females) (mean age 11.03, SD ± 1.85, p = 0687) were evaluated for visuomotor skills with the Visual-Motor Integration Scale (VMI). PMNE subjects show a worse performance on average to VMI, especially in the total visual-motor integration test. This finding emphasizes the importance of a framework for global and more complex than is commonly implemented, across the border but framing the subject of enuretic symptoms in a more global perspective

Motor skills in children with primary headache: A pilot case-control study

Background: Headache is the most common painful manifestation in the developmental age, often accompanied by severe disability such as scholastic absenteeism, low quality of academic performance and compromised emotional functioning. The aim of the study is to evaluate praxic abilities in a population of children without aural migraine. Materials and methods: The test population consists of 10 subjects without migraine without aura (MwA), (8 Males) (mean age 8.40, SD ± 1.17) and 11 healthy children (7 Males) (mean age 8.27; SD ± 1.10; p = 0.800). All subjects underwent evaluation of motor coordination skills through the Battery for Children Movement Assessment (M-ABC). Results: The two groups (10 MwA vs 11 Controls) were similar for age (8.40 ± 1.17 vs 8.27 ± 1.10; p = 0.800), sex (p = 0.730), and BMI (p = 0.204). The migraine subjects show an average worse performance than the Movement ABC; specifically, migraineurs show significantly higher total score values (31.00 ± 23.65 vs 4.72 ± 2.61; p = 0.001), manual dexterity (12.10 ± 11.20 vs 2.04 ± 2.65; p = 0.009) and balance (14.85 ± 10.08 vs. 1.04 ± 1.05; p <0.001). The mean percentile of migraine performance is significantly reduced compared to controls (9.00 ± 3.82 vs 51.00 ± 24.34, p <0.001) (Table 1). Conclusion: Migraine can alter many cognitive and executive functions such as motor skills in developmental age

A brief review about anxiety and aggressive behavior in pediatric age

Anxiety can be considered a normal experience of the human being and as such also of the child. It manifests itself in different ways according to the level of development: in the smaller the child, the more anxiety is expressed with manifestations that involve the whole organism, becoming evident either with motor excitement or with physical discomfort. As the psychic apparatus is structured, anxiety is experienced as an inner phenomenon and is experienced as an unpleasant state. Fortunately, we are all a bit anxious, even if there are some people who are more, others less

Neuropsychomotricity in water: A new rehabilitative tool for neruodevelop-mental disorders

Neuropsychomotricity in water is a rehabilitative practice that avails itself just of the liquid element, as a mediator of relationships: in water yes they upset all dynamics, be they relational, of equilibrium, of movement and perception, due to the fact that proprioceptive sensations, created by bodily contact with water, they are different than those generated by contact with air

Probing sporadic and familial Alzheimer's disease using induced pluripotent stem cells.

Our understanding of Alzheimer's disease pathogenesis is currently limited by difficulties in obtaining live neurons from patients and the inability to model the sporadic form of the disease. It may be possible to overcome these challenges by reprogramming primary cells from patients into induced pluripotent stem cells (iPSCs). Here we reprogrammed primary fibroblasts from two patients with familial Alzheimer's disease, both caused by a duplication of the amyloid-β precursor protein gene (APP; termed APP(Dp)), two with sporadic Alzheimer's disease (termed sAD1, sAD2) and two non-demented control individuals into iPSC lines. Neurons from differentiated cultures were purified with fluorescence-activated cell sorting and characterized. Purified cultures contained more than 90% neurons, clustered with fetal brain messenger RNA samples by microarray criteria, and could form functional synaptic contacts. Virtually all cells exhibited normal electrophysiological activity. Relative to controls, iPSC-derived, purified neurons from the two APP(Dp) patients and patient sAD2 exhibited significantly higher levels of the pathological markers amyloid-β(1-40), phospho-tau(Thr 231) and active glycogen synthase kinase-3β (aGSK-3β). Neurons from APP(Dp) and sAD2 patients also accumulated large RAB5-positive early endosomes compared to controls. Treatment of purified neurons with β-secretase inhibitors, but not γ-secretase inhibitors, caused significant reductions in phospho-Tau(Thr 231) and aGSK-3β levels. These results suggest a direct relationship between APP proteolytic processing, but not amyloid-β, in GSK-3β activation and tau phosphorylation in human neurons. Additionally, we observed that neurons with the genome of one sAD patient exhibited the phenotypes seen in familial Alzheimer's disease samples. More generally, we demonstrate that iPSC technology can be used to observe phenotypes relevant to Alzheimer's disease, even though it can take decades for overt disease to manifest in patients

Psychopathological and psychodynamic hypotheses for pediatric stuttering

Stuttering is a common language alteration in pediatric age consisting in repetitions and blocks, which entail a break in the rhythm and melody of the speech. According to the WHO it is a disorder of the rhythm of the word, the subject knows precisely what he would like to say, but at the same time he is not able to say it. It is a great inconvenience for those affected, also because the slowing down of speaking is not about thought or cognitive skills

Forensic considerations on violent parasomnias during lifespan

Nocturnal parasomnias are a group of sleep complex manifestation that don't alter the sleep macrostructure, but when persistent during adulthood may be assume violent aspects with relevant forensic implications about the guiltiness

Animals-assisted therapy: A brief review

In rehabilitative setting, the presence of animals can be considered as an important stimulus for verbal and social communication, and for mood regulation. Interaction with an animal is beneficial for children's development and numerous psychological tests have revealed that growing up with pets has a beneficial effect on children's self-esteem and self-confidence, can improve empathy, a sense of responsibility and cognitive development, as well as social status within the peer group

A PC-Based Instrument for Automatic Monitoring and Control of a CPVT Power Plant

A PC-based instrument has been developed for the monitoring and control of a concentrated photovoltaic and thermal (CPVT) power plant. The instrument allows acquiring both electrical and thermal quantities. Moreover it implements the solar tracking algorithm used to optimize the power production