Dopamine agonist therapy in Parkinson's disease: Spanish expert consensus on its use in different clinical situations.

BACKGROUND: Different types of therapies were proven effective for the medical management of motor and non-motor symptoms in Parkinson's disease (PD). We aimed to gain consensus on the dopamine agonist (DA) therapy use in different clinical scenarios of Parkinson's disease (PD) patients. METHODS: This consensus study was based on the nominal group technique. Initially, a consensus group comprising 12 expert neurologists in the PD field identified the topics to be addressed and elaborated different evidence-based preliminary statements. Next, a panel of 48 Spanish neurologists expressed their opinion on an internet-based systematic voting program. Finally, initial ideas were reviewed and rewritten according to panel contribution and were ranked by the consensus group using a Likert-type scale. The analysis of data was carried out by using a combination of both qualitative and quantitative methods. The consensus was achieved if the statement reached ≥ 3.5 points in the voting process. RESULTS: The consensus group produced 76 real-world recommendations. The topics addressed included 12 statements related to DA therapy in early PD, 20 statements concerning DA treatment strategy in patients with motor complications, 11 statements associated with DA drugs and their side effects, and 33 statements regarding DA therapy in specific clinical scenarios. The consensus group did not reach a consensus on 15 statements. CONCLUSION: The findings from this consensus method represent an exploratory step to help clinicians and patients in the appropriate use of DA in different stages and clinical situations of PD.

Response of Phragmites australis to increasing As(V) concentrations: Accumulation and speciation of As, and plant oxidative stress.

The use of macrophytes has been proposed recently as a suitable option for the phytostabilization or rhizofiltration of soils or waters contaminated by trace elements. As one of the most representative species of this type of plant, common reed (Phragmites australis (Cav.) Trin. ex Steud.) has shown tolerance to high concentrations of potentially hazardous elements, as is the case of arsenic. However, a deeper knowledge of how these plants deal with this toxicity, including their oxidative response, is needed for the optimum utilization of this species in phytoremediation procedures. In fact, little is known about how common reed plants react to As toxicity or the tolerance limits and accumulation potential of this species. In this work, common reed plants were exposed to a range of As(V) mass concentrations (0.5-10 mg L-1) in a hydroponic experiment, and the performance of the plants (growth, photosynthetic pigments, and oxidative stress related parameters) was evaluated and related to the major As species present in the different parts of the plants. The plants did not show any apparent symptom of toxicity and no significant effects were found for any of the different plant parameters analyzed. Arsenic was mostly accumulated as As(III) in the roots of the plants, and almost no translocation to the aerial part of the plants was observed for any of the As species analyzed. Common reed has shown a high capacity for As accumulation in its roots with no signs of toxicity, despite small nutrient imbalances. Thus, it can be considered to be a good candidate for use in the rhizofiltration and phytostabilization of As contaminated waters and soils, respectively.

Management of Parkinson's disease and other movement disorders in woman of childbearing age: Part 1. / Manejo de la enfermedad de Parkinson y otros trastornos del movimiento en mujeres en edad fértil: Parte 1.

INTRODUCTION: The main challenge of Parkinson's disease in women of childbearing age is managing symptoms and drugs during pregnancy and breastfeeding. The increase in the age at which women are having children makes it likely that these pregnancies will become more common in future. OBJECTIVES: This study aims to define the clinical characteristics of women of childbearing age with Parkinson's disease and the factors affecting their lives, and to establish a series of guidelines for managing pregnancy in these patients. RESULTS: This consensus document was developed through an exhaustive literature search and a discussion of the available evidence by a group of movement disorder experts from the Spanish Society of Neurology. CONCLUSIONS: Parkinson's disease affects all aspects of sexual and reproductive health in women of childbearing age. Pregnancy should be well planned to minimise teratogenic risk. A multidisciplinary approach should be adopted in the management of these patients in order to take all relevant considerations into account.

Management of Parkinson's disease and other movement disorders in women of childbearing age: Part 2. / Manejo de la enfermedad de Parkinson y otros trastornos del movimiento en mujeres en edad fértil: parte 2.

INTRODUCTION: Many diseases associated with hyperkinetic movement disorders manifest in women of childbearing age. It is important to understand the risks of these diseases during pregnancy, and the potential risks of treatment for the fetus. OBJECTIVES: This study aims to define the clinical characteristics and the factors affecting the lives of women of childbearing age with dystonia, chorea, Tourette syndrome, tremor, and restless legs syndrome, and to establish guidelines for management of pregnancy and breastfeeding in these patients. RESULTS: This consensus document was developed through an exhaustive literature search and a discussion of the content by a group of movement disorder experts from the Spanish Society of Neurology. CONCLUSIONS: We must evaluate the risks and benefits of treatment in all women with hyperkinetic movement disorders, whether pre-existing or with onset during pregnancy, and aim to reduce effective doses as much as possible or to administer drugs only when necessary. In hereditary diseases, families should be offered genetic counselling. It is important to recognise movement disorders triggered during pregnancy, such as certain types of chorea and restless legs syndrome.

[Impact of the COVID-19 pandemic on the training of Spanish neurology residents]. / Repercusión de la pandemia por COVID-19 en la formación de los residentes de neurología españoles.

Introduction: The COVID-19 pandemic has transformed medical practice and severely disrupted the training of medical residents worldwide. The Spanish Society of Neurology conducted a study to assess its impact on the training of neurology residents in Spain. Methods: We performed a descriptive, cross-sectional study through a survey distributed by e-mail to all neurology residents belonging to the Society. The survey included questions on demographic variables, care activity, and personal and educational impact of the pandemic, as well as respondents' expectations for the future of their work in the post-pandemic era. Results: Of 422 surveys sent, we received a total of 152 responses (36%); 79 respondents (52%) were women and 73 (48%) were men. By year of residency, 51 respondents (33.6%) were in the fourth year, 45 (29.6%) in the third year, 28 (18.4%) in the second year, and 28 (18.4%) in the first year. A total of 139 respondents (90.8%) reported changes in hospital activity, and 126 (82.8%) considered the situation to have had a negative impact on their training, with 99 (64.7%) having lost non-recoverable rotations. Sixty-six percent of respondents (n=101) expressed a desire to extend their residency period. Conclusions: The pandemic has had an extremely severe impact on all areas of the health system, with trainee physicians being one of the most affected groups. Among neurology residents, the crisis has caused significant shortcomings in their training and clinical activities, through the suspension of specific rotations. A high percentage of respondents wished to extend the residency period.

Major As species, lipid peroxidation and protein carbonylation in rice plants exposed to increasing As(V) concentrations.

Arsenic (As) uptake by plants is mainly carried out as arsenate (As(V)), whose chemical analogy with phosphate is largely responsible for its elevated toxicity. Arsenate is known to stimulate reactive oxygen species (ROS) formation in plants that provoke oxidative stress. This manuscript reports the results of a hydroponics study using rice (Oryza sativa L.) seedlings as a test plant, where the effects of increasing arsenate concentrations (0-10 mg L-1) on both lipid and protein oxidation, as well as As accumulation and speciation in plant roots and shoots were examined. Plant yield was negatively affected by increasing As concentration. Accumulation in plant roots was higher than in shoots at low arsenate doses (0.5-2.5 mg L-1), while root to shoot transport was drastically enhanced at the highest doses (5 and 10 mg L-1). Moreover, As(V) was the dominating species in the shoots and As(III) in the roots. Rice leaves in the 10 mg As L-1 treatment showed the highest lipid peroxidation damage (malondialdehyde concentration), whilst protein oxidation was not remarkably influenced by As dose. Lipid peroxidation seems to be therefore conditioned by As accumulation in rice plants, particularly by the presence of high As(V) concentrations in the aerial part of the plants as a consequence of unregulated translocation from roots to shoots above a threshold concentration (1.25-2.5 mg L-1) in the growing media. These results provide relevant information regarding As(V) toxic concentrations for rice plants, highlight the importance of major As species analysis in plant tissues regarding As toxicity and contribute to better understand plants response to elevated As concentrations in the growing media.

Ischaemic stroke and SARS-CoV-2 infection: A causal or incidental association? / Ictus isquémico e infección por SARS-CoV-2, ¿asociación casual o causal?

INTRODUCTION: Ischaemic stroke has been reported in patients with COVID-19, particularly in more severe cases. However, it is unclear to what extent this is linked to systemic inflammation and hypercoagulability secondary to the infection. METHODS: We describe the cases of 4 patients with ischaemic stroke and COVID-19 who were attended at our hospital. Patients are classified according to the likelihood of a causal relationship between the hypercoagulable state and ischaemic stroke. We also conducted a review of studies addressing the possible mechanisms involved in the aetiopathogenesis of ischaemic stroke in these patients. RESULTS: The association between COVID-19 and stroke was probably causal in 2 patients, who presented cortical infarcts and had no relevant arterial or cardioembolic disease, but did show signs of hypercoagulability and systemic inflammation in laboratory analyses. The other 2 patients were of advanced age and presented cardioembolic ischaemic stroke; the association in these patients was probably incidental. CONCLUSIONS: Systemic inflammation and the potential direct action of the virus may cause endothelial dysfunction, resulting in a hypercoagulable state that could be considered a potential cause of ischaemic stroke. However, stroke involves multiple pathophysiological mechanisms; studies with larger samples are therefore needed to confirm our hypothesis. The management protocol for patients with stroke and COVID-19 should include a complete aetiological study, with the appropriate safety precautions always being observed.

An initial experience with intraoperative O-Arm for deep brain stimulation surgery: can it replace post-operative MRI?

Deep brain stimulation (DBS) is used to treat movement disorders, severe psychiatric disorders, and neuropathic pain, among other diseases. Advanced neuroimaging techniques allow direct or indirect localization of the target site, which is verified in many centers by the intraoperative recording of unitary neuronal activity. Intraoperative image acquisition technology (e.g., O-Arm) is increasingly used for accurate electrode positioning throughout the surgery. The aim of our study is to analyze the initial experience of our team in the utilization of O-Arm for planning DBS and monitoring its precision and accuracy throughout the procedure. The study included 13 patients with movement disorders. All underwent DBS with the intraoperative O-arm image acquisition system (iCT) and Medtronic StealthStation S7 cranial planning system, placing a total of 25 electrodes. For each patient, we calculated the difference between real and theoretic x, y, z coordinates, using the paired Student's t test to evaluate absolute and directional differences and the one-sample Student's t test to analyze differences in Euclidean distances. No statistically significant differences were found in absolute, directional, or Euclidean distances between intended and actual x, y, and z coordinates, based on iCT scan. Our experience confirms that utilization of the O-Arm system in DBS provides accurate and precise verification of electrode placements throughout the procedure. Recent studies found no significant differences between iCT and postoperative MRI, the current gold standard. Further prospective studies are warranted to test the elimination of postoperative MRI when this system is used.

Combination of soil organic and inorganic amendments helps plants overcome trace element induced oxidative stress and allows phytostabilisation.

Trace element (TE)-contaminated soils require the improvement of their physico-chemical properties in order to allow their restoration through phytostabilization technologies. This study aimed to determine the usefulness of oxidative stress related parameters to validate the suitability of two different combinations of organic (solid fraction of pig slurry) and inorganic (paper mill sludge or a commercial red mud derivative) amendments for the phytostabilization of an acidic (4.2) TE-contaminated mine soil from SE Spain. Two wild species (Silybum marianum and Piptatherum miliaceum) were greenhouse cultivated and the development of the plants, their ionome, and oxidative stress related parameters were determined. Both amendment combinations increased significantly soil pH (to 5-6) and soil/pore water total organic C and total N concentrations, allowing an adequate plant growth and development (plants did not grow in untreated soils). The combination of amendments significantly reduced metal availability and showed to be effective (specially the one including the red mud derivative) in limiting shoot TE concentrations, which were all within common ranges (exclusion based tolerance of these species). Both protein carbonylation and lipid peroxidation were significantly higher in S. marianum plants from phytostabilized soils than in those from non-contaminated soils, which confirms the oxidative stress these plants suffer despite their satisfactory growth in the treated soils. P. miliaceum plants showed no differences between phytostabilized and non-contaminated soils. Therefore, the combination of amendments and TE-tolerant autochthonous species would be a suitable option for the phytostabilisation of soils contaminated by mining activities, reducing TE solubility and allowing an adequate plant growth.

Mitochondrial ascorbate-glutathione cycle and proteomic analysis of carbonylated proteins during tomato (Solanum lycopersicum) fruit ripening.

In non-photosynthetic tissues, mitochondria are the main source of energy and of reactive oxygen species. Accumulation of high levels of these species in the cell causes damage to macromolecules including several proteins and induces changes in different metabolic processes. Fruit ripening has been characterized as an oxidative phenomenon; therefore, control of reactive oxygen species levels by mitochondrial antioxidants plays a crucial role on this process. In this work, ascorbate-glutathione cycle components, hydrogen peroxide levels and the proteomic profile of carbonylated proteins were analyzed in mitochondria isolated from tomato (Solanum lycopersicum) fruit at two ripening stages. A significant increase on most ascorbate-glutathione cycle components and on carbonylated proteins was observed in mitochondria from breaker to light red stage. Enzymes and proteins involved in diverse cellular and mitochondrial metabolic pathways were identified among the carbonylated proteins. These results suggest that protein carbonylation is a post-translational modification involved in tomato fruit ripening regulation.

Abnormal thermography in Parkinson's disease.

BACKGROUND: An autonomic denervation and abnormal vasomotor reflex in the skin have been described in Parkinson's disease (PD) and might be evaluable using thermography with cold stress test. METHODS: A cross-sectional pilot study was undertaken in 35 adults: 15 patients with PD and abnormal [(123)I]-metaiodobenzylguanidine cardiac scintigraphy and 20 healthy controls. Baseline thermography of both hands was obtained before immersing one in cold water (3 ± 1 °C) for 2 min. Continuous thermography was performed in: non-immersed hand (right or with lesser motor involvement) during immersion of the contralateral hand and for 6 min afterward; and contralateral immersed hand for 6 min post-immersion. The region of interest was the dorsal skin of the third finger, distal phalanx. RESULTS: PD patients showed a lower mean baseline hand temperature (p = 0.037) and greater thermal difference between dorsum of wrist and third finger (p = 0.036) and between hands (p = 0.0001) versus controls, regardless of the motor laterality. Both tests evidenced an adequate capacity to differentiate between groups: in the non-immersed hand, the PD patients did not show the normal cooling pattern or final thermal overshoot observed in controls (F = 5.29; p = 0.001), and there was an AUC of 0.897 (95%CI 0.796-0.998) for this cooling; in the immersed hand, thermal recovery at 6 min post-immersion was lesser in patients (29 ± 17% vs. 55 ± 28%, p = 0.002), with an AUC of 0.810 (95%CI 0.662-0.958). CONCLUSIONS: PD patients reveal abnormal skin thermal responses in thermography with cold stress test, suggesting cutaneous autonomic dysfunction. This simple technique may be useful to evaluate autonomic dysfunction in PD.

The thioredoxin/peroxiredoxin/sulfiredoxin system: current overview on its redox function in plants and regulation by reactive oxygen and nitrogen species.

In plants, the presence of thioredoxin (Trx), peroxiredoxin (Prx), and sulfiredoxin (Srx) has been reported as a component of a redox system involved in the control of dithiol-disulfide exchanges of target proteins, which modulate redox signalling during development and stress adaptation. Plant thiols, and specifically redox state and regulation of thiol groups of cysteinyl residues in proteins and transcription factors, are emerging as key components in the plant response to almost all stress conditions. They function in both redox sensing and signal transduction pathways. Scarce information exists on the transcriptional regulation of genes encoding Trx/Prx and on the transcriptional and post-transcriptional control exercised by these proteins on their putative targets. As another point of control, post-translational regulation of the proteins, such as S-nitrosylation and S-oxidation, is of increasing interest for its effect on protein structure and function. Special attention is given to the involvement of the Trx/Prx/Srx system and its redox state in plant signalling under stress, more specifically under abiotic stress conditions, as an important cue that influences plant yield and growth. This review focuses on the regulation of Trx and Prx through cysteine S-oxidation and/or S-nitrosylation, which affects their functionality. Some examples of redox regulation of transcription factors and Trx- and Prx-related genes are also presented.

Analysis of the antioxidant response of Nicotiana benthamiana to infection with two strains of Pepper mild mottle virus.

The present study was carried out to investigate the role of reactive oxygen species (ROS) metabolism in symptom development and pathogenesis in Nicotiana benthamiana plants upon infection with two strains of Pepper mild mottle virus, the Italian (PMMoV-I) and the Spanish (PMMoV-S) strains. In this host, it has been shown that PMMoV-I is less virulent and plants show the capability to recover 21 d after inoculation. Analyses of oxidative stress biomarkers, ROS-scavenging enzyme activities, and antioxidant compounds were conducted in plants at different post-infection times. Only PMMoV-I stimulated a defence response through: (i) up-regulation of different superoxide dismutase isozymes; (ii) maintenance of adequate levels of three peroxiredoxins (2-Cys Prx, Prx IIC, and Prx IIF); and (iii) adjustments in the glutathione pool to maintain the total glutathione content. Moreover, there was an increase in the level of oxidized glutathione and ascorbate in the recovery phase of PMMoV-I-infected plants. The antioxidant response and the extent of oxidative stress in N. benthamiana plants correlates to: (i) the severity of the symptoms elicited by either strain of PMMoV; and (ii) the high capacity of PMMoV-I-infected plants for symptom recovery and delayed senescence, compared with PMMoV-S-infected plants.

Change of the melanocortin system caused by bilateral subthalamic nucleus stimulation in Parkinson's disease.

OBJECTIVES - Determine whether bilateral subthalamic nucleus stimulation (STN-DBS) in Parkinson's disease (PD) is associated with an increase in neuropeptide Y (NPY) and/or resistance to inhibition by leptin in relation to post-surgery weight gain. MATERIALS AND METHODS - This prospective study included 20 patients who underwent bilateral STN-DBS and 17 who refused surgery. Data were obtained at baseline, 3 and 6 months on neurological and nutritional status, including determination of body mass index (BMI) and serum NPY and leptin levels. RESULTS - NPY and leptin levels changed over time, with a distinct pattern. The BMI increase at 6 months was greater in the surgical group (5.5 ± 6.3% vs 0.5 ± 3.5%; P = 0.035). Medical group exhibited a reduction in leptin level (-2.0 ± 4.3 ng/ml) and a consequent increase in NPY level (72.4 ± 58.7 pmol/ml). However, STN-DBS patients showed an increase in leptin (3.1 ± 5.0 ng/ml; P = 0.001 vs medical group) and also in NPY (12.1 ± 53.6 pmol/ml; P = 0.022 vs medical group) levels, which suggests resistance to inhibition by leptin. Rise in NPY level correlated with higher stimulation voltages. CONCLUSIONS - Bilateral STN-DBS causes disruption of the melanocortin system, probably related to diffusion of the electric current to the hypothalamus. This mechanism may in part explain the weight gain of patients with PD after surgery.

Computerized evaluation of mean residence times in multicompartmental linear system and pharmacokinetics.

Deriving mean residence times (MRTs) is an important task both in pharmacokinetics and in multicompartmental linear systems. Taking as starting point the analysis of MRTs in open or closed (Garcia-Meseguer et al., Bull Math Biol 2003, 65, 279) multicompartmental linear systems, we implement a versatile software, using the Visual Basic 6.0 language for MS-Windows, that is easy to use and with a user-friendly format for the input of data and the output of results. For any multicompartmental linear system of up to 512 compartments, whether closed or open, with traps or without traps and with zero input in one or more of the compartments, this software allows the user to obtain the symbolic expressions, in the most simplified form, and/or the numerical values of the MRTs in any of its compartments, in the entire system or in a part of the system. As far as we known from the literature, such a software has not been implemented before. The advantage of the present software is that it reduces on the work time needed and minimizes the human errors that are frequent in compartmental systems even those that are relatively staightforward. The software bioCelTer, along with instructions, can be downloaded from http://oretano.iele-ab.uclm.es/~fgarcia/bioCelTer/.

Phase transitions induced by complex nonlinear noise in a system of self-propelled agents.

We propose a comprehensive dynamical model for cooperative motion of self-propelled particles, e.g., flocking, by combining well-known elements such as velocity-alignment interactions, spatial interactions, and angular noise into a unified Lagrangian treatment. Noise enters into our model in an especially realistic way: it incorporates correlations, is highly nonlinear, and it leads to a unique collective behavior. Our results show distinct stability regions and an apparent change in the nature of one class of noise-induced phase transitions, with respect to the mean velocity of the group, as the range of the velocity-alignment interaction increases. This phase-transition change comes accompanied with drastic modifications of the microscopic dynamics, from nonintermittent to intermittent. Our results facilitate the understanding of the origin of the phase transitions present in other treatments.

Characterisation and changes in the antioxidant system of chloroplasts and chromoplasts isolated from green and mature pepper fruits.

Purification and characterisation of pepper (Capsicum annuum L) chloroplasts and chromoplasts isolated from commercial green, red and yellow mature fruits were undertaken. Induction of the synthesis of several antioxidants in organelles isolated from mature fruits was found. The ultrastructure of organelles and the presence and activity of SOD isozymes and enzymes involved in the ASC-GSH cycle, together with the non-enzymatic antioxidant content and some oxidative parameters, were analysed. It was found that lipids, rather than proteins, seem to be a target for oxidation in the chromoplasts. The ascorbate and glutathione contents were elicited during differentiation of chloroplasts into chromoplasts in both red and yellow fruits. The activity of SOD and of components of the ASC-GSH cycle was up-regulated, suggesting that these enzymes may play a role in the protection of plastids and could act as modulators of signal molecules such as O(2) ( -) and H(2)O(2) during fruit maturation. The presence of an Mn-SOD in chromoplasts isolated from yellow pepper fruits was also investigated in terms of structural and antioxidant differences between the two cultivars.

[Diagnostic value of cardiac 123I-metaiodobenzylguanidine (123I-MIBG) scintigraphy in Lewy body disorders]. / Valor diagnóstico de la gammagrafía cardíaca con 123I-metaiodobenzilguanidina en las enfermedades con cuerpos de Lewy.

INTRODUCTION: Lewy body disorders such as Parkinson's disease (PD) and Lewy body dementia (LBD) are associated with cardiac sympathetic denervation, which can be visualized on 123I-MIBG scintigraphy. Our objectives were to study the diagnostic value of this technique in Lewy body disorders and its relationship with PD clinical variables. PATIENTS AND METHODS: We studied 90 patients: 51 with PD, 19 with LBD, 9 with multiple system atrophy (MSA) and 11 controls. Scintigraphy images were qualitatively evaluated and early and delayed heart-to-mediastinum ratios (HMR) were calculated. The main confounding factors (ischemic heart disease, diabetes, hypertension and drugs) were controlled by multivariate linear regression analysis. We investigated correlations between scintigraphy variables and PD variables. RESULTS: The delayed HMR, which showed better discriminative ability was 2.03 +/- 0.32 in controls, 1.37 +/- 0.30 in PD (p<0.001 vs controls), 1.47+/-0.45 in LBD (p=0.001 vs controls) and 1.69+/-0.28 in MSA (p=0.02 vs controls; p=0.004 vs PD). This ratio was influenced by PD/LBD diagnosis (beta= -0.638; p<0.001) and to a lesser degree, by ischemic heart disease (beta= -0.244; p=0.028). Optimal cut-off value between PD/LBD and controls was 1.71 (83% sensitivity and 82% specificity). Within the PD group, those with a family history of PD/LB showed higher delayed HMR values (1.65+/-0.34 vs 1.30+/-0.24 without history; p<0.001) and proportion with normal scintigraphy (56% vs 5%; p=0.001). CONCLUSIONS: Cardiac 123I-MIBG scintigraphy is useful in the diagnosis of Lewy body disorders, although its value in PD is conditioned by having a family history of PD.