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Opuntia ficus indica METHANOLIC FRUIT EXTRACT COUNTERACTS OXIDIZED LDL-MEDIATED HUMAN ENDOTHELIAL CELL DYSFUNCTION THROUGH THE INHIBITION OF NF- B ACTIVATION. [Extracted from the article]

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. [ABSTRACT FROM AUTHOR]

Recently, the statistical analysis of muscle activation patterns highlighted that not only one, but several activation patterns can be identified in the gait of healthy adults, with different occurrence. Although its potential, the application of this approach in pathological populations is still limited and specific implementation issues need to be addressed. This study aims at applying a statistical approach to analyze muscle activation patterns of gait in Parkinson's Disease, integrating gait symmetry and co-activation. Surface electromyographic signal of tibialis anterior and gastrocnemius medialis were recorded during a 6-min walking test in 20 patients. Symmetry between right and left stride time series was verified, different activation patterns identified, and their occurrence (number and timing) quantified, as well as the co-activation of antagonist muscles. Gastrocnemius medialis presented five activation patterns (mean occurrence ranging from 2% to 43%) showing, with respect to healthy adults, the presence of a first shorted and delayed activation (between flat foot contact and push off, and in the final swing) and highlighting a new second region of anticipated activation (during early/mid swing). Tibialis anterior presented five activation patterns (mean occurrence ranging from 3% to 40%) highlighting absent or delayed activity at the beginning of the gait cycle, and generally shorter and anticipated activations during the swing phase with respect to healthy adults. Three regions of co-contraction were identified: from heel strike to mid-stance, from the pre- to initial swing, and during late swing. This study provided a novel insight in the analysis of muscle activation patterns in Parkinson's Disease patients with respect to the literature, where unique, at times conflicting, average patterns were reported. The proposed integrated methodology is meant to be generalized for the analysis of muscle activation patterns in pathologic subjects. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

The author conveys his thoughts on how oncology nurses can support surgical patients with esophageal cancer. Information about the Esophageal Cancer Education Foundation is presented. Oncology nurses can connect their patients to necessary resources as they undergo treatment and surgery for esophageal cancer. The book "Esophagectomy Post-Surgical Guide: Questions and Answers" is mentioned.

The original version of this article unfortunately contained a mistake. The funding information was incorrect. The corrected funding information is given below. [ABSTRACT FROM AUTHOR]

BACKGROUND: Pisa syndrome (PS) is a clinical condition frequently associated with Parkinson's disease (PD). It is characterized by a trunk lateral flexion higher than 10 degrees and reversible when lying. One pathophysiological hypothesis is the altered verticality perception, due to a somatosensory impairment. Osteopathic Manipulative Treatment (OMT) manages fascial-system alterations, linked to somatic dysfunctions. Fascial system showed to be implicated in proprioceptive sensibility. OBJECTIVE: The aim of the study was to assess OMT efficacy on postural control in PD-PS patients by stabilometry. METHODS: In this single-blinded trial we studied 24 PD-PS patients, 12 of whom were randomly assigned to receive a multidisciplinary physical therapy protocol (MIRT) and sham OMT, while the other 12 received four OMT plus MIRT, for one month. The primary endpoint was the eye closed sway area assessment after the intervention. Evaluation of trunk lateral flexion (TLF) with DIERS formetrics was also performed. RESULTS: At one month, the sway area of the OMT group significantly decreased compared to placebo (mean delta OMT – 326.00±491.24 mm2, p = 0.01). In the experimental group TLF showed a mean inclination reduction of 3.33 degrees after treatment (p = 0.044, mean d = 0.54). Moreover, a significant positive association between delta ECSA and delta TLF was observed (p = 0.04, r = 0.46). DISCUSSION: Among PD-PS patients, MIRT plus OMT showed preliminary evidence of postural control and TLF improvement, compared to the control group. [ABSTRACT FROM AUTHOR]

Background: the social impact of Parkinson's is difficult to capture in quantitative research given the condition's variable presentation, so qualitative research is needed to support a person-centred approach. Aims: to describe how people with Parkinson's experience living with their condition over time. Methods: 27 audio-recorded verbatim-transcribed interviews were analysed through the grounded theory method. Findings: past, present and future were the core categories that emerged. Past is the dimension of regretted memories of past life overturned by the communication of diagnosis. Present is the time dimension in which patients concretely experience the hindrances associated with the condition (loss of autonomy, submissive acceptance and social embarrassment), and the resources (search for autonomy, serene or in-progress acceptance, and social support). Future is characterised by both positive visions of tomorrow and negative ones (worry, resignation, denial). Conclusion: these results, highlighting what living with Parkinson's means over time, may contribute to a better tailoring of nursing practice to the person's needs and rhythm, in a perspective of continuous adaptation. [ABSTRACT FROM AUTHOR]

Summary: The aim of this study was to evaluate the antiproliferative activity of bioaccessible fractions (BFs) obtained by the internationally standardized INFOGEST static digestion method to Sicilian honeys of three distinct floral origins (Sulla, Thistle and Dill) and the Manuka honey (gold standard), and to compare their effects based on total polyphenol content (TPC). Differentiated CaCo‐2 cells (intestinal‐like) and non‐differentiated CaCo‐2 and HCT‐116 colonic tumour‐like cells were incubated for 24 h with BFs of honeys to test viability, apoptosis, mitochondrial membrane potential (MMP), ROS and cell cycle. TPC after digestion ranked in the following order: Dill > Thistle > Sulla > Manuka. No decrease in cell viability in differentiated CaCo‐2 cells was observed, while a reduction to 25–85% (CaCo‐2) and 20–80% (HCT‐116) of viability was obtained. This descent in viability was caused by a cell cycle block with an increase in apoptosis through dissipation of MMP and raise in ROS levels, being Thistle and Dill the most effective honeys followed by Sulla and finally Manuka, in agreement with TPC after digestion. [ABSTRACT FROM AUTHOR]

Background: Optimal management in expert centers for Parkinson's disease (PD) usually involves pharmacological and non-pharmacological interventions, delivered by a multidisciplinary approach. However, there is no guideline specifying how this model should be organized. Consequently, the nature of multidisciplinary care varies widely. Objective: To optimize care delivery, we aimed to provide recommendations for the organization of multidisciplinary care in PD. Methods: Twenty expert centers in the field of multidisciplinary PD care participated. Their leading neurologists completed a survey covering eight themes: elements for optimal multidisciplinary care; team members; role of patients and care partners; team coordination; team meetings; inpatient versus outpatient care; telehealth; and challenges towards multidisciplinary care. During a consensus meeting, outcomes were incorporated into concept recommendations that were reviewed by each center's multidisciplinary team. Three patient organizations rated the recommendations according to patient priorities. Based on this feedback, a final set of recommendations (essential elements for delivery of multidisciplinary care) and considerations (desirable elements) was developed. Results: We developed 30 recommendations and 10 considerations. The patient organizations rated the following recommendations as most important: care is organized in a patient-centered way; every newly diagnosed patient has access to a core multidisciplinary team; and each team has a coordinator. A checklist was created to further facilitate its implementation. Conclusion: We provide a practical tool to improve multidisciplinary care for persons with PD at the organizational level. Future studies should focus on implementing these recommendations in clinical practice, evaluating their potential applicability and effectiveness, and comparing alternative models of PD care. [ABSTRACT FROM AUTHOR]

Background: Under water gait training (UT) has been proposed as an innovative rehabilitative strategy for the treatment of axial disorders in Parkinson Disease (PD) patients, in particular for balance and gait impairment. However, the basis for the improvement is unclear.Research Question: The aim of this study was to evaluate improvements in the muscular activation in the lower limbs in a cohort of PD patients after UT.Methods: Ten PD participants in the "off" state and 10 controls (mean ± standard deviation of age and BMI were respectively: 71 ± 6 years, 28 ± 3 kg/m2; 65.5 ± 7 years, 28 ± 3 kg/m2) were enrolled in the study. After signing informed consent, they walked barefoot at their preferred speed on a 10 m walkway, before and after UT. The electrical activity of four muscles were collected bilaterally by means of a surface electromyography system (sEMG), two force plates and a motion capture system. All signals were synchronized in time with the gait cycle. The sEMG activity of Rectus Femoris (RF), Tibialis Anterior (TA), Biceps Femoris (BF) and Gastrocnemius Lateralis (GL) were acquired. The average from each signal was used to extract the peak of the Envelope (PoE) and its occurrence with respect to the gait cycle (PoPE%). Time and space parameters were determined.Results: Our results showed that UT in PD patients improved the muscle's recruitment pattern towards normal. The PD patients POPE% was comparable with the one of the controls (TA: 20-35 %, 75-80 % of gait cycle; GL: 0-15 %, 25-45 %, 85-100 % of gait cycle) after UT on each muscle with the exception of BF. The muscle co-activation plots failed to show improvement in line with the muscle activation.Significance: These results suggest that the muscle activation improvement with UT in PD participants might be due to a reorganisation at the executive rather than at the command level. [ABSTRACT FROM AUTHOR]

Background Freezing of gait (FOG) is one of the most disabling symptoms of Parkinson disease (PD). Different land-based rehabilitation approaches based on motor and cognitive strategies can be effective in treating FOG. Although there are data about the efficacy of aquatic therapy in ameliorating this phenomenon, no study has explored the combined effect of land-based therapies plus aquatic therapy in patients with PD who have FOG. Objective The objective was to investigate the effectiveness of a multidisciplinary, intensive, motor-cognitive rehabilitation treatment (MIRT) in improving FOG and whether implementation with aquatic therapy (MIRT-AT) adds further benefits. Design The design consisted of a single-blind, parallel-group, 1:1 allocation ratio, randomized trial. Setting The Department of Parkinson Disease, Movement Disorders and Brain Injury Rehabilitation at "Moriggia-Pelascini" Hospital (Gravedona ed Uniti, Como, Italy) was used as the setting. Participants Sixty hospitalized patients with PD who had FOG in Hoehn and Yahr stage 2 or 5-3 were included. Intervention Sixty patients with PD + FOG were randomly assigned to 2 groups: 30 underwent a 4-week MIRT and 30 underwent a 4-week MIRT-AT. Measurements The primary outcome measure was the Freezing of Gait Questionnaire; secondary outcome measures were total Unified Parkinson Disease Rating Scale (UPDRS), UPDRS II, UPDRS III, Berg Balance Scale, Timed Up and Go Test, and 6-Minute Walk Test. These measures were assessed both at admission and discharge. Results Participants in the 2 groups had similar age, sex distribution, Hoehn and Yahr stage, and most-affected side. At baseline, no difference in outcome measures was observed between the 2 groups. After treatment, a significant time effect was observed for all variables in both groups. No significant time × group interaction was observed. A between-group analysis showed nonsignificant differences between values at T1 and values at T0 for all variables. Limitations The limitations were the lack of a control group and follow-up. Conclusions We showed that a multidisciplinary, intensive, and goal-based rehabilitation treatment, such as MIRT, improves FOG in patients with PD. Although aquatic therapy could be considered a useful approach for treating FOG, it does not add further benefits to this kind of motor-cognitive rehabilitation. [ABSTRACT FROM AUTHOR]

Parkinson’s disease (PD) is characterized by motor and cognitive dysfunctions, affecting the motor behaviour. We summarize evidence that the interplay between motor and cognitive approaches is crucial in PD rehabilitation. Rehabilitation is complementary to pharmacological therapy and effective in reducing the PD disturbances, probably acting by inducing neuroplastic effects. The motor behaviour results from a complex integration between cortical and subcortical areas, underlying the motor, cognitive and motivational aspects of movement. The close interplay amongst these areas makes possible to learn, control and express habitual-automatic actions, which are dysfunctional in PD. The physiopathology of PD could be considered the base for the development of effective rehabilitation treatments. As the volitional action control is spared in early-medium stages of disease, rehabilitative approaches engaging cognition permit to achieve motor benefits and appear to be the most effective for PD. We will point out data supporting the relevance of targeting both motor and cognitive aspects in PD rehabilitation. Finally, we will discuss the role of cognitive engagement in motor rehabilitation for PD. [ABSTRACT FROM AUTHOR]

Dopaminergic medication can induce severe addictive behaviours (e.g., pathological gambling) in susceptible Parkinson's disease (PD) patients. It is still unknown which particular neurocognitive processes become exacerbated or dysfunctional in PD patients with addictive behaviours. We sought to systematically review the relevant literature to identity potential neurocognitive correlates of medication-induced addictive behaviours in PD. We framed our review around neurocognitive processes central to four dominant accounts of substance addiction: ‘aberrant learning’, ‘incentive sensitization’, ‘impulsivity to compulsivity’ and ‘impaired response inhibition and salience attribution’. Searches of the PubMed and Scopus databases were completed on June 23, 2017. To be included, studies were required to involve: (a) medicated PD patients, without a history of deep brain stimulation, with and without addictive behaviours; (b) a reward-related or decision-making task; and (c) statistical comparison of addictive and non-addictive groups’ ‘on’ medication performance on the task(s). Studies were summarised qualitatively with statistically significant ( p <.05) group differences and effect sizes (Cohen's d ) highlighted. 35 studies were included. Findings showed that the extant literature is highly heterogeneous. The domains of reward and punishment learning, reflection impulsivity and disadvantageous decision-making exemplify this. More homogeneity exists in domains in which (a) neurocognitive dysfunction is not apparent (motor control, cognitive/attentional flexibility and cognitive control) or (b) typical neurocognitive processes appear exacerbated by medication (reward motivation and choice impulsivity). Future large-scale neurocognitive studies are still required to develop our scientific understanding of addictive behaviours in PD and aid their clinical treatment and prediction. [ABSTRACT FROM AUTHOR]

Background: Dopamine Replacement Therapy (DRT) represents the most effective treatment for Parkinson’s disease (PD). Nevertheless, several symptoms are unresponsive to treatment and its long-term use leads to serious side effects. To optimize the pharmacological management of PD, dopamine-agonists are often prescribed to “de-novo” patients. Moreover, several studies have shown the effectiveness and the synergic effect of rehabilitation in treating PD.Objective: To evaluate the synergism between DRT and rehabilitation in treating PD, by investigating the short and the long-term effectiveness of a multidisciplinary, intensive and goal-based rehabilitation treatment (MIRT) in a group of patients treated with Rotigotine.Materials and methods: In this multicenter, single blinded, parallel-group, 1:1 allocation ratio, randomized, non-inferiority trial, 36 “de-novo” PD patients were evaluated along 18 months: 17 were treated with Rotigotine plus MIRT; 19 were treated with Rotigotine alone (R). The primary outcome measure was the total score of Unified Parkinson’s Disease Rating Scale (UPDRS). The secondary outcomes included the UPDRS sub-sections II and III (UPDRS II-III), the 6-Minute Walk Test (6MWT), the Timed Up and Go Test (TUG) and the amount of Rotigotine. Patients were evaluated at baseline (T0), 6 months (T1), 1 year (T2), and at 18 months (T3).Results: No differences in UPDRS scores in the two groups (total score, III part and II part, p = 0.48, p = 0.90 and p = 0.40, respectively) were found in the time course. Conversely, a greater improvement in Rotigotine + MIRT group was observed for 6MWT (p < 0.0001) and TUG (p = 0.03). Along time, the dosage of Rotigotine was higher in patients who did not undergo MIRT, at all observation times following T0.Conclusions: Over the course of 18 months, the effectiveness of the combined treatment (Rotigotine + MIRT) on the patients’ global clinical status, evaluated with total UPDRS, was not inferior to that of the pharmacological treatment with Rotigotine alone. Importantly, rehabilitation allowed patients to gain better motor performances with lower DRT dosage. [ABSTRACT FROM AUTHOR]

Almond production generates large amounts of by-products rich in polyphenols. In this study, almond skin was explored as a valuable food ingredient in bread making. To this purpose, almond skin was used to produce functional products modifying a traditional sourdough bread recipe. The doughs were prepared replacing semolina with powdered almond skin (PAS) at 5 and 10 % (w/w). Sourdough inoculum was started with a mix of lactic acid bacteria (LAB) and propagated in semolina until reaching pH 3.7. The pH of PAS added breads was higher than that of control (CTR) breads before and after fermentation. Plate counts showed a similar evolution of LAB and total mesophilic microorganisms, but members of Enterobacteriaceae and coliform were detectable in PAS doughs. Illumina data clearly showed a dominance of lactobacilli in all trials, but PAS doughs displayed the presence of Bacillus. The final bread characteristics were influenced by PAS and its addition percentage; in particular, crust and crumb colour resulted darker, the alveolation decreased and, regarding sensory attributes, odour intensity increased, while bread odour diminished. In presence of PAS, bread emissions were characterized by lower percentages of alcohols and aromatic hydrocarbons and higher percentages of the other volatile compound classes, especially terpenoids like β-pinene, β-myrcene and limonene than CTR trial. After in vitro simulated digestion, the final release of phytochemicals from 10 % PAS bread was almost 100 %. Thus, PAS determined an increase of the antioxidant capacity of the breads. Phytochemicals released from digested PAS-fortified bread can provide antioxidant protection in a complex biological environment such as human intestinal-like cells. Besides the positive functional properties of PAS, this work also evidenced the hygienic issues of almond skin and, in order to avoid potential risks for the human health, highlighted the need to preserve its microbiological characteristics during storage for their reuse in bread production. • Powder almond skin (PAS) did not affect the growth of starter lactic acid bacteria. • PAS slightly slowed down the acidification process. • Lactobacilli were absent in PAS, but detected in all doughs at relative abundances. • PAS phytochemicals provided antioxidant protection to human intestinal-like cells. [ABSTRACT FROM AUTHOR]

Introduction: Our objective is to describe the dietary habits, food preferences and adherence to Mediterranean diet (MeDi) of a large sample of Italian Parkinson's Disease (PD) patients compared to a group of controls.Methods: Dietary habits of 600 PD patients from throughout Italy and 600 controls matched by gender, age, education, physical activity level and geographical residence, were collected using the ON-GP Food Frequency Questionnaire. Then, we compared patients by disease duration and the presence of swallowing disturbances.Results: Overall, adherence of PD patients (males, 53.8%; mean disease duration, 9.2 ± 7.0 years) to MeDi was similar to controls (score, 4.8 ± 1.7 vs. 4.9 ± 1.6; P = 0.294). Patients consumed less alcohol and fish and drank significantly less water, coffee, and milk which resulted also in lower total fluids intake. On the contrary, they ate more fruit, cooked vegetables, cereals and baked items, more dressings and more sweets in general. Disease duration was associated with increased intake of several food groups but it was not associated with changes in MeDi score (P = 0.721). Patients with swallowing disturbances (n = 72) preferred softer and more viscous food but preferences did not result in differences in dietary pattern. However, patients with dysphagia drank less fluids (P = 0.043).Discussion: PD patients presented different dietary habits and food preferences compared to the general population and adherence to MeDi was not associated with disease duration. Self-reported dysphagia was associated with reduced intake of fluids. These aspects may be amenable to change in order to improve the management of nutritional issues in this patient population. [ABSTRACT FROM AUTHOR]

The final goal of motor learning, a complex process that includes both implicit and explicit (or declarative) components, is the optimization and automatization of motor skills. Motor learning involves different neural networks and neurotransmitters systems depending on the type of task and on the stage of learning. After the first phase of acquisition, a motor skill goes through consolidation (i.e., becoming resistant to interference) and retention, processes in which sleep and long-term potentiation seem to play important roles. The studies of motor learning in Parkinson's disease have yielded controversial results that likely stem from the use of different experimental paradigms. When a task’s characteristics, instructions, context, learning phase and type of measures are taken into consideration, it is apparent that, in general, only learning that relies on attentional resources and cognitive strategies is affected by PD, in agreement with the finding of a fronto-striatal deficit in this disease. Levodopa administration does not seem to reverse the learning deficits in PD, while deep brain stimulation of either globus pallidus or subthalamic nucleus appears to be beneficial. Finally and most importantly, patients with PD often show a decrease in retention of newly learned skill, a problem that is present even in the early stages of the disease. A thorough dissection and understanding of the processes involved in motor learning is warranted to provide solid bases for effective medical, surgical and rehabilitative approaches in PD. [ABSTRACT FROM AUTHOR]

Objectives To estimate prevalence of sarcopenia and dynapenia in outpatients with Parkinson disease (PD) and to investigate their association with the features of the disease. Design Cross-sectional study. Setting A specialized tertiary care center. Participants Consecutive patients (n = 364) aged 65 years or older, affected by parkinsonian syndromes. Measurements Skeletal muscle mass (SMM), as well as strength and gait speed (GS) were assessed by bioimpedence analysis, handgrip dynamometry, and the 4-meter walking test, respectively. Based on these assessments, sarcopenia was diagnosed using the European Working Group on Sarcopenia in Older People criteria. Dynapenia was defined as handgrip strength less than 30 kg in men and less than 20 kg in women. Results In total, 235 patients (64.6%) had a diagnosis of idiopathic PD. Low SMM index was recorded in 27 patients. Due to gait disturbances and postural instability, GS could not be measured in 98 patients and was found to be reduced in 61.3% of those assessed. Prevalence of sarcopenia and dynapenia was 6.6% (95% confidence interval [CI] 4.3–9.7) and 75.5% (95% CI 70.8–79.9), respectively. Sarcopenia tended to be higher in patients unable to perform GS assessment and was unrelated to the type of parkinsonian syndrome. It was associated with older age, longer disease duration, more severe disease, and higher disability in activities of daily living, as assessed by disease-specific clinical rating scale. Dynapenia was directly associated with parkinsonism other than PD, older age, and disability, whereas regular physical therapy appeared to be a preventive factor. However, it was unrelated to disease duration and severity. Finally, the disability score of activities of daily living was inversely correlated with handgrip strength and GS, whereas no association was found with SMM index. Conclusion Being primarily motor disorders, parkinsonian syndromes are characterized by progressive disability in performing activities of daily living. Impaired functional status is a prominent feature of this patient population, independently of disease duration and severity. Sarcopenia is mainly related to advancing disease and, due to a significant sparing of SMM, is an infrequent condition, likely to play a minor role in disability. Several factors could be responsible for this favorable body composition (eg, motor symptoms, levodopa therapy) and deserve further investigation. The prognostic impact of sarcopenia also needs to be addressed. [ABSTRACT FROM AUTHOR]

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. We experimentally prove that the guiding is much less affected by the beam chromatic dispersion with respect to a conventional bending magnet and, with the support of numerical simulations, we show that it can even be made dispersionless by employing larger discharge currents. This proof-of-principle experiment extends the use of plasma-based devices, that revolutionized the field of particle accelerators enabling the generation of GeV beams in few centimeters. Compared to state-of-the-art technology based on conventional bending magnets and quadrupole lenses, these results provide a compact and affordable solution for the development of next-generation tabletop facilities.

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 p21 waf1 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/p21 waf1 axis. Ind can be a phytochemical of interest in combo-therapy.

Oxidized low-density lipoproteins (oxLDL) play a pivotal role in the etiopathogenesis of atherosclerosis through the activation of inflammatory signaling events eventually leading to endothelial dysfunction and senescence. In the present work, we investigated the effects of indicaxanthin, a bioavailable, redox-modulating phytochemical from Opuntia ficus indica fruits, with anti-inflammatory activity, against oxLDL-induced endothelial dysfunction. Human umbilical vein cord cells (HUVEC) were stimulated with human oxLDL, and the effects of indicaxanthin were evaluated in a range between 5 and 20 μ M, consistent with its plasma level after a fruit meal (7 μ M). Pretreatment with indicaxanthin significantly and concentration-dependently inhibited oxLDL-induced cytotoxicity; ICAM-1, VCAM-1, and ELAM-1 increase; and ABC-A1 decrease of both protein and mRNA levels. From a mechanistic perspective, we also provided evidence that the protective effects of indicaxanthin were redox-dependent and related to the pigment efficacy to inhibit NF- κ B transcriptional activity. In conclusion, here we demonstrate indicaxanthin as a novel, dietary phytochemical, able to exert significant protective vascular effects in vitro , at nutritionally relevant concentrations.

Cigarette smoking has been linked with oxidative stress and inflammation. In turn, eryptosis, the suicidal erythrocyte death similar to apoptosis that can be triggered by oxidative stress, has been associated with chronic inflammatory diseases including atherosclerosis. However, the link between smoking and eryptosis has not been explored so far. The aim of the present study was to determine the level of eryptotic erythrocytes in healthy male smokers (n = 21) compared to non-smokers (n = 21) and assess its relationship with systemic inflammation (CRP) as well as with antioxidant defense (GSH) and their resistance to ex-vivo induced hemolysis. Smoking caused an increase in phosphatidylserine translocation outside the erythrocyte membrane (hallmark of eryptosis), significantly correlated to the plasma level of CRP (r = 0.546) and GSH concentration in erythrocytes (r=-0.475). With respect to non-smokers, smokers show a marginal increase of total leucocytes and erythrocyte volume, no modifications of the RBC resistance to oxidative stress-induced hemolysis and hematological and lipid parameters unvaried. We conclude that the inflammatory status (high CRP levels) and RBC oxidative stress (low GSH levels) caused by cigarette smoking are associated with an increase of eryptotic erythrocytes, a yet unknown relationship potentially involved with atherosclerosis and cardiovascular disease in smokers., (Copyright © 2018 Elsevier B.V. All rights reserved.)