Biomedicine represents one of the main study areas for dendrimers, which have proven to be valuable both in diagnostics and therapy, due to their capacity for improving solubility, absorption, ...bioavailability and targeted distribution. Molecular cytotoxicity constitutes a limiting characteristic, especially for cationic and higher-generation dendrimers. Antineoplastic research of dendrimers has been widely developed, and several types of poly(amidoamine) and poly(propylene imine) dendrimer complexes with doxorubicin, paclitaxel, imatinib, sunitinib, cisplatin, melphalan and methotrexate have shown an improvement in comparison with the drug molecule alone. The anti-inflammatory therapy focused on dendrimer complexes of ibuprofen, indomethacin, piroxicam, ketoprofen and diflunisal. In the context of the development of antibiotic-resistant bacterial strains, dendrimer complexes of fluoroquinolones, macrolides, beta-lactamines and aminoglycosides have shown promising effects. Regarding antiviral therapy, studies have been performed to develop dendrimer conjugates with tenofovir, maraviroc, zidovudine, oseltamivir and acyclovir, among others. Furthermore, cardiovascular therapy has strongly addressed dendrimers. Employed in imaging diagnostics, dendrimers reduce the dosage required to obtain images, thus improving the efficiency of radioisotopes. Dendrimers are macromolecular structures with multiple advantages that can suffer modifications depending on the chemical nature of the drug that has to be transported. The results obtained so far encourage the pursuit of new studies.
Summary
Restless legs syndrome (RLS) is a sensorimotor neurological disorder characterised by an urge to move the limbs with a circadian pattern (occurring in the evening/at night), more prominent at ...rest, and relieved with movements. RLS is one of the most prevalent sleep disorders, occurring in 5%–10% of the European population. Thomas Willis first described RLS clinical cases already in the 17th century, and Karl‐Axel Ekbom described the disease as a modern clinical entity in the 20th century. Despite variable severity, RLS can markedly affect sleep (partly through the presence of periodic leg movements) and quality of life, with a relevant socio‐economic impact. Thus, its recognition and treatment are essential. However, screening methods present limitations and should be improved. Moreover, available RLS treatment options albeit providing sustained relief to many patients are limited in number. Additionally, the development of augmentation with dopamine agonists represents a major treatment problem. A better understanding of RLS pathomechanisms can bring to light novel treatment possibilities. With emerging new avenues of research in pharmacology, imaging, genetics, and animal models of RLS, this is an interesting and constantly growing field of research. This review will update the reader on the current state of RLS clinical practice and research, with a special focus on the contribution of European researchers.
Objectives
Sleep‐wake disorders are common in the general population and in most neurological disorders but are often poorly recognized. With the hypothesis that neurologists do not get sufficient ...training during their residency, the Young European Sleep Neurologist Association (YESNA) of the European Academy of Neurology (EAN) performed a survey on postgraduate sleep education.
Methods
A 16‐item questionnaire was developed and distributed among neurologists and residents across European countries. Questions assessed demographic, training and learning preferences in sleep disorders, as well as a self‐evaluation of knowledge based on five basic multiple‐choice questions (MCQs) on sleep‐wake disorders.
Results
The questionnaire was completed by 568 participants from 20 European countries. The mean age of participants was 31.9 years (SD 7.4 years) and was composed mostly of residents (73%). Three‐quarters of the participants reported undergraduate training in sleep medicine, while fewer than 60% did not receive any training on sleep disorders during their residencies. Almost half of the participants (45%) did not feel prepared to treat neurological patients with sleep problems. Only one‐third of the participants correctly answered at least three MCQs. Notably, 80% of participants favoured more education on sleep‐wake disorders during the neurology residency.
Conclusions
Education and knowledge on disorders in European neurological residents is generally insufficient, despite a strong interest in the topic. The results of our study may be useful for improving the European neurology curriculum and other postgraduate educational programmes.
Sleep‐wake disorders are common in the general population and in most neurological disorders but often poorly recognised. Education and knowledge on sleep‐wake disorders in European neurological residents is generally insufficient, despite a strong interest in the topic. Our study results may be useful to improve the European Neurology curriculum and other postgraduate educational programs.
Objectives
Rapid eye movement (REM) sleep behavior disorder (RBD) is proposed as an early diagnostic marker in Parkinson's disease (PD). We investigated the frequency of RBD during the progression of ...PD in the advanced stages and identified potential risk factors for developing RBD earlier or later.
Patients and Methods
We performed a retrospective analysis and determined the frequency of RBD in all PD in‐patients (Hoehn and Yahr stages ≥3) with motor fluctuations who had undergone video‐polysomnography (vPSG) for a sleep complaint or daytime sleepiness. To correct for selection bias, we analyzed the prevalence of RBD in PD patients from the DeNoPa cohort. PD patients with RBD were compared with PD without RBD. To identify potential risk factors, we performed multiple regression modeling.
Results
A total of 504 PD patients had vPSG. 37 were excluded due to missing REM or artifacts during REM. RBD was present in 406/467 (86.9%) PD patients. PD + RBD patients were older than PDnonRBD (69 ± 7.7 vs. 64 ± 9.2 years, P < 0.01), were more likely to have postural instability 234 (59.1%) vs. 19 (33.9%), P < 0.01, and were treated more often with antidepressants (other than SSRIs) 141 (34.7%) vs. 7 (13%), P < 0.01. Multiple regression modeling identified predictors of RBD with an AUC of 0.78.
Conclusion
The prevalence of RBD in patients with advanced PD is high and increases with disease severity, motor deficits, postural instability, orthostatic symptoms, and age. This suggests RBD is a progression marker of PD in patients with sleep complaints.
Background
Rapid eye movement (REM) sleep behavior disorder (RBD) is associated with neurodegenerative diseases; however, few longitudinal studies assess the individual evolution of RBD and REM sleep ...without atonia (RWA) in Parkinson's disease (PD).
Objectives
We aimed to evaluate RBD and RWA changes over time as well as potentially influential factors.
Methods
RBD and RWA were analyzed using video‐supported polysomnography (vPSG) in initially de novo PD patients at baseline and every 2 years for a total of 6 years. The influence of time, age, sex, levodopa equivalent daily dose (LEDD), unified Parkinson's disease rating scale (UPDRS) sum scores, benzodiazepine intake, Mini‐Mental State Examination (MMSE) total scores, and dyskinesia on RWA were investigated using mixed‐effect models to account for intra‐individual correlations.
Results
After 6 years, vPSG data were available from 98 of the initial 159 de novo PD patients. RBD prevalence increased from 25% at baseline to 52%. Of the 31 PD patients with RBD and valid vPSGs at all time‐points, RWA increased from an average of 19% at baseline to 41% at 6‐year follow‐up modeled to grow by 29.7% every 2 years (P < 0.001). Time was an independent factor (P < 0.001) for RWA increase. Age was an independent factor influencing RWA increase (P = 0.04). Sex, LEDD, UPDRS sum scores, benzodiazepines, MMSE total scores, and dyskinesia did not have any significant influence.
Conclusions
RBD and RWA increased significantly over time in PD; time and age were independent factors in a prospective cohort. RBD and RWA can be considered PD progression markers.
Restless legs syndrome during pregnancy: an overview Muntean, Maria-Lucia; Trenkwalder, Claudia; Bartl, Michael
Somnologie : Schlafforschung und Schlafmedizin = Somnology : sleep research and sleep medicine,
12/2021, Letnik:
25, Številka:
4
Journal Article
Recenzirano
Restless legs syndrome (RLS) is a frequent neurological disorder that is twice as common in women as in men. RLS affects up to 20% of pregnant women, particularly in the third trimester. In most ...cases, symptoms disappear after delivery, but the risk of developing RLS after pregnancy and during future pregnancies is increased in these women. The diagnosis of RLS during pregnancy is made using the essential criteria of the International Restless Legs Study Group (IRLSSG). The differential diagnosis and exclusion of mimics such as venous stasis, legs cramps, and leg edema are important. Aggravating factors (anemia, sleep apnea, medications that aggravate RLS) should be eliminated before initiation of a specific treatment. Nonpharmacological treatments such as moderate exercise and yoga should be considered first. Pharmacological treatment including iron supplementation, levodopa/carbidopa, clonazepam, and oxycodone can be applied during the course after critical assessment of the indication.
Several automated methods for scoring periodic limb movements during sleep (PLMS) and rapid eye movement (REM) sleep without atonia (RSWA) have been proposed, but most of them were developed and ...validated on data recorded in the same clinic, thus they may be biased. This work aims to validate our data‐driven algorithm for muscular activity detection during sleep, originally developed based on data recorded and manually scored at the Danish Center for Sleep Medicine. The validation was carried out on a cohort of 240 participants, including de novo Parkinson's disease (PD) patients and neurologically healthy controls, whose sleep data were recorded and manually evaluated at Paracelsus‐Elena Klinik, Kassel, Germany. In the German cohort, the algorithm showed generally good agreement between manual and automated PLMS indices, and identified with 88.75% accuracy participants with PLMS index above 15 PLMS per hour of sleep, and with 84.17% accuracy patients suffering from REM sleep behaviour disorder (RBD) showing RSWA. By comparing the algorithm performances in the Danish and German cohorts, we hypothesized that inter‐clinical differences may exist in the way limb movements are manually scored and how healthy controls are defined. Finally, the algorithm performed worse in PD patients, probably as a result of increased artefacts caused by abnormal motor events related to neurodegeneration. Our algorithm can identify, with reasonable performance, participants with RBD and increased PLMS index from data recorded in different centres, and its application may reveal inter clinical differences, which can be overcome in the future by applying automated methods.
The advent of Surface-Enhanced Raman Scattering (SERS) has enabled the exploration and detection of small molecules, particularly in biological fluids such as serum, blood plasma, urine, saliva, and ...tears. SERS has been proposed as a simple diagnostic technique for various diseases, including cancer. Renal cell carcinoma (RCC) ranks as the sixth most commonly diagnosed cancer in men and is often asymptomatic, with detection occurring incidentally. The onset of symptoms typically aligns with advanced disease, aggressive histology, and unfavorable prognosis, and therefore new methods for an early diagnosis are needed. In this study, we investigated the utility of label-free SERS in urine, coupled with two multivariate analysis approaches: Principal Component Analysis combined with Linear Discriminant Analysis (PCA-LDA) and Support Vector Machine (SVM), to discriminate between 50 RCC patients and 44 healthy donors. Employing LDA-PCA, we achieved a discrimination accuracy of 100% using 13 principal components, and an 88% accuracy in discriminating between different RCC stages. The SVM approach yielded a training accuracy of 100%, a validation accuracy of 99% for discriminating between RCC and controls, and an 80% accuracy for discriminating between stages. The comparative analysis of raw and normalized SERS spectral data shows that while raw data disclose relative concentration variations in urine metabolites between the two classes, the normalization of spectral data significantly improves the accuracy of discrimination. Moreover, the selection of principal components with markedly distinct scores between the two classes serves to alleviate overfitting risks and reduces the number of components employed for discrimination. We obtained the accuracy of the discrimination between the RCC patients cases and healthy donors of 90% for three PCs and a linear discrimination function, and a 88% accuracy of discrimination between stages using six PCs, mitigating practically the risk of overfitting and increasing the robustness of our analysis. Our findings underscore the potential of label-free SERS of urine in conjunction with chemometrics for non-invasive and early RCC detection.
To investigate electroencephalographic (EEG), electrooculographic (EOG) and micro-sleep abnormalities associated with rapid eye movement (REM) sleep behavior disorder (RBD) and REM behavioral events ...(RBEs) in Parkinson's disease (PD).
We developed an automated system using only EEG and EOG signals. First, automatic macro- (30-s epochs) and micro-sleep (5-s mini-epochs) staging was performed. Features describing micro-sleep structure, EEG spectral content, EEG coherence, EEG complexity, and EOG energy were derived. All features were input to an ensemble of random forests, giving as outputs the probabilities of having RBD or not (P (RBD) and P (nonRBD), respectively). A patient was classified as having RBD if P (RBD)≥P (nonRBD). The system was applied to 107 de novo PD patients: 54 had normal REM sleep (PDnonRBD), 26 had RBD (PD + RBD), and 27 had at least two RBEs without meeting electromyographic RBD cut-off (PD + RBE). Sleep diagnoses were made with video-polysomnography (v-PSG).
Considering PDnonRBD and PD + RBD patients only, the system identified RBD with accuracy, sensitivity, and specificity over 80%. Among the features, micro-sleep instability had the highest importance for RBD identification. Considering PD + RBE patients, the ones who developed definite RBD after two years had significantly higher values of P (RBD) at baseline compared to the ones who did not. The former were distinguished from the latter with sensitivity and specificity over 75%.
Our method identifies RBD in PD patients using only EEG and EOG signals. Micro-sleep instability could be a biomarker for RBD and for proximity of conversion from RBEs, as prodromal RBD, to definite RBD in PD patients.
•RBD in PD patients is associated to micro-sleep abnormalities.•PD patients with RBD may have more severe neurodegeneration.•RBEs are confirmed as a prodromal stage to RBD in PD patients.•Micro-sleep instability could predict transition from RBEs to definite RBD.
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