Intensity of respiratory cortical arousals is a distinct pathophysiologic feature and is associated with disease severity in obstructive sleep apnea patients

Background: We investigated whether the number, duration and intensity of respiratory arousals (RA) on C3-electroencephalographic (EEG) recordings correlate with polysomnography (PSG)-related disease severity in obstructive sleep apnea (OSA) patients. We also investigated if every patient might have an individual RA microstructure pattern, independent from OSA-severity. Methods: PSG recordings of 20 OSA patients (9 female; age 27–80 years) were analyzed retrospectively. Correlation coefficients were calculated between RA microstructure (duration, EEG-intensity) and RA number and respiratory disturbance index (RDI), oxygen desaturation index (ODI) and arousal index (AI). Intraclass correlations (ICC) for both RA duration and intensity were calculated. Sleep stage-specific and apnea- and hypopnea-specific analyses were also done. The probability distributions of duration and intensity were plotted, interpolated with a kernel which fits the distribution. A Bayesian posterior distribution analysis and pair-wise comparisons of each patient with all other 19 patients were performed. Results: Of the analyzed 2600 RA, strong positive correlations were found between average RA intensity and both RDI and AI. The number of PSG-recorded RA was strongly positively correlated with RDI. Significant correlations between average RA intensity in REM, NREM2 and NREM3 sleep stages and total ODI were identified. No sleep stage-specific correlations of arousal microstructure with age, sex, RDI or AI were identified. Although between-subjects ICC values were 0.7 (all p < 0.05). While apnea-related RA duration did not differ from hypopnea-related RA duration, RA intensity was significantly higher (p = 0.00135) in hypopneas than in apneas. A clear individual pattern of arousal duration for each patient was made distinct. For arousal intensity, a Gaussian distribution was identified in most patients. The Bayesian statistics regarding the arousal microstructure showed significant differences between each pair of patients. Conclusions: Each individual patient with OSA might have an individual pattern of RA intensity and duration indicating a distinct individual pathophysiological feature. Arousal intensity was significantly higher in hypopneic than in apneic events and may be related causally to the diminished (compared to apneas) respiratory distress associated with hypopneas. RA intensity in REM, NREM2 and NREM3 strongly correlated with ODI

Transcriptional response of Lactococcus lactis during bacterial emulsification

Microbial surface properties are important for interactions with the environment in which cells reside. Surface properties of lactic acid bacteria significantly vary and some strains can form strong emulsions when mixed with a hydrocarbon. Lactococcus lactis NCDO712 forms oil-in-water emulsions upon mixing of a cell suspension with petroleum. In the emulsion the bacteria locate at the oil-water interphase which is consistent with Pickering stabilization. Cells of strain NCDO712 mixed with sunflower seed oil did not stabilize the oil droplets. This study shows that the addition of either ethanol or ammonium sulfate led to cell aggregation, which subsequently allowed stabilizing oil-in-water emulsions. From this, we conclude that bacterial cell aggregation is important for emulsion droplet stabilization. To determine how bacterial emulsification influences the microbial transcriptome RNAseq analysis was performed on lactococci taken from the oil-water interphase. In comparison to cells in suspension 72 genes were significantly differentially expressed with a more than 4-fold difference. The majority of these genes encode proteins involved in transport processes and the metabolism of amino acids, carbohydrates and ions. Especially the proportion of genes belonging to the CodY regulon was high. Our results also point out that in a complex environment such as food fermentations a heterogeneous response of microbes might be caused by microbe-matrix interactions. In addition, microdroplet technologies are increasingly used in research. The understanding of interactions between bacterial cells and oil-water interphases is of importance for conducting and interpreting such experiments

Corticoperipheral neuromuscular disconnection in obstructive sleep apnoea

The roles of central nervous mechanisms and cortical output in obstructive sleep apnea remain unclear. We addressed corticomuscular coupling between cortical sensorimotor areas and lower facial motor units as a mechanistic pathway and as a possible surrogate marker of cortico-peripheral motor control in obstructive sleep apnea. In this exploratory cross-sectional retrospective study we analysed EEG (C3- and C4-leads) and chin EMG from polysomnography recordings in 86 participants (22 females; age range: 26-81 years), 27 with mild (respiratory disturbance index = 5-15 events/hour), 21 with moderate (15-30 events/h) and 23 with severe obstructive sleep apnea (> 30 events/h) and 15 control subjects (<5 events/h). By computing C3-/C4-EEG- chin EMG coherence of signal dynamics in time and frequency domains we investigated corticomuscular coupling between cortical sensorimotor areas and lower facial motor units with increasing obstructive sleep apnea severity during the entire sleeping time, during different sleep stages and during obstructive respiratory events, including 5 seconds before (stable breathing) and after events (breathing resumption). Additionally, we studied a possible influence of body-mass-index and autonomic nervous system activation. We found that both average and respiratory event-specific corticomuscular coupling between cortical sensorimotor areas and lower facial motor units weakened significantly with increasing obstructive sleep apnea severity, was strongest during N3 and weakened in N1, N2 and rapid-eye-movement stages (in decreasing order). Coupling increases significantly during the obstructive respiratory events compared with coupling just before and following them. Results were independent of body-mass-index or autonomic nervous system activation. We conclude that obstructive respiratory events in obstructive sleep apnea are very strongly associated both quantitatively and temporally with the degree of disconnection within the cortical sensorimotor areas - lower facial motor units pathway. This quite coordinated activity pattern suggests a cortical sensorimotor area-driven obstructive respiratory event pattern generator and a central motor output disorder in obstructive sleep apnea

An AI-supported diagnostic tool for obstructive sleep apnea patients based on delta-alpha connectivity at the sensorimotor cortex [Abstract]

Background: The modulation of delta-alpha phase-amplitude cross-frequency coupling (PACFC) may influence information processing throughout the human cerebral cortex. We investigated whether this frequency band-specific modulation is impaired in patients with obstructive sleep apnea (OSA). Patients & Methods: In this study, the C3- and C4- electroencephalographic recordings of 170 participants (86 in main dataset: age 27-84 years, 44 subjects had moderate or severe OSA with respiratory disturbance index RDI>15/h; 84 in validation dataset: age 35 -75 years, 42 subjects with RDI>15/h) who underwent full-night polysomnography (PSG) were evaluated. We tested if the delta-alpha PACFC modulation index (MI) at the sensorimotor cortex differs between OSA patients with RDI>15/h and those with RDI≤15/h in distinct sleep stages. Further, by making use of a Support Vector Machine (SVM) algorithm, we tested if the sleep stage – specific MIs could predict RDI values of OSA patients. Results: In both datasets, in OSA patients with RDI >15/h, the delta-alpha CFC-MI was significantly (p< 0.05) reduced at the sensorimotor cortex during REM and NREM1 stages, while increased during NREM2 compared to patients with RDI ≤15/h. In addition, the delta-alpha MI in REM sleep stage could provide with use of an SVM algorithm a quite reliable (82% accuracy) prediction of the RDI in OSA patients. Conclusions: This increase in disconnection at the cortical sensorimotor areas with increasing respiratory distress during sleep further supports the concept of a cortical sensorimotor dysfunction in OSA patients. Additionally, the delta – alpha MI during REM sleep may provide an objective neurophysiologic surrogate marker of respiratory distress in OSA patients

KI-gestützte Diagnostik der obstruktiven Schlafapnoe mittels delta – alpha Konnektivität am sensorimotorischen Cortex [Abstract]

Fragestellung: Die Modulation der delta-alpha Phasenamplituden-Kreuzfrequenzkopplung (PAKFK) kann die cerebro-corticale Informationsverarbeitung beeinflussen. Wir haben untersucht, ob diese frequenzband-spezifische Modulation bei Patienten mit obstruktiver Schlafapnoe (OSA) beeinträchtigt wird. Patienten und Methoden: Es wurden die C3- und C4- elektroencephalographischen Aufnahmen der Polysomnographien von 170 Teilnehmern (86 im Hauptdatensatz, 27 - 84 Jahre alt, 44 Teilnehmer mit Respiratorischen Disturbance Index RDI>15/h und 84 im Validierungsdatensatz, 35 - 75 Jahre alt, 42 davon mit RDI>15/h) ausgewertet. Der delta-alpha KFK-Modulationsindex (MI) wurde bei Patienten mit unterschiedlichem OSA-Schweregrad in den unterschiedlichen Schlafstadien am sensorimotorischen Cortex berechnet. Auch die Möglichkeit der Vorhersage des RDI mit Hilfe der Schlafstadien-spezifischen MIs unter Verwendung eines Support Vector Machine (SVM) - Algorithmus wurde getestet. Ergebnisse: In beiden Datensätzen wurde der delta-alpha KFK-MI an den kortikalen sensorimotorischen Bereichen bei Patienten mit RDI>15/h im Vergleich zu Patienten mit RDI≤15/h im Stadium NREM1 und REM signifikant (p15/h signifikant erhöht im Vergleich zu Patienten mit RDI≤15/h. Delta-alpha MI im REM-Stadium konnte mittels SVM zuverlässig (82% Genauigkeit) den RDI vorhersagen. Schlussfolgerungen: Diese Frequenzband- und Schlafstadien-spezifische sensorimotorische Diskonnektion unterstützt das Konzept einer kortikalen sensorimotorischen Dysfunktion bei OSA-Patienten. Zudem, bietet der delta-alpha MI im REM–Schlaf einen potenziellen objektiven neurophysiologischen Ersatzmarker der respiratorischen Störung bei OSA-Patienten an

Concordance of Skin Prick Test, Intradermal Testing, Serum IgE Levels and Symptoms in Patients with Allergic Rhinitis

Background: Diagnosis of allergic rhinitis is achieved by a combination of patient history and different screening tools, followed by specific provocation testing. Screening tools usually involve a skin prick test (SPT), specific serum IgE or a combination of both. Objective: The purpose of this study was to evaluate the correlation of SPT, intradermal testing and specific serum IgE testing in certain allergens and to evaluate sensitization rates, symptom patterns and time of symptoms in a cohort of patients with suspected allergic rhinitis. Methods: Data on 4653 patients with suspected allergic rhinitis were included and divided into five groups: spring bloomers (birch, hazel, etc.), summer bloomers (grasses and rye), autumn bloomers (ribwort and mugwort), mites and mold. Correlation of SPT, intradermal testing and specific IgE test results using Cohen’s kappa and logistic regression were carried out to evaluate the probability of symptoms. Results: Comparison of SPT and specific serum IgE led to kappa coefficients between 0.33 and 0.47, corresponding to a minor to moderate concordance. Comparing the symptoms reported by patients with sensitization diagnosed by SPT, a correlation was only found for spring and summer bloomers with an odds ratio of 1.5 and 2.1, respectively. The most prevalent symptom in the study cohort was rhinitis, followed by others such as asthma, sense of smell and atopic dermatitis. Conclusions: SPT seems to be more sensitive than specific IgE for detection of sensitization. Patients’ symptoms as well as the timing of symptoms, especially for perennial allergies, are not always very pronounced

Characterisation of the recruitmentdomain of the Rho-GTPases RhoA and RhoC

Bakterien der Gattung Shigella sind die Erreger der bakteriellen Ruhr beim Menschen. Der wesentliche Virulenzfaktor der Shigellen ist ihre Fähigkeit zur Invasion. Die Invasion in Epithelzellen ist Ausdruck des erregerspezifischen Infektionsprozesses, der gekennzeichnet ist durch eine vom Bakterium induzierte zelluläre Aufnahme über einen Phagozytose-ähnlichen Mechanismus. In dessen Verlauf kommt es zur charakteristischen Reorganisation des Zytoskeletts der Zelle mit Ausbildung einer blütenartigen Membranstruktur an der bakteriellen Eintrittsstelle, deren Bildung von der kleinen GTPase Rho abhängig ist. Es wurde gezeigt, dass die Rho-Isoformen RhoA und RhoC selbst an den bakteriellen Invasionslocus rekrutiert werden. Trotz hoher Sequenzhomologie der Isoformen untereinander existiert aber ein unterschiedliches Rekrutierungsmuster: RhoA akkumuliert vorwiegend um die eindringenden Bakterien herum während RhoC in die bakterieninduzierten zellulären Protrusionen rekrutiert wird. Für diese differentielle Rekrutierung ist die polybasische Rekrutierungsdomäne am C-Terminus der beiden Rho- Isoformen notwendig und ausreichend. Um eine weitere Charakterisierung der Rekrutierungsdomäne zu ermöglichen wurden Konstrukte mit dieser polybasischen Domäne kloniert und exprimiert. Die exprimierten Proteine wurden in Kooperation mit der Arbeitsgruppe von Konrad Büssow in einem Overlayassay eingesetzt. In einer vorläufigen Auswertung konnte eine Vielzahl von potentiellen in-vitro Bindungspartnern der Rekrutierungsdomäne von RhoA und RhoC nachgewiesen werden. Fast alle Zellkompartimente waren vertreten, Einschränkungen hinsichtlich der Proteinfunktion waren nicht ersichtlich. Die Ergebnisse sprechen für eine pleiotrope Wirkung von RhoA und RhoC auf verschiedene Funktionen und Bereiche der Zelle und haben weitreichende Konsequenzen für die funktionelle Rolle der beiden Rho-GTPasen über die Epithelzellinvasion durch Shigella hinaus.Shigella is the etiologic agent of human bacillary dysentry, an infectious large bowel disease. A major feature of Shigella’s pathogenic potential is the capacity to invade epithelial cells. Shigella entry into epithelial cells is considered a parasite-induced internalization requiring cytosceletal rearrangements; Shigella entry induces a blossom-like membrane structure at the bacterial entry site. This membrane folding process is dependent on the small GTPase Rho. It has been shown that the two Rho isoforms RhoA and RhoC are recruited into bacterial entry sites with different localization relative to the membrane structures. While RhoA preferentially accumulates in close vicinity to entering bacteria, RhoC is recruited into the tips of Shigella- induced cellular protrusions. This differential recruitment is mediated by a polybasic recruitment-domain at the C-terminal end of the Rho-GTPases. To further characterise this polybasic region we cloned and expressed constructs containing the tagged Rho C-terminus. In cooperation with Konrad Büssow´s group the purified proteins were used to probe a human expression library for binding. In a preliminary evaluation of the results we found a multitude of potential in-vitro binding partners of this protein domain. These results are of importance for the functional role of the Rho-GTPases not only during Shigella-invasion into epithelial cells but also for their role in the regulation of cellular processes

Obstructive Sleep Apnea in Patients with Head and Neck Cancer—More than Just a Comorbidity?

Obstructive sleep apnea is the most common type of sleep-disordered breathing with growing prevalence. Its presence has been associated with poor quality of life and serious comorbidities. There is increasing evidence for coexisting obstructive sleep apnea in patients suffering from head and neck cancer, a condition that ranks among the top ten most common types of cancer worldwide. Routinely, patients with head and neck cancer are treated with surgery, radiation therapy, chemotherapy, immunotherapy or a combination of these, all possibly interfering with the anatomy of the oral cavity, pharynx or larynx. Thus, cancer treatment might worsen already existing obstructive sleep apnea or trigger its occurrence. Hypoxia, the hallmark feature of obstructive sleep apnea, has an impact on cancer biology and its cure. Early diagnosis and sufficient treatment of coexisting obstructive sleep apnea in patients with head and neck cancer may improve quality of life and could also potentially improve oncological outcomes

Obstructive Sleep Apnea in Patients with Head and Neck Cancer—More than Just a Comorbidity?

Obstructive sleep apnea is the most common type of sleep-disordered breathing with growing prevalence. Its presence has been associated with poor quality of life and serious comorbidities. There is increasing evidence for coexisting obstructive sleep apnea in patients suffering from head and neck cancer, a condition that ranks among the top ten most common types of cancer worldwide. Routinely, patients with head and neck cancer are treated with surgery, radiation therapy, chemotherapy, immunotherapy or a combination of these, all possibly interfering with the anatomy of the oral cavity, pharynx or larynx. Thus, cancer treatment might worsen already existing obstructive sleep apnea or trigger its occurrence. Hypoxia, the hallmark feature of obstructive sleep apnea, has an impact on cancer biology and its cure. Early diagnosis and sufficient treatment of coexisting obstructive sleep apnea in patients with head and neck cancer may improve quality of life and could also potentially improve oncological outcomes