The environmental epidemiology of primary dystonia

Background: Dystonia is a movement disorder characterized by involuntary muscle contractions that cause twisting movements and abnormal postures. Primary dystonia is the most common form and is thought to be a multifactorial condition in which one or more genes combine with environmental factors to reach disease. Methods: We reviewed controlled studies on possible environmental risk factors for primary early‐ and late‐onset dystonia. Results: Environmental factors associated with primary early‐onset dystonia are poorly understood. Early childhood illnesses have been reported to be more frequent in patients with DYT1 dystonia than in subjects carrying the DYT1 mutation that did not manifest dystonia, thus raising the possibility that such exposures precipitate dystonia among DYT1 carriers. Conversely, several environmental factors have been associated with primary adult‐onset focal dystonias compared to control subjects. Namely, eye diseases, sore throat, idiopathic scoliosis, and repetitive upper limb motor action seem to be associated with blepharospasm (BSP), laryngeal dystonia (LD), cervical dystonia (CD), and upper limb dystonia, respectively. In addition, an inverse association between coffee drinking and BSP has been observed in both case‐unrelated control and family‐based case‐control studies. Additional evidence supporting a causal link with different forms of primary late‐onset dystonia is only available for diseases of the anterior segment of the eye, writing activity, and coffee intake. Conclusion: There is reasonable epidemiological evidence that some environmental factors are risk‐modifying factors for specific forms of primary adult‐onset focal dystonia

Bethe-Salpeter bound-state structure in Minkowski space

The quantitative investigation of the scalar Bethe-Salpeter equation in Minkowski space, within the ladder-approximation framework, is extended to include the excited states. This study has been carried out for an interacting system composed by two massive bosons exchanging a massive scalar, by adopting (i) the Nakanishi integral representation of the Bethe-Salpeter amplitude, and (ii) the formally exact projection onto the null plane. Our analysis, on one hand, confirms the reliability of the method already applied to the ground state and, on the other one, extends the investigation from the valence distribution in momentum space to the corresponding quantity in the impact-parameter space, pointing out some relevant features, like (i) the equivalence between Minkowski and Euclidean transverse-momentum amplitudes, and (ii) the leading exponential fall-off of the valence wave function in the impact-parameter space.Comment: 15 pages, 7 figure

La riabilitazione termale nel 150° Anniversario dell'Unità d'Italia. Un testimonial d'eccezione: Giuseppe Garibaldi.

Nell’anno in cui si celebra il 150° Anniversario dell’Unità d’Italia, il riemergere di alcune lettere di Giuseppe Garibaldi - che fanno riferimento ad un periodo di cure termali effettuato presso le Terme della Ficoncella e di Traiano (vicino Civitavecchia, Roma) - ci ha dato lo spunto per questo lavoro che intende considerare i numerosi trattamenti effettuati presso diverse stazioni termali italiane dall’Eroe dei Due Mondi per una patologia reumatica (probabilmente una poliartrite reumatoide) e per gli esiti di varie ferite di guerra, in particolare la ben nota ferita da arma da fuoco subita a livello dell’arto inferiore destro nel corso della battaglia d’Aspromonte, nel 1862

A cerebral bridge from olfactory cognition to spatial navigation

An evolutionary paradox is the variability of the olfactory bulb size, in contrast to the other brain regions, which are sized proportionally to the peripheral function. This variability seems to be the result of selection for the olfactory function. This disagreement may derive from considering smell as a sense linked to odorous discrimination. In many vertebrates and in terrestrial and marine mammals, the sense of smell has evolved into functions related to the eco-localization. So, if the olfactory function involves spatial perception and navigation, this, couldexplain the proportional discrepancy between the olfactory bulb and olfactory cortex. Humans are able to discriminate a spatial position as a function of olfactory cues. Vice versa, in neurodegenerative syndromes the orientation capacity and olfactory perception are impaired. This leads us to think that could be a common cross-modal processing, of phylogenetic origin, which links olfactory perception and spatial orientation. Starting from these theoretical assumptions, we conducted a basic research, on 100 healthy subjects, investigating, through both behavioral and electroencephalographic data, the connection between spatial memory span and olfactory spatial memory span. Subjects were assessed through a three-condition task: normal Corsi Block Test (CBT), ‘Olfactory’ Block Test (OBT) and a ‘Semantic-Olfactory’ Block Test (SOBT). CBT consisted in a test on spatial memory span; OBT consisted in a presentation a spatial sequences of 9 different odorants (i.e., Eucalyptol, Carvone, Eugenol, Isoamyl Acetate, Geraniol, Phenethyl Alcohol, Acetophenone, Cinnamon, Hexanal) instilled on paper square not recognizable by any sign, positioned on a CBT, and showed in a spatial navigation way, and SOBT consisted of a semantic labelled of olfactory spatial navigation. A GLM repeated measure highlighted significant differences during the three conditions. Subjects had different SPANs due to different conditions. The Semantic olfactory memory SPAN was inferior respect Olfactory span and Spatial Span. Furthermore was found a significant positive correlation between the three condition. The 5 subjects with higher SPAN scores, 5 with medium scores and the 5 subjects with lower SPAN scores were recruited to investigate ERP components elicited during the cross-modal task. Subjects had to perform, during a high-density EEG recording, an olfactory task (administered through the device US2017127971 (A1) “? 2017-05-11), an EEG Posner spatial cueing task and a go/no-go olfactory semantic categorization task. The results of this study will be discussed in light of a theoretical connection between these three aspects of cortical functions that seem strongly interconnected

Treatment of esophageal achalasia in children: Today and tomorrow

Esophageal achalasia (EA) is a rare esophageal motility disorder in children. Laparoscopic Heller myotomy (LHM) represents the treatment of choice in young patients. Peroral endoscopic myotomy (POEM) is becoming an alternative to LHM. The aim of this study is to evaluate the effectiveness, safety, and outcomes of POEM vs LHM in treatment of children with EA. Data of pediatric patients with EA, who underwent LHM and POEM from February 2009 to December 2013 in two centers, were collected. Eighteen patients (9 male, mean age: 11.6 years; range: 2-17 years) were included. Nine patients (6 male, mean age: 10.7 years; range: 2-16 years) underwent LHM, and the other 9 (3 males, mean age: 12.2 years; range: 6-17 years) underwent POEM procedure. Mean operation time was shorter in POEM group compared with LHM group (62/149 minutes). Myotomy was longer in POEM group than in LHM group (11/7 cm). One major complication occurred after LHM (esophageal perforation). No clinical and manometric differences were observed between LHM and POEM in follow-up. The incidence of iatrogenic gastroesophageal reflux disease was low (1 patient in both groups). Results of a midterm follow-up show that LHM and POEM are safe and effective treatments also in children. Besides, POEM is a mini-invasive technique with an inferior execution timing compared to LHM. A skilled endoscopic team is mandatory to perform this procedur

miR-29b and miR-198 overexpression in CD8⁺ T cells of renal cell carcinoma patients down-modulates JAK3 and MCL-1 leading to immune dysfunction

Background: Mammalian microRNAs (miR) regulate the expression of genes relevant for the development of adaptive and innate immunity against cancer. Since T cell dysfunction has previously been reported in patients with renal cell carcinoma (RCC; clear cell type), we aimed to analyze these immune cells for genetic and protein differences when compared to normal donor T cells freshly after isolation and 35 days after in vitro stimulation (IVS) with HLA-matched RCC tumor cells. Methods: We investigated gene expression profiles of tumor-reactive CD8+ T cells obtained from RCC patient and compared with their HLA-matched healthy sibling donors using a microarray approach. In addition, miRNAs analysis was performed in a validation cohort of peripheral blood CD8+ T cells from 25 RCC patients compared to 15 healthy volunteers. Results: We observed that CD8+ T cells from RCC patients expressed reduced levels of anti-apoptotic and proliferation-associated gene products when compared with normal donor T cells both pre- and post-IVS. In particular, JAK3 and MCL-1 were down-regulated in patient CD8+ T cells versus their normal counterparts, likely due to defective suppressor activity of miR-29b and miR-198 in RCC CD8+ T cells. Indeed, specific inhibition of miR-29b or miR-198 in peripheral blood mononuclear cells (PBMCs) isolated from RCC patients, resulted in the up-regulation of JAK3 and MCL-1 proteins and significant improvement of cell survival in vitro. Conclusions: Our results suggest that miR-29b and miR-198 dysregulation in RCC patient CD8+ T cells is associated with dysfunctional immunity and foreshadow the development of miR-targeted therapeutics to correct such T cell defects in vivo

CD40 cross-linking induces migration of renal tumor cell through nuclear factor of activated T cells (NFAT) activation

CD40 crosslinking plays an important role in regulating cell migration, adhesion and proliferation in renal cell carcinoma (RCC). CD40/CD40L interaction on RCC cells activates different intracellular pathways but the molecular mechanisms leading to cell scattering are not yet clearly defined. Aim of our study was to investigate the main intracellular pathways activated by CD40 ligation and their specific involvement in RCC cell migration. CD40 ligation increased the phosphorylation of extracellular signal-regulated kinase (ERK), c-Jun NH (2)-terminal kinase (JNK) and p38 MAPK. Furthermore, CD40 crosslinking activated different transcriptional factors on RCC cell lines: AP-1, NFkB and some members of the Nuclear Factor of Activated T cells (NFAT) family. Interestingly, the specific inhibition of NFAT factors by cyclosporine A, completely blocked RCC cell motility induced by CD40 ligation. In tumor tissue, we observed a higher expression of NFAT factors and in particular an increased activation and nuclear migration of NFATc4 on RCC tumor tissues belonging to patients that developed metastases when compared to those who did not. Moreover, CD40-CD40L interaction induced a cytoskeleton reorganization and increased the expression of integrin β1 on RCC cell lines, and this effect was reversed by cyclosporine A and NFAT inhibition. These data suggest that CD40 ligation induces the activation of different intracellular signaling pathways, in particular the NFATs factors, that could represent a potential therapeutic target in the setting of patients with metastatic RCC