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Prevalence of Obstructive Sleep Apnea in Head and Neck Squamous Cell Carcinoma Patients before and after Treatment
Get PDFBackground and Objectives: Obstructive sleep apnea (OSA) is common not only in the general population but even more so in patients with tumors of the head and neck region. Untreated, it leads to reduced quality of life, increased daytime sleepiness, and other comorbidities. The aim of this study was to determine the difference in the occurrence of OSA in the patient population with head and neck tumors compared with the general population as represented by the Trend cohort of the Study of Health in Pomerania (SHIP), and to assess the influence of tumor treatment. Materials and Methods: Between July 2018 and December 2021, preoperative polysomnography was conducted in 47 patients with histologically confirmed squamous cell carcinoma in the oropharynx, hypopharynx, or larynx. A follow-up polysomnography was performed in 23 patients 2–11 months after completing treatment. The collected data were correlated with tumor treatment and tumor size. Results: Of the included patients, 43 were male and 4 were female. Age ranged from 54 to 90 years. The pretherapeutic measurement found no significant difference in the prevalence of a pathologically elevated apnea–hypopnea index (AHI) in our patients compared with the SHIP Trend cohort. In the follow-up measurement after completion of treartment, a significant deterioration in AHI was observed. Initially, 70% of patients had an AHI > 5; after therapy, this increased to 87% (p = 0.008). The effect was particularly pronounced in the group of patients with advanced tumor stages who had received primary chemoradiation. Conclusions: OSA is a relevant condition in patients with head and neck cancer. Tumor treatment can lead to an increased occurrence of sleep-related breathing disorders, especially in patients with advanced tumor stages undergoing primary chemoradiation. Additional studies are necessary to better understand the exact mechanism involved
A Comparative Study of the Sensitivity and Specificity of the Ishihara Test With Various Displays
Get PDFObjectives
Visual colour differentiation in clinical research requires colour-competent (CC) participants. The Ishihara colour charts (ICC) have established themselves as the standard for CC screening of colour vision deficiencies (CVD). However, the extent to which the results can be compared with a presentation of the colour charts on a smartphone display (SD) is currently unknown. The aim of this in vitro study was to determine the sensitivity and specificity of the Ishihara colour deficiency test depending on the presentation mode.
Methods
Dental students (female n = 28; male n = 10; mean age, 23.5 ± 2.65 years; median age, 23.0 ± 13.0 years) evaluated 25 Ishihara test plates on their SD (n = 38) and/or a calibrated monitor (HP monitor, 22-inch; n = 18). The median size of the SD was 6.0 inches. Datasets with more than 2 failed charts were scored.
Results
When the Ishihara test charts were presented on a PC screen, the sensitivity was 94.4% and the specificity was 82.4% (0 mistakes: n = 14, .05).
Conclusions
The presentation of ICC on an SD is useful and can be used for the investigation of a possible CVD of large groups. Comparable results to data projection can be achieved with a high degree of certainty. For CVD screening of larger groups (eg, students in preclinical training as part of CC training), the presentation of ICC on the SD can be used. This research was able to demonstrate that the sensitivity and specificity of the usual presentation method (Ishihara's booklet or data projection) is comparable
Can transcutaneous auricular vagus nerve stimulation mitigate vigilance loss? Examining the effects of stimulation at individualized versus constant current intensity
Get PDFAccording to the arousal model of vigilance, the locus coeruleus‐norepinephrine (LC‐NE) system modulates sustained attention over long periods by regulating physiological arousal. Recent research has proposed that transcutaneous auricular vagus nerve stimulation (taVNS) modulates indirect physiological markers of LC‐NE activity, although its effects on vigilance have not yet been examined. Aiming to develop a safe and noninvasive procedure to prevent vigilance failures in prolonged tasks, the present study examined whether taVNS can mitigate vigilance loss while modulating indirect markers of LC‐NE activity. Following a preregistered protocol (https://osf.io/tu2xy/), 50 participants completed three repeated sessions in a randomized order, in which either active taVNS at individualized intensity set by participant, active taVNS set at 0.5 mA for all participants, or sham taVNS, was delivered while performing an attentional and vigilance task (i.e., ANTI‐Vea). Changes in salivary alpha‐amylase and cortisol concentrations were measured as markers of LC‐NE activity. Self‐reports of feelings associated with stimulation and guessing rate of active/sham conditions supported the efficacy of the single‐blind procedure. Contrary to our predictions, the observed vigilance decrement was not modulated by active taVNS. Pairwise comparisons showed a mitigation by active taVNS on cortisol reduction across time. Interestingly, Spearman's correlational analyses showed some interindividual effects of taVNS on indirect markers of LC‐NE, evidenced by positive associations between changes in salivary alpha‐amylase and cortisol in active but not sham taVNS. We highlight the relevance of replicating and extending the present outcomes, investigating further parameters of stimulation and its effects on other indirect markers of LC‐NE activity
Predicting complications in paediatric ulcerative colitis: A longitudinal multicentre cohort study
Get PDFBackground
To prevent complications of paediatric ulcerative colitis (UC), it is critical to understand their predictors. The Paediatric Inflammatory Bowel Disease Ahead (PIBD Ahead) program identified the relevant outcomes and their potential predictors. However, external validation of these results in larger cohorts is required.
Aims
The aim of this study is to investigate these outcomes and their predictors.
Methods
We included 743 patients aged under 18 years with UC from the multicentre German‐Austrian CEDATA‐GPGE registry. We performed Cox regressions, Kaplan–Meier estimator, and receiver operating characteristics curve analyses to analyse predictors of poor outcomes.
Results
Older age at diagnosis was associated with relapse, hospitalisation, the use of immunomodulators, use of biologics, and therapy escalation. Higher disease activity, as in acute severe colitis in the first 3 months, was significantly associated with further acute severe colitis and the need for biologics. Upper gastrointestinal tract involvement was a risk factor for the need of intravenous corticosteroids and biologics. A faecal calprotectin of 685 μg/g was associated with a higher risk of subsequent acute severe colitis with a sensitivity of 79.0% and a specificity of 59.1%. A lower haematocrit at diagnosis was predictive of the use of biologics. Colectomy was rare.
Conclusions
This study validates predictors of poor outcomes in paediatric patients with UC. Our results might help physicians to anticipate poor outcomes and initiate appropriate treatment strategies at an early stage
Klebsiella pneumoniae exhibiting a phenotypic hyper-splitting phenomenon including the formation of small colony variants
Get PDFIn this study, we characterized a Klebsiella pneumoniae strain in a patient with shrapnel hip injury, which resulted in multiple phenotypic changes, including the formation of a small colony variant (SCV) phenotype. Although already described since the 1960s, there is little knowledge about SCV phenotypes in Enterobacteriaceae. The formation of SCVs has been recognized as a bacterial strategy to evade host immune responses and compromise the efficacy of antimicrobial therapies, leading to persistent and recurrent courses of infections. In this case, 14 isolates with different resisto- and morpho-types were distinguished from the patient’s urine and tissue samples. Whole genome sequencing revealed that all isolates were clonally identical belonging to the K. pneumoniae high-risk sequence type 147. Subculturing the SCV colonies consistently resulted in the reappearance of the initial SCV phenotype and three stable normal-sized phenotypes with distinct morphological characteristics. Additionally, an increase in resistance was observed over time in isolates that shared the same colony appearance. Our findings highlight the complexity of bacterial behavior by revealing a case of phenotypic “hyper-splitting” in a K. pneumoniae SCV and its potential clinical significance
In-vitro biofilm removal from TiUnite® implant surface with an air polishing and two different plasma devices
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We investigated the efficacy of two different cold atmospheric pressure jet plasma devices (CAP09 and CAPmed) and an air polishing device with glycine powder (AP) either applied as monotherapies or combined therapies (AP + CAP09; AP + CAPmed), in microbial biofilm removal from discs with anodised titanium surface.
Methods
Discs covered with 7-day-old microbial biofilm were treated either with CAP09, CAPmed, AP, AP + CAP09 or AP + CAPmed and compared with negative and positive controls. Biofilm removal was assessed with flourescence and electron microscopy immediately after treatment and after 5 days of reincubation of the treated discs.
Results
Treatment with CAP09 or CAPmed did not lead to an effective biofilm removal, whereas treatment with AP detached the complete biofilm, which however regrew to baseline magnitude after 5 days of reincubation. Both combination therapies (AP + CAP09 and AP + CAPmed) achieved a complete biofilm removal immediately after cleaning. However, biofilm regrew after 5 days on 50% of the discs treated with the combination therapy.
Conclusion
AP treatment alone can remove gross biofilm immediately from anodised titanium surfaces. However, it did not impede regrowth after 5 days, because microorganisms were probably hidden in holes and troughs, from which they could regrow, and which were inaccessible to AP. The combination of AP and plasma treatment probably removed or inactivated microorganisms also from these hard to access spots. These results were independent of the choice of plasma device
Integrating tumor and healthy epithelium in a micro-physiology multi-compartment approach to study renal cell carcinoma pathophysiology
Get PDFThe advent of micro-physiological systems (MPS) in biomedical research has enabled the introduction of more complex and relevant physiological into in vitro models. The recreation of complex morphological features in three-dimensional environments can recapitulate otherwise absent dynamic interactions in conventional models. In this study we developed an advanced in vitro Renal Cell Carcinoma (RCC) that mimics the interplay between healthy and malignant renal tissue. Based on the TissUse Humimic platform our model combines healthy renal proximal tubule epithelial cells (RPTEC) and RCC. Co-culturing reconstructed RPTEC tubules with RCC spheroids in a closed micro-perfused circuit resulted in significant phenotypical changes to the tubules. Expression of immune factors revealed that interleukin-8 (IL-8) and tumor necrosis factor-alfa (TNF-α) were upregulated in the non-malignant cells while neutrophil gelatinase-associated lipocalin (NGAL) was downregulated in both RCC and RPTEC. Metabolic analysis showed that RCC prompted a shift in the energy production of RPTEC tubules, inducing glycolysis, in a metabolic adaptation that likely supports RCC growth and immunogenicity. In contrast, RCC maintained stable metabolic activity, emphasizing their resilience to external factors. RNA-seq and biological process analysis of primary RTPTEC tubules demonstrated that the 3D tubular architecture and MPS conditions reverted cells to a predominant oxidative phosphorylate state, a departure from the glycolytic metabolism observed in 2D culture. This dynamic RCC co-culture model, approximates the physiology of healthy renal tubules to that of RCC, providing new insights into tumor-host interactions. Our approach can show that an RCC-MPS can expand the complexity and scope of pathophysiology and biomarker studies in kidney cancer research
Teacher autonomy support counters declining trend in intrinsic reading motivation across secondary school
Get PDFStudents’ intrinsic motivation to read, which is relevant to all forms of learning, tends to decline throughout secondary school. Based on self-determination theory (SDT), this study examines whether this downward trend is slowed when students perceive greater autonomy support in the classroom. We used large-scale panel data from the NEPS comprising N = 8193 students in Germany who reported their intrinsic motivation to read and their perceived autonomy support from German teachers at annual intervals from fifth to eighth grade. Scalar longitudinal measurement invariance was found for intrinsic reading motivation (IRM) and teacher autonomy support (TAS). A dual change score model showed a decline in IRM and a negative, non-significant decrease in TAS over time. Confirming our hypothesis, the decline in IRM was slowed by earlier levels of TAS. We discuss methods to counteract the decline in intrinsic reading motivation
Untersuchungen zum OATP- abhängigen Transport der Opioide Fentanyl und Sufentanil sowie die Generierung von stabil transfizierten Zelllinien mithilfe des Flp-In™ Systems
Get PDFIn der Klinik wird eine inter- und intraindividuelle Variabilität in Wirkung und Nebenwirkung von Opioiden beobachtet [5,6]. Ursächlich hierfür könnte unter anderem eine individuelle Ausstattung mit Transportproteinen sein, welche pharmakologische Substanzen wie zum Beispiel Opioide über körpereigene Barrieren zu ihren Wirkorten transportieren. Mit dieser Arbeit sollte die Affinität der Opioide Fentanyl und Sufentanil zu ausgewählten organic anion transporting polypeptides (OATP) untersucht werden. Ein weiteres Ziel war die Generierung eines neuen OATP1A2-Transportmodells. Im Vergleich zum bisherig verwendeten Modell mit pQCXIN::OATP1A2 sollte eine Zelllinie mit definiert integriertem Transportprotein-Gen für eine reproduzierbarere OATP1A2-Überexpression generiert werden.
Eine Affinität von Fentanyl zu OATP1A2 konnte in Kompetitionsversuchen
(IC50 14,17 µM) belegt werden. Für die Kombination Fentanyl/ OATP1B1 war keine Inhibition des Transporters nachweisbar. Sufentanil inhibierte OATP1A2 geringfügig, konnte aber herstellerbedingt nicht in vergleichbaren Konzentrationen untersucht werden. Es zeigte sich kein Transport von Fentanyl durch OATP1A2.
Da Funktionskontrollen mit den vorhandenen HEK-pQCXIN::OATP-Zelllinien mit zunehmender Passagennummer fluktuierende oder abnehmende Aktivitäten zeigten, sollten stabile Zelllinien mit definierter vorzugsweise singulärer Integration des Zielgens in HEK-293-Zellen generiert werden. Mittels Flp-In™-System wurden über drei verschiedene Klonierungsstrategien Klone von T-REx™-pcDNA5/FRT::OATP1A2 hergestellt. Auf RNA- und DNA-Ebene konnte die korrekte Integration der OATP1A2-Sequenz nachgewiesen werden. In der Funktionskontrolle zeigte sich aber nur eine maximal 1,7 fache erhöhte Aktivität gegenüber Kontrollzellen. Mit keiner der drei gewählten Klonierungsstrategien konnten ausreichend funktionelle OATP1A2 überexprimierende Zellen generiert werden, trotz intakt integrierter OATP1A2-Sequenz sowie korrekter Übergänge, Startcodon und Kozak-Sequenz, bestätigt durch Sequenzierung des Genoms der T-REx™-pcDNA5/FRT::OATP1A2 (Variante 3). In stabil transfizierten Zellen ließ sich durch Immunfluoreszenz keine Expression, ordnungsgemäße Lokalisation und Überexpression von OATP1A2 darstellen. Ob dies an einer Proteinfehlfaltung oder einer zu niedrigen Proteinexpression liegt, konnte nicht zweifelsfrei bestimmt werden.
Insgesamt trägt diese Arbeit zur Beantwortung der Frage bei, inwiefern Fentanyl die Aufnahmetransporter der OATP-Familie beeinflusst und somit durch pharmakologische Hemmung die Wirkungen und Nebenwirkungen anderer Arzneimittel verändern kann. Obwohl die Generierung OATP1A2-überexprimierender T-REx™-pcDNA5/FRT::OATP mit dem Flp-In™-System im Rahmen dieser Arbeit nicht erfolgreich verlief, konnten weitere Erfahrungen zum Flp-In™-System gesammelt werden
Validierung der kardiovaskulären Risikoprädiktion für das arriba-Instrument auf Basis der Daten der Study of Health in Pomerania - Vergleich der Risikoinstrumente arriba, SCORE-Deutschland und PROCAM
Get PDFHintergrund:
Kardiovaskuläre Präventionsleitlinien empfehlen unterschiedliche Instrumente zur kardiovaskulären 10-Jahres-Risikobestimmung. In der hausärztlichen Praxis wird dafür häufig das arriba-Instrument verwendet und durch die Leitlinie „Hausärztliche Risikoberatung zur kardiovaskulären Prävention“ empfohlen. Ziel der Studie ist die Validierung der arriba-Risikoprädiktion auf Basis von Morbiditäts- und Mortalitätsdaten der bevölkerungsbasierten Study of Health in Pomerania.
Methoden:
In einer retrospektiven Längsschnittanalyse wurde für Probanden ohne vorheriges kardiovaskuläres Ereignis das kardiovaskuläre 10-Jahres-Gesamtrisiko (Myokardinfarkt oder Schlaganfall) zur Basisuntersuchung mit dem arriba-, SCORE-Deutschland- und PROCAM-Algorithmus (Myokardinfarkt) berechnet. Aus Daten der Folgeuntersuchungen wurden kardiovaskuläre Ereignisraten ermittelt und Diskriminierungs- und Kalibrierungsmaße für die Risikobestimmungsinstrumente berechnet.
Ergebnisse:
In die Analyse wurden 2277 Proband:innen (Durchschnittsalter 53 ± 13 Jahre, 50% Männer) eingeschlossen. Nach durchschnittlich 10,2 Jahren betrug die kardiovaskuläre Ereignisrate 8,6% (196/2277). Das Verhältnis aus prädizierter und beobachteter Ereignisrate betrug für Proband:innen mit niedrigem, mittlerem und hohem kardiovaskulären Risiko 0,8, 1,5 und 1,3. Arriba unterschätzte bei Frauen und überschätzte in den Altersgruppen 30-44 und 45-59 Jahren die kardiovaskulären Ereignisraten.
Schlussfolgerung:
Diskriminierungswerte für das arriba-Instrument sind mit SCORE-Deutschland und PROCAM vergleichbar, eine individuelle Anpassung an die Zielpopulation ist jedoch nötig.Background:
Cardiovascular disease (CVD) prevention guidelines recommend different tools for 10-year CVD risk estimation. The arriba-tool is frequently used by GPs in Germany and recommended by the German Association of General Practicioners and Family Medicine (“Deutsche Gesellschaft für Allgemeinmedizin”). This study aims to investigate external validity of CVD risk estimation with arriba using morbidity- and mortality data from the population-based Study of Health in Pomerania.
Methods:
10-year-CVD risk (myocardial infarction, MI or Stroke) was estimated at baseline for study participants without prior CVD event using arriba, SCORE-Germany and PROCAM (MI). CVD-event rates were derived from follow-up data. We assessed discrimination and calibration for the CVD risk estimation tools.
Results:
2277 Participants were included (mean age 53 ± 13 years, 50% men). After 10,2 years of follow-up, the CVD event rate was 8,6% (196/2277). The predicted-over-observed ratios were 0,8, 1,5 und 1,3. arriba underestimated CVD risk in women and overestimated risk in the age groups 30-44 and 45-59 years.
Conclusions:
Discrimination for the arriba-tool is comparable to SCORE-Deutschland and PROCAM. However, a better calibration to the target population is needed