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Verwendung der Optischen Kohärenztomographie zur Verbesserung der Prognose bei Multipler Sklerose und verwandten Erkrankungen
No full textMultiple sclerosis (MS) is a chronic disease characterized by autoimmune-mediated neuroinflammation of the central nervous system, resulting in demyelination and neuroaxonal injury. MS can have heterogenous disease courses, including relapses with acute deterioration of neurological function and progressive accumulation of disability independent of relapses. Therefore, sensitive biomarkers that improve diagnosis, predict disease activity, and evaluate treatment response are of great importance. In MS, the afferent visual pathway is commonly involved and affected by inflammation, demyelination and degeneration. Retinal neuroaxonal damage can be visualized by optical coherence tomography (OCT), a non-invasive technique that allows for high-resolution visualization of the retinal layers. Therefore, OCT-derived measures have emerged to become promising imaging biomarkers for disease monitoring in MS.
The objective of this work was to (1) evaluate the potential of a biomarker composite involving OCT and serum neurofilament light chain protein (sNfL) measures for disease activity prognostication, (2) establish retinal layer thickness standardization, as well as (3) explore other retinal structural features, including foveal morphometry and homonymous hemi-macular atrophy (HHMA) patterns, as potential biomarkers for MS and related disorders, including aquaporin-4 (AQP4)-IgG seropositive neuromyelitis optica spectrum disorders (NMOSD) and myelin oligodendrocyte glycoprotein antibody-associated disease.
In people with early MS (PweMS), having either thinner ganglion cell and inner plexiform layer (GCIP) thickness or elevated sNfL concentrations alone increases the risk of new disease activity, as evidenced by clinical relapses, new brain lesions, or confirmed disability worsening. This risk is further amplified when both factors are present. Considering the impact of age on retinal layer thinning, an age-adjusted reference database has been developed, enabling standardized OCT measures to achieve superior predictive performance compared to raw OCT measures. Furthermore, longitudinal optic radiation lesion volume changes were associated with attack-independent GCIP thinning and even HHMA, suggesting HHMA a potential marker to reflect disease activity in MS. Lastly, an association between higher serum glial fibrillary acidic protein (sGFAP) levels and retinal neuroaxonal damage and foveal flattening was found in clinically stable AQP4-IgG seropositive NMOSD, indicating sGFAP may be a sensitive biomarker for disease activity in NMOSD. The evidence on these biomarkers will be essential for future multi-modality biomarker approaches to improve clinical understanding in NMOSD.
In conclusion, OCT measures are valuable imaging biomarkers for predicting future disease activity in MS. Integrating OCT with other biomarkers in a multi-modality approach can enhance the accuracy of disease course predictions, paving the way for personalized treatment strategies. The discovery of novel retinal structural features further expands the clinical utility of OCT and contributes valuable insights to clinical trial designs. Together, these advancements represent significant steps towards precision and personalized medicine for MS and related disorders.Multiple Sklerose (MS, multiple sclerosis) ist eine chronische Erkrankung, die durch eine autoimmunvermittelte Neuroinflammation des zentralen Nervensystems gekennzeichnet ist, die zu Demyelinisierung und neuroaxonalen Schäden führt. MS kann heterogene Krankheitsverläufe aufweisen, beispielsweise Schübe mit akuter Verschlechterung der neurologischen Funktion oder fortschreitende Anhäufung von Behinderungen unabhängig von Schüben. Daher sind sensitive Biomarker, die die Diagnose verbessern, die Krankheitsaktivität vorhersagen und das Ansprechen auf eine Immuntherapie bewerten, von großer Bedeutung. Bei MS ist der afferente Sehbahn häufig von Entzündungen, Demyelinisierung und Degeneration betroffen. Retinale neuroaxonale Schäden können durch optische Kohärenztomographie (OCT, optical coherence tomography), eine nicht-invasive Technik, die eine hochauflösende Visualisierung der Netzhautschichten ermöglicht, sichtbar gemacht werden. Daher haben sich OCT-basierte Messungen als vielversprechende bildgebende Biomarker für die Krankheitsüberwachung bei MS erwiesen.
Das Ziel dieser Arbeit bestand darin, (1) das Potenzial des Biomarker-Komposits, das OCT- und Serum-Neurofilament-Leichtkettenprotein (sNfL, serum neurofilament light chain protein)-Messungen beinhaltet, für die Prognose der Krankheitsaktivität zu bewerten, (2) eine Standardisierung der Netzhautschichtdicke zu etablieren sowie (3) andere strukturelle Merkmale der Netzhaut wie foveale Morphometrie und homonymen Hemimakulatrophie (HHMA, homonymous hemi-macular atrophy) als potenzielle Biomarker für MS und verwandte Erkrankungen zu untersuchen, darunter Aquaporin-4 (AQP4)-IgG-seropositive Neuromyelitis-optica-Spektrum-Erkrankungen (NMOSD, neuromyelitis optica spectrum disorder) und Myelin-Oligodendrozyten-Glykoprotein-Antikörper-assoziierte Erkrankungen.
Im Frühstadium der MS (PweMS, people with early MS) erhöht eine geringere Dicke der Ganglienzellen und der inneren plexiformen Schicht (GCIP, ganglion cell and inner plexiform layer) oder eine erhöhte sNfL-Werte das Risiko einer neuen Krankheitsaktivität, was sich in klinischen Rezidiven, neuen Hirnläsionen oder einer bestätigten Verschlechterung der Behinderung (CDW, confirmed disability worsening) zeigt. Dieses Risiko wird noch verstärkt, wenn beide Faktoren vorliegen. Unter Berücksichtigung des Einflusses des Alters auf die Ausdünnung der Netzhautschicht wurde eine altersangepasste Referenzdatenbank entwickelt, mit der standardisierte OCT-Messungen eine bessere Vorhersageleistung erzielen als OCT-Rohmessungen. Außerdem waren longitudinale Volumenänderungen der optischen Strahlungsläsion mit einer anfallsunabhängigen Ausdünnung der GCIP und sogar HHMA verbunden, was darauf hindeutet, dass HHMA ein potenzieller Marker für die Krankheitsaktivität bei MS ist. Schließlich wurde bei klinisch stabilen AQP4-IgG-seropositiven NMOSD ein Zusammenhang zwischen höheren Serumspiegeln des sauren Gliafaserproteins (sGFAP, serum glial fibrillary acidic protein) und neuroaxonalen Schäden der Netzhaut sowie einer Abflachung der Fovea festgestellt, was darauf hindeutet, dass sGFAP ein empfindlicher Biomarker für die Krankheitsaktivität bei NMOSD sein könnte. Die Erkenntnisse zu diesen Biomarkern werden für zukünftige multimodale Biomarker-Ansätze zur Verbesserung des klinischen Verständnisses von NMOSD von entscheidender Bedeutung sein.
Zusammenfassend lässt sich sagen, dass OCT-Messungen wertvolle bildgebende Biomarker zur Vorhersage der zukünftigen Krankheitsaktivität bei MS sind. Die Integration von OCT mit anderen Biomarkern in einem multimodalen Ansatz kann die Genauigkeit von Krankheitsverlaufsvorhersagen verbessern und den Weg für personalisierte Behandlungsstrategien ebnen. Die Entdeckung neuartiger Netzhautstrukturmessungen erweitert den klinischen Nutzen von OCT weiter und liefert wertvolle Erkenntnisse für die Gestaltung klinischer Studien. Zusammen stellen diese Fortschritte einen bedeutenden Beitrag zur Präzisions- und personalisierten Medizin für MS und verwandte Erkrankungen dar
Physical activity and psychosocial characteristics of individuals with and without chronic low back pain in daily life: protocol for the PRIA intensive longitudinal study
No full textIntroduction
Despite the high prevalence of chronic low back pain (cLBP), its underlying mechanisms remain poorly understood. Addressing modifiable psychosocial resources and health behaviours such as physical activity offers a promising avenue for reducing the impact of cLBP. Furthermore, although the relationship between physical activity and pain is theorised as a within-person process, previous research has primarily focused on between-person differences. In this article, we present the protocol for the prospective observational study PRIA (Psychologie und Rückengesundheit im Alltag), which is part of a larger interdisciplinary research consortium investigating preventive, diagnostic and therapeutic aspects of cLBP. Drawing on theories from health and pain psychology, the outlined study examines the interplay between different dimensions of cLBP and back health, physical activity and their psychosocial determinants within individuals in their everyday lives.
Methods and analysis
This prospective longitudinal study combines online questionnaires with ecological momentary assessment of health behaviours, cognitions, affect, social support and pain using a smartphone-based app (movisensXS) and continuous measurement of physical activity by accelerometry (movisens Move 4). Parameters will be recorded at baseline (T0), daily for the following 14 days (five times per day at 09:00, 12:00, 15:00, 18:00 and 21:00, resulting in up to 70 measurement occasions), 3 and 6 months later (T1 and T2). A total of 230 participants (115 individuals with cLBP and 115 without cLBP) aged 18–64 years will be enrolled. The associations between cLBP and the measured parameters will be examined using multilevel models.
Ethics and dissemination
The university’s ethics committee at the MSB Medical School Berlin approved the study on 8 March 2021 (approval number MSB-2021/59, amendment approved on 10 November 2023, amendment number MSB-2023/145). Ethical approval for the FOR 5177 initial screening was granted by Charité – Universitätsmedizin Berlin (EA1/058/21). All participants provided written informed consent. The results of this research will be published in peer-reviewed international journals, presented at national and international conferences, and reported to the German Research Foundation.
Trial registration number
DRKS00032978
Groundwater Recharge Estimation Based on Environmental Isotopes, Chloride Mass Balance and SWAT Model in Arid Lands, Southwestern Saudi Arabia
No full textEstimated groundwater recharge is considered the essential factor for groundwater management and sustainability, especially in arid lands such as the Kingdom of Saudi Arabia (KSA). Consequently, assessing groundwater recharge is a key process for forecasting groundwater accessibility to sustain safe withdrawal. So, this study focused on environmental isotopes, the chloride mass balance (CMB) method, and a SWAT model by integrating GIS with hydrological and hydrochemical techniques to detect the origin of coastal aquifer groundwater and to compute the recharging rate in the study area. This study is based on the results of chemical analysis of 78 groundwater samples and environmentally stable isotopes, including deuterium (2H) and oxygen-18O, in 29 representative samples. The results revealed that the origin of groundwater recharge comes through precipitation, where the ranges of δ18O and δ2H isotopes in the analyzed groundwater were from −1.10‰ to +1.03‰ and from −0.63‰ to 11.63‰, respectively. The CMB finding for estimating the average recharge is 3.57% of rainfall, which agrees with a previous study conducted in the wadi Qanunah basin (north of the study area), where the estimated average value of recharge was 4.25% of rainfall. Meanwhile, the estimated annual recharge using a SWAT model ranged between 1 mm and 16.5 mm/year at an average value of approximately 8.75 mm/year. The results obtained by the two techniques are different due to some reasons such as the presence of additional chloride sources, as well as evaporation. Outputs of this study will be valuable for the local community, officials, and decision-makers who are concerned with groundwater resources
Cut or bind? Antigen-specific processing mechanisms define CD4+ T cell immunodominant epitopes for SARS-CoV-2 S and N proteins
No full textBackground
CD4⁺ T cell responses are key to adaptive immunity, yet the mechanisms underlying peptide selection and immunodominance across MHC class II variants in humans remain poorly defined. Two non-mutually exclusive models — First Bind-then cut (FBtc) and First Cut-then bind (FCtb) — have been proposed to explain immunodominant peptide selection, but experimental evidence in humans is mostly limited to a single allotype (HLA-DRB1*01:01).
Methods
To generalize processing mechanisms across DRB1 alleles we developed an integrative strategy combining in silico prediction and a reconstituted antigen processing system. The independent and combined outcome of both approaches was validated on curated SARS-CoV-2 epitope data (IEDB) for responses to the Spike and Nucleocapsid proteins across a panel of 11 DRB1 allotypes, covering over 90% of European Caucasian populations. Potential immunogenic regions identified by the combination of both methods enabled the design of minimalistic peptide pools whose performance was validated via flow cytometry and ELISpot assays in post-Covid19 and pre-pandemic donors. Mechanistic insights for the selection of immunodominant peptides were derived analyzing biophysical parameters and proteolysis of the model antigens.
Results
Three prediction tools used showed limited concordance for some allotypes (< 5%), but their combined output for all allotypes considered revealed potential immunogenic hotspots in the model antigens. Complementary, the reconstituted in vitro system identified allotype-dependent and promiscuous peptide candidates. Minimal peptide pools designed from the overlap of both methods featured improved performance to identify IEDB entries and induced robust CD4⁺ T cell activation in post-COVID-19 donors. Mechanistic modeling classified most immunodominant peptides from the Spike protein as arising via FCtb while FBtc predominated for Nucleocapsid. Epitope selection pathways are therefore antigen-dependent defined by proteolytic resistance and solvent accessibility.
Conclusions
We establish a scalable, genomics-informed framework for decoding CD4⁺ T cell immunodominance across diverse HLA contexts. Our findings reveal that antigen-intrinsic features govern the preferential processing pathway — FCtb for Spike and FBtc for Nucleocapsid — and validate the utility of minimal peptide pools for population-level immune-monitoring. These insights inform the design of personalized immunotherapies and broadly effective vaccines
The Pretense Mode of Fiction. On the Practice of Fiction in Literary Studies
No full textSince the late twentieth century, fiction, once primarily connected to the arts, has gradually become a much-debated topic in a wide range of research fields and disciplines including law and philosophy. However, as many different disciplines are now increasingly thematizing fiction and various usages of the term “fiction” exist, there is danger of mixing up the different definitions of this term, making it difficult to compare the approaches. In order to enable a comparison between “fiction” in those disciplines which this special issue focusses on, this article discusses fiction from a literary studies perspective. The aim is to unfold what it means for a literary text to be considered fiction and by doing so, elaborate on the peculiarities of fiction in the literary field. To facilitate the comparison, some essential distinctions that have become established in German scholarship require explanation first. The differentiation between fictionality as a potential property of texts and fictivity as a potential property of objects within fiction is rarely found in Anglo-American discussions of fictionality in literature but has become a central distinction in German discussions. By distinguishing between these two levels of fiction, it also becomes clear why reality does not necessarily function as fiction’s opposite—an assumption that can still be found frequently, especially in the everyday usage of the term “fiction.” Furthermore, this article will show that literary fictions do not even have to include invented characters, actions, and events, because the crucial point lies in the specific communicative stance authors of fiction demand from their readers. Hence, simply defining fiction as texts or other media that deal with invented characters, actions, or events would be inaccurate according to recent, pragmatic approaches in literary studies that clearly dominate the contemporary discourse on fiction. From the perspective of pragmatic approaches, what constitutes fiction is a very intricate question and cannot be answered by merely focusing on textual or semantic properties. That fiction cannot be determined through the content level will be demonstrated by evaluating the four most prominent and plausible accounts of fiction. After briefly discussing the pros and cons of these major accounts, I will focus on why this article favors John R. Searle’s approach to fiction, which emphasizes the pretense aspect as the peculiarity of fiction-making in communicative terms. The introduction concludes with a discussion of two core licenses that follow from the pretense strategy for authors of fiction, namely the license to choose any mode of presentation for their fictional story (communicative freedom), and secondly, the license to depict any topic and content they want (ontological freedom). Due to its clarificatory purpose, this essay does not offer a new understanding or even approach to fiction. Instead, it provides an overview of the core ideas regarding literary fiction for a readership that might come from various disciplines, albeit the special focus is on law as this issue’s central one. The article is deliberately written as a concise introduction to major approaches to fiction and fictionality in the field of literary studies or literary theory with a focus on the discussion in German scholarship in comparison to Anglo-American scholarship. This is meant to pave the way for the more detailed interdisciplinary and international discourse and discussion which make up the main bulk of the special issue
Unterstützung der frühzeitigen Differentialdiagnose zwischen bipolarer und unipolarer Depression mithilfe genomischer Methoden
No full textAccurate diagnosis of bipolar disorder (BD) is difficult in clinical practice, with an aver-age delay between symptom onset and diagnosis of about 7 years. One of the main reasons is that the first manic episode is often preceded by a depressive one, making it difficult to distinguish BD from unipolar major depressive disorder (MDD). Initial mis-diagnosis can have significant consequences, including poor clinical outcomes and ultimately high healthcare costs.
Here, we aim to identify genetic factors differentiating between these two clinical phe-notypes and to develop predictors that may aid early differential diagnosis. To do so, we directly assess the genetic differences between BD and MDD, using a systematic approach of combining individual-level genetic data from different cohorts.
Specifically, based on individual genotypes from case-control cohorts of BD and MDD shared through the Psychiatric Genomics Consortium, we compile case-case-control cohorts, applying a careful merging and quality control procedure. In a resulting sam-ple with a total size of 51,149 individuals (15,532 BD cases, 12,920 MDD cases and 22,697 controls), we perform genome-wide association studies (GWAS) based on a variety of methods, heritability analysis and polygenic risk scores (PRS) analysis.
While our GWAS is not well-powered to identify genome-wide significant loci, we find significant SNP-heritability and demonstrate the ability of the resulting PRS to distin-guish BD from MDD, including BD cases with a depressive onset. We also replicate our PRS findings in an independent Danish cohort (iPSYCH 2015 case-cohort study, N=25,966). We observe strong genetic correlation between our GWAS and that of BD, supporting the hypothesis that Controls – MDD — BD primarily lie on a continuum of genetic risk.
Overall, our findings demonstrate the potential of genetic predictors to become useful in clinical practice, facilitating early diagnosis in BD and preventing misdiagnosis. Our results are particularly encouraging for BD patients with a first onset of depression, who are the most likely to receive an initial diagnosis of MDD.Die Diagnostik der bipolaren Störung (BD) stellt in der klinischen Praxis eine Herausforderung dar. Durchschnittlich vergehen 7 Jahre zwischen dem ersten Auftreten von Symptomen und der Diagnosestellung. Einer der Ursachen hierfür ist, dass die erste depressive Episode oft einer manischen Episode vorausgeht, was es schwierig macht, BD von unipolarer schwerer depressiver Störung (MDD) zu unter-scheiden. Eine solche Fehldiagnose kann erhebliche Konsequenzen haben, darunter einen ungünstigen klinischen Verlauf und infolgedessen hohe Behandlungskosten.
Ziel der präsentierten Studie ist die Identifizierung genetischer Faktoren, die zwischen diesen beiden klinischen Phänotypen unterscheiden und Prädiktoren zu entwickeln, die eine frühe Differenzialdiagnose unterstützen könnten. Hierzu erfassen wir die ge-netischen Unterschiede zwischen BD und MDD anhand eines systematischen An-satzes, indem wir Individualdaten aus verschiedenen Kohorten kombinieren.
Basierend auf den individuellen Genotypen aus BD und MDD Fall-Kontroll-Kohorten, welche über das Psychiatric Genomics Consortium bereitgestellt wurden, erstellen wir aggregierte Fall-Fall-Kontroll-Kohorten, wobei wir ein sorgfältiges Procedere zur Zusammenführung und Qualitätskontrolle anwenden.
In der resultierenden Stichprobe aus 51.149 Personen (15.532 BD-Fälle, 12.920 MDD-Fälle und 22.697 Kontrollen) führen wir genomweite Assoziationsstudien (GWAS) unter Verwendung verschiedener Methoden, Heritabilitätsanalysen und poly-genes Risiko Scoring (PRS)- durch.
Obwohl unsere GWAS nicht über genügend Teststärke verfügt, um genomweit signifi-kante Loci zu identifizieren, identifizieren wir eine signifikante SNP-Heritabilität und zeigen, dass PRS BD von MDD differenzieren können, einschließlich BD-Fällen mit einem depressiven Krankheitsbeginn. Wir replizieren diese PRS-Ergebnisse in einer unabhängigen dänischen Kohorte (iPSYCH 2015 Fall-Kohorten-Studie, N=25.966). Wir beobachten außerdem eine starke genetische Korrelation zwischen unserer Fall-Fall-Kontroll GWAS mit BD, was die Hypothese unterstützt, dass Kontrollen, MDD und BD auf einem genetischen Kontinuum liegen.
Insgesamt deuten unsere Ergebnisse darauf hin, dass genetische Vorhersagen das Potenzial haben, in der klinischen Praxis nützlich zu sein, um eine frühzeitige Diag-nose bei BD zu unterstützen und Fehldiagnosen zu vermeiden. Unsere Ergebnisse sind besonders vielversprechend für die Diagnostik von BD-Patienten, bei denen zunächst Depressionen auftreten und initial mit MDD diagnostiziert warden
Design of facilitated dissociation enables timing of cytokine signalling
No full textProtein design has focused on the design of ground states, ensuring that they are sufficiently low energy to be highly populated1. Designing the kinetics and dynamics of a system requires, in addition, the design of excited states that are traversed in transitions from one low-lying state to another2,3. This is a challenging task because such states must be sufficiently strained to be poorly populated, but not so strained that they are not populated at all, and because protein design methods have focused on generating near-ideal structures4,5,6,7. Here we describe a general approach for designing systems that use an induced-fit power stroke8 to generate a structurally frustrated9 and strained excited state, allosterically driving protein complex dissociation. X-ray crystallography, double electron–electron resonance spectroscopy and kinetic binding measurements show that incorporating excited states enables the design of effector-induced increases in dissociation rates as high as 5,700-fold. We highlight the power of this approach by designing rapid biosensors, kinetically controlled circuits and cytokine mimics that can be dissociated from their receptors within seconds, enabling dissection of the temporal dynamics of interleukin-2 signalling
Loading of Dicarboxylatoplatinum(II)-NHC Complexes in Bacterial Ghosts as an Advanced Development in Cancer Therapy
No full textThis study aimed to improve the drug-like properties of benzimidazole-based Pt(II)-N-heterocyclic carbene (NHC) complexes, particularly by enhancing their water solubility and delivery to cancer cells. Accordingly, four new Pt(II) complexes of the benzimidazol-2-ylidene type, featuring monodentate carboxylato ligands, were prepared and their structures confirmed through a combination of spectroscopic and crystallographic techniques. Their stability in aqueous solution and cell culture medium was investigated by 1H NMR spectroscopy and HPLC-MS analysis. Cytotoxicity was assessed using the MTT assay in ovarian cancer cell lines (A2780wt (cisplatin sensitive) and A2780cis (cisplatin resistant)) and a noncancerous bone marrow stromal cell line (HS-5). Most complexes exhibited cytotoxicity comparable to or exceeding that of carboplatin, with preferential activity toward cancer cells. Loading of all four Pt(II) complexes into bacterial ghost cells (BGs) derived from two different nonpathogenic bacterial strains, Escherichia coli (E. coli) Nissle 1917 and E. coli NM522 notably enhanced the intracellular accumulation and cytotoxicity. Furthermore, mechanistic studies demonstrated that all tested compounds, regardless of formulation, induced apoptosis. Their potential to trigger immunogenic cell death was also evaluated, though only a modest effect was observed on selected hallmarks. Collectively, these findings highlight the potential of dicarboxylatoplatinum(II)-NHC complexes, particularly loaded into BG-based formulations, as promising anticancer drug candidates
Experimental investigation of three sleep-trackers for accuracy and practicability in the experience of sleep medicine
No full textHintergrund
Tragbare Messgeräte finden zunehmend Verbreitung. Auch für die medizinische Diagnostik werden diese Geräte zur Ressourcenentlastung in Betracht gezogen. In Validierungsstudien wurden bisher vor allem Schlaftracker untersucht, die am Handgelenk getragen werden, selten solche in Ringform. Unklar ist auch, inwiefern die Anwendung dieser Geräte im klinischen Alltag von Nutzen ist und welche Geräte am angenehmsten wären.
Ziel dieser Studie war es herauszufinden, ob diese Wearables eine adäquate Messung des Schlafes im Vergleich zur Polysomnographie gewährleisten können. Der klinische Einsatz und die Befragung von Patient:innen sollte in Erfahrung bringen, ob eine Anwendung in der schlafmedizinischen Praxis sinnvoll wäre.
Methodik
Es wurden drei Schlaftracker in Ringform von Oura Health Oy, Shenzhen Sleepon Technology Co., Ltd. (Handelsname SLEEPON) und Porta Medical UG (Handelsname Circul) untersucht. Die Proband:innen wurden im Schlaflabor der Charité – Universitätsmedizin Berlin in simultaner Messung zur PSG untersucht. Die Daten der Ringe wurden per mobiler Applikation der Hersteller mit einem Studientelefon synchronisiert und die Rohdaten exportiert. Zusätzlich beantworteten die Proband:innen Fragebögen. Die ermittelten Zeiten für die Gesamtschlafzeit (TST) und die Wachzeit nach dem Einschlafen (WASO) wurden in der statistischen Analyse verglichen. Auch eine Epochenanalyse für die Sensitivität, Spezifität und Genauigkeit wurde angeschlossen. Bland-Altman-Plots dienen zur Veranschaulichung der Analysen. Zur Einordnung der Ergebnisse wurde eine Literaturrecherche zum Thema Schlaftracker in Ringform in Pubmed und Google Scholar durchgeführt.
Ergebnisse
Es wurden 45 Proband:innen eingeschlossen (60,0% männlich, 23-70 Jahre, Durchschnittsalter 54,6 Jahre).
Die Werte der Konfidenzintervalle der gemessenen TST der Ringe lagen alle außerhalb der festgelegten Äquivalenzgrenze von +/-26 Minuten, d.h. kein Ring erreichte eine äquivalente Messung im Vergleich zum Goldstandard. Der Oura Ring überschätzte im Vergleich zur PSG die TST um durchschnittlich 18,3 Minuten, der SLEEPON Ring um 60,2 Minuten und der Circul Ring unterschätzte die TST um 21,8 Minuten. Bland-Altman-Plots veranschaulichen diese Messungen.
Die Epochenanalyse ergab eine Genauigkeit von 85,8% (Oura), 84,5% (SLEEPON) und 66,6% (Circul), eine Sensitivität für die Phase Schlaf von 93,1% (Oura), 97,0% (SLEEPON) und 74,5% (Circul). Die Spezifität für die Wachphasen ergab 47,3% (Oura), 39,2% (SLEEPON) und 36,9% (Circul). Bei der Patientenzufriedenheit schnitt Oura am besten, SLEEPON am schlechtesten ab.
Schlussfolgerung
Insgesamt haben die untersuchten Ringe keine ausreichende Messgenauigkeit für die untersuchten Parameter erreicht. Wenngleich die Ergebnisse zur Epochenanalyse eine gute Spezifität, Sensitivität und Genauigkeit aufweisen, kann auf Basis der Ergebnisse, keine grundsätzliche Empfehlung zur Anwendung in der klinischen Diagnostik gegeben werden.Introduction
Portable measuring devices have become increasingly widespread. These devices are also being considered in sleep medicine to relieve the strain on resources. In validation studies, sleep trackers that are worn around the wrist have been examined, but rarely ring-shaped sleep trackers. It is also unclear to what extent these devices can be integrated into everyday clinical practice and which trackers would be most convenient.
The aim of this study was to find out whether one of those wearables can ensure equivalent measurement. Clinical use and questioning of patients should find out if it would be possible to use it in everyday sleep medicine.
Material and methods
Three ring-shaped sleep trackers from Oura Health Oy, Shenzhen Sleepon Technology Co., Ltd. (trade name SLEEPON) and Porta Medical UG (trade name Circul) were examined. The subjects were included in the sleep laboratory of the Charité – Universitätsmedizin Berlin. In addition to the polysomnography probes, they wore three ring-shaped sleep trackers. The ring data was synchronized with a study phone via an app and the raw data was exported. In addition, the subjects answered a questionnaire. Values for total sleep time (TST) and wake time after sleep onset (WASO), measured by polysomnography and the rings, were compared in statistical analysis. Furthermore, epoch analyses were carried out to evaluate sensitivity, specificity and accuracy of the wearables. Bland-Altman-Plots visualize the data. A literature search about ring-shaped sleep trackers was carried out on Pubmed and Google Scholar and used to classify the results.
Results
45 subjects were included (23 to 70 years, 60,0% male, mean age 54,6 years).
Confidence interval values for the total sleep time, measured by the rings, crossed the borders of the a priori established equivalence limit of +/-26 minutes, meaning no ring has an equivalent measurement compared to the gold standard. The Oura ring overestimated polysomnography by an average of 18,3 minutes, the SLEEPON ring by 60,2 minutes, and the Circul ring underestimated the measurement by 21,8 minutes. Bland-Altman plots were prepared to illustrate the measurements.
Epoch analysis revealed an accuracy of 85,8% (Oura), 84,5% (SLEEPON) and 66,6% (Circul) and a sensitivity for the phase asleep of 93,1% (Oura), 97,0% (SLEEPON) and 74,5% (Circul). The specificity for the phase awake was 47,3% (Oura), 39,2% (SLEEPON) and 36,9% (Circul). When it came to patient satisfaction, all in all Oura was the best and SLEEPON the worst.
Discussion
Overall, compared to the gold standard of polysomnography, the rings do not provide an equivalent measurement for the cumulatively measured times. Although the results of the epoch analysis show good specificity, sensitivity and accuracy, no general recommendation for use in clinical diagnostics can be given based on the current state of knowledge
Virtual reality interventions in the assessment and treatment of alcohol use disorder - a systematic scoping review on methodology
No full textBackground
Virtual reality (VR) technology has been increasingly employed to develop innovative treatments for Alcohol use disorder (AUD) and overcome limitations of currents therapies. However, previous research in this field has yielded inconclusive results. To improve the quality and comparability of studies, a critical analysis of the research methodology employed in this field is necessary.
Objectives
This scoping review aims to provide an overview of existing studies with a focus on their objectives, methodology, treatment paradigms, and VR design characteristics.
Methods
A systematic literature research was conducted in the electronic databases MEDLINE (PubMed), APA PsychInfo, APA PsychArticles, PSYINDEX (EBSCOhost), Scopus, Web of Science and by search in the reference list of included publication to identify relevant publications. Clinical studies and study protocols using VR for the assessment or treatment of patients with AUD were included.
Results
The literature search yielded 1.197 studies, of which 22 met the inclusion criteria. Completed trials (n = 16) and study protocols (n = 6) were included. The majority of the studies (n = 19) used a VR cue exposure paradigm to induce craving. The studies can be classified either as assessment (n = 9) or treatment studies (n = 13). The duration (7–60 min) and number of applied sessions (1–13) varied significantly depending on the type of study. Craving outcomes were based on subjective and physiological measurements. All studies used alcoholic beverages and VR scenarios such as bars, pubs, parties and restaurants, with additional scenarios varying, except for one study using a hospital and subway scenario as aversive scenarios. Moreover, synchronized olfactory stimuli were frequently used.
Conclusions
Despite the heterogeneity of VR software features and VR interventions, it was possible to identify a similarity within the main VR scenarios employed, as well as consistent positive results concerning the induction of subjective craving by alcohol-associated VR cues. While VR interventions for AUD show methodological progress, future research should adopt standardized protocols, include objective psychophysiological outcomes, and evaluate long-term efficacy and feasibility in clinical settings. Integration of emerging VR paradigms and technologies may further enhance the therapeutic potential