Essentials
Risk stratification for venous thromboembolism (VTE) in patients with brain tumors is challenging.
Patients with IDH1 wildtype and high podoplanin expression have a 6‐month VTE risk of ...18.2%.
Patients with IDH1 mutation and no podoplanin expression have a 6‐month VTE risk of 0%.
IDH1 mutation and podoplanin overexpression in primary brain tumors appear to be exclusive.
Summary
Background
Venous thromboembolism (VTE) is a frequent complication in primary brain tumor patients. Independent studies revealed that podoplanin expression in brain tumors is associated with increased VTE risk, whereas the isocitrate dehydrogenase 1 (IDH1) mutation is associated with very low VTE risk.
Objectives
To investigate the interrelation between intratumoral podoplanin expression and IDH1 mutation, and their mutual impact on VTE development.
Patients/Methods
In a prospective cohort study, intratumoral IDH1 R132H mutation and podoplanin were determined in brain tumor specimens (mainly glioma) by immunohistochemistry. The primary endpoint of the study was symptomatic VTE during a 2‐year follow‐up.
Results
All brain tumors that expressed podoplanin to a medium‐high extent showed also an IDH1 wild‐type status. A score based on IDH1 status and podoplanin expression levels allowed prediction of the risk of VTE. Patients with wild‐type IDH1 brain tumors and high podoplanin expression had a significantly increased VTE risk compared with those with mutant IDH1 tumors and no podoplanin expression (6‐month risk 18.2% vs. 0%).
Conclusions
IDH1 mutation and podoplanin overexpression seem to be exclusive. Although brain tumor patients with IDH1 mutation are at very low risk of VTE, the risk of VTE in patients with IDH1 wild‐type tumors is strongly linked to podoplanin expression levels.
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FZAB, GEOZS, GIS, IJS, IMTLJ, IZUM, KILJ, KISLJ, NLZOH, NUK, OILJ, PILJ, PNG, SAZU, SBCE, SBJE, SBMB, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
Allochthonous plant species are considered among the main environmental issues worldwide, being especially accused in the Mediterranean basin. The present study aims to update Balearic Alien Flora ...and discuss its time and spatial variation and invasiveness. Information regarding allochthonous plant records of the Balearic Islands were gathered and analysed based on published checklists and online databases. For each species several general traits were assigned based on previous references to characterise the alien Balearic Flora. Records of allochthonous species between 1827 and 2023 indicate that Alien Balearic Flora is composed of 624 taxa recorded unevenly among islands, with lower records in smaller islands. Alien flora is mainly composed of therophytes and phanerophytes being held mainly in human related habitats. Introduction pathway is mainly ornamental, with over 50% of taxa entering through gardening and horticultural practices. Main biogeographical origins are American, Mediterranean, Euroasiatic and Cape origins. Invasive status of Balearic alien flora shows that 44% of all taxa can be regarded as casual, while 35% are naturalised, and 17% can be considered invasive, being the latter increased in smaller islands. Time variations trends starting mainly in the 70 s and predictive models show that alien species increase exponentially, being the most represented taxa from synanthropic habitats, introduced as ornamentals, lianas, phanerophytes and therophytes from
Cactaceae
,
Asteraceae
and
Leguminosae
families. The results of the present study can serve as a model to facilitate the scientifically informed decision making and management of plant invasions both in the Balearic Islands and other continental insular systems and Mediterranean regions.
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EMUNI, FIS, FZAB, GEOZS, GIS, IJS, IMTLJ, KILJ, KISLJ, MFDPS, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, SBMB, SBNM, UKNU, UL, UM, UPUK, VKSCE, ZAGLJ
An autosomal dominantly inherited defect in the GCH1 gene that encodes guanosine triphosphate cyclohydrolase 1 (GTPCH1) is the most common cause of dopa-responsive dystonia (DRD). A classic phenotype ...of young-onset lower-limb dystonia, diurnal fluctuations and excellent response to levodopa has been well recognised in association with GCH1 mutations, and rare atypical presentations have been reported. However, a number of clinical issues remain unresolved including phenotypic variability, long-term response to levodopa and associated non-motor symptoms, and there are limited data on long-term follow-up of genetically proven cases.
A detailed clinical evaluation of 34 patients (19 women, 15 men), with confirmed mutations in the GCH1 gene, is presented.
The classic phenotype was most frequent (n = 23), with female predominance (F:M = 16:7), and early onset (mean 4.5 years) with involvement of legs. However, a surprisingly large number of patients developed craniocervical dystonia, with spasmodic dysphonia being the predominant symptom in two subjects. A subset of patients, mainly men, presented with either a young-onset (mean 6.8 years) mild DRD variant not requiring treatment (n = 4), or with an adult-onset (mean 37 years) Parkinson disease-like phenotype (n = 4). Two siblings were severely affected with early hypotonia and delay in motor development, associated with compound heterozygous GCH1 gene mutations. The study also describes a number of supplementary features including restless-legs-like symptoms, influence of female sex hormones, predominance of tremor or parkinsonism in adult-onset cases, initial reverse reaction to levodopa, recurrent episodes of depressive disorder and specific levodopa-resistant symptoms (writer's cramp, dysphonia, truncal dystonia). Levodopa was used effectively and safely in 20 pregnancies, and did not cause any fetal abnormalities.
Nonmotor symptoms (NMS) have a great impact on patients with Parkinson disease (PD). The Non-Motor Symptoms Scale (NMSS) is an instrument specifically designed for the comprehensive assessment of NMS ...in patients with PD. NMSS psychometric properties have been tested in this study.
Data were collected in 12 centers across 10 countries in America, Asia, and Europe. In addition to the NMSS, the following measures were applied: Scales for Outcomes in Parkinson's Disease (SCOPA)-Motor, SCOPA-Psychiatric Complications (SCOPA-PC), SCOPA-Cognition, Hoehn and Yahr Staging (HY), Clinical Impression of Severity Index for Parkinson's Disease (CISI-PD), SCOPA-Autonomic, Parkinson's Disease Sleep Scale (PDSS), Parkinson's Disease Questionnaire-39 items (PDQ-39), and EuroQol-5 dimensions (EQ-5D). NMSS acceptability, reliability, validity, and precision were analyzed.
Four hundred eleven patients with PD, 61.3% men, were recruited. The mean age was 64.5 +/- 9.9 years, and mean disease duration was 8.1 +/- 5.7 years. The NMSS score was 57.1 +/- 44.0 points. The scale was free of floor or ceiling effects. For domains, the Cronbach alpha coefficient ranged from 0.44 to 0.85. The intraclass correlation coefficient (0.90 for the total score, 0.67-0.91 for domains) and Lin concordance coefficient (0.88) suggested satisfactory reproducibility. The NMSS total score correlated significantly with SCOPA-Autonomic, PDQ-39, and EQ-5D (r(S) = 0.57-0.70). Association was close between NMSS domains and the corresponding SCOPA-Autonomic domains (r(S) = 0.51-0.65) and also with scales measuring related constructs (PDSS, SCOPA-PC) (all p < 0.0001). The NMSS total score was higher for women (p < 0.02) and for increasing disease duration, HY, and CISI-PD severity level (p < 0.001). The SEM was 13.91 for total score and 1.71 to 4.73 for domains.
The Non-Motor Symptoms Scale is an acceptable, reproducible, valid, and precise assessment instrument for nonmotor symptoms in Parkinson disease.
The neural mechanisms and the circuitry involved in levodopa-induced dyskinesia (LID) are still partially obscure. LID can be considered the consequence of an abnormal pattern or code of activity ...that originates and is conveyed from the basal ganglia to the thalamus and the cortical motor areas. However, not only striatothalamocortical motor circuits but also other interconnected pathways could be implicated in its pathogenesis.
In a series of experiments, we applied repetitive transcranial magnetic stimulation (rTMS) over the lateral cerebellum in a group of patients with advanced Parkinson disease, to investigate whether modulation of cerebellothalamocortical circuits by means of rTMS may result in a modification of a dyskinetic state induced by levodopa ingestion.
We found that a single session of cerebellar continuous theta burst stimulation (cTBS) was capable of transiently reducing LID. In the same patients, we observed that cerebellar cTBS changed the profile of activation of intracortical circuits in the contralateral primary motor cortex. Cerebellar cTBS reduced short intracortical inhibition and increased long intracortical inhibition, inducing a cortical reorganization that is associated with a reduction of LID. Furthermore, in another experiment, we observed that a 2-week course of bilateral cerebellar cTBS induced persistent clinical beneficial effects, reducing peak-dose LID for up to 4 weeks after the end of the daily stimulation period.
Our study demonstrates that cerebellar continuous theta burst stimulation has an antidyskinetic effect in Parkinson disease patients with levodopa-induced dyskinesia, possibly due to modulation of cerebellothalamocortical pathways.
Human disturbance and seawater intrusion have unpredictable effects on coastal species. Dune systems are crucial coastal habitats because they provide natural front protection against seawater ...influence. Adult plant stands in dunes are important since they maintain dune structure. This study evaluated salinity stress responses in adult plants of two key dune-building grasses differing in salt tolerance:
Thinopyrum junceum
(tolerant) and
Calamagrostis arenaria
(less tolerant). Cultivated plants were exposed to various seawater (SW) dilutions (Tap-Water, 6.25%, 12.5%, 25%, 50%, and 100%) and gas exchange measurements and oxidative stress biomarkers were determined after two months of treatment. Stress conditions were maintained until flowering to assess effects on the reproductive effort. The reproductive response showed high plasticity at various inflorescence stages in
T. junceum
, minimizing abortion processes.
C. arenaria
showed lower plasticity and higher abortion rates. Physiological traits responded similarly to salinity in both species, with greater effect on
F
v
/
F
m
decrease and non-photochemical quenching increase for
T. junceum
. Biochemical patterns of response were also similar, with increasing enzymatic activities at 25% SW treatment, mainly for glutathione reductase and peroxidase (GSH and GPx), and stress damage occurring at 50% and 100% SW treatments for increased malonaldehyde (MDA) levels. These findings provide insight into the salinity tolerance mechanisms of dune-building grasses. Higher salinity tolerance is suggested for
T. junceum
based on better reproductive effort. Higher juvenile tolerance, faster growth, and plant cycle adjustments are indicated as key traits for higher salinity tolerance of
T. junceum
in contrast to
C. arenaria
.
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EMUNI, FIS, FZAB, GEOZS, GIS, IJS, IMTLJ, KILJ, KISLJ, MFDPS, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, SBMB, SBNM, UKNU, UL, UM, UPUK, VKSCE, ZAGLJ
Background and purpose
The objective of this study was to analyze the relationship between motor complications and non‐motor symptom (NMS) burden in a population of patients with Parkinson’s disease ...(PD) and also in a subgroup of patients with early PD.
Methods
Patients with PD from the COPPADIS cohort were included in this cross‐sectional study. NMS burden was defined according to the Non‐Motor Symptoms Scale (NMSS) total score. Unified Parkinson’s Disease Rating Scale (UPDRS) part IV was used to establish motor complication types and their severity. Patients with ≤5 years of symptoms from onset were included as patients with early PD.
Results
Of 690 patients with PD (62.6 ± 8.9 years old, 60.1% males), 33.9% and 18.1% presented motor fluctuations and dyskinesia, respectively. The NMS total score was higher in patients with motor fluctuations (59.2 ± 43.1 vs. 38.3 ± 33.1; P < 0.0001) and dyskinesia (63.5 ± 40.7 vs. 41.4 ± 36.3; P < 0.0001). In a multiple linear regression model and after adjustment for age, sex, disease duration, Hoehn & Yahr stage, UPDRS‐III score and levodopa equivalent daily dose, UPDRS‐IV score was significantly related to a higher NMSS total score (β = 0.27; 95% confidence intervals, 2.81–5.61; P < 0.0001), as it was in a logistic regression model on dichotomous NMSS total score (≤40, mild or moderate vs. >40, severe or very severe) (odds ratio, 1.31; 95% confidence intervals, 1.17–1.47; P < 0.0001). In the subgroup of patients with early PD (n = 396; mean disease duration 2.7 ± 1.5 years), motor fluctuations were frequent (18.1%) and similar results were obtained.
Conclusions
Motor complications were frequent and were associated with a greater NMS burden in patients with PD even during the first 5 years of disease duration.
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BFBNIB, FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SBCE, SBMB, UL, UM, UPUK
Purpose
The study’s objective was to develop diagnostic predictive models using data from two commonly used
123
IFP-CIT SPECT assessment methods: region-of-interest (ROI) analysis and whole-brain ...voxel-based analysis.
Methods
We included retrospectively 80 patients with vascular parkinsonism (VP) and 164 patients with Parkinson’s disease (PD) who underwent
123
IFP-CIT SPECT. Nuclear-medicine specialists evaluated the scans and calculated bilateral caudate and putamen
123
IFP-CIT uptake and asymmetry indices using BRASS software. Statistical parametric mapping (SPM) was used to compare the radioligand uptake between the two diseases at the voxel level. Quantitative data from these two methods, together with potential confounding factors for dopamine transporter availability (sex, age, disease duration and severity), were used to build predictive models following a tenfold cross-validation scheme. The performance of logistic regression (LR), linear discriminant analysis and support vector machine (SVM) algorithms for ROI data, and their penalized versions for SPM data (penalized LR, penalized discriminant analysis and SVM), were assessed.
Results
Significant differences were found in the ROI analysis after covariate correction between VP and PD patients in
123
IFP-CIT uptake in the more affected side of the putamen and the ipsilateral caudate. Age, disease duration and severity were also found to be informative in feeding the statistical model. SPM localized significant reductions in
123
IFP-CIT uptake in PD with respect to VP in two specular clusters comprising areas corresponding to the left and right striatum. The diagnostic predictive accuracy of the LR model using ROI data was 90.3 % and of the SVM model using SPM data was 90.4 %.
Conclusion
The predictive models built with ROI data and SPM data from
123
IFP-CIT SPECT provide great discrimination accuracy between VP and PD. External validation of these methods is necessary to confirm their applicability across centres.
Full text
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DOBA, EMUNI, FIS, FZAB, GEOZS, GIS, IJS, IMTLJ, IZUM, KILJ, KISLJ, MFDPS, NLZOH, NUK, OILJ, PILJ, PNG, SAZU, SBCE, SBJE, SBMB, SBNM, SIK, UILJ, UKNU, UL, UM, UPUK, VKSCE, VSZLJ, ZAGLJ
•Depression is associated with impulse-compulsive behaviors in Parkinson’s disease.•Pathological gambling, eating behavior, and hobbyism-punding were related to depression.•Quality of life is worse ...in patients who have impulse-compulsive behaviors to add to depression.
Depression and impulse control disorders (ICDs) are both common in Parkinson’s disease (PD) patients and their coexistence is frequent. Our aim was to determine the relationship between depression and impulsive-compulsive behaviors (ICBs) in a large cohort of PD patients.
PD patients recruited from 35 centers of Spain from the COPPADIS cohort from January 2016 to November 2017 were included in the study. The QUIP-RS (Questionnaire for Impulsive-Compulsive Disorders in Parkinson's Disease-Rating Scale) was used for screening ICDs (cutoff points: gambling ≥6, buying ≥8, sex≥8, eating≥7) and compulsive behaviors (CBs) (cutoff points: hobbyism-punding ≥7). Mood was assessed with the BDI-II (Beck Depression Inventory – II) and major, minor, and subthreshold depression were defined.
Depression was more frequent in PD patients with ICBs than in those without: 66.3% (69/104) vs 47.5% (242/509); p<0.0001. Major depression was more frequent in this group as well: 22.1% 23/104 vs 14.5% 74/509; p=0.041. Considering types of ICBs individually, depression was more frequent in patients with pathological gambling (88.9% 8/9 vs 50.2% 303/603; p=0.021), compulsive eating behavior (65.9% 27/41 vs 49.7% 284/572; p=0.032), and hobbyism-punding (69% 29/42 vs 49.4% 282/571; p=0.010) than in those without, respectively. The presence of ICBs was also associated with depression (OR=1.831; 95%CI 1.048-3.201; p=0.034) after adjusting for age, sex, civil status, disease duration, equivalent daily levodopa dose, antidepressant treatment, Hoehn&Yahr stage, non-motor symptoms burden, autonomy for activities of daily living, and global perception of QoL.
Cross-sectional design.
Depression is associated with ICBs in PD. Specifically, with pathological gambling, compulsive eating behavior, and hobbyism-punding.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
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