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It has long been assumed that lichen-forming fungi have very large distribution ranges, and that endemic species are rare in this group of organisms. This is likely a consequence of the "everything small is everywhere" paradigm that has been traditionally applied to cryptogams. However, the description of numerous endemic species over the last decades, many of them in oceanic islands, is challenging this view. In this study, we provide another example, Xanthoparmelia ramosae , a species that is described here as new to science on the basis of morphological, chemical, and macroclimatic data, and three molecular markers ( ITS rDNA, nuLSU rDNA, and mtSSU ). The new species is endemic to the island of Gran Canaria but clusters into a clade composed exclusively of specimens collected in Eastern Africa, a disjunction that is here reported for the first time in lichen-forming fungi. Through the use of dating analysis, we have found that Xanthoparmelia ramosae diverged from its closely related African taxa in the Pliocene. This result, together with the reproductive strategy of the species, points to the Relict theory as a likely mechanism behind the disjunction, although the large gap in lichenological knowledge in Africa makes this possibility hard to explore any further.

This work reports the first electrochemical bioplatform developed for the determination of human endostatin (HE), a biomarker with recognized antiangiogenic potential whose elevated circulating levels have also been associated with the development of aggressive cancers. The developed electroanalytical biotool combines the benefits of using magnetic microparticles for the implementation of sandwich immunoassays and amperometric transduction on disposable carbon electrodes. A limit of detection (LOD) of 34.1 pg mL -1 for HE standards and a selectivity suitable for its foray into the clinical oncology area, are demonstrated. The determination of HE in clinical samples such as lysates and secretomes of colorectal cancer (CRC) cells, plasma, and tissue samples from patients with CRC in different stages, has been faced with satisfactory results showing the ability for discriminating the metastatic capabilities of cells and for identifying and staging CRC patients. The developed bioplatform allows precise quantitative determinations, requiring minimal pre-treatments and sample amounts in only 75 min. In addition, due to the instrumentation and the type of substrates used in the detection step, the biotool is compatible with implementation in multiplexed and/or point-of-need devices, features in which this bioplatform is advantageous with respect to the enzyme linked immunosorbent assay (ELISA) or immunoblotting technologies., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 The Author(s). Published by Elsevier B.V. All rights reserved.)

Detecting overexpression of cancer biomarkers is an excellent tool for diagnostic/prognostic and follow-up of patients with cancer or their response to treatment. This work illustrates the relevance of interrogating the levels of T-cell immunoglobulin and mucin domain 1 (TIM-1) protein as a diagnostic/prognostic biomarker of high-prevalence breast and lung cancers by using an amperometric disposable magnetic microparticles-assisted immunoplatform. The developed method integrates the inherent advantages of carboxylic acid-functionalized magnetic beads (HOOC-MBs) as pre-concentrator support and the amperometric transduction at screen-printed carbon electrodes (SPCEs). The immunoplatform involves a sandwich-type immunoassay assembled on HOOC-MBs through the specific capture/labeling of TIM-1 using capture antibodies and horseradish peroxidase (HRP)-conjugated biotinylated detection antibodies as biorecognition elements. The magnetic immunoconjugates were confined onto the working electrode (WE) surface of the SPCEs for amperometric detection using the hydroquinone/hydrogen peroxide/HRP (HQ/H 2 O 2 /HRP) redox system. The method allows the selective detection of TIM-1 protein over the 87-7500 pg mL -1 concentration range in only 45 min, with a limit of detection of 26 pg mL -1 . The developed bioplatform was successfully applied to the analysis of breast and lung cancer cell extracts, providing the first quantitative results of the target glycoprotein in these types of samples., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 The Authors. Published by Elsevier B.V. All rights reserved.)

The progressive aging and comorbidities of the population have led to an increase in the number of patients with polypharmacy attended to in the emergency department. Drug-related problems (DRPs) have become a major cause of admission to these units, as well as a high rate of short-term readmissions. Anticoagulants, antibiotics, antidiabetics, and opioids have been shown to be the most common drugs involved in this issue. Inappropriate polypharmacy has been pointed out as one of the major causes of these emergency visits. Different ways of conducting chronic medication reviews at discharge, primary care coordination, and phone contact with patients at discharge have been shown to reduce new hospitalizations and new emergency room visits due to DRPs, and they are key elements for improving the quality of care provided by emergency services.

This study explores the diversity of photobionts associated with the Mediterranean lichen-forming fungus Cladonia subturgida . For this purpose, we sequenced the whole ITS rDNA region by Sanger using a metabarcoding method for ITS2. A total of 41 specimens from Greece, Italy, France, Portugal, and Spain were studied. Additionally, two specimens from Spain were used to generate four cultures. Our molecular studies showed that the genus Myrmecia is the main photobiont of C. subturgida throughout its geographic distribution. This result contrasts with previous studies, which indicated that the main photobiont for most Cladonia species is Asterochloris . The identity of Myrmecia was also confirmed by ultrastructural studies of photobionts within the lichen thalli and cultures. Photobiont cells showed a parietal chloroplast lacking a pyrenoid, which characterizes the species in this genus. Phylogenetic analyses indicate hidden diversity within this genus. The results of amplicon sequencing showed the presence of multiple ASVs in 58.3% of the specimens studied.

Background: Frailty assessment allows the identification of patients at risk of death. The aim here was to study the ability of Frail-VIG Index (FI-VIG) in order to discriminate frailty groups of older adults and garner its correlation with mortality in an Emergency-Department Short-Stay Unit (ED-SSU)., Methods: Our observational, single-center, prospective study consecutively included patients over 65-years-old admitted between March 1, 2021, and April 30, 2021., Results: 302 patients were included (56 % women), mean age 83 ± 8 years, and 39.1 % of them had a functional disability whilst 16.5 % of them had dementia. A total of 174 patients (58 %) met the frailty criteria (FI-VIG ≥ 0.2): 111 (63.8 %) had mild frailty (FI-VIG 0.2-0.36), 52 (29.9 %) had moderate frailty (FI-VIG 0.36-0.55), and 11 (6.3 %) had advanced frailty (FI-VIG > 0.55). Mortality at 30 days, 6 months, and 1 year was analyzed: no frailty was 6.3 %, 10.8 %, and 12.5 %, respectively; mild frailty was 10.8 %, 22.5 %, and 22.5 %, respectively; moderate frailty was 25 %, 34.6 %, and 42.3 %, respectively; advanced frailty was 36.4 %, 54.5 %, and 3.6 %, respectively. This shows the significant differences between the groups (1-year mortality p < 0.001). Mild frailty vs. non-frail HR was 2.47 (95 %CI 1.12-5.46), moderate frailty vs. non-frail HR was 6.93 (95 %CI 3.16-15.23), and advanced frailty vs. non-frail HR was 11.29 (95 %CI 3.54-36.03). The mean test time was 7 min., Conclusions: There was a strong correlation between frailty degree and mortality at 1, 6, and 12 months. FI-VIG is fast and easy-to-use in this setting. It is routine implementation in ED-SSUs could enable early risk stratification., Competing Interests: Declaration of Competing Interest The authors declare no conflict of interest., (Copyright © 2023 The Author(s). Published by Elsevier B.V. All rights reserved.)

This paper analyzes gender differences regarding the effect of the COVID-19 pandemic on the likelihood of job loss, differentiating between employment transitions towards unemployment, inactivity and furlough schemes, and the role that teleworking may have had as a protector of job loss in Spain. Based on more than 1,800 types of jobs defined by occupation and economic activity combinations, we propose an Evidence-Based Teleworking Index that considers the intensity of telework use in a given type of job, but also reflects the actual ability of firms to adapt to telework. Using multinomial probit models with sample selection, we found that more women than men suffered job loss during the pandemic. The findings also confirm that the ability to telework has acted as a potential cushion against employment losses, but the effect has been mainly driven by males. The shielding effects of telework have been especially relevant in reducing transitions from employment to furlough schemes, while the power of telework to protect against inactivity and unemployment seems to be much more modest, even during the pandemic., Competing Interests: Declaration of Competing Interest None., (Copyright © 2023 The Authors. Published by Elsevier B.V. All rights reserved.)

Using Spanish microdata from the Survey on mental health during the COVID-19 pandemic conducted in February 2021 by the Centre for Sociological Research (CIS), this paper aims at identifying individual factors associated with an increased risk of mental or emotional distress arising from two different sources: a general pattern of depression or anxiety and distress specifically associated with the pandemic as measured by fears and worries about one's own or others' lives and job and income insecurity due to the COVID-19 health crisis. We explore gender differences in both types of mental distress as well as the role of individual religiosity, measured as religious beliefs and behaviours, as a potential coping strategy. In both general and COVID-specific mental distress, our results provide evidence of gender differences in the risk of suffering these conditions, with a higher incidence among women. We also find that religious beliefs and practice seem to have served as a coping strategy that has allowed females to narrow the gender gap, particularly for practising Catholics. The evidence is stronger for mental distress associated with anxiety or depression. However, it is still present, albeit to a lesser extent, for suffering caused by pandemic-related mental stressors. Our results suggest that religious practices and beliefs might play a key role in alleviating additional distress symptoms caused by emergency situations such as those suffered during the COVID-19 pandemic., (Copyright © 2023 The Authors. Published by Elsevier B.V. All rights reserved.)

Background: Drug-related problems (DRPs) are prevalent and avoidable disease that patients experience due to drug use or nonuse. However, secondary prevention policies have not yet been systematized., Objective: To assess the clinical impact of a secondary prevention bundle for DRPs in patients who visited the emergency department (ED) for medicine-related problems., Methods: A single-center randomized clinical trial was conducted from August 28, 2019, to January 28, 2021, with 1-month follow-up. We included 769 adult patients who visited ED with a DRP associated with cardiovascular, alimentary tract, and metabolic system medications. For the intervention group, a DRP prevention bundle, consisting of a combined strategy initiated in the ED was applied. Patients in the control group received standard pharmaceutical care. Intervention was evaluated in terms of 30-day hospital readmission due to any cause., Results: Final analysis included 769 patients, of which 68 (8.8%) were readmitted within 30 days (control group, 40 of 386 [cumulative incidence: 10.4%]; intervention group, 28 of 383 [cumulative incidence, 7.3%]). After adjustment of the model for chronic heart failure, there was a lower incidence of hospital readmission among patients in the intervention group compared with those in the control group, odds ratio: 0.59 [95% confidence interval: 0.37-0.97]; number needed to treat (NNT) = 32. No significant differences in other outcomes were observed., Conclusion and Relevance: In this clinical trial, DRP prevention bundle in adjusted analysis decreased the rate of 30-day hospital readmission for any cause in patients who visited ED for a DRP., Trial Registration: ClinicalTrials.gov (Identifier: NCT03607097).

This work reports a dual immunoplatform for the simultaneous detection of two epithelial glycoproteins of the mucin family, mucin 1 (MUC1) and mucin 16 (MUC16), whose expression is related to adverse prognosis and minimal residual disease (MRD) in colorectal cancer (CRC). The developed immunoplatform involves functionalised magnetic microparticles (MBs), a set of specific antibody pairs (a capture antibody, cAb, and a biotinylated detector antibody b-dAb labelled with a streptavidin-horseradish peroxidase, Strep-HRP, polymer) for each target protein and amperometric detection at dual screen-printed carbon electrodes (SPdCEs) using the hydroquinone (HQ)/horseradish peroxidase (HRP)/H 2 O 2 system. This dual immunoplatform allows, under the optimised experimental conditions, to achieve LOD values of 50 and 1.81 pg mL -1 (or mU mL -1 ) for MUC1 and MUC16, respectively, and adequate selectivity for the determination of the two targets in the clinic. The developed immunoplatform was employed to analyse CRC cell protein extracts (1.0 μg/determination) with different metastatic potential providing results in agreement with those obtained by blotting technologies but using affordable and applicable point-of-care instruments. This new biotool also emerges competitive in state-of-the-art electrochemical immunoplatforms seeking a compromise among simplicity, reduction of test time and analytical characteristics., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023. Published by Elsevier B.V.)

Background and Purpose: Visual hallucinations (VH) and subjective cognitive complaints (SCC) are associated with cognitive impairment (CI) in Parkinson's disease. Our aims were to determine the association between VH and SCC and the risk of CI development in a cohort of patients with Parkinson's disease and normal cognition (PD-NC)., Methods: Patients with PD-NC (total score of >80 on the Parkinson's Disease Cognitive Rating Scale [PD-CRS]) recruited from the Spanish COPPADIS cohort from January 2016 to November 2017 were followed up after 2 years. Subjects with a score of ≥1 on domain 5 and item 13 of the Non-Motor Symptoms Scale at baseline (V0) were considered as "with SCC" and "with VH," respectively. CI at the 2-year follow-up (plus or minus 1 month) (V2) was defined as a PD-CRS total score of <81., Results: At V0 ( n =376, 58.2% males, age 61.14±8.73 years [mean±SD]), the frequencies of VH and SCC were 13.6% and 62.2%, respectively. VH were more frequent in patients with SCC than in those without: 18.8% (44/234) vs 4.9% (7/142), p <0.0001. At V2, 15.2% (57/376) of the patients had developed CI. VH presenting at V0 was associated with a higher risk of CI at V2 (odds ratio [OR]=2.68, 95% confidence interval=1.05-6.83, p =0.0.039) after controlling for the effects of age, disease duration, education, medication, motor and nonmotor status, mood, and PD-CRS total score at V0. Although SCC were not associated with CI at V2, presenting both VH and SCC at V0 increased the probability of having CI at V2 (OR=3.71, 95% confidence interval=1.36-10.17, p =0.011)., Conclusions: VH were associated with the development of SCC and CI at the 2-year follow-up in patients with PD-NC., Competing Interests: Santos-García D. has received honoraria for educational presentations and advice service by Abbvie, UCB Pharma, Lundbeck, KRKA, Zambon, Bial, Italfarmaco, and Teva., (Copyright © 2023 Korean Neurological Association.)

Background: Detection of suicidal ideation (SI) is key for trying to prevent suicide. The aim of this study was to analyze the frequency of SI and related factors in Spanish people with Parkinson's Disease (PwPD) and to compare them with a control group., Methods: PD patients and controls recruited from the Spanish cohort COPPADIS from January 2016 to November 2017 were included. Two visits were conducted: V0 (baseline); V2 (2-year ± 1 month follow-up). SI was defined as a score ≥1 on item nine of the Beck Depression Inventory-II (BDI-II). Regression analyses were conducted to identify factors related to SI., Results: At baseline, 693 PwPD (60.2% males; 62.59 ± 8.91 years old) and 207 controls (49.8% males; 60.99 ± 8.32 years old) were included. No differences between PwPD and controls were detected in SI frequency at either V0 (5.1% [35/693] vs. 4.3% [9/207]; p = 0.421) or at V2 (5.1% [26/508] vs. 4.8% [6/125]; p = 0.549). Major depression (MD) and a worse quality of life were associated with SI at both visits in PwPD: V0 (MD, OR = 5.63; p = 0.003; PDQ-39, OR = 1.06; p = 0.021); V2 (MD, OR = 4.75; p = 0.027; EUROHIS-QOL8, OR = 0.22; p = 0.006). A greater increase in the BDI-II total score from V0 to V2 was the only factor predicting SI at V2 (OR = 1.21; p = 0.002) along with an increase in the total number of non-antiparkinsonian drugs (OR = 1.39; p = 0.041)., Conclusion: The frequency of SI (5%) in PwPD was similar to in controls. Depression, a worse quality of life, and a greater comorbidity were related to SI., (© 2023 John Wiley & Sons Ltd.)

Electrochemical biosensors are widely used in a multitude of applications, such as medical, nutrition, research, among other fields. These sensors have been historically used and have not undergone many changes in terms of the involved electrochemical processes. In this work, we propose a new approach on the immobilization and enhancement of the electrochemical properties of the sensing layers through the control and bioconjugation of hemoproteins (hemoglobin, myoglobin, and cytochrome C) on anisotropic gold nanoparticles (gold nanotriangles (AuNTs)). The hemeproteins and the AuNTs are mixed in a solution, resulting in stable bioconjugates that are deposited onto the electrode surface to obtain the biosensors. All the systems proposed herein exhibited direct well-defined redox responses, highlighting the key role of the AuNTs acting as mediators of such electron transfers. Several protein layers surrounding the AuNTs are electroactive, as demonstrated from the charge measured by cyclic voltammetry. The retention of the stability of the hemeproteins once they are part of the bioconjugates is evidenced towards the electrocatalytic reduction of hydrogen peroxide, oxygen, and nitrite. The parameters obtained for the proposed biosensors are similar or even lower than those previously reported for similar systems based on nanomaterials, and they exhibit attractive properties that make them potential candidates for the latest developments in the field of sensing devices.

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., Competing Interests: Santos García D. has received honoraria for educational presentations and advice service by Abbvie, UCB Pharma, Lundbeck, KRKA, Zambon, Bial, Italfarmaco, Teva, Archímedes, Esteve, Stada, and grants from the Spanish Ministry of Economy and Competitiveness [PI16/01575] co-founded by ISCIII (Concesión de subvenciones de Proyectos de Investigación en Salud de la convocatoria 2020 de la Acción Estratégica en Salud 2017–2020 por el proyecto “PROGRESIÓN NO MOTORA E IMPACTO EN LA CALIDAD DE VIDA EN LA ENFERMEDAD DE PARKINSON”). De Deus Fonticoba T.: None. Cores Bartolomé C. has received honoraria for educational presentations and advice service by Lundbeck and UCB Pharma. Feal Painceiras M. J.: None. Íñiguez Alvarado MC: None. Jesús S. has received honoraria from AbbVie, Bial, Merz, UCB, and Zambon and holds the competitive contract “Juan Rodés” supported by the Instituto de Salud Carlos III. She has received grants from the Spanish Ministry of Economy and Competitiveness (PI18/01898) and the Consejería de Salud de la Junta de Andalucía (PI-0459-2018). Buongiorno M. T.: Planellas LL.: None. Cosgaya M.: None. García Caldentey J. has received honoraria for educational presentations and advice service by Qualigen, Nutricia, Abbvie, Italfarmaco, UCB Pharma, Lundbeck, Zambon, Bial, and Teva. Caballol N. has received honoraria from Bial, Italfarmaco, Qualigen, Zambon, UCB, Teva, and KRKA and sponsorship from Zambon, TEVA, and Abbvie for attending medical conferences. Legarda I. has received honoraria for educational presentations and advice service by Abbvie, UCB Pharma, Zambon, Bial, and Teva. Hernández Vara J. has received travel bursaries and educational grants from Abbvie and has received honoraria for educational presentations from Abbvie, Teva, Bial, Zambon, Italfarmaco, and Sanofi-Genzyme. Cabo I. has received honoraria for educational presentations and advice service by Abbvie, Zambon, and Bial. López Manzanares L.: Compensated advisory services, consulting, research grant support, or speaker honoraria: AbbVie, Acorda, Bial, Intec Pharma, Italfarmaco, Pfizer, Roche, Teva, UCB, and Zambon. González Aramburu I.: None. Ávila Rivera MA. has received honoraria from Zambon, UCB Pharma, Qualigen, Bial, and Teva and sponsorship from Zambon and Teva for attending conferences. Gómez Mayordomo V.: None. Nogueira V.: None. Puente V. has served as consultant for Abbvie and Zambon; has received grant/research from Abbvie. Dotor García-Soto J.: Compensated advisory services, consulting, research grant support, or speaker honoraria: Merck, Sanofi-Genzyme, Allergan, Biogen, Roche, UCB, and Novartis. Borrué C.: None. Solano Vila B. has received honoraria for educational presentations and advice service by UCB, Zambon, Teva, Abbvie, and Bial. Álvarez Sauco M. has received honoraria for educational presentations and advice service by Abbvie, UCB Pharma, Zambon, Bial, and Teva. Vela L. has received honoraria for educational presentations and advice service by Abbvie, UCB Pharma, Lundbeck, KRKA, Zambon, Bial, and Teva. Escalante S. has received honoraria for educational presentations and advice service by Abbvie, Zambon, and Bial. Cubo E.: Travel grants: Abbvie, Allergan, Boston; Lecturing honoraria: Abbvie, International Parkinson´s disease Movement Disorder Society. Carrillo Padilla F. has received honoraria from Zambon (SEN Congress assistance). Martínez Castrillo JC. has received research support from Lundbeck, Italfarmaco, Allergan, Zambon, Merz, and Abbvie. He has received speaking honoraria from AbbVie, Bial, Italfarmaco, Lundbeck, Krka, TEVA, UCB, Zambon, Allergan, Ipsen, and Merz. Sánchez Alonso P. has received honoraria for educational presentations and advice service by Abbvie, UCB Pharma, Lundbeck, KRKA, Zambon, Bial, and Teva. Alonso Losada M. G. has received honoraria for educational presentations and advice service by Zambon and Bial. López Ariztegui N. has received honoraria for educational presentations and advice service by Abbvie, Italfarmaco, Zambon, and Bial. Gastón I. has received research support from Abbvie and Zambon and has served as a consultant for Abbvie, Exelts, and Zambon. Kulisevsky J.: (1) Consulting fees: Roche, Zambon; (2) Stock/allotment: No; (3) Patent royalties/licensing fees: No; (4) Honoraria (e.g. lecture fees): Zambon, Teva, Bial, UCB; (5) Fees for promotional materials: No; (6) Research funding: Roche, Zambon, Ciberned; Instituto de SaludCarlos III; FundacióLa Maratóde TV3; (7) Scholarship from corporation: No; (8) Corporate laboratory funding: No; (9) Others (e.g. trips, travel, or gifts): No. Blázquez Estrada M. has received honoraria for educational presentations and advice service by Abbvie, Abbott, UCB Pharma, Allergan, Zambon, Bial, and Qualigen. Seijo M. has received honoraria for educational services from KRKA, UCB, Zambon, Bial; travel grants from Daiichi and Roche. Ruiz Martínez J. has received honoraria for educational presentations, attending medical conferences, and advice service by Abbvie, UCB Pharma, Zambon, Italfarmaco, Bial, and Teva. Valero C. has received honoraria for educational services from Zambon, Abbvie, and UCB. Kurtis M. has received honoraria from Bial, the Spanish Neurology Society, and the International and Movement Disorders Society. de Fábregues O. has received honoraria for educational presentations and advice service by Bial, Zambon, Abbvie, KRKA, and Teva. González Ardura J. has recieved honoraria for speking from italofarma, Krka, Genzyme, UCB, Esteve, Psyma iberica marketing research SL and Ferrer, course grant from Teva and travel grant from Merck. Alonso Redondo R.: None. Ordás C.: None. López Díaz L. M. has received honoraria from UCB, Lundbeck, and KRKA. McAfee D.: None. Martínez-Martin P. has received honoraria from National School of Public Health (ISCIII), Editori-al Viguera and Takeda Pharmaceuticals for lecturing in courses, and from the International Parkinson and Movement Disorder Society (MDS) for management of the Program on Rating Scales. Mir P. has received honoraria from AbbVie, Abbott, Allergan, Bial, Merz, UCB, and Zambon and have received grants from the Spanish Ministry of Economy and Competitiveness [PI16/01575] co-founded by ISCIII (Subdirección General de Evaluación y Fomento de la Investigación) and by Fondo Europeo de Desarrollo Regional (FEDER), the Consejería de Economía, Innovación, Ciencia y Empleo de la Junta de Andalucía [CVI-02526, CTS-7685], the Consejería de Salud y Bienestar Social de la Junta de Andalucía [PI-0437-2012, PI-0471-2013], the Sociedad Andaluza de Neurología, the Jacques and Gloria Gossweiler Foundation, the Fundación Alicia Koplowitz, the Fundación Mutua Madrileña., (Copyright © 2023 Diego Santos-García et al.)

Identification of Nocardia and Mycobacterium species by matrix-assisted laser desorption/ionization-time of flight mass spectrometry (MALDI-TOF MS) is still a challenging task that requires both suitable protein extraction procedures and extensive databases. This study aimed to evaluate the VITEK MS Plus system coupled with updated RUO (v4.17) and IVD (v3.2) databases for the identification of Nocardia spp. and Mycobacterium spp. clinical isolates. Sample preparation was carried out using the VITEK MS Mycobacterium/Nocardia kit for protein extraction. From 90 Nocardia spp. isolates analysed, 86 (95.6%) were correctly identified at species or complex level using IVD and 78 (86.7%) using RUO. Only two strains were misidentified as other species pertaining to the same complex. Among the 106 non-tuberculous Mycobacterium clinical isolates tested from a liquid culture medium, VITEK MS identified correctly at species or complex level 96 (90.6%) isolates in the IVD mode and 89 (84.0%) isolates in the RUO mode. No misidentifications were detected. Although the IVD mode was unable to differentiate members of the M. fortuitum complex, the RUO mode correctly discriminated M. peregrinum and M. septicum. The robustness and accuracy showed by this system allow its implementation for routine identification of these microorganisms in clinical laboratories., (© 2022 The Authors. Microbial Biotechnology published by Society for Applied Microbiology and John Wiley & Sons Ltd.)

Introduction: Deep brain stimulation of the subthalamic nucleus (STN-DBS) is the most common surgical treatment for Parkinson's disease (PD). Patient selection and genetic background can modify the response to this treatment. The objective of this study was to compare both clinical and pharmacologic response of STN-DBS between patients with monogenic forms of PD and non-mutation carriers with idiopathic PD., Methods: A retrospective analysis among 23 carriers of genetic mutations (8 PRKN and 15 LRRK2) and 74 patients with idiopathic PD was performed. The study included comparisons of Unified Parkinson's Disease Rating Scale (UPDRS) II and III scores, Schwab and England (S&E) scale values, Hoehn & Yahr (H&Y) stage scores, and equivalent doses of levodopa before and after the surgery (at 6 and 12 months) between both groups., Results: The mean age at the time in which STN-DBS was performed was 59.5 ± 8.6. Linear mixed models showed the absence of statistically significant differences between mutation and non-mutation carriers regarding levodopa doses (p = 0.576), UPDRS II (p = 0.956) and III (p = 0.512) scores, and S&E scale scores (0.758). The only difference between the two groups was observed with respect to H&Y stage in OFF medication/ON stimulation status being lower in genetic PD at 6 months after surgery (p = 0.030)., Conclusion: Clinical and pharmacological benefit of bilateral STN-DBS is similar in PRKN and LRRK2 mutation carriers and patients with idiopathic PD., (Published by Elsevier Ltd.)

Background: There is a need for identifying risk factors for hospitalization in Parkinson's disease (PD) and also interventions to reduce acute hospital admission., Objective: To analyze the frequency, causes, and predictors of acute hospitalization (AH) in PD patients from a Spanish cohort., Methods: PD patients recruited from 35 centers of Spain from the COPPADIS-2015 (COhort of Patients with PArkinson's DIsease in Spain, 2015) cohort from January 2016 to November 2017, were included in the study. In order to identify predictors of AH, Kaplan-Meier estimates of factors considered as potential predictors were obtained and Cox regression performed on time to hospital encounter 1-year after the baseline visit., Results: Thirty-five out of 605 (5.8%) PD patients (62.5±8.9 years old; 59.8% males) presented an AH during the 1-year follow-up after the baseline visit. Traumatic falls represented the most frequent cause of admission, being 23.7% of all acute hospitalizations. To suffer from motor fluctuations (HR [hazard ratio] 2.461; 95% CI, 1.065-5.678; p = 0.035), a very severe non-motor symptoms burden (HR [hazard ratio] 2.828; 95% CI, 1.319-6.063; p = 0.008), falls (HR 3.966; 95% CI 1.757-8.470; p = 0.001), and dysphagia (HR 2.356; 95% CI 1.124-4.941; p = 0.023) was associated with AH after adjustment to age, gender, disease duration, levodopa equivalent daily dose, total number of non-antiparkinsonian drugs, and UPDRS-IIIOFF. Of the previous variables, only falls (HR 2.998; 95% CI 1.080-8.322; p = 0.035) was an independent predictor of AH., Conclusion: Falls is an independent predictor of AH in PD patients.

Objectives: To evaluate short-term mortality in people transferred from aged care homes for treatment in a hospital emergency department (ED) and to analyze factors associated with mortality., Material and Methods: Multicenter study of a random sample of retrospective data of patients treated in 5 EDs in Catalonia in 2017. The patients were over the age of 65 years and lived in residential care facilities. In addition to short-term mortality (in the ED or within 30 days of discharge), we analyzed sociodemographic characteristics, prior functional and cognitive status, multimorbidity, triage level on arrival, length of stay in the ED, and hospital admission. Odds ratios (ORs) for factors associated with short-term mortality were calculated by multivariate regression analysis., Results: A total of 2444 ED admissions were analyzed. The patients' mean (SD) age was 85.9 (7.1) years, and 67.7% .were women. Short-term mortality (in 15.5%) was associated with age >90 years (OR, 1.50; 95% CI, 1.5-1.95 years), a Charlson index >2 (OR, 1.47; 95% CI, 1.14-1.90), and dependency assessed as moderate (OR, 1.50; 95% CI, 1.03- 2.20) or severe (OR, 2.56; 95% CI, 1.84-3.55). Other associated factors were a higher level of urgency on triage, duration of ED stay, and hospital admission., Conclusion: Aged residents with the characteristics associated with short-term mortality could benefit from interventions for potentially avoiding unnecessary transfers to an ED, and from the implementation of comprehensive geriatric care within the ED. This could be useful to support good quality of care at the end of life.

This work deals with a physical and chemical surface characterization of quaternary 18K, 14K, and 9K gold alloys and pure polycrystalline gold substrates. Surface microstructure and composition are evaluated by scanning electron microscopy (SEM), X-ray photoelectron spectroscopy (XPS), and X-ray fluorescence spectroscopy. Corrosion resistance of 18K gold alloys is explored by potentiodynamic polarization showing the influence of the manufacturing process on materials fabricated as plates and wires. The research is also in the framework of one of the most common strategies on the modification of metallic surface properties, i.e., the building of self-assembled monolayers (SAM) from organic thiols. The metal affinity of the head group to produce the coating of the substrate by covalent binding is approached by using thiol compounds with different molecular structures and functional group chemistries exposed to an electrolyte solution. Therefore, a comparative study on the surface protection of a quaternary 18K gold alloy and pure gold substrates by SAMs of 6-mercaptopurine (6MP), 1-decanethiol (DT), and 11-mercaptoundecanoic acid (MUA) has been carried out. Surface modification and SAM organization are followed by cyclic voltammetry (CV), and the behavior of the double layer of the electrode-electrolyte interface is evaluated by electrochemical impedance spectroscopy (EIS). The study of these materials allows us to extract fundamental knowledge for its potential application in improving the bioactive properties of different jewelry pieces based on 18K gold alloys.

Background: Previous studies suggest a link between CAG repeat number in the HTT gene and non-Huntington neurodegenerative diseases., Objective: The aim is to analyze whether expanded HTT CAG alleles and/or their size are associated with the risk for developing α-synucleinopathies or their behavior as modulators of the phenotype., Methods: We genotyped the HTT gene CAG repeat number and APOE-Ɛ isoforms in a case-control series including patients with either clinical or neuropathological diagnosis of α-synucleinopathy., Results: We identified three Parkinson's disease (PD) patients (0.30%) and two healthy controls (0.19%) carrying low-penetrance HTT repeat expansions whereas none of the dementia with Lewy bodies (DLB) or multisystem atrophy (MSA) patients carried pathogenic HTT expansions. In addition, a clear increase in the number of HTT CAG repeats was found among DLB and PD groups influenced by the male gender and also by the APOE4 allele among DLB patients. HTT intermediate alleles' (IAs) distribution frequency increased in the MSA group compared with controls (8.8% vs. 3.9%, respectively). These differences were indeed statistically significant in the MSA group with neuropathological confirmation. Two MSA HTT CAG IAs carriers with 32 HTT CAG repeats showed isolated polyQ inclusions in pons and basal nuclei, which are two critical structures in the neurodegeneration of MSA., Conclusions: Our results point to a link between HTT CAG number, HTT IAs, and expanded HTT CAG repeats with other non-HD brain pathology and support the hypothesis that they can share common neurodegenerative pathways. © 2022 International Parkinson and Movement Disorder Society., (© 2022 International Parkinson and Movement Disorder Society.)

This work reports the first dual magnetic beads (MBs) assisted immunoplatform for the simultaneous determination of BAFF (B cell activation factor) and APRIL (a proliferation-induced ligand), two cytokines related to immunity and tumour invasion, growth and metastasis. The electrochemical immunoplatform involves sandwich-type immunoassays implemented on magnetic microparticles functionalized with neutravidin (NA-MBs) or carboxylic groups (HOOC-MBs), and amperometric detection (E app  =  - 0.20 V vs. Ag pseudo-reference electrode) at screen-printed dual carbon electrodes (SPdCE) using the H 2 O 2 /hydroquinone (HQ) system. The developed immunosensors provide improved sensitivity, with LOD values of 0.33 and 16.4 pg mL -1 for BAFF and APRIL, respectively, and much shorter assay time that those claimed for ELISA kits and allow their simultaneous determination. The dual immunosensor permits discrimination between healthy individuals and patients diagnosed with Systemic Lupus Erythematosus (SLE) or colorectal cancer (CRC) through the determination of both cytokines in 100-times diluted human sera with results in agreement with those provided by the individual ELISA methodologies., (Copyright © 2022 Elsevier B.V. All rights reserved.)

Background and Objective: Caregiver burden in Parkinson's disease (PD) has been studied in many cross-sectional studies but poorly in longitudinal ones. The aim of the present study was to analyze the change in burden, strain, mood, and quality of life (QoL) after a 2-year follow-up in a cohort of caregivers of patients with PD and also to identify predictors of these changes., Patients and Methods: PD patients and their caregivers who were recruited from January/2016 to November/2017 from 35 centers of Spain from the COPPADIS cohort were included in the study. They were evaluated again at 2-year follow-up. Caregivers completed the Zarit Caregiver Burden Inventory (ZCBI), Caregiver Strain Index (CSI), Beck Depression Inventory-II (BDI-II), and EUROHIS-QOL 8-item index (EUROHIS-QOL8) at baseline (V0) and at 2-year follow-up (V2). General linear model repeated measure and lineal regression models were applied., Results: Significant changes, indicating an impairment, were detected on the total score of the ZCBI (p < 0.0001), CSI (p < 0.0001), BDI-II (p = 0.024), and EUROHIS-QOL8 (p = 0.002) in 192 PD caregivers (58.82 ± 11.71 years old; 69.3% were females). Mood impairment (BDI-II; β = 0.652; p < 0.0001) in patients from V0 to V2 was the strongest factor associated with caregiver's mood impairment after the 2-year follow-up. Caregiver's mood impairment was the strongest factor associated with an increase from V0 to V2 on the total score of the ZCBI (β = 0.416; p < 0.0001), CSI (β = 0.277; p = 0.001), and EUROHIS-QOL (β = 0.397; p = 0.002)., Conclusion: Burden, strain, mood, and QoL were impaired in caregivers of PD patients after a 2-year follow-up. Mood changes in both the patient and the caregiver are key aspects related to caregiver burden increase., (© 2022 John Wiley & Sons Ltd.)

This work reports the first electrochemical bioplatform for the determination of soy traces in food. The bioplatform involves sandwich-type immunoassays using specific antibodies for β-conglycinin and glycinin, which are the main allergenic soy proteins, and carboxylic acid-modified magnetic microbeads. Amperometric detection at -0.20 V (vs. an Ag pseudo-reference electrode) was performed using single or dual screen-printed carbon electrodes and the H 2 O 2 /hydroquinone (HQ) system. The measured variation in the cathodic current was directly proportional to the concentration of target allergenic proteins. The developed bioplatforms exhibit a good selectivity and sensitivity providing limits of detection (LOD) values of 0.03 and 0.02 ng mL -1 for β-conglycinin and glycinin, respectively. The determination of both proteins can be carried out in only 1.5 h. The electrochemical bioplatforms allow their accurate determinations (with results statistically comparable to those provided by ELISA methodologies) in raw cookie dough and baked cookies enriched with soy flour. The results obtained confirm, in a pioneering way with electrochemical biosensors, the possibility of discriminating samples incurred with as little as 0.0005 ppm of a food allergen in model cookie extracts., (Copyright © 2022 The Authors. Published by Elsevier B.V. All rights reserved.)

Serial murder is a specific type of violent crime that falls into the crime category of multicide. According to the nomenclature of the Federal Bureau of Investigation's Violent Crime Classification Manual and Academic Researchers for the Classification of Violent Crimes, most serial killers are adults. However, serial murder is also committed by young people, although to a lesser extent. Young serial killers are a topic of relevance in areas such as psychology, criminology, and the justice system. Given that the study of the variables that could be the basis of such multicide criminality is not conclusive, the need for further research is evident. The homicides perpetrated by children and young people point to a social panorama that is alarming due to their young age. This issue is prevalent enough to conduct a review. The performed review concludes the importance of psychosocial factors to better understand the process by which children and young people commit crimes as serious as serial murders. The scope of the problem of serial murders perpetrated by minors is controversial because it often depends on how the number of real cases is counted. Although official statistics indicate the low prevalence of juvenile serial killers, childhood is a period in which antisocial behaviour can have its beginning. Some authors consider that it is not uncommon for the first murder of this type to occur in adolescence. It is important to consider psychopathy as an influential factor in the various forms of serial criminal conduct committed by children and young people. The research works consulted provide evidence of the special relevance of psychopathy in the generation of serious juvenile delinquency.

Background: Previous studies linked disease-progression variables such as age at onset or survival to both genetic, and non-genetic factors in Parkinson's disease (PD) patients., Objective: The aim of this study was to assess how genetic and non genetic factors act as modifiers of age at onset and survival and in a cohort of 753 PD patients, and to determine how these variables interact to define the overall risk., Methods: We analyzed the effect of gender, tobacco, alcohol, type of PD (genetic, gPD or idiopathic, iPD) and three genetic variants rs5848- GRN, rs1042522- TP53 and APOE. We studied two cohorts (PPMI and IPDGC) to replicate positive results., Results: Regarding age at onset, male smokers PD had a significantly lower mean age compared to non-smoker (p = 0.001). APOE-Ɛ4 carriers had a younger onset-age compared to non-carriers (p = 0.03) in the Spanish cohort, but these results were not replicated in the other cohorts. Concerning survival, PD patients with an early onset (below 50 years) had an increased survival rate (p < 0.001)., Conclusions: Our study showed how several genetic and non-genetic risk factors influenced the age at onset and survival in PD., (Copyright © 2022 Elsevier Ltd. All rights reserved.)

This work reports the first electroanalytical bioplatform to date for the determination of antibodies against aquaporin-4 (AQP4-Abs), whose serum level is considered as relevant biomarker for certain autoimmune diseases. The bioplatform relies on the use of magnetic microparticles modified with the biotinylated protein for the capture of specific antibodies. The captured IgGs are enzymatically labelled with a secondary antibody conjugated to the horseradish peroxidase (HRP) enzyme. Amperometric transduction is performed using the H 2 O 2 /hydroquinone (HQ) system, which results in a cathodic current variation directly proportional to the concentration of the target antibodies. The evaluation of the analytical and operational characteristics of the developed bioplatform shows that it is competitive in terms of sensitivity with the only biosensor reported to date as well as with the commercially available ELISA kits. The achieved limit of detection value is 8.8 pg mL -1 . In addition, compared to ELISA kits, the developed bioplatform is advantageous in terms of cost and point of care operation ability. The bioplatform was applied to the analysis of control serum samples with known AQP4-Abs contents as well as of sera from healthy individuals and patients diagnosed with Systemic Lupus Erythematosus (SLE) and Alzheimer (AD) diseases, providing results in agreement with the ELISA methodology., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2021 Elsevier B.V. All rights reserved.)

A dual immunosensor is reported for the simultaneous determination of two important immunity-related cytokines: BAFF (B cell activation factor) and APRIL (a proliferation-induced signal). Sandwich-type immunoassays with specific antibodies (cAbs) and a strategy for signal amplification based on labelling the detection antibodies (dAbs) with binary MoS 2 /MWCNTs nanostructures and using horseradish peroxidase (HRP) were implemented. Amperometric detection was carried out at screen-printed dual carbon electrodes (SPdCEs) through the hydroquinone HQ/H 2 O 2 system. The developed dual immunosensor provided limit of detection (LOD) of 0.08 and 0.06 ng mL -1 for BAFF and APRIL, respectively, and proved to be useful for the determination of both cytokines in cancer cell lysates and serum samples from patients diagnosed with autoimmune diseases and cancer. The obtained results agreed with those found using ELISA methodologies., (© 2022. The Author(s).)

This research analyzes the executive functions in minors between 7 and 16 years of age who have suffered physical abuse and neglect, as well as minors in residential care centers with other measures of protection. Most studies focus on the neurobiological consequences of the abuse, and mainly at an early age. However, there are very few studies that analyze the executive functions of victims of child abuse, while also taking into account the type of abuse suffered. This study aims to identify whether the consequences of child abuse for the executive functions are different for those minors who have been victims of physical abuse and neglect, in comparison with minors with other protective measures. The participants were 44 minors who had suffered child abuse and 24 minors with other protective measures, distinct from abuse. Three neuropsychological tests were used: (a) the Five Digits Test (FDT), (b) the Behavioral Assessment of the Dysexecutive Syndrome in Children (BADS-C), and (c) the Wechsler Intelligence Scale for Children-V (WISC-V). The results showed difficulties in those minors who had been victim of physical abuse and neglect, in their cognitive flexibility capabilities, inhibitory control, the ability to take decisions, the ability to organize and plan their behavior, control of emotions, and attention control. It was the minors who were victims of physical neglect that showed the greatest difficulties in their executive functions. The results of the study will permit us to design an educational intervention in the residential care centers that can encourage advances in the affected areas through the setting up of different strategies to favor the stimulation, reinforcement, and rehabilitation of the executive functions.

Over the past century, evidence has emerged that endocrine disrupting chemicals (EDCs) have an impact on reproductive health. An increased frequency of reproductive disorders has been observed worldwide in both wildlife and humans that is correlated with accidental exposures to EDCs and their increased production. Epidemiological and experimental studies have highlighted the consequences of early exposures and the existence of key windows of sensitivity during development. Such early in life exposures can have an immediate impact on gonadal and reproductive tract development, as well as on long-term reproductive health in both males and females. Traditionally, EDCs were thought to exert their effects by modifying the endocrine pathways controlling reproduction. Advances in knowledge of the mechanisms regulating sex determination, differentiation and gonadal development in fish and rodents have led to a better understanding of the molecular mechanisms underlying the effects of early exposure to EDCs on reproduction. In this manuscript, we review the key developmental stages sensitive to EDCs and the state of knowledge on the mechanisms by which model EDCs affect these processes, based on the roadmap of gonad development specific to fish and mammals., (Copyright © 2021 The Authors. Published by Elsevier Inc. All rights reserved.)

Speciation in oceanic islands has attracted the interest of scientists since the 19th century. One of the most striking evolutionary phenomena that can be studied in islands is adaptive radiation, that is, when a lineage gives rise to different species by means of ecological speciation. Some of the best-known examples of adaptive radiation are charismatic organisms like the Darwin finches of the Galapagos and the cichlid fishes of the great African lakes. In these and many other examples, a segregation of the trophic niche has been shown to be an important diversification driver. Radiations are known in other groups of organisms, such as lichen-forming fungi. However, very few studies have investigated their adaptive nature, and none have focused on the trophic niche. In this study, we explore the role of the trophic niche in a putative radiation of endemic species from the Macaronesian Region, the Ramalina decipiens group. The photobiont diversity was studied by Illumina MiSeq sequencing of the ITS2 region of 197 specimens spanning the phylogenetic breadth and geographic range of the group. A total of 66 amplicon sequence variants belonging to the four main clades of the algal genus Trebouxia were found. Approximately half of the examined thalli showed algal coexistence, but in most of them, a single main photobiont amounted to more than 90% of the reads. However, there were no significant differences in photobiont identity and in the abundance of ITS2 reads across the species of the group. We conclude that a segregation of the trophic niche has not occurred in the R. decipiens radiation., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Blázquez, Hernández-Moreno, Gasulla, Pérez-Vargas and Pérez-Ortega.)

Biocidal substances and their environmental relevant metabolites are highly toxic for fish. However, an important scarcity of toxicity data for metabolites is recognised. This article provides new data about the toxicity to fish of these compounds and evaluates the potential use of fish cell lines as screening tools to assess the acute toxicity of these compounds in fish. To this aim, acute toxicity of 7 substances was tested in Oncorhynchus mykiss (OECD TG203) and cytotoxicity of 16 substances was assessed in fish cell lines from two species; Poeciliopsis lucida (PLHC-1) and O. mykiss (RTH-149, RTG-2 and RTgill-W1) performing three cytotoxicity tests: Alamar-Blue, 5-carboxyfluorescein diacetate, acetoxymethyl ester and Neutral Red Uptake. Additionally, in vitro and in vivo data from the LIFE-COMBASE database were included in a dataset finally comprising 33 biocides and 14 metabolites. Hazard data were categorized into 4 toxicity groups, according to the intervals established in Regulation (EC) 1272/2008. Finally, the Spearman correlation test was performed and coincidences between in vitro-in vivo data established. In vitro and in vivo results revealed a high positive correlation, with a complete coincidence for 56.5% of the substances, a 2% of false positives (non-toxic in vivo) and a 13% of false negatives (toxic in vivo) for the 4 toxicity categories. However, when results were grouped in toxic or non-toxic coincidence was obtained for 85% of the substances. In conclusion, although fish denote a greater sensitivity, the use of at least two fish cell lines and three cytotoxicity endpoints appear to be valid approaches for fish acute toxicity screening of biocides and their metabolites., (Copyright © 2021. Published by Elsevier B.V.)

Background: Motor phenotype (MP) can be associated with a different prognosis in Parkinson's disease (PD), but it is not fixed and can change over time., Objective: Our aim was to analyze how the MP changed over time and to identify factors associated with the changes in PD patients from a multicenter Spanish PD cohort., Methods: PD patients who were recruited from January-2016 to November-2017 (baseline visit; V0) and evaluated again at a 2-year±30 days follow-up (V2) from 35 centers of Spain from the COPPADIS cohort, were included in this study.MP was calculated at both visits based on Jankovic classification in TD (tremor dominant), IND (indeterminate), or PIGD (postural instability and gait difficulty). Sociodemographic and clinical data were collected, including serum biomarkers., Results: Five hundred eleven patients (62.57±8.59 years old; 59.2%males) were included in the study. At V0, MP was: 47.4%(242/511) TD; 36.6%(187/511) PIGD; 16%(82/511) IND. Up to 38%(194/511) of the patients changed their phenotype from V0 to V2, being the most frequent from TD to IND (8.4%) and from TD to PIGD (6.7%). A worse cognitive status (OR = 0.966) and less autonomy for activities of daily living (OR  =  0.937) at V0 and a greater increase in the globalNMS burden (OR  =  1.011) from V0 to V2 were associated with changing from TD to another phenotype after 2-year follow-up., Conclusion: The MP in PD can change over time. With disease progression, the percentage of cases with non-tremoric MP increases. PD patients who changed from TD to postural instability and gait difficulty increased NMS burden significantly.

Background: Constipation has been linked to cognitive impairment development in Parkinson's disease (PD)., Objective: Our aim was to analyze cognitive changes observed in PD patients and controls from a Spanish cohort with regards to the presence or not of constipation., Methods: PD patients and controls recruited from 35 centers of Spain from the COPPADIS cohort from January 2016 to November 2017 were followed-up during 2 years. The change in cognitive status from baseline (V0) to 2-year follow-up was assessed with the PD-CRS (Parkinson's Disease Cognitive Rating Scale). Subjects with a score ≥1 on item 21 of the NMSS (Non-Motor Symptoms Scale) at baseline (V0) were considered as "with constipation". Regression analyses were applied for determining the contribution of constipation in cognitive changes., Results: At V0, 39.7% (198/499) of PD patients presented constipation compared to 11.4% of controls (14/123) (p < 0.0001). No change was observed in cognitive status (PD-CRS total score) neither in controls without constipation (from 100.24±13.72 to 100.27±13.68; p = 0.971) and with constipation (from 94.71±10.96 to 93.93±13.03; p = 0.615). The PD-CRS total score decreased significantly in PD patients with constipation (from 89.14±15.36 to 85.97±18.09; p < 0.0001; Coehn's effect = -0.35) compared to patients without constipation (from 93.92±15.58 to 93.14±17.52; p = 0.250) (p = 0.018). In PD patients, to suffer from constipation at V0 was associated with a decrease in the PD-CRS total score from V0 to V2 (β= -0.1; 95% CI, -4.36 - -0.27; p = 0.026) and having cognitive impairment at V2 (OR = 1.79; 95% CI, 1.01 - 3.17; p = 0.045)., Conclusion: Constipation is associated with cognitive decline in PD patients but not in controls.

Background and Objective: Diplopia is relatively common in Parkinson's disease (PD) but is still understudied. Our aim was to analyze the frequency of diplopia in PD patients from a multicenter Spanish cohort, to compare the frequency with a control group, and to identify factors associated with it., 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 days follow-up (V2) from 35 centers of Spain from the COPPADIS cohort were included in this longitudinal prospective study. The patients and controls were classified as "with diplopia" or "without diplopia" according to item 15 of the Non-Motor Symptoms Scale (NMSS) at V0, V1 (1-year ± 15 days), and V2 for the patients and at V0 and V2 for the controls., Results: The frequency of diplopia in the PD patients was 13.6% (94/691) at V0 (1.9% in controls [4/206]; p < 0.0001), 14.2% (86/604) at V1, and 17.1% (86/502) at V2 (0.8% in controls [1/124]; p < 0.0001), with a period prevalence of 24.9% (120/481). Visual hallucinations at any visit from V0 to V2 (OR = 2.264; 95%CI, 1.269-4.039; p = 0.006), a higher score on the NMSS at V0 (OR = 1.009; 95%CI, 1.012-1.024; p = 0.015), and a greater increase from V0 to V2 on the Unified Parkinson's Disease Rating Scale-III (OR = 1.039; 95%CI, 1.023-1.083; p < 0.0001) and Neuropsychiatric Inventory (OR = 1.028; 95%CI, 1.001-1.057; p = 0.049) scores were independent factors associated with diplopia (R 2 = 0.25; Hosmer and Lemeshow test, p = 0.716)., Conclusions: Diplopia represents a frequent symptom in PD patients and is associated with motor and non-motor severity.

Quality of life (QOL) plays an important role in independent living in Parkinson's disease (PD) patients, being crucial to know what factors impact QoL throughout the course of the disease. Here we identified predictors of QoL impairment in PD patients from a Spanish cohort. PD patients recruited from 35 centers of Spain from the COPPADIS cohort from January 2016, to November 2017, were followed up during 2 years. Health-related QoL (HRQoL) and global QoL (GQoL) were assessed with the 39-item Parkinson's disease Questionnaire (PDQ-39) and the EUROHIS-QOL 8-item index (EUROHIS-QOL8), respectively, at baseline (V0) and at 24 months ± 1 month (V2). Clinically significant QoL impairment was defined as presenting an increase (PDQ-39SI) or decrement (EUROHIS-QOL8) at V2 ≥ 10% of the score at baseline (V0). A comparison with a control group was conducted for GQoL. GQoL did not change significantly in PD patients (N = 507; p = 0.686) or in the control group (N = 119; p = 0.192). The mean PDQ-39SI was significantly increased in PD patients (62.7 ± 8.5 years old; 58.8% males; N = 500) by 21.6% (from 16.7 ± 13 to 20.3 ± 16.4; p < 0.0001) at V2. Ninety-three patients (18.6%) presented a clinically significant HRQoL impairment at V2. To be younger (OR = 0.896; 95% CI 0.829-0.968; p = 0.006), to be a female (OR = 4.181; 95% CI 1.422-12.290; p = 0.009), and to have a greater increase in BDI-II (Beck Depression Inventory-II) (OR = 1.139; 95% CI 1.053-1.231; p = 0.001) and NMSS (Non-Motor Symptoms Scale) (OR = 1.052; 95% CI 1.027-1.113; p < 0.0001) total scores from V0 to V2 were associated with clinically significant HRQoL impairment at the 2-year follow-up (Hosmer-Lemeshow test, p = 0.665; R 2  = 0.655). An increase in ≥5 and ≥10 points of BDI-II and NMSS total score at V2 multiplied the probability of presenting clinically significant HRQoL impairment by 5 (OR = 5.453; 95% CI 1.663-17.876; p = 0.005) and 8 (OR = 8.217; 95% CI, 2.975-22.696; p = 0.002), respectively. In conclusion, age, gender, mood, and non-motor impairment were associated with clinically significant HRQoL impairment after the 2-year follow-up in PD patients., (© 2021. The Author(s).)

Background: Identifying modifiable risk factors for cognitive impairment in the early stages of Parkinson's disease (PD) and estimating their impact on cognitive status may help prevent dementia (PDD) and the design of cognitive trials., Methods: Using a standard approach for the assessment of global cognition in PD and controlling for the effects of age, education and disease duration, we explored the associations between cognitive status, comorbidities, metabolic variables and lifestyle variables in 533 PD participants from the COPPADIS study., Results: Among the overall sample, 21% of participants were classified as PD-MCI (n = 114) and 4% as PDD (n = 26). The prevalence of hypertension, diabetes and dyslipidemia was significantly higher in cognitively impaired patients while no between-group differences were found for smoking, alcohol intake or use of supplementary vitamins. Better cognitive scores were significantly associated with regular physical exercise (p < 0.05) and cognitive stimulation (< 0.01). Cognitive performance was negatively associated with interleukin 2 (Il2) (p < 0.05), Il6 (p < 0.05), iron (p < 0.05), and homocysteine (p < 0.005) levels, and positively associated with vitamin B12 levels (p < 0.005)., Conclusions: We extend previous findings regarding the positive and negative influence of various comorbidities and lifestyle factors on cognitive status in early PD patients, and reinforce the need to identify and treat potentially modifiable variables with the intention of exploring the possible improvement of the global cognitive status of patients with PD., (© 2021. The Author(s).)

Safinamide is a new add-on drug to levodopa for the treatment of Parkinson's disease (PD) with motor fluctuations. Due to the recent incorporation of safinamide into routine clinical practice, no post-authorisation phase IV studies on the safety of safinamide have been conducted to date. This study provides clinical management guidelines for safinamide based on the opinion of a group of experts in movement disorders. This project was developed in 2 phases: 16 local meetings in phase 1 and a national meeting in phase 2. The meetings followed a pre-established agenda. The present clinical practice guidelines are based on the main conclusions reached during the national meeting. The group concluded that safinamide is effective in reducing motor and non-motor fluctuations. PD patients with mild-to-moderate fluctuations benefit most from treatment, although the drug may also improve the clinical status of patients with advanced PD. The dose of other dopaminergic drugs may be reduced after introducing safinamide, which would contribute to reducing such adverse reactions as impulse control disorder. At doses higher than those usually prescribed, safinamide may also improve dyskinesia. The experts agreed that safinamide is well tolerated and causes few adverse reactions when compared with placebo., (Copyright © 2020. Published by Elsevier España, S.L.U.)

Background and Objective: The aim of this study was to compare the progression of independence in activities of daily living (ADL) in Parkinson's disease (PD) patients versus a control group, as well as to identify predictors of disability progression and functional dependency (FD)., Patients and Methods: PD patients and control subjects, who were recruited from 35 centers of Spain from the COPPADIS cohort between January 2016 and November 2017 (V0), were included. Patients and subjects were then evaluated again at the 2-year follow-up (V2). Disability was assessed with the Schwab & England Activities of Daily Living Scale (S&E-ADLS) at V0 and V2. FD was defined as an S&E-ADLS score less than 80%., Results: In the PD group, a significant decrease in the S&E-ADLS score from V0 to V2 (N = 507; from 88.58 ± 10.19 to 84.26 ± 13.38; p < 0.0001; Cohen's effect size = -0.519) was observed but not in controls (N = 124; from 98.87 ± 6.52 to 99.52 ± 2.15; p = 0.238). When only patients considered functional independent at baseline were included, 55 out of 463 (11.9%) converted to functional dependent at V2. To be a female (OR = 2.908; p = 0.009), have longer disease duration (OR = 1.152; p = 0.002), have a non-tremoric motor phenotype at baseline (OR = 3.574; p = 0.004), have a higher score at baseline in FOGQ (OR = 1.244; p < 0.0001) and BDI-II (OR = 1.080; p = 0.008), have a lower score at baseline in PD-CRS (OR = 0.963; p = 0.008), and have a greater increase in the score from V0 to V2 in UPDRS-IV (OR = 1.168; p = 0.0.29), FOGQ (OR = 1.348; p < 0.0001) and VAFS-Mental (OR = 1.177; p = 0.013) (adjusted R-squared 0.52; Hosmer and Lemeshow test = 0.94) were all found to be independent predictors of FD at V2., Conclusions: In conclusion, autonomy for ADL worsens in PD patients compared to controls. Cognitive impairment, gait problems, fatigue, depressive symptoms, more advanced disease, and a non-tremor phenotype are independent predictors of FD in the short-term.

The fluorescent properties of cadmium telluride (CdTe) containing quantum dots (QDs) have led to novel products and applications in the ink and pigment industry. The toxic effects of the emissions associated to the use of printing ink containing CdTe QDs might differ from those of conventional formulations which do not integrate nanoparticles, as CdTe QDs might be emitted. Within this work, the airborne emissions of a water-soluble fluorescent ink containing polyethylene glycol (PEG)-coated CdTe QDs of 3-5 nm diameter have been characterized and studied under controlled conditions during household inkjet printing in a scenario simulating the use phase. Subsequently, the cytotoxicological potential of atomized CdTe QDs ink in an acute exposure regimen simulating an accidental, worse-case scenario has been evaluated in vitro at the air-liquid interface (ALI) using the pulmonary cell line BEAS-2B. Endpoints screened included cell viability, oxidative stress and inflammatory effects. We have observed that CdTe QDs ink at 54.7 ng/mL decreased cell viability by 25.6 % when compared with clean air after 1h of exposure; a concentration about 65 times higher was needed to observe a similar effect in submerged conditions. However, we did not observe oxidative stress or inflammatory effects. The present study integrates the development of scenarios simulating the use phase of nano-additivated inks and the direct cell exposure for in vitro effects assessment, thus implementing a life-cycle oriented approach in the assessment of the toxicity of CdTe QDs., Competing Interests: Declaration of Competing Interest The authors report no declarations of interest., (Copyright © 2021. Published by Elsevier B.V.)

Parkinson's disease (PD) is a chronic progressive and irreversible disease and the second most common neurodegenerative disease worldwide. In Spain, it affects around 120.000-150.000 individuals, and its prevalence is estimated to increase in the future. PD has a great impact on patients' and caregivers' lives and also entails a substantial socioeconomic burden. The aim of the present study was to examine the current situation and the 10-year PD forecast for Spain in order to optimize and design future management strategies. This study was performed using the modified Delphi method to try to obtain a consensus among a panel of movement disorders experts. According to the panel, future PD management will improve diagnostic capacity and follow-up, it will include multidisciplinary teams, and innovative treatments will be developed. The expansion of new technologies and studies on biomarkers will have an impact on future PD management, leading to more accurate diagnoses, prognoses, and individualized therapies. However, the socio-economic impact of the disease will continue to be significant by 2030, especially for patients in advanced stages. This study highlighted the unmet needs in diagnosis and treatment and how crucial it is to establish recommendations for future diagnostic and therapeutic management of PD.

In this work, the methoxy terminated oligo- and polyethylene glycol of different chain lengths (EG n , n = 7, 18, 45 and 136) is grafted on AuNP surfaces under conditions where they attain maximum grafting densities. These EG n -AuNPs gain stability relative to the pristine c-AuNPs in aqueous solutions and in a wide temperature interval and they form stable suspensions in solutions of high NaCl concentrations. To show the thermoresponsive properties of these EG n -AuNPs, temperature titration experiments are carried out in the presence of increasing amounts of salts. The concentrations of NaCl are chosen by checking the stability of EG n -AuNPs at room temperature and choosing the highest concentrations that allow them to form stable suspensions. The analysis of the temperature titration experiments monitored by UV-visible spectroscopy and dynamic light scattering allows us to establish the existence of transitions from individual to assembled nanoparticles, the reversibility of the temperature transitions and hysteretic behaviour in these systems. While EG7-AuNPs only show reversible temperature transitions in the presence of 5 mM NaCl, EG18-AuNPs do up to 1 M NaCl, becoming only partially reversible in 2 M NaCl. The titrations of EG45-AuNPs in 3 and 5 M NaCl show irreversible temperature transitions. Finally, EG136-AuNPs present a complex and interesting behaviour with two temperature transitions, the first one showing hysteresis and the second being reversible., Competing Interests: There are no conflicts to declare., (This journal is © The Royal Society of Chemistry.)

Background and Objective: Non-motor symptoms (NMS) progress in different ways between Parkinson's disease (PD) patients. The aim of the present study was to (1) analyze the change in global NMS burden in a PD cohort after a 2-year follow-up, (2) to compare the changes with a control group, and (3) to identify predictors of global NMS burden progression in the PD group. Material and Methods: PD patients and controls, recruited from 35 centers of Spain from the COPPADIS cohort from January 2016 to November 2017, were followed-up with after 2 years. The Non-Motor Symptoms Scale (NMSS) was administered at baseline (V0) and at 24 months ± 1 month (V2). Linear regression models were used for determining predictive factors of global NMS burden progression (NMSS total score change from V0 to V2 as dependent variable). Results: After the 2-year follow-up, the mean NMS burden (NMSS total score) significantly increased in PD patients by 18.8% (from 45.08 ± 37.62 to 53.55 ± 42.28; p < 0.0001; N = 501; 60.2% males, mean age 62.59 ± 8.91) compared to no change observed in controls (from 14.74 ± 18.72 to 14.65 ± 21.82; p = 0.428; N = 122; 49.5% males, mean age 60.99 ± 8.32) ( p < 0.0001). NMSS total score at baseline (β = -0.52), change from V0 to V2 in PDSS (Parkinson's Disease Sleep Scale) (β = -0.34), and change from V0 to V2 in NPI (Neuropsychiatric Inventory) (β = 0.25) provided the highest contributions to the model (adjusted R-squared 0.41; Durbin-Watson test = 1.865). Conclusions: Global NMS burden demonstrates short-term progression in PD patients but not in controls and identifies worsening sleep problems and neuropsychiatric symptoms as significant independent predictors of this NMS progression.

Background: Intermediate Alleles (IAs) are expansions of CAG repeats in the HTT gene between 27 and 35 repeats which pathogenic meaning remains controversial. They are present in the general population but there is an increasing number of cases with Huntington-like phenotype reported., Methods: We reviewed the medical records of cases in our centre where the neurologist suspected Huntington's disease (HD) as one of the feasible diagnoses and genetic testing showed the number of CAG repeats was in the "intermediate range". We gathered the type of symptoms in all cases and the main neuroimaging findings when available., Results: We found 14 cases, 8 males and 6 females, with average age at onset at 64 years old. Most cases exhibited some type of extrapyramidal symptoms. Cognitive and/or behavioral symptoms were also present in most cases (being depression, anxiety and cognitive impairment the most frequent ones). In one case we found deposits of iron in the basal ganglia in the MRI, and in another case we found diffuse cortical hypometabolism with predominantly frontal bilateral involvement and bilateral focal deficit of both caudate and thalamus in the FDG-PET., Conclusion: The clinical and neuroimaging findings of some cases with IA in this series are compatible with the clinical picture of HD but also with several other alternative diagnoses. Therefore we can not establish association between IA and HD. Larger series with more comprehensive diagnostic workout and neuropathological studies are needed to confirm or rule out whether IAs in the HTT gene may cause HD., (Copyright © 2021 Elsevier B.V. All rights reserved.)

Introduction: In a degenerative disorder such as Parkinson's disease (PD), it is important to establish clinical stages that allow to know the course of the disease. Our aim was to analyze whether a scale combining Hoehn and Yahr's motor stage (H&Y) and the nonmotor symptoms burden (NMSB) (assessed by the nonmotor symptoms scale (NMSS)) provides information about the disability and the patient's quality of life (QoL) with regard to a defined clinical stage., Materials and Methods: Cross-sectional study in which 603 PD patients from the COPPADIS cohort were classified according to H&Y (1, stage I; 2, stage II; 3, stage III; 4, stage IV/V) and NMSB (A: NMSS = 0-20; B: NMSS = 21-40; C: NMSS = 41-70; D: NMSS ≥ 71) in 16 stages (HY.NMSB, from 1A to 4D). QoL was assessed with the PDQ-39SI, PQ-10, and EUROHIS-QOL8 and disability with the Schwab&England ADL (Activities of Daily Living) scale., Results: A worse QoL and greater disability were observed at a higher stage of H&Y and NMSB ( p < 0.0001). Combining both (HY.NMSB), patients in stages 1C and 1D and 2C and 2D had significantly worse QoL and/or less autonomy for ADL than those in stages 2A and 2B and 3A and 3B, respectively ( p < 0.005; e.g., PDQ-39SI in 1D [ n  = 15] vs 2A [ n  = 101]: 28.6 ± 17.1 vs 7.9 ± 5.8; p < 0.0001)., Conclusion: The HY.NMSB scale is simple and reflects the degree of patient involvement more accurately than the H&Y. Patients with a lower H&Y stage may be more affected if they have a greater NMS burden., Competing Interests: Santos García D has received honoraria for educational presentations and advice service by AbbVie, UCB Pharma, Lundbeck, KRKA, Zambon, Bial, Italfarmaco, and Teva. Paz González JM has received honoraria for educational presentations and/or advice service by UCB Pharma, Lundbeck, KRKA, and Zambon. Jesús S has received honoraria from AbbVie, Bial, Merz, UCB, and Zambon and holds the competitive contract “Juan Rodés” supported by the Instituto de Salud Carlos III. She has received grants from the Spanish Ministry of Economy and Competitiveness (PI18/01898) and the Consejería de Salud de la Junta de Andalucía (PI-0459-2018). Aguilar M obtained from UCB and Schwabe with assistance to a Congress and Nutricia with assistance to a Congress and payment of lecture. Planellas LL has received travel bursaries grant from AbbVie. García Caldentey J has received honoraria for educational presentations and advice service by Qualigen, Nutricia, AbbVie, Italfarmaco, UCB Pharma, Lundbeck, Zambon, Bial and Teva. Caballol N has received honoraria from Bial, Italfarmaco, Qualigen, Zambon, UCB, Teva, and KRKA and sponsorship from Zambon, TEVA, and AbbVie for attending medical conferences. Legarda I has received honoraria for educational presentations and advice service by AbbVie, UCB Pharma, Zambon, Bial, and Teva. Hernández Vara J has received travel bursaries and educational grants from AbbVie and has received honoraria for educational presentations from AbbVie, Teva, Bial, Zambon, Italfarmaco, and Sanofi-Genzyme. Cabo I has received honoraria for educational presentations and advice service by AbbVie, Zambon, and Bial. López Manzanares L compensated advisory services, consulting, research grant support, or speaker honoraria from AbbVie, Acorda, Bial, Intec Pharma, Italfarmaco, Pfizer, Roche, Teva, UCB, and Zambon. Ávila Rivera MA has received honoraria from Zambon, UCB Pharma, Qualigen, Bial, and Teva and ana sponsorship from Zambon and Teva for attending conferences. Puente V has served as consultant for AbbVie and Zambon and has received grant/research from AbbVie. García Moreno JM has received honoraria for educational presentations and advice service by AbbVie, Ital-Pharma, Lundbeck, Merz, KRKA, UCB, Pharma, Zambon, Bial, and Teva. Solano Vila B has received honoraria for educational presentations and advice service by UCB, Zambon, Teva, AbbVie, Bial. Álvarez Sauco M has received honoraria for educational presentations and advice service by AbbVie, UCB Pharma, Zambon, Bial, and Teva. Vela L has received honoraria for educational presentations and advice service by AbbVie, UCB Pharma, Lundbeck, KRKA, Zambon, Bial, and Teva. Escalante S has received honoraria for educational presentations and advice service by AbbVie, Zambon, and Bial. Cubo E has travel grants from AbbVie, Allergan, and Boston; lecturing honoraria from AbbVie and International Parkinson's Disease Movement Disorder Society. Carrillo Padilla F has received honoraria from Zambon (SEN Congress assistance). Martínez Castrillo JC has received research support from Lundbeck, Italfarmaco, Allergan, Zambon, Merz, and AbbVie and speaking honoraria from AbbVie, Bial, Italfarmaco, Lundbeck, Krka, TEVA, UCB, Zambon, Allergan, Ipsen, and Merz. Sánchez Alonso P has received honoraria for educational presentations and advice service by AbbVie, UCB Pharma, Lundbeck, KRKA, Zambon, Bial, and Teva. Alonso Losada MG has received honoraria for educational presentations and advice service by Zambon and Bial. López Ariztegui N has received honoraria for educational presentations and advice service by AbbVie, Italfarmaco, Zambon, and Bial. Gastón I has received research support from AbbVie and Zambon and has served as a consultant for AbbVie, Exelts, and Zambon. Kulisevsky J has obtained the following: (1) consulting fees: Roche and Zambon; (2) honoraria (e.g., lecture fees): Zambon, Teva, Bial, and UCB; (3) research funding: Roche, Zambon, Ciberned, Instituto de SaludCarlos III, and Fundació La Marató De TV3. Blázquez Estrada M has received honoraria for educational presentations and advice service by AbbVie, Abbott, UCB Pharma, Allergan, Zambon, Bial, and Qualigen. Seijo M has received honoraria for educational services from KRKA, UCB, Zambon, and Bial and travel grants from Daiichi and Roche. Ruiz Martínez J has received honoraria for educational presentations, attending medical conferences, and advice service by AbbVie, UCB Pharma, Zambon, Italfarmaco, Bial, and Teva. Valero C has received honoraria for educational services from Zambon AbbVie and UCB. Kurtis M has received honoraria from Bial, the Spanish Neurology Society, and the International and Movement Disorders Society. de Fábregues O has received honoraria for educational presentations and advice service by Bial, Zambon, AbbVie, KRKA, and Teva. González Ardura J has received honoraria for speaking from Italfarmaco, Krka, Genzyme, UCB, Esteve, Psyma iberica marketing research SL and Ferrer, course grant from Teva, and travel grant from Merck. López Díaz L has received honoraria from UCB, Lundbeck, and KRKA. Mir P has received honoraria from AbbVie, Abbott, Allergan, Bial, Merz, UCB, and Zambon and has received grants from the Spanish Ministry of Economy and Competitiveness (PI16/01575) cofounded by ISCIII (Subdirección General de Evaluación y Fomento de la Investigación) and by Fondo Europeo de Desarrollo Regional (FEDER), the Consejería de Economía, Innovación, Ciencia y Empleo de la Junta de Andalucía (CVI-02526, CTS-7685), the Consejería de Salud y Bienestar Social de la Junta de Andalucía (PI-0437-2012, PI-0471-2013), the Sociedad Andaluza de Neurología, the Jacques and Gloria Gossweiler Foundation, the Fundación Alicia Koplowitz, and the Fundación Mutua Madrileña. Martínez-Martin P has received honoraria from Editorial Viguera for lecturing in courses, International Parkinson and Movement Disorder Society (IPMDS) for management of the Program on Rating Scales, Air Liquide, AbbVie, and HM Hospitales de Madrid for advice in clinic-epidemiological studies; license fee payments for the King's Parkinson's Disease Pain scale; financial support by the IPMDS for attending the IPMDS International Congress 2018; and grant for research from IPMDS for development and validation of the MDS-NMS. Borrué C, Ordás C, Catalán MJ, Nogueira V, González Aramburu I, Cosgaya M, Pastor P, De Deus T, Cores Bartolomé C, Valdés Aymerich L, Muñoz Enríquez JG, and Suárez declare that they have no conflicts of interest., (Copyright © 2021 D. Santos García et al.)

Background: Many evidences suggest a pathological link between neurodegenerative diseases and cancer. In fact, several epidemiologic studies indicate a decreased incidence of most cancer types in Parkinson's disease (PD) patients and some PD genes are involved in cancer networks., Objective: The aim of this study is to assess the influence of several factors in the risk of cancer in a cohort of 753 PD patients and to study how these variables interact with each other., Methods: We analyzed the effect of gender, tobacco, alcohol, type of PD (genetic or idiopathic PD), and two genetic variants, previously associated with cancer, rs5848-GRN and rs1042522-TP53., Results: A higher age at PD onset was observed in patients who develop cancer before PD (p < 0.001). Alcohol consumption was a risk factor to develop cancer in PD patients (p = 0.011), while smoking was not a cancer risk factor in our cohort (p = 0.098). Among the genetic factors, the genotype TT GRN-rs5848 was statistically more frequent in PD patients without cancer (p = 0.05)., Conclusions: Our study identified several factors, genetic and nongenetic, which contribute to the risk for cancer in PD., (© 2021 S. Karger AG, Basel.)

The purpose of this study was to determine the acute toxicity in aquatic organisms of one biocidal active substance and six metabolites derived from biocidal active substances and to assess the suitability of available QSAR models to predict the obtained values. We have reported the acute toxicity in sewage treatment plant (STP) microorganisms, in the freshwater microalgae Pseudokirchneriella subcapitata and in Daphnia magna following OECD test methods. We have also identified in silico models for acute toxicity of these trophic levels currently available in widely recognized platforms such as VEGA and the OECD QSAR ToolBox. A total of six, four and two models have been selected for Daphnia, algae and microorganisms, respectively. Finally, we have compared the in silico and in vivo data for the seven compounds plus two previously assayed biocidal substances. None of the compounds tested were toxic for Daphnia and STP microorganisms. For microalgae, CGA71019 (1,2,4 triazole) presented an ErC 50 value of 38.3 mg/L. The selected in silico models have provided lower EC 50 values and are therefore more conservative. Models from the OECD QSAR ToolBox predicted values for 7 out of 9 and for 4 out of 9 chemicals for Daphnia and P. subcapitata, respectively. No predictive models were identified in such platform for STP microorganism's acute effects. In terms of models's specificity, biocide-specific models, developed from curated datasets integrated by biocidal active substances and implemented in VEGA, perform better in the case of microalgae but for Daphnia an alternative, non biocide-specific has revealed a better performance. For STP microorganisms only biocide-specific models have been identified., (Copyright © 2020 Elsevier Inc. All rights reserved.)