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Presence of psychiatric comorbidities is well documented in narcolepsy type-1 (NT1) but there are limited data on patients with 'other central disorders of hypersomnolence' (OCH). This study aimed to investigate frequency of psychiatric comorbidities in patients with NT1 and OCH, and to evaluate their impact on quality of life and sleep as an additive factor in combination with hypersomnolence-related symptoms. This study was conducted within the scope of the international Swiss Primary Hypersomnolence and Narcolepsy Cohort Study (iSPHYNCS), which aims to find new biomarkers in central disorders of hypersomnolence (CDH). Study participants underwent Mini International Neuropsychiatric Interview and completed questionnaires related to quality of life and sleep. Comparative analysis was conducted to investigate group differences, and multivariable regression models were used to reveal the impact of psychiatric comorbidities. Among a total of 90 patients, 26 were diagnosed with NT1 and 64 with OCH. In all, 38 patients showed at least one psychiatric disorder, 27% of NT1 and 48% of OCH, with female dominance (50% in females versus 23% in males, p < 0.02). Major depressive episodes (n = 29) were most common, followed by suicidality (n = 13). Patients with a psychiatric diagnosis were more fatigued (β = 0.70, p < 0.05), apathic (β = -5.41, p < 0.002), had more disturbed sleep (β = 0.55, p < 0.02), worse sleep (β = 1.89, p < 0.001) and general health (β = -12.55, p < 0.02) quality. Comorbid psychiatric disorders are frequent in patients with CDH and worsen the impact of hypersomnolence-related symptoms on daily activities regardless of the type of CDH. Psychiatric comorbidities may create a vicious circle with fatigue and avoidance of physical activities, which aggravates hypersomnolence-related symptoms., (© 2024 The Author(s). Journal of Sleep Research published by John Wiley & Sons Ltd on behalf of European Sleep Research Society.)

The Swiss Primary Hypersomnolence and Narcolepsy Cohort Study (SPHYNCS) is a multicenter research initiative to identify new biomarkers in central disorders of hypersomnolence (CDH). Whereas narcolepsy type 1 (NT1) is well characterized, other CDH disorders lack precise biomarkers. In SPHYNCS, we utilized Fitbit smartwatches to monitor physical activity, heart rate, and sleep parameters over 1 year. We examined the feasibility of long-term ambulatory monitoring using the wearable device. We then explored digital biomarkers differentiating patients with NT1 from healthy controls (HC). A total of 115 participants received a Fitbit smartwatch. Using a adherence metric to evaluate the usability of the wearable device, we found an overall adherence rate of 80% over 1 year. We calculated daily physical activity, heart rate, and sleep parameters from 2 weeks of greatest adherence to compare NT1 (n = 20) and HC (n = 9) participants. Compared to controls, NT1 patients demonstrated findings consistent with increased sleep fragmentation, including significantly greater wake-after-sleep onset (p = .007) and awakening index (p = .025), as well as standard deviation of time in bed (p = .044). Moreover, NT1 patients exhibited a significantly shorter REM latency (p = .019), and sleep latency (p = .001), as well as a lower peak heart rate (p = .008), heart rate standard deviation (p = .039) and high-intensity activity (p = .009) compared to HC. This ongoing study demonstrates the feasibility of long-term monitoring with wearable technology in patients with CDH and potentially identifies a digital biomarker profile for NT1. While further validation is needed in larger datasets, these data suggest that long-term wearable technology may play a future role in diagnosing and managing narcolepsy., (© The Author(s) 2024. Published by Oxford University Press on behalf of Sleep Research Society. All rights reserved. For commercial re-use, please contact reprints@oup.com for reprints and translation rights for reprints. All other permissions can be obtained through our RightsLink service via the Permissions link on the article page on our site—for further information please contact journals.permissions@oup.com.)

Sleep is crucial in rehabilitation processes, promoting neural plasticity and immune functions. Nocturnal body postures can indicate sleep quality and frequent repositioning is required to prevent bedsores for bedridden patients after a stroke or spinal cord injury. Polysomnography (PSG) is considered the gold standard for sleep assessment. Unobtrusive methods for classifying sleep body postures have been presented with similar accuracy to PSG, but most evaluations have been done in research lab environments. To investigate the challenges in the usability of a previously validated device in a clinical setting, we recorded the sleep posture of 17 patients with a sensorized mattress. Ground-truth labels were collected automatically from a PSG device. In addition, we manually labeled the body postures using video data. This allowed us also to evaluate the quality of the PSG labels. We trained neural networks based on the VGG-3 architecture to classify lying postures and used a self-label correction method to account for noisy labels in the training data. The models trained with the video labels achieved a higher classification accuracy than those trained with the PSG labels (0.79 vs. 0.68). The self-label correction could further increase the models' scores based on video and PSG labels to 0.80 and 0.70, respectively. Unobtrusive sensors validated in clinics can, therefore, potentially improve the quality of care for bedridden patients and advance the field of rehabilitation.

AASM guidelines are the result of decades of efforts aiming at standardizing sleep scoring procedure, with the final goal of sharing a worldwide common methodology. The guidelines cover several aspects from the technical/digital specifications, e.g., recommended EEG derivations, to detailed sleep scoring rules accordingly to age. Automated sleep scoring systems have always largely exploited the standards as fundamental guidelines. In this context, deep learning has demonstrated better performance compared to classical machine learning. Our present work shows that a deep learning-based sleep scoring algorithm may not need to fully exploit the clinical knowledge or to strictly adhere to the AASM guidelines. Specifically, we demonstrate that U-Sleep, a state-of-the-art sleep scoring algorithm, can be strong enough to solve the scoring task even using clinically non-recommended or non-conventional derivations, and with no need to exploit information about the chronological age of the subjects. We finally strengthen a well-known finding that using data from multiple data centers always results in a better performing model compared with training on a single cohort. Indeed, we show that this latter statement is still valid even by increasing the size and the heterogeneity of the single data cohort. In all our experiments we used 28528 polysomnography studies from 13 different clinical studies., (© 2023. The Author(s).)

Introduction: Post-COVID-19 syndrome affects approximately 10-25% of people suffering from COVID-19 infection, irrespective of initial COVID-19 severity. Fatigue is one of the major symptoms, occurring in 30-90% of people with post-COVID-19 syndrome. This study aims at describing factors associated with fatigue in people with Post-COVID-19 seen in our newly established Post-Covid clinic., Methods: This retrospective single center study included 42 consecutive patients suffering from Post-COVID-19 syndrome treated at the Department of Neurology, University Hospital Bern, between 11/2020 and05/2021. Clinical phenomenology of Post-COVID-19 syndrome with a special focus on fatigue and risk factor identification was performed using Mann-Whitney U Test, Pearson Correlation, and Chi-Quadrat-Test., Results: Fatigue (90.5%) was the most prevalent Post-COVID-19 symptom followed by depressive mood (52.4%) and sleep disturbance (47.6%). Fatigue was in mean severe (Fatigue severity scale (FSS) mean 5.5 points (95% Confidence interval (95CI) 5.1 - 5.9, range .9 - 6.9, n = 40), and it was unrelated to age, COVID-19 severity or sex. The only related factors with fatigue severity were daytime sleepiness and depressed mood., Conclusion: Fatigue is the main symptom of the Post-COVID-19 syndrome in our cohort. Further studies describing this syndrome are needed to prepare the healthcare systems for the challenge of treating patients with Post-COVID-19 syndrome., Competing Interests: Declaration of conflicting interests: The author(s) declared the following potential conflicts of interest with respect to the research, authorship, and/or publication of this article: Diem L received travel grants from Merck, Biogen, Roche and Bayer Schweiz. She also received speaker’s honoraria from Biogen and Merck. Hammer H received research support and travel grants from Biogen, Merck, Roche & BMS. Friedli C received travel grants from Biogen and Sanofi Genzyme, as well as speaker honoraria from Biogen and Merck, not related to this work. He reports no conflicts of interest related to this manuscript. Kamber N received travel and/or speaker honoraria and served on advisory boards for Alexion, Biogen, Merck, Sanofi Genzyme and Roche and received research support from Biogen. Bigi S received research support from the Swiss MS Society, Novartis, Sanofi Genzyme and Roche, all not related to this work. Bassetti CL received honoraria for consultancy and board memberships from the Rehaklinik Zihlschlacht and research support from the Swiss National Science Foundation (SNF). Chan A received speakers’/board honoraria from Actelion (Janssen/J&J), Almirall, Bayer, Biogen, Celgene (BMS), Genzyme, Merck KGaA (Darmstadt, Germany), Novartis, Roche, and Teva, all for hospital research funds. He received research support from Biogen, Genzyme, and UCB, the European Union, and the Swiss National Foundation. He serves as associate editor of the European Journal of Neurology, on the editorial board for Clinical and Translational Neuroscience and as topic editor for the Journal of International Medical Research. Funke-Chambour M received research grants from Roche and Boehringer Ingelheim, speaker’s fees from Novartis and GSK. She reports no conflicts of interest related to this manuscript. Salmen A received speaker honoraria and/or travel compensation for activities with Almirall Hermal GmbH, Biogen, Merck, Novartis, Roche and Sanofi Genzyme, and research support of Baasch Medicus Foundation and the Swiss MS society, not related to this work. Hoepner R received speaker/advisor honorary from Merck, Novartis, Roche, Biogen, Alexion, Sanofi, Bristol-Myers Squibb, and Almirall. He received research support within the last 5 years from Roche, Merck, Sanofi, Biogen, and Bristol-Myers Squibb. He also received research grants from the Swiss MS Society. All not related to that work., (© The Author(s) 2022.)

Narcolepsy type 1 (NT1) is a disorder with well-established markers and a suspected autoimmune aetiology. Conversely, the narcoleptic borderland (NBL) disorders, including narcolepsy type 2, idiopathic hypersomnia, insufficient sleep syndrome and hypersomnia associated with a psychiatric disorder, lack well-defined markers and remain controversial in terms of aetiology, diagnosis and management. The Swiss Primary Hypersomnolence and Narcolepsy Cohort Study (SPHYNCS) is a comprehensive multicentre cohort study, which will investigate the clinical picture, pathophysiology and long-term course of NT1 and the NBL. The primary aim is to validate new and reappraise well-known markers for the characterization of the NBL, facilitating the diagnostic process. Seven Swiss sleep centres, belonging to the Swiss Narcolepsy Network (SNaNe), joined the study and will prospectively enrol over 500 patients with recent onset of excessive daytime sleepiness (EDS), hypersomnia or a suspected central disorder of hypersomnolence (CDH) during a 3-year recruitment phase. Healthy controls and patients with EDS due to severe sleep-disordered breathing, improving after therapy, will represent two control groups of over 50 patients each. Clinical and electrophysiological (polysomnography, multiple sleep latency test, maintenance of wakefulness test) information, and information on psychomotor vigilance and a sustained attention to response task, actigraphy and wearable devices (long-term monitoring), and responses to questionnaires will be collected at baseline and after 6, 12, 24 and 36 months. Potential disease markers will be searched for in blood, cerebrospinal fluid and stool. Analyses will include quantitative hypocretin measurements, proteomics/peptidomics, and immunological, genetic and microbiota studies. SPHYNCS will increase our understanding of CDH and the relationship between NT1 and the NBL. The identification of new disease markers is expected to lead to better and earlier diagnosis, better prognosis and personalized management of CDH., (© 2021 The Authors. Journal of Sleep Research published by John Wiley & Sons Ltd on behalf of European Sleep Research Society.)

Serum acetate increases upon systemic infection. Acutely, assimilation of acetate expands the capacity of memory CD8 + T cells to produce IFN-γ. Whether acetate modulates memory CD8 + T cell metabolism and function during pathogen re-encounter remains unexplored. Here we show that at sites of infection, high acetate concentrations are being reached, yet memory CD8 + T cells shut down the acetate assimilating enzymes ACSS1 and ACSS2. Acetate, being thus largely excluded from incorporation into cellular metabolic pathways, now had different effects, namely (1) directly activating glutaminase, thereby augmenting glutaminolysis, cellular respiration, and survival, and (2) suppressing TCR-triggered calcium flux, and consequently cell activation and effector cell function. In vivo, high acetate abundance at sites of infection improved pathogen clearance while reducing immunopathology. This indicates that, during different stages of the immune response, the same metabolite-acetate-induces distinct immunometabolic programs within the same cell type., Competing Interests: Declaration of Interests The authors declare no conflicts of interest., (Copyright © 2020 Elsevier Inc. All rights reserved.)

A hallmark of the biology of Plasmodium falciparum blood stage parasites is their extensive host cell remodelling, facilitated by parasite proteins that are exported into the erythrocyte. Although this area has received extensive attention, only a few exported parasite proteins have been analysed in detail, and much of this remodelling process remains unknown, particularly for gametocyte development. Recent advances to induce high rates of sexual commitment enable the production of large numbers of gametocytes. We used this approach to study the Plasmodium helical interspersed subtelomeric (PHIST) protein GEXP02, which is expressed during sexual development. We show by immunofluorescence that GEXP02 is exported to the gametocyte-infected host cell periphery. Co-immunoprecipitation revealed potential interactions between GEXP02 and components of the erythrocyte cytoskeleton as well as other exported parasite proteins. This indicates that GEXP02 targets the erythrocyte cytoskeleton and is likely involved in its remodelling. GEXP02 knock-out parasites show no obvious phenotype during gametocyte maturation, transmission through mosquitoes, and hepatocyte infection, suggesting auxiliary or redundant functions for this protein. In summary, we performed a detailed cellular and biochemical analysis of a sexual stage-specific exported parasite protein using a novel experimental approach that is broadly applicable to study the biology of P. falciparum gametocytes., (© 2019 John Wiley & Sons Ltd.)

Cutaneous melanoma is least common (only about 1% of skin cancers) but is the deadliest malignant tumor. Moreover, amelanotic types of melanoma are very difficult for clinical diagnosis. The standard therapy can cause a lot of side effects, e.g., nausea, vomiting, and headaches, which means that novel and effective strategies are required. Interestingly, phenothiazine derivatives possess sedative, antiemetic, and anticancer activity. Our goal was to determine the effect of perphenazine and prochlorperazine on cell viability, motility, microphthalmia-associated transcription factor (MITF) and tyrosinase content in melanotic and amelanotic melanoma cells. The viability of C32 and COLO829 melanoma cells was evaluated by the WST-1 colorimetric assay; impact on motility of human melanoma was performed by wound-healing assay, while tyrosinase and MITF content were determined by Western blot. In the present study, we explore the anticancer effect of perphenazine and prochlorperazine in human melanotic (COLO829) and amelanotic (C32) melanoma cells concluding that prochlorperazine inhibits cell viability in a concentration-dependent manner, impairs motility, and decreases tyrosinase and MITF amounts. Moreover, the analyzed drugs decrease/increase MITF amount depending on the type of melanoma. We demonstrated that the decrease of MITF and tyrosinase protein induces motility inhibition of C32 cells, which suggests the ability of those drugs to restore cancer cell sensitivity to treatment. The ability of prochlorperazine to contain the spread of the amelanotic melanoma in vivo may be helpful in the development of a new and effective antimelanoma therapies.

The asexual intraerythrocytic development of Plasmodium falciparum , causing the most severe form of human malaria, is marked by extensive host cell remodeling. Throughout the processes of invasion, intracellular development, and egress, the erythrocyte membrane skeleton is remodeled by the parasite as required for each specific developmental stage. The remodeling is facilitated by a plethora of exported parasite proteins, and the erythrocyte membrane skeleton is the interface of most of the observed interactions between the parasite and host cell proteins. Host cell remodeling has been extensively described and there is a vast body of information on protein export or the description of parasite-induced structures such as Maurer's clefts or knobs on the host cell surface. Here we specifically review the molecular level of each host cell-remodeling step at each stage of the intraerythrocytic development of P. falciparum We describe key events, such as invasion, knob formation, and egress, and identify the interactions between exported parasite proteins and the host cell cytoskeleton. We discuss each remodeling step with respect to time and specific requirement of the developing parasite to explain host cell remodeling in a stage-specific manner. Thus, we highlight the interaction with the host membrane skeleton as a key event in parasite survival., (Copyright © 2019 American Society for Microbiology.)

E-cigarettes are used by millions of people despite the fact that the harmful effect of aerosol emitted from these products to the human organism is still not clear. In this paper, toxicity of vapor generated using different solutions and battery output voltage on A549 cells viability is presented. The obtained EC 50 values for commercially available propylene glycol/glycerol solution 1:1 e-liquids based on 3.2 V (0.127%), 4.0 V (0.112%) and 4.8 V (0.038%) were about 1.5-4.5 times higher than in tobacco smoke (0.0086%). Furthermore, it was shown that the increase of battery output voltage decreased A549 cell viability. In addition, commercially available extracts were more cytotoxic than laboratory made extracts. Owing to the expansiveness of e-cigarettes, it is very important to estimate their impact on public health. Our results not only confirm less cytotoxicity of e-liquid aerosol than cigarette smoke, but also demonstrate that solutions used in e-liquids and, for the first time, battery output voltage have a significant impact on cytotoxicity of e-cigarette vapor. Thus, the results of this study are very important for the current and future legal regulations on e-cigarettes., (Copyright © 2018 John Wiley & Sons, Ltd.)

During the asexual cycle, Plasmodium falciparum extensively remodels the human erythrocyte to make it a suitable host cell. A large number of exported proteins facilitate this remodeling process, which causes erythrocytes to become more rigid, cytoadherent, and permeable for nutrients and metabolic products. Among the exported proteins, a family of 89 proteins, called the Plasmodium helical interspersed subtelomeric (PHIST) protein family, has been identified. While also found in other Plasmodium species, the PHIST family is greatly expanded in P. falciparum. Although a decade has passed since their first description, to date, most PHIST proteins remain uncharacterized and are of unknown function and localization within the host cell, and there are few data on their interactions with other host or parasite proteins. However, over the past few years, PHIST proteins have been mentioned in the literature at an increasing rate owing to their presence at various localizations within the infected erythrocyte. Expression of PHIST proteins has been implicated in molecular and cellular processes such as the surface display of PfEMP1, gametocytogenesis, changes in cell rigidity, and also cerebral and pregnancy-associated malaria. Thus, we conclude that PHIST proteins are central to host cell remodeling, but despite their obvious importance in pathology, PHIST proteins seem to be understudied. Here we review current knowledge, shed light on the definition of PHIST proteins, and discuss these proteins with respect to their localization and probable function. We take into consideration interaction studies, microarray analyses, or data from blood samples from naturally infected patients to combine all available information on this protein family., (Copyright © 2016, American Society for Microbiology. All Rights Reserved.)