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We present a new approach that demonstrates the deflection and guiding of relativistic electron beams over curved paths by means of the magnetic field generated in a plasma-discharge capillary. The active bending plasma (ABP) represents a promising solution that has been recently demonstrated with a proof of principle experiment. An ABP device consists of a curved capillary where large discharges (of the order of kA) are propagated in a plasma channel. Unlike conventional bending magnets, in which the field is constant over the bending plane, in the ABP, the azimuthal magnetic field generated by the discharge grows with the distance from the capillary axis. This features makes the device less affected by the beam chromatic dispersion so that it can be used to efficiently guide particle beams with non-negligible energy spreads. The study we present in the following aims to provide a theoretical basis of the main ABP features by presenting an analytical description of a single-particle motion and rms beam dynamics. The retrieved relationships are verified by means of numerical simulations and provide the theoretical matrix formalism needed to completely characterize such a new transport device.

The EuPRAXIA EU project is at the forefront of advancing particle accelerator research and the development of photon sources through innovative plasma acceleration approaches. Within this framework, the EuAPS project aims to exploit laser wakefield acceleration to build and operate a betatron radiation source at the INFN Frascati National Laboratory. The EuAPS source will provide femtosecond X-ray pulses in the spectral region between about 1 and 10 keV, unlocking a realm of experimental ultrafast methodologies encompassing diverse imaging and X-ray spectroscopy techniques. This paper presents a description of the EuAPS betatron source, including simulations of the photon beam parameters, outlines the preliminary design of the dedicated photon beamline, and provides an insightful overview of its photon science applications.

X-ray production through betatron radiation emission from electron bunches is a valuable resource for several research fields. The EuAPS (EuPRAXIA Advanced Photon Sources) project, within the framework of EuPRAXIA, aims to provide 1–10 keV photons (X-rays), developing a compact plasma-based system designed to exploit self-injection processes that occur in the highly nonlinear laser-plasma interaction (LWFA) to drive electron betatron oscillations. Since the emitted radiation spectrum, intensity, angular divergence, and possible coherence strongly depend on the properties of the self-injected beam, accurate preliminary simulations of the process are necessary to evaluate the optimal diagnostic device specifications and to provide an initial estimate of the source’s performance. A dedicated tool for these tasks has been developed; electron trajectories from particle-in-cell (PIC) simulations are currently undergoing numerical analysis through the calculation of retarded fields and spectra for various plasma and laser parameter combinations. The implemented forward approach evaluation of the fields could allow for the integration of the presented scheme into already existing PIC codes. The spectrum calculation is thus performed in detector time, giving a linear complex exponential phase; this feature allows for a semi-analitical Fourier transform evaluation. The code structure and some trajectories analysis results are presented.

Abstract The assessment of cognitive deficits is pivotal for diagnosis and management in patients with parkinsonisms. Low levels of correspondence are observed between evaluations assessed with screening cognitive tests in comparison with those assessed with in-depth neuropsychological batteries. A new tool, we named CoMDA (Cognition in Movement Disorders Assessment), was composed by merging Mini-Mental State Examination (MMSE), Montreal Cognitive Assessment (MoCA), and Frontal Assessment Battery (FAB). In total, 500 patients (400 with Parkinson’s disease, 41 with vascular parkinsonism, 31 with progressive supranuclear palsy, and 28 with multiple system atrophy) underwent CoMDA (level 1–L1) and in-depth neuropsychological battery (level 2–L2). Machine learning was developed to classify the CoMDA score and obtain an accurate prediction of the cognitive profile along three different classes: normal cognition (NC), mild cognitive impairment (MCI), and impaired cognition (IC). The classification accuracy of CoMDA, assessed by ROC analysis, was compared with MMSE, MoCA, and FAB. The area under the curve (AUC) of CoMDA was significantly higher than that of MMSE, MoCA and FAB (p

The EuPRAXIA EU project is at the forefront of advancing particle accelerator research and the development of photon sources through innovative plasma acceleration approaches. Within this framework, the EuAPS project aims to exploit laser wakefield acceleration to build and operate a betatron radiation source at the INFN Frascati National Laboratory. The EuAPS source will provide femtosecond X-ray pulses in the spectral region between about 1 and 10 keV, unlocking a realm of experimental ultrafast methodologies encompassing diverse imaging and X-ray spectroscopy techniques. This paper presents a description of the EuAPS betatron source, including simulations of the photon beam parameters, outlines the preliminary design of the dedicated photon beamline, and provides an insightful overview of its photon science applications. [ABSTRACT FROM AUTHOR]

IntroductionDopaminergic medications can trigger impulsive-compulsive behaviors (ICBs) in pre-disposed patients with Parkinson's disease (PD), but what this implies on a neurocognitive level is unclear. Previous findings highlighted potentially exacerbated incentive motivation (willingness to work for rewards) and choice impulsivity (preferring smaller, immediate rewards over larger, delayed rewards) in PD patients with ICBs (PD + ICBs).MethodsTo deeply understand this evidence, we studied 24 PD + ICBs and 28 PD patients without ICBs (PD-ICBs). First of all, patients underwent the assessment of impulsivity traits, mood, anxiety, and addiction condition. We further administered robust objective and subjective measures of specific aspects of motivation. Finally, we explored whether these processes might link to any heightened antisocial behavior (aggression and risky driving) in PD + ICBs.ResultsHigh levels of positive urgency trait characterized PD + ICBs. They choose to exert more effort for rewards under the conditions of low and medium reward probability and as reward magnitude increases. Findings on choice impulsivity show a great tendency to delay discounting in PD + ICBs, other than a high correlation between delay and probability discounting. In addition, we found what appears to be the first evidence of heightened reactive aggression in PD patients with ICBs. Exacerbated incentive motivation and delay discounting trended toward positively predicting reactive aggression in PD + ICBs.DiscussionOur promising results suggest that there might be immense value in future large-scale studies adopting a transdiagnostic neurocognitive endophenotype approach to understanding and predicting the addictive and aggressive behaviors that can arise from dopaminergic medication in PD.

This article discusses the successful treatment of sub-erythrodermic psoriasis with bimekizumab, a humanized monoclonal antibody targeting IL-17A/F. The patient in the case study had a history of plaque psoriasis and had previously been treated with cyclosporine and methotrexate, but experienced a worsening of his condition. After starting infliximab, his condition worsened further, transitioning to sub-erythrodermic psoriasis. Bimekizumab was then administered and resulted in significant improvement after just one administration. The article highlights the efficacy and rapid onset of action of bimekizumab in treating sub-erythrodermic psoriasis, but acknowledges the need for further research to establish treatment guidelines for this condition. [Extracted from the article]

ObjectiveFreezing of gait (FoG) is a debilitating problem in patients with PD. The multifactorial pathogenesis of FoG remains poorly understood. We aimed to find which factors are most strongly associated with the occurrence of FoG.MethodsThree hundred five PD patients were enrolled and subdivided according to the presence (FoG +, n = 128) or absence (FoG-, n = 177) of FoG. Several clinical, functional, and neuropsychological data were collected and compared between groups. The association between the probability of presence of FoG and possible explanatory variables was assessed by logistic regression analysis.ResultsFoG + patients were younger at the diagnosis (p = 0.04), and their mean daily dose of dopaminergic drugs (p < 0.0001) was higher in comparison with FoG- patients. FoG + patients get worse in Frontal Assessment Battery (p = 0.005), had higher scores in Apathy Evaluation Scale (p = 0.03), and were much more impaired on Wisconsin Card Sorting Test (WCST) (p = 0.018), Trail Making Test A (p = 0.0013), and Ray Auditory Verbal Learning Test (p = 0.012). Levodopa equivalent dose, age (direct), age at disease onset (inverse), and WCST were significant predictors of FoG (p = 0.01, p = 0.0025, p = 0.0016, and p = 0.029, respectively).ConclusionFoG + patients show more deficits in executive functions and in motivation. The main explanatory variables of FoG occurrence are levodopa equivalent dose, age, age at disease onset, and WCST. These data suggest that a specific involvement of frontal cortical circuits in PD is responsible for certain cognitive–behavioral alterations related to the occurrence of FoG.

Background: constipation is one of the most common and disabling non-motor symptoms of Parkinson Disease (PD) and Parkinsonisms (PS). Few studies evaluate the difference of prevalence between PD and PS and the cause leading to a severe constipation in this diseases.Objective: Aim of our study is to evaluate the prevalence of constipation in a population of patients with PD and PS and to evaluate which factors influence the development of severe constipation.Methods: Two hundred and fifty outpatients with PD and 39 with PS were enrolled. Sixty five age-matched healthy subjects served as control. Constipation was assessed using the “Constipation Scoring System” (CSS). All patients underwent a global clinical, functional and neuropsychological assessment including: Unified Parkinson's disease Rating Scale (UPDRS), 6-min Walk Test (6MWT), and Mini-Mental State Examination (MMSE).Results: Data confirm the high prevalence of constipation among patients with PD and PS. Severe constipation affects much more patients with PS. A significant association between total CSS and age, H and Y stage, 6MWT, MMSE, total UPDRS, and UPDRS III was found in PD. In PS patients total CSS was associated with age, 6MWT, total UPDRS, and UPDRS III. Multivariable regression analysis showed that the only variables significantly and independently associated with total CSS in PD patients were age and total UPDRS, both with direct relationship.Conclusions: The reduction of motor performance seems to be the primary cause for developing severe constipation in PD and PS patients. These data suggest that maintain a good quality of gait and endurance may be helpful to reduce the risk of constipation.

Background. Hand functionality and finger dexterity are impaired in patients with Parkinson’s disease (PD). These disturbances lead to a dependency in activities of daily living (ADL) and poor quality of life (QoL). Objective. We aimed to evaluate whether a specific occupational therapy (OT) program is effective in improving finger and hand dexterity and its impact on ADL in PD patients. Methods. We retrospectively studied PD patients, hospitalized for a 4-week multidisciplinary intensive rehabilitation treatment (MIRT) between January 2015 and June 2018. All patients underwent 1 h/day OT treatment, 5 days a week. The primary outcome measure was the O’Connor finger dexterity test; secondary outcome measures were the Minnesota dexterity test, UPDRS II, and Self-Assessment Parkinson’s Disease Disability Scale (SPDDS). These measures were assessed at admission (T0) and discharge (T1). Results. Based on the Hoehn and Yahr scale (H&Y), patients were divided into two groups: 262 subjects in H&Y stage

Background: Attention is crucial to voluntary perform actions in Parkinson’s disease (PD), allowing patients to bypass the impaired habitual motor control. The asymmetrical degeneration of the dopaminergic system could affect the attentional functions.Objective: To investigate the relationship between the asymmetric dopaminergic degeneration and the attentional resources in Parkinsonian patients with right-side (RPD) and left-side (LPD) motor symptoms predominance.Methods: 50 RPD, 50 LPD, and 34 healthy controls underwent visual (V), auditory (A), and multiple choices (MC) reaction time (RTs) tasks. For PD patients, these tasks were performed before and after a 4-week intensive, motor-cognitive rehabilitation treatment (MIRT). The effectiveness of treatment was evaluated assessing Unified Parkinson’s disease Rating Scale (UPDRS) III and Timed-up and Go Test (TUG).Results: RTs did not differ between PD patients and healthy controls. Before MIRT, no differences between LPD and RPD patients were observed in RTs (p = 0.20), UPDRS III (p = 0.60), and TUG (p = 0.38). No differences in dopaminergic medication were found between groups (p = 0.44 and p = 0.66 before and after MIRT, respectively). After MIRT, LPD patients showed a significant reduction in MC RTs (p = 0.05), V RTs (p = 0.02), and MC-V RTs. A significant association between changes in RTs and improvements in UPDRS III and TUG was observed in LPD patients.Conclusion: attention does not differ among RPD patients, LPD patients and healthy controls. Only LPD patients improved their performances on attentional tasks after MIRT. We argue that the increased early susceptibility of the left nigrostriatal system to degeneration affects differently the cognitive modifiability and the neuroplastic potential. Our results could provide insight into new therapeutic approaches, highlighting the importance to design different treatments for RPD patients and LPD patients.

Manna is produced from the spontaneous solidification of the sap of some Fraxinus species, and, owing its content in mannitol, is used in medicine as a mild laxative. Manna is also a rich source of characteristic bio-phenols with reducing, antioxidant and anti-inflammatory properties. This study assesses the activity of a hydrophilic extract of manna (HME) on cellular and molecular events in human colon-rectal cancer cells. HME showed a time- and concentration-dependent anti-proliferative activity, measured by MTT assay, in all the cell lines examined, namely Caco-2, HCT-116 and HT-29. The amounts of HME that caused 50% of cell death after a 24 h treatment were 8.51 ± 0.77, 10.73 ± 1.22 and 28.92 ± 1.99 mg manna equivalents/mL, respectively; no toxicity was observed in normally differentiated Caco-2 intestinal cells. Hydroxytyrosol, a component of HME known for its cytotoxic effects on colon cancer cells, was ineffective, at least at the concentration occurring in the extract. Through flow-cytometric techniques and Western blot analysis, we show that HME treatment causes apoptosis, assessed by phosphatidylserine exposure, as well as a loss of mitochondrial membrane potential, an intracellular formation of reactive oxygen species (ROS), increases in the levels of cleaved PARP-1, caspase 3 and Bax, and a decrease in Bcl-2 expression. Moreover, HME interferes with cell cycle progression, with a block at the G1/S transition. In conclusion, the phytocomplex extracted from manna exerts an anti-proliferative activity on human colon cancer cells through the activation of mitochondrial pathway-mediated apoptosis and cell cycle arrest. Our data may suggest that manna could have the potential to exert chemo-preventive effects for the intestine.

Combining phytochemicals with chemotherapics is an emerging strategy to treat cancer to overcome drug toxicity and resistance with natural compounds. We assessed the effects of indicaxanthin (Ind), a pigment obtained from Opuntia ficus-indica (L. Mill) fruit, combined with cisplatin (CDDP) against cervical cancer cells (HeLa). Measured cell viability via Trypan blue assay; cell morphology via fluorescence microscopy; apoptosis, cell cycle, mitochondrial membrane potential (MMP) and cell redox balance via flow-cytometry; expression levels of apoptosis-related proteins via western blot. Cell viability assays and Chou-Talalay plot demonstrated that the combination of CDDP and Ind had synergistic cytotoxic effects. Combined treatment had significant effects (p < 0.05) on phosphatidylserine externalization, cell morphological changes, cell cycle arrest, fall in MMP, ROS production and GSH decay compared with the individual treatment groups. Bax, cytochrome c, p53 and p21waf1 were over-expressed, while Bcl-2 was downregulated. Pre-treatment with N-acetyl-l-cysteine abolished the observed synergistic effects. We also demonstrated potentiation of CDDP anticancer activity by nutritionally relevant concentrations of Ind. Oxidative stress-dependent mitochondrial cell death is the basis of the chemosensitizing effect of Ind combined with CDDP against HeLa cancer cells. ROS act as upstream signaling molecules to initiate apoptosis via p53/p21waf1 axis. Ind can be a phytochemical of interest in combo-therapy.

In this study cytotoxicity of organotin(IV) compounds with 1,2,4-triazolo[1,5-a]pyrimidines, Me3Sn(5tpO) (1), n-Bu3Sn(5tpO) (2), Me3Sn(mtpO) (3), n-Bu3Sn(mtpO) (4), n-Bu3Sn(HtpO2) (5), Ph3Sn(HtpO2) (6) where 5HtpO = 4,5-dihydro-5-oxo-[1,2,4]triazolo-[1,5-a]pyrimidine, HmtpO = 4,7-dihydro-5-methyl-7-oxo-[1,2,4]triazolo-[1,5-a]pyrimidine, and H2tpO2 = 4,5,6,7-tetrahydro-5,7- dioxo-[1,2,4]triazolo-[1,5-a]-pyrimidine, was assessed on three different human tumor cell lines: HCT-116 (colorectal carcinoma), HepG2 (hepatocarcinoma) and MCF-7 (breast cancer). While 1 and 3 were inactive, compounds 2, 4, 5 and 6 inhibited the growth of the three tumor cell lines with IC50 values in the submicromolar range and showed high selectivity indexes towards the tumor cells (SI > 90). The mechanism of cell death triggered by the organotin(IV) derivatives, investigated on HCT-116 cells, was apoptotic, as evident from the externalization of phosphatidylserine to the cell surface, and occurred via the intrinsic pathway with fall of mitochondrial inner membrane potential and production of reactive oxygen species. While compound 6 arrested the cell progression in the G2/M cell cycle phase and increased p53 and p21 levels, compounds 2, 4 and 5 blocked cell duplication in the G1 phase without affecting the expression of either of the two tumor suppressor proteins. Compounds 1 and 2 were also investigated using single crystal X-ray diffraction and found to be, in both cases, coordination polymers forming 1 D chains based on metal-ligand interactions. Interestingly, for n-Bu3Sn(5tpO)(2) H-bonding interactions between 5tpO− ligands belonging to adjacent chains were also detected that resemble the “base-pairing” assembly and could be responsible for the higher biological activity compared to compound 1. In addition, they are the first example of bidentate N(3), O coordination for the 5HtpO ligand on two adjacent metal atoms.

Purpose: Early decannulation is considered a main rehabilitative goal in tracheostomized patients. Our aim is to evaluate whether a very early rehabilitation protocol helps to reduce the tracheostomy duration in patients affected by an Acquired Brain Injury (ABI).Methods: Data about consecutive tracheostomized patients admitted in our Neuro-Rehabilitation Unit (NRU) were retrospectively collected. We defined two groups: Early Rehabilitation Group patients came from our ICU, where they started the rehabilitative treatment; Delayed Rehabilitation Group patients arrived from external ICUs and started rehabilitation in our NRU. Primary outcome was the time from tracheostomy to decannulation. Secondary outcomes were: ICU length of stay, time from NRU admission to decannulation, Glasgow Coma Scale, Coma Recovery Scale revised and Levels of Cognitive Functioning scores at NRU discharge and the re-cannulation rate.Results: We enrolled 66 patients, 40 in the Early Rehabilitation Group and 26 in the Delayed Rehabilitation Group. 70% of patients for each group could be decannulated (p = 0.73) and were analyzed. Only one patient was re-cannulated. Early Rehabilitation Group showed a shorter tracheostomy duration (61.0 vs. 94.5 days, p = 0.013), a higher probability of occurrence of decannulation (p = 0.008) and a lower ICU length of stay (30.0 vs. 52.0 days, p = 0.001). The time to decannulation in NRU was similar between groups (30.0 vs. 45.50 days, p = 0.14). All the scale scores had a significant improvement in both groups (p < 0.0001 all).Conclusions: The present study shows that an early neuro-rehabilitation protocol helps to reduce the time to decannulation in tracheostomized patients affected by ABI.

Objective: To report a rare case of hypokalemic rhabdomyolysis induced by the heavy and prolonged ingestion of cola-based beverages, and its uneventful recovery after kalemia normalization. Methods: We report a 38-year-old Caucasian male presented in our emergency room with a recent and progressive weakness of the lower limbs proximal muscles. Results: A dietary history revealed a prolonged ingestion of cola-based beverages. Blood tests showed severe hypokalemia and marked increase in serum creatine phosphokinase. The analysis of cerebrospinal fluid resulted normal. Electromyography was suggestive for a myopathy. The clinical, laboratory and neurophysiological data were evocative for a cola-induced hypokalemic rhabdomyolysis. After kalemia normalization, the improvements of the electromyographic findings paralleled the clinical recovery. Conclusion: Chronic consumption of large amount of cola-based soft drinks may result in severe symptomatic hypokalemia, eventually leading in turn to myopathy. To our knowledge, this is the first description of the electromyographic findings of the cola-induced hypokalemic rhabdomyolysis. An early diagnosis and a prompt treatment appear to be crucial for a benign clinical course.

BACKGROUND:to date, there are no medical or surgical treatments for progressive supranuclear palsy (PSP). It is possible to speculate that patients with PSP could benefit from rehabilitative treatments designed for Parkinson's disease, including the use of robot-assisted walking training. OBJECTIVE:to evaluate whether the use of the robotic device Lokomat® is superior in PSP patients to the use of treadmill with visual cues and auditory feedbacks (treadmill-plus) in the context of an aerobic, multidisciplinary, intensive, motor-cognitive and goal-based rehabilitation treatment (MIRT) conceived for Parkinsonian patients. METHODS:we enrolled twenty-four PSP patients. Twelve subjects underwent a 4-week MIRT exploiting the use of the treadmill-plus (MIRT group). Twelve subjects underwent the same treatment, but replacing the treadmill-plus with Lokomat® (MIRT-Lokomat group). Subjects were evaluated with clinical and functional scales at admission and discharge. The primary outcomes were the total PSP Rating Scale (PSPRS) score and its "limb" and "gait" sub-scores. Secondary outcomes were Berg Balance Scale (BBS), Six Minutes Walking test (6MWT) and the number of falls. RESULTS:total PSPRS, PSPRS-gait sub-score, BBS, 6MWT and number of falls improved significantly in both groups (p ≤ 0.003 all, except 6MWT, p = 0.032 and p = 0.018 in MIRT-Lokomat and MIRT group respectively). The PSPRS-limb sub-score improved significantly only in the MIRT group (p = 0.002). A significant difference between groups was observed only for total PSPRS, indicating a slightly better improvement for patients in the MIRT group (p = 0.047). No differences between groups were revealed for the other outcomes, indicating that the effect of rehabilitation was similar in both groups. CONCLUSIONS:Lokomat® training, in comparison with treadmill-plus training, does not provide further benefits in PSP patients undergoing MIRT. Our findings suggest the usefulness of an aerobic, multidisciplinary, intensive, motor-cognitive and goal-based approach for the rehabilitation of patients suffering from such a complex disease as PSP. TRIAL REGISTRATION:This trial was registered on ClinicalTrials.gov, NCT02109393.

Parkinson’s disease (PD) is a neurodegenerative disease characterized by motor and nonmotor symptoms. Both of them imply a negative impact on Health-Related Quality of Life. A significant one is the stigma experienced by the parkinsonian patients and their caregivers. Moreover, stigma may affect everyday life and patient’s subjective and relational perception and it may lead to frustration and isolation. Aim of the present work is to qualitatively describe the stigma of PD patients stemming from literature review, in order to catch the subjective experience and the meaning of the stigma construct. Literature review was performed on PubMed database and Google Scholar (keywords: Parkinson Disease, qualitative, stigma, social problem, isolation, discrimination) and was restricted to qualitative data: 14 articles were identified to be suitable to the aim of the present overview. Results are divided into four core constructs: stigma arising from symptoms, stigma linked to relational and communication problems, social stigma arising from sharing perceptions, and caregiver’s stigma. The principal relations to these constructs are deeply analyzed and described subjectively through patients’ and caregiver’s point of view. The qualitative research may allow a better understanding of a subjective symptom such as stigma in parkinsonian patients from an intercultural and a social point of view.