Mutations in proteins involved in E-C coupling and SOCE and congenital myopathies

In skeletal muscle, Ca2+ necessary for muscle contraction is stored and released from the sarcoplasmic reticulum (SR), a specialized form of endoplasmic reticulum through the mechanism known as excitation-contraction (E-C) coupling. Following activation of skeletal muscle contraction by the E-C coupling mechanism, replenishment of intracellular stores requires reuptake of cytosolic Ca2+ into the SR by the activity of SR Ca2+-ATPases, but also Ca2+ entry from the extracellular space, through a mechanism called store-operated calcium entry (SOCE). The fine orchestration of these processes requires several proteins, including Ca2+ channels, Ca2+ sensors, and Ca2+ buffers, as well as the active involvement of mitochondria. Mutations in genes coding for proteins participating in E-C coupling and SOCE are causative of several myopathies characterized by a wide spectrum of clinical phenotypes, a variety of histological features, and alterations in intracellular Ca2+ balance. This review summarizes current knowledge on these myopathies and discusses available knowledge on the pathogenic mechanisms of disease

Successful transition to groundwork combat during Junior and Senior Judo World Championships

The main goal of the present study was to describe the successful transition phases from standing combat to groundwork combat in a high-level judo competition (2017 World Championship) to determine the type of transition (turtle, supine, prone, half-guard, besides, guard, standing and seated) and their rhythms (i.e. time spent by the scoring athletes) mostly used by these athletes. Our sample was based on the junior and senior, male and females, 2017 Judo World Championships. Transition phases (n = 373) that resulted in a score during the junior (n = 179) and senior (n = 194) were analysed. The main findings of this study indicated an immediate link between standing and groundwork actions observed in almost half of the occurrences. Most of the scoring actions (~75%) were achieved through an osae-komi-waza (immobilisation techniques), and these actions were performed mainly when the match was tied (~71%). No significant differences (p > 0.05) were observed between sex and age groups concerning the type of techniques and body position. The different types of transitions were used similarly along the competition phases, indicating that athletes need to be able to cope with different situations in the transition phase to be successful

Psychiatric profile of motor subtypes of de novo drug-naïve Parkinson's disease patients

Background: Parkinson's disease (PD) is a heterogeneous neurodegenerative disorder. It is well established that different motor subtypes of PD evolve with different clinical courses and prognoses. The complete psychiatric profile underlying these different phenotypes since the very early stage of the disease is debated. Aims of the study: We aimed at investigating the psychiatric profile of the three motor subtypes of PD (akinetic-rigid, tremor-dominant, and mixed) in de novo drug-naïve patients with PD. Methods: Sixty-eight patients with PD, divided into 39 akinetic-rigid (AR), seven mixed (MIX), and 22 tremor-dominant (TD) patients underwent a complete assessment of psychiatric, cognitive, and motor symptoms. Results: No significant differences were found among groups. Conclusions: Our results suggest that a differentiation of the psychiatric symptoms associated with specific motor subtypes of PD is not detectable in de novo drug-naïve patients. Previous evidence that emerges later along the disease progression may be a consequence of the dopaminergic and nondopaminergic damage increase

Towards 3d multi-layer scaffolds for periodontal tissue engineering applications: Addressing manufacturing and architectural challenges

Reduced periodontal support, deriving from chronic inflammatory conditions, such as periodontitis, is one of the main causes of tooth loss. The use of dental implants for the replacement of missing teeth has attracted growing interest as a standard procedure in clinical practice. However, adequate bone volume and soft tissue augmentation at the site of the implant are important prerequisites for successful implant positioning as well as proper functional and aesthetic reconstruction of patients. Three-dimensional (3D) scaffolds have greatly contributed to solve most of the challenges that traditional solutions (i.e., autografts, allografts and xenografts) posed. Nevertheless, mimicking the complex architecture and functionality of the periodontal tissue represents still a great challenge. In this study, a porous poly(ε-caprolactone) (PCL) and Sr-doped nano hydroxyapatite (Sr-nHA) with a multi-layer structure was produced via a single-step additive manufacturing (AM) process, as a potential strategy for hard periodontal tissue regeneration. Physicochemical characterization was conducted in order to evaluate the overall scaffold architecture, topography, as well as porosity with respect to the original CAD model. Furthermore, compressive tests were performed to assess the mechanical properties of the resulting multi-layer structure. Finally, in vitro biological performance, in terms of biocompatibility and osteogenic potential, was evaluated by using human osteosarcoma cells. The manufacturing route used in this work revealed a highly versatile method to fabricate 3D multi-layer scaffolds with porosity levels as well as mechanical properties within the range of dentoalveolar bone tissue. Moreover, the single step process allowed the achievement of an excellent integrity among the different layers of the scaffold. In vitro tests suggested the promising role of the ceramic phase within the polymeric matrix towards bone mineralization processes. Overall, the results of this study demonstrate that the approach undertaken may serve as a platform for future advances in 3D multi-layer and patient-specific strategies that may better address complex periodontal tissue defects

Verifica degli impatti socioeconomici ed ambientali conseguenza dei mutamenti climatici in atto nel bacino del Mediterraneo, attraverso l’uso del telerilevamento satellitare

Oggi l’uomo è pericolosamente prossimo ad un punto di non ritorno, in cui può decidere di cambiare rotta od accettare di vedere avverarsi ciò che più temeva l'economista statunitense Premio Nobel Paul Robin Krugmani, il quale sosteneva che le future generazioni non avrebbero più potuto contare, come avevano sempre fatto le precedenti, su di un tenore di vita migliore rispetto a quello di padri e nonni. Questo potrebbe avvenire perché è stato ormai sollevato il problema dell’assoluta carenza di risorse naturali, questione che per lungo tempo è stata risolta dai paesi più industrializzati con l’esclusione della maggioranza della popolazione mondiale dai consumi di massa propri dell’Occidente. Ma la problematica riguardante questa scarsità segue, ogni giorno di più, quella altrettanto drammatica che investe il clima e per la comunità scientifica è ormai ovvio che entrambi sono due facce di una stessa medaglia. Sempre più spesso, dunque, siamo chiamati a confrontarci non solo con la miseria, in preoccupante aumento in ogni Paese dopo la crisi economica globale iniziata nel 2008 e non ancora conclusasi, ma, anche, con tematiche come calamità naturali, eventi estremi, squilibri ecologici, avvenimenti pure essi in apparente, decisa crescita. Privazioni e mutamenti climatici hanno un costo economico e sociale altissimo e l’unico metodo per risolvere queste difficoltà parrebbe quello di ricondurre la dottrina al significato primigenio della parola economia, “oikos nomos”, che circa 2700 anni fa significava gestione della casa comune, ovvero la Terra, pianeta in cui viviamo. In questo contesto è da inquadrare il programma di studio interministeriale che ha per titolo “Modello integrato per l’evoluzione degli ecosistemi naturali ed agricoli in relazione ai cambiamenti climatici nell’area mediterranea (FISR-MICENA)”; il lavoro che qui si presenta è parte integrante dell’attività di ricerca n.19 di questo progetto

Evaluation of trueness and precision of removable partial denture metal frameworks manufactured with digital technology and different materials

PURPOSE. The aim of this study is to evaluate the accuracy of removable partial denture (RPD) frameworks produced using different digital protocols. MATERIALS AND METHODS. 80 frameworks for RPDs were produced using CAD-CAM technology and divided into four groups of twenty (n = 20): Group 1, Titanium frameworks manufactured by digital metal laser sintering (DMLS); Group 2, Co-Cr frameworks manufactured by DMLS; Group 3, Polyamide PA12 castable resin manufactured by multi-jet fusion (MJF); and Group 4, Metal (Co-Cr) casting by using lost-wax technique. After the digital acquisition, eight specific areas were selected in order to measure the Δ-error value at the intaglio surface of RPD. The minimum value required for point sampling density (0.4 mm) was derived from the sensitivity analysis. The obtained Δ-error mean value was used for comparisons: 1. between different manufacturing processes; 2. between different manufacturing techniques in the same area of interest (AOI); and 3. between different AOI of the same group. RESULTS. The Δ-error mean value of each group ranged between -0.002 (Ti) and 0.041 (Co-Cr) mm. The Pearson’s Chi-squared test revealed significant differences considering all groups paired two by two, except for group 3 and 4. The multiple comparison test documented a significant difference for each AOI among group 1, 3, and 4. The multiple comparison test showed significant differences among almost all different AOIs of each group. CONCLUSION. All Δ-mean error values of all digital protocols for manufacturing RPD frameworks optimally fit within the clinical tolerance limit of trueness and precision

Interplay of the electronic and lattice degrees of freedom in A_{1-x}Fe_{2-y}Se_{2} superconductors under pressure

The local structure and electronic properties of Rb$_{1-x}$Fe$_{2-y}$Se$_2$ are investigated by means of site selective polarized x-ray absorption spectroscopy at the iron and selenium K-edges as a function of pressure. A combination of dispersive geometry and novel nanodiamond anvil pressure-cell has permitted to reveal a step-like decrease in the Fe-Se bond distance at $p\simeq11$ GPa. The position of the Fe K-edge pre-peak, which is directly related to the position of the chemical potential, remains nearly constant until $\sim6$ GPa, followed by an increase until $p\simeq 11$ GPa. Here, as in the local structure, a step-like decrease of the chemical potential is seen. Thus, the present results provide compelling evidence that the origin of the reemerging superconductivity in $A_{1-x}$Fe$_{2-y}$Se$_2$ in vicinity of a quantum critical transition is caused mainly by the changes in the electronic structure

Successful subthalamic stimulation, but levodopa-induced dystonia, in a genetic Parkinson's disease

Recently, it is under scrutiny the possibility to anticipate the stereotactic implantation of the subthalamic nucleus (STN) even in relatively mild Parkinson's disease (PD) patients with an unsatisfying response to drugs. In addition, it is debated whether levodopa (LD) and deep brain stimulation (DBS) are congruent or, instead, mutually exclusive. A 56-year-old LRRK2-positive PD patient, with 7 years of disease history, dominated by severe left resting tremor, was submitted to bilateral implantation of the subthalamic nucleus (STN). Before surgery, the combination of LD and dopamine agonists failed to handle tremor unless administered at doses, which induced undesirable adverse events. STN deep brain stimulation (DBS) abolished tremor but did not provide satisfying control of hypokinetic-rigid symptoms. The condition STIM-ON plus LD, albeit transiently beneficial, installed a painful dystonia developing slowly after 24-36 h. Only a chronic therapy combining rotigotine plus STN-DBS proved effective without side effects. This case report, based upon the surprising difference between the therapeutic response to the combination of LD and dopamine agonist (before surgery) and the combination of DBS and agonist after surgery, emphasizes how STIM and LD target different motor domains through mechanisms with differential plasticity and confirms the efficacy of STN-DBS in LRKK2 patient

Involvement of subcortical brain structures during olfactory stimulation in multiple chemical sensitivity

Multiple chemical sensitivity (MCS) patients usually react to odour compounds and the majority of neuroimaging studies assessed, especially at the cortical level, many olfactory-related correlates. The purpose of the present study was to depict sub-cortical metabolic changes during a neutral (NC) and pure (OC) olfactory stimulation by using a recently validated 18F-2-fluoro-2-deoxy-D-glucose (FDG)-positron emission tomography/computer tomography procedure in 26 MCS and 11 healthy (HC) resting subjects undergoing a battery of clinical tests. Twelve subcortical volumes of interest were identified by the automated anatomical labeling library and normalized to thalamus FDG uptake. In both groups, when comparing OC to NC, the within-subjects ANOVA demonstrated a relative decreased metabolism in bilateral putamen and hippocampus and a relative increased metabolism in bilateral amygdala, olfactory cortex (OLF), caudate and pallidum. The between-groups ANOVA demonstrated in MCS a significant higher metabolism in bilateral OLF during NC. As in HC subjects negative correlations were found in OC between FDG uptake in bilateral amygdala and hippocampus and odor pleasantness scale, the latter positively correlated with MCS subjects\u27 bilateral putamen FDG uptake in OC. Besides FDG uptake resemblances in both groups were found, for the first time a relative higher metabolism increase in OLF in MCS subjects at rest with respect to HC was found. When merging this aspect to the different subcortical FDG uptake correlations patterns in the two groups, the present study demonstrated to describe a peculiar metabolic index of behavioral and neurological aspects of MCS complaints