Levodopa-Induced Dyskinesias are Frequent and Impact Quality of Life in Parkinson's Disease: A 5-Year Follow-Up Study.

BACKGROUND: Levodopa-induced dyskinesias (LID) are frequent in Parkinson's disease (PD). OBJECTIVE: To analyze the change in the frequency of LID over time, identify LID related factors, and characterize how LID impact on patients' quality of life (QoL). PATIENTS AND METHODS: PD patients from the 5-year follow-up COPPADIS cohort were included. LID were defined as a non-zero score in the item "Time spent with dyskinesia" of the Unified Parkinson's Disease Rating Scale-part IV (UPDRS-IV). The UPDRS-IV was applied at baseline (V0) and annually for 5 years. The 39-item Parkinson's disease Questionnaire Summary Index (PQ-39SI) was used to asses QoL. RESULTS: The frequency of LID at V0 in 672 PD patients (62.4 ± 8.9 years old; 60.1% males) with a mean disease duration of 5.5 ± 4.3 years was 18.9% (127/672) and increased progressively to 42.6% (185/434) at 5-year follow-up (V5). The frequency of disabling LID, painful LID, and morning dystonia increased from 6.9%, 3.3%, and 10.6% at V0 to 17.3%, 5.5%, and 24% at V5, respectively. Significant independent factors associated with LID (P < 0.05) were a longer disease duration and time under levodopa treatment, a higher dose of levodopa, a lower weight and dose of dopamine agonist, pain severity and the presence of motor fluctuations. LID at V0 (ß = 0.073; P = 0.027; R2 = 0.62) and to develop disabling LID at V5 (ß = 0.088; P = 0.009; R2 = 0.73) were independently associated with a higher score on the PDQ-39SI. CONCLUSION: LID are frequent in PD patients. A higher dose of levodopa and lower weight were factors associated to LID. LID significantly impact QoL.

Staging Parkinson's disease according to the MNCD classification correlates with caregiver burden.

BACKGROUND AND OBJECTIVE: Recently, we demonstrated that staging Parkinson's disease (PD) with a novel simple classification called MNCD, based on four axes (motor, non-motor, cognition, and dependency) and five stages, correlated with disease severity and patients' quality of life. Here, we analyzed the correlation of MNCD staging with PD caregiver's status. PATIENTS AND METHODS: Data from the baseline visit of PD patients and their principal caregiver recruited from 35 centers in Spain from the COPPADIS cohort from January 2016 to November 2017 were used to apply the MNCD total score (from 0 to 12) and MNCD stages (from 1 to 5) in this cross-sectional analysis. Caregivers completed the Zarit Caregiver Burden Inventory (ZCBI), Caregiver Strain Index (CSI), Beck Depression Inventory-II (BDI-II), PQ-10, and EUROHIS-QOL 8-item index (EUROHIS-QOL8). RESULTS: Two hundred and twenty-four PD patients (63 ± 9.6 years old; 61.2% males) and their caregivers (58.5 ± 12.1 years old; 67.9% females) were included. The frequency of MNCD stages was 1, 7.6%; 2, 58.9%; 3, 31.3%; and 4-5, 2.2%. A more advanced MNCD stage was associated with a higher score on the ZCBI (p < .0001) and CSI (p < .0001), and a lower score on the PQ-10 (p = .001), but no significant differences were observed in the BDI-II (p = .310) and EUROHIS-QOL8 (p = .133). Moderate correlations were observed between the MNCD total score and the ZCBI (r = .496; p < .0001), CSI (r = .433; p < .0001), and BDI-II (r = .306; p < .0001) in caregivers. CONCLUSION: Staging PD according to the MNCD classification is correlated with caregivers' strain and burden.

Cognitive impairment and dementia in young onset Parkinson's disease.

BACKGROUND AND OBJECTIVE: Patients with young-onset Parkinson's disease (YOPD) have a slower progression. Our aim was to analyze the change in cognitive function in YOPD compared to patients with a later onset and controls. PATIENTS AND METHODS: Patients with Parkinson's disease (PD) and controls from the COPPADIS cohort were included. Cognitive function was assessed with the Parkinson's Disease Cognitive Rating Scale (PD-CRS) at baseline (V0), 2-year ± 1 month (V2y), and 4-year ± 3 months follow-up (V4y). Regarding age from symptoms onset, patients were classified as YOPD (< 50 years) or non-YOPD (≥ 50). A score in the PD-CRS < 81 was defined as cognitive impairment (CI): ≤ 64 dementia; 65-80 mild cognitive impairment (MCI). RESULTS: One-hundred and twenty-four YOPD (50.7 ± 7.9 years; 66.1% males), 234 non-YOPD (67.8 ± 7.8 years; 59.3% males) patients, and 205 controls (61 ± 8.3 years; 49.5% males) were included. The score on the PD-CRS and its subscore domains was higher at all visits in YOPD compared to non-YOPD patients and to controls (p < 0.0001 in all analysis), but no differences were detected between YOPD patients and controls. Only non-YOPD patients had significant impairment in their cognitive function from V0 to V4y (p < 0.0001). At V4y, the frequency of dementia and MCI was 5% and 10% in YOPD compared to 25.2% and 22.3% in non-YOPD patients (p < 0.0001). A lower score on the Parkinson's Disease Sleep Scale at baseline was a predictor of CI at V4y in YOPD patients (Adjusted R2 = 0.61; OR = 0.965; p = 0.029). CONCLUSION: Cognitive dysfunction progressed more slowly in YOPD than in non-YOPD patients.

Prevalence and Factors Associated with Drooling in Parkinson's Disease: Results from a Longitudinal Prospective Cohort and Comparison with a Control Group.

Introduction: Drooling in Parkinson's disease (PD) is frequent but often goes underrecognized. Our aim was to examine the prevalence of drooling in a PD cohort and compare it with a control group. Specifically, we identified factors associated with drooling and conducted subanalyses in a subgroup of very early PD patients. Patients and Methods. PD patients who were recruited from January 2016 to November 2017 (baseline visit; V0) and evaluated again at a 2-year ± 30-day follow-up (V2) from 35 centers in Spain from the COPPADIS cohort were included in this longitudinal prospective study. Subjects were classified as with or without drooling according to item 19 of the NMSS (Nonmotor Symptoms Scale) at V0, V1 (1-year ± 15 days), and V2 for patients and at V0 and V2 for controls. Results: The frequency of drooling in PD patients was 40.1% (277/691) at V0 (2.4% (5/201) in controls; p < 0.0001), 43.7% (264/604) at V1, and 48.2% (242/502) at V2 (3.2% (4/124) in controls; p < 0.0001), with a period prevalence of 63.6% (306/481). Being older (OR = 1.032; p = 0.012), being male (OR = 2.333; p < 0.0001), having greater nonmotor symptom (NMS) burden at the baseline (NMSS total score at V0; OR = 1.020; p < 0.0001), and having a greater increase in the NMS burden from V0 to V2 (change in the NMSS total score from V0 to V2; OR = 1.012; p < 0.0001) were identified as independent predictors of drooling after the 2-year follow-up. Similar results were observed in the group of patients with ≤2 years since symptom onset, with a cumulative prevalence of 64.6% and a higher score on the UPDRS-III at V0 (OR = 1.121; p = 0.007) as a predictor of drooling at V2. Conclusion: Drooling is frequent in PD patients even at the initial onset of the disease and is associated with a greater motor severity and NMS burden.

Staging Parkinson's Disease According to the MNCD (Motor/Non-motor/Cognition/Dependency) Classification Correlates with Disease Severity and Quality of Life.

BACKGROUND: Recently, a novel simple classification called MNCD, based on 4 axes (Motor; Non-motor; Cognition; Dependency) and 5 stages, has been proposed to classify Parkinson's disease (PD). OBJECTIVE: Our aim was to apply the MNCD classification in a cohort of PD patients for the first time and also to analyze the correlation with quality of life (QoL) and disease severity. METHODS: Data from the baseline visit of PD patients recruited from 35 centers in Spain from the COPPADIS cohort fromJanuary 2016 to November 2017 were used to apply the MNCD classification. Three instruments were used to assess QoL:1) the 39-item Parkinson's disease Questionnaire [PDQ-39]); PQ-10; the EUROHIS-QOL 8-item index (EUROHIS-QOL8). RESULTS: Four hundred and thirty-nine PD patients (62.05±7.84 years old; 59% males) were included. MNCD stage was:stage 1, 8.4% (N = 37); stage 2, 62% (N = 272); stage 3, 28.2% (N = 124); stage 4-5, 1.4% (N = 6). A more advancedMNCD stage was associated with a higher score on the PDQ39SI (p < 0.0001) and a lower score on the PQ-10 (p< 0.0001) and EUROHIS-QOL8 (p< 0.0001). In many other aspects of the disease, such as disease duration, levodopa equivalent daily dose, motor symptoms, non-motor symptoms, and autonomy for activities of daily living, an association between the stage and severity was observed, with data indicating a progressive worsening related to disease progression throughout the proposed stages. CONCLUSION: Staging PD according to the MNCD classification correlated with QoL and disease severity. The MNCD could be a proper tool to monitor the progression of PD.

A Technological System for Post-Earthquake Damage Scenarios Based on the Monitoring by Means of an Urban Seismic Network.

A technological system capable of automatically producing damage scenarios at an urban scale, as soon as an earthquake occurs, can help the decision-makers in planning the first post-disaster response, i.e., to prioritize the field activities for checking damage, making a building safe, and supporting rescue and recovery. This system can be even more useful when it works on densely populated areas, as well as on historic urban centers. In the paper, we propose a processing chain on a GIS platform to generate post-earthquake damage scenarios, which are based: (1) on the near real-time processing of the ground motion, that is recorded in different sites by MEMS accelerometric sensor network in order to take into account the local effects, and (2) the current structural characteristics of the built heritage, that can be managed through an information system from the local public administration authority. In the framework of the EU-funded H2020-ARCH project, the components of the system have been developed for the historic area of Camerino (Italy). Currently, some experimental fragility curves in the scientific literature, which are based on the damage observations after Italian earthquakes, are implemented in the platform. These curves allow relating the acceleration peaks obtained by the recordings of the ground motion with the probability to reach a certain damage level, depending on the structural typology. An operational test of the system was performed with reference to an ML3.3 earthquake that occurred 13 km south of Camerino. Acceleration peaks between 1.3 and 4.5 cm/s2 were recorded by the network, and probabilities lower than 35% for negligible damage (and then about 10% for moderate damage) were calculated for the historical buildings given this low-energy earthquake.

Comparison of PRISMA Data with Model Simulations, Hyperion Reflectance and Field Spectrometer Measurements on 'Piano delle Concazze' (Mt. Etna, Italy).

In this work, we compare first acquisitions from the ASI-PRISMA (Agenzia Spaziale Italiana-PRecursore IperSpettrale della Missione Applicativa) space mission with model simulations, past data acquired by the Hyperion sensor and field spectrometer measurements. The test site is 'Piano delle Concazze' (Mt. Etna, Italy), suitable for calibration purposes due to its homogeneity characteristics. The area measures at about 0.2 km2 and is composed of very homogeneous trachybasalt rich in plagioclase and olivine. Three PRISMA acquisitions, achieved on 31 July and 8 and 17 August 2019, are analyzed. Firstly, spectral profiles of PRISMA top of atmosphere (TOA) radiance are compared with MODerate resolution atmospheric TRANsmission (MODTRAN) simulations. The Pearson correlation coefficient is equal to 0.998 and 0.994 for VNIR (Visible and Near InfraRed) and SWIR (Short-Wave InfraRed) spectral ranges, respectively. PRISMA radiance overestimates values simulated by MODTRAN for all considered days, showing a mean bias of +5.22 and of +0.91 Wm-2sr-1µm-1 for VNIR and SWIR, respectively. The relative mean difference between reflectance values estimated by PRISMA and Hyperion, on the test area, is around +19%, despite the great difference in time acquisition (up to 19 years); PRISMA slightly overestimates Hyperion reflectance with an absolute mean difference of about +0.0083, within the variability of Hyperion acquisitions of ±0.0250 (corresponding to ±2 standard deviation). Finally, FieldSpec measurements also confirm the great quality of PRISMA reflectance estimations. The absolute mean difference results are around +0.0089 (corresponding to a relative error of about +21%). In the study, we investigate only the lower values of reflectance characterizing the test site. A more complete evaluation of PRISMA performances needs to consider other test sites with different optical characteristics.

Genome-Wide Association Study of VKORC1 and CYP2C9 on acenocoumarol dose, stroke recurrence and intracranial haemorrhage in Spain.

Acenocoumarol is an oral anticoagulant with significant interindividual dose variations. Variants in CYP2C9 and VKORC1 have been associated with acenocoumarol maintenance dose. We analysed whether any of the 49 polymorphisms in CYP2C9 and VKORC1 previously associated with acenocoumarol maintenance dose in a Genome-Wide Association study (GWAs) in Dutch population are associated with stroke recurrence, intracranial haemorrhage (ICH) and acenocoumarol maintenance dose in a Spanish population. We performed a GWAs using Human Core Exome-chip (Illumina) in 78 patients stroke patients treated with acenocoumarol for secondary prevention enrolled as part of the prospective investigator-initiated study (IIS) SEDMAN Study. Patients were followed-up a median of 12.8 months. Three and eight patients had recurrent stroke and ICH events, respectively. We found 14 of the 49 published variants associated with acenocoumarol maintenance dose (p < 0.05). Six polymorphisms were associated with stroke recurrence and four variants with ICH (p < 0.05). In conclusion, variants in VKORC1 and CYP2C9 are associated with acenocoumarol maintenance dose, stroke recurrence and ICH in a Spanish cohort. These results highlight the relevance of studying pharmacogenetics associated with efficacy and safety of anticoagulant drugs and justify studies with larger sample size and different ethnic populations.

Reconocimiento de emociones faciales en niños con trastorno por déficit de atención/hiperactividad / Facial emotion recognition in children with attention-deficit/hyperactivity disorder

INTRODUCCIÓN: En sujetos con trastorno por déficit de atención/hiperactividad (TDAH), se observan dificultades en las relaciones interpersonales que se atribuyen a una afectación en las habilidades de reconocimiento de emociones faciales. Los estudios realizados no siempre tuvieron presente la naturaleza del estímulo seleccionado en pediatría, lo cual es fundamental porque la familiaridad en los rostros, en cuanto a sus características fisonómicas, favorece el reconocimiento de las expresiones. OBJETIVO: Identificar el perfil de reconocimiento de emociones en sujetos pediátricos con TDAH, utilizando como estímulo fotos de niños y niñas. Sujetos y métodos: Estudio analítico de corte transversal de casos y controles. Se analizaron los resultados obtenidos de 54 participantes de 7-13 años divididos en dos grupos: 26 en el grupo control y 28 en el grupo con TDAH. Realizaron una evaluación con la escala de inteligencia de Wechsler para niños (WISC-V), el Conners Continuous Performance Test II (CPT-II) y el Child Affective Facial Expression set (CAFE). RESULTADOS: El grupo con TDAH mostró un rendimiento menor en el reconocimiento de emociones en general, con mayor dificultad en el reconocimiento de enojo, sorpresa y expresión neutral en particular. No se encontró una relación entre el reconocimiento de emociones y la edad, el sexo, el cociente intelectual total o las variables de atención del CPT-II. CONCLUSIONES: Los sujetos con TDAH presentan déficits en el reconocimiento de emociones, especialmente en el reconocimiento de enojo, sorpresa y expresión neutral, que podrían explicar las dificultades en la interacción y deberían tratarse dentro del marco terapéutico

INTRODUCTION: There are difficulties in relationships that are attributed to a commitment in facial emotions recognition skills in subjects with attention-deficit/hyperactivity disorder (ADHD). The studies carried out did not always take into account the nature of the stimulus selected in pediatrics, which is important because the familiarity in faces, in terms of their physiognomic characteristics, makes it easier the recognition of the expressions. AIM: To identify the profile of recognition of emotions in pediatric subjects with ADHD, using as a stimulus photos of boys and girls. Subjects and methods: Analytical cross-sectional study of cases and controls. We analyzed the results obtained from 54 participants between 7 and 13 years divided into two groups: 26 in control group and 28 in ADHD group. They conducted an assessment with the Wechsler Intelligence Scale for Children (WISC-V), Conners' Continuous Performance Test II (CPT-II), and Child Affective Facial Expression set (CAFE). RESULTS: The ADHD group showed a lower performance in recognition of emotions in general, with greater difficulty in the recognition of anger, surprise and neutral expression in particular. No relationship was found between the recognition of emotions and age, sex, total intelligence quotient or CPT-II care variables. CONCLUSIONS: The subjects with ADHD present deficits in the recognition of emotions, especially in the recognition of anger, surprise and neutral expression, which could explain the difficulties in the interaction and that should be treated within the therapeutic framework

Unmanned aerial mass spectrometer systems for in-situ volcanic plume analysis.

Technology advances in the field of small, unmanned aerial vehicles and their integration with a variety of sensor packages and instruments, such as miniature mass spectrometers, have enhanced the possibilities and applications of what are now called unmanned aerial systems (UAS). With such technology, in situ and proximal remote sensing measurements of volcanic plumes are now possible without risking the lives of scientists and personnel in charge of close monitoring of volcanic activity. These methods provide unprecedented, and otherwise unobtainable, data very close in space and time to eruptions, to better understand the role of gas volatiles in magma and subsequent eruption products. Small mass spectrometers, together with the world's smallest turbo molecular pump, have being integrated into NASA and University of Costa Rica UAS platforms to be field-tested for in situ volcanic plume analysis, and in support of the calibration and validation of satellite-based remote sensing data. These new UAS-MS systems are combined with existing UAS flight-tested payloads and assets, such as temperature, pressure, relative humidity, SO2, H2S, CO2, GPS sensors, on-board data storage, and telemetry. Such payloads are capable of generating real time 3D concentration maps of the Turrialba volcano active plume in Costa Rica, while remote sensing data are simultaneously collected from the ASTER and OMI space-borne instruments for comparison. The primary goal is to improve the understanding of the chemical and physical properties of emissions for mitigation of local volcanic hazards, for the validation of species detection and abundance of retrievals based on remote sensing, and to validate transport models.

Combined use of terrestrial laser scanning and IR thermography applied to a historical building.

The conservation of architectural heritage usually requires a multidisciplinary approach involving a variety of specialist expertise and techniques. Nevertheless, destructive techniques should be avoided, wherever possible, in order to preserve the integrity of the historical buildings, therefore the development of non-destructive and non-contact techniques is extremely important. In this framework, a methodology for combining the terrestrial laser scanning and the infrared thermal images is proposed, in order to obtain a reconnaissance of the conservation state of a historical building. The proposed case study is represented by St. Augustine Monumental Compound, located in the historical centre of the town of Cosenza (Calabria, South Italy). Adopting the proposed methodology, the paper illustrates the main results obtained for the building test overlaying and comparing the collected data with both techniques, in order to outline the capabilities both to detect the anomalies and to improve the knowledge on health state of the masonry building. The 3D model, also, allows to provide a reference model, laying the groundwork for implementation of a monitoring multisensor system based on the use of non-destructive techniques.

High cerebrospinal tau levels are associated with the rs242557 tau gene variant and low cerebrospinal ß-amyloid in Parkinson disease.

Cerebrospinal fluid (CSF) tau and phospho-tau levels have been associated with certain tau gene variants and low CSF amyloid-ß (Aß) levels in Alzheimer disease (AD), constituting potential biomarkers of molecular mechanisms underlying neurodegeneration. We aimed to assess whether such CSF-genetic endophenotypes are also present in Parkinson disease (PD). CSF tau, phospho-tau and Aß levels were obtained from 38 PD patients (19 with dementia) using specific ELISA techniques. All cases were genotyped for a series of tau gene polymorphisms (rs1880753, rs1880756, rs1800547, rs1467967, rs242557, rs2471738 and rs7521). The A-allele rs242557 polymorphism was the only tau gene variant significantly associated with higher CSF tau and phospho-tau levels, under both dominant and dose-response model. This association depended on the presence of dementia, and was only observed in individuals with low (<500pg/mL) CSF Aß levels. Such genetic-CSF endophenotypes are probably a reflection of the presence of AD-like molecular changes in part of PD patients in the setting of dementia.

Inhibition of Mononuclear Cell Procoagulant Activity by Lipophosphoglycan of Leishmania donovani.

BACKGROUND: Since fibrin formation is an expression of the response of the host to parasite spread, the lipophosphoglycan (LPG) of Leishmania donovani and its carbohydrate fragment (PG) were examined for their capacity to inhibit procoagulant activity (PCA) production by human mononuclear cells stimulated with Escherichia coli endotoxin in vitro. METHODS: the putative inhibitory effect of LPG and its PG fragment was evaluated on the basis of their in vitro capacity to prolong significantly the time required for coagulation induced by endotoxin-stimulated mononuclear cells. RESULTS: LPG exhibited the most inhibitory activity, whereas the carbohydrate domain was not effective. These results are in agreement with the notion that LPG (but not PG) has an inhibitory effect on protein kinase C activity which plays a key role in the production of PCA by human monocytes. CONCLUSIONS: From a pathophysiological point of view, these data suggest the possibility that Leishmania avoids fibrin entrapment in the host through this inhibitory mechanism.