A Comparison of the Effects of Continuous Illumination and Day/Night Regimes on PHB Accumulation in Synechocystis Cells.

Poly(3-hydroxybutyrate) (PHB) is a biobased and biodegradable polymer with properties comparable to polypropylene and therefore has the potential to replace conventional plastics. PHB is intracellularly accumulated by prokaryotic organisms. For the cells PHB functions manly as carbon and energy source, but all possible functions of PHB are still not known. Synechocystis (cyanobacteria) accumulates PHB using light as energy and CO2 as carbon source. The main trigger for PHB accumulation in cyanobacteria is nitrogen and phosphorous depletion with simultaneous surplus of carbon and energy. For the above reasons, obtaining knowledge about external factors influencing PHB accumulation is of highest interest. This study compares the effect of continuous light exposure and day/night (16/8 h) cycles on selected physiology parameters of three Synechocystis strains. We show that continuous illumination at moderate light intensities leads to an increased PHB accumulation in Synechocystis salina CCALA 192 (max. 14.2% CDW - cell dry weight) compared to day/night cycles (3.7% CDW). In addition to PHB content, glycogen and cell size increased, while cell density and cell viability decreased. The results offer new approaches for further studies to gain deeper insights into the role of PHB in cyanobacteria to obtain bioplastics in a more sustainable and environmentally friendly way.

Difficulty Falling Asleep is Associated with Poorer Therapeutic Outcomes in Unilateral Hypoglossal Nerve Stimulation.

Purpose: The coexistence of insomnia and obstructive sleep apnea (OSA) is very prevalent. Hypoglossal nerve stimulation (HGNS) is an established second-line therapy for patients suffering OSA. Studies investigating the effect of the different aspects of insomnia on the therapeutic outcome are largely missing. Therefore, this study aimed to understand the impact of the different aspects of insomnia on the therapeutic outcome under HGNS therapy in clinical routine. Patients and Methods: This is a retrospective study including 30 consecutive patients aged 55.40 ± 8.83 years (8 female; 22 male) undergoing an HGNS implantation in our tertiary medical center between 2020 and 2023. All patients underwent preoperative polysomnography (PSG) according to AASM. First follow-up PSG was performed 95.40 ± 39.44 days after activation (30 patients) and second follow-up PSG was performed 409.89 ± 122.52 days after activation (18 patients). Among others, the following PSG-related parameters were evaluated: apnea-hypopnea index (n/h) (AHI) and oxygen desaturation index (n/h) (ODI). Insomnia was assessed by the insomnia severity index (ISI) questionnaire. Preoperatively, all patients included filled out each ISI item. Spearman's-rho correlation coefficient was calculated for correlations. Results: Preoperative score of ISI item 1 (difficulty falling asleep) was 1.93 ± 1.34 and preoperative cumulative ISI score (item1-7) was 18.67 ± 5.32. Preoperative AHI was 40.61 ± 12.02 (n/h) and preoperative ODI was 38.72 ± 14.28 (n/h). In the second follow-up, the mean difference in AHI was ∆ 10.47 ± 15.38 (n/h) and the mean difference in ODI was ∆ 8.17 ± 15.67 (n/h). Strong significant correlations were observed between ISI item 1 (difficulty falling asleep) and both ∆ AHI (r: -0.65, p=0.004) and ∆ ODI (r: -0.7; p=0.001) in the second follow-up. Conclusion: Difficulty falling asleep may hence negatively influence HGNS therapeutic outcome. Insomnia-related symptoms should be considered in the preoperative patient evaluation for HGNS.

Heart Rate Variability as a Surrogate Marker of Severe Chronic Coronary Syndrome in Patients with Obstructive Sleep Apnea.

BACKGROUND AND OBJECTIVES: Obstructive sleep apnea (OSA) is a known risk factor for chronic coronary syndrome (CCS). CCS and OSA are separately associated with significant changes in heart rate variability (HRV). In this proof-of-concept study, we tested whether HRV values are significantly different between OSA patients with concomitant severe CCS, and OSA patients without known CCS. MATERIAL AND METHODS: The study comprised a retrospective assessment of the historical and raw polysomnography (PSG) data of 32 patients who presented to a tertiary university hospital with clinical complaints of OSA. A total of 16 patients (four females, mean age 62.94 ± 2.74 years, mean body mass index (BMI) 31.93 ± 1.65 kg/m2) with OSA (median apnea-hypopnea index (AHI) 39.1 (30.5-70.6)/h) and severe CCS were compared to 16 patients (four females, mean age 62.35 ± 2.06 years, mean BMI 32.19 ± 1.07 kg/m2) with OSA (median AHI 40 (30.6-44.5)/h) but without severe CCS. The short-long-term HRV (in msec) was calculated based on the data of a single-lead electrocardiogram (ECG) provided by one full-night PSG, using the standard deviation of the NN, normal-to-normal intervals (SDNN) and the heart rate variability triangular index (HRVI) methods, and compared between the two groups. RESULTS: A significant reduction (p < 0.05) in both SDNN and HRVI was found in the OSA group with CCS compared to the OSA group without CCS. CONCLUSIONS: Severe CCS has a significant impact on short-long-term HRV in OSA patients. Further studies in OSA patients with less-severe CCS may shed more light onto the involved mechanistic processes. If confirmed in future larger studies, this physiologic metric has the potential to provide a robust surrogate marker of severe CCS in OSA patients.

Drug-Induced Sleep Endoscopy Findings and Hypoglossal Nerve Stimulation Therapy Outcomes.

Hypoglossal-nerve stimulation (HGNS) is an established second-line therapy for patients with obstructive sleep apnea (OSA). Existing studies investigating the effect of preoperative drug-induced sleep endoscopic (DISE) findings on HGNS outcomes have mainly focused on the apnea/hypopnea index (AHI) among polysomnography (PSG) parameters, and have less frequently tested other PSG parameters such as the apnea index (AI), hypopnea index (HI), oxygen desaturation index (ODI), snoring index, and arousal index, or patient-reported excessive daytime sleepiness. The aim of this study was to investigate the correlation between DISE findings and the above-mentioned metrics after HGNS therapy. We only included patients with DISE findings providing detailed information about the degree of the anteroposterior velar (APV), oropharyngeal lateral wall (OPLW), or tongue-base (BT) obstruction based on the velum, oropharynx, base of tongue, and epiglottis (VOTE) classification. The data of 25 patients (9 female (36%)) were retrospectively evaluated. The mean age at the date of implantation was 54.52 ± 9.61 years, and the mean BMI was 29.99 ± 3.97 kg/m2. Spearman's rho correlation coefficients were calculated. Significant correlations were found between the degree of APV obstruction and postoperative HI (r = -0.5, p < 0.05), and between the degree of OPLW obstruction and postoperative snoring index (r = 0.42, p < 0.05). BT obstruction was strongly correlated with postoperative metrics such as AHI (r = -0.57, p < 0.01), AI (r = -0.5, p < 0.05), ODI (r = -0.57, p < 0.01), ∆ AHI (r = 0.58, p < 0.01), ∆ AI (r = 0.54, p < 0.01) and ∆ ODI (r = 0.54, p < 0.01). No significant correlation was found between DISE findings and postoperative Epworth Sleepiness Scale values. These findings suggest that preoperative DISE findings, especially the degree of BT obstruction, are important for predicting an HGNS therapy outcome.

Central Apneic Event Prevalence in REM and NREM Sleep in OSA Patients: A Retrospective, Exploratory Study.

Patients with sleep-disordered breathing show a combination of different respiratory events (central, obstructive, mixed), with one type being predominant. We observed a reduced prevalence of central apneic events (CAEs) during REM sleep compared to NREM sleep in patients with predominant obstructive sleep apnea (OSA). The aim of this retrospective, exploratory study was to describe this finding and to suggest pathophysiological explanations. The polysomnography (PSG) data of 141 OSA patients were assessed for the prevalence of CAEs during REM and NREM sleep. On the basis of the apnea-hypopnea index (AHI), patients were divided into three OSA severity groups (mild: AHI < 15/h; moderate: AHI = 15-30/h; severe: AHI > 30/h). We compared the frequency of CAEs adjusted for the relative length of REM and NREM sleep time, and a significantly increased frequency of CAEs in NREM was found only in severely affected OSA patients. Given that the emergence of CAEs is strongly associated with the chemosensitivity of the brainstem nuclei regulating breathing mechanics in humans, a sleep-stage-dependent chemosensitivity is proposed. REM-sleep-associated neuronal circuits in humans may act protectively against the emergence of CAEs, possibly by reducing chemosensitivity. On the contrary, a significant increase in the chemosensitivity of the brainstem nuclei during NREM sleep is suggested.

Insomnia in Patients Undergoing Hypoglossal Nerve Stimulation Therapy for Obstructive Sleep Apnea.

Hypoglossal nerve stimulation (HGNS) is a treatment for obstructive sleep apnea (OSA) patients with intolerance of positive airway pressure therapy. Comorbid insomnia is quite prevalent in OSA patients. We investigated the impact of insomnia and excessive daytime sleepiness (EDS) on polysomnography metrics after HGNS treatment. Data of 27 consecutive patients (9 female; mean age 55.52 ± 8.6 years) were retrospectively evaluated. Insomnia was assessed using the ISI (insomnia severity index) and EDS using the Epworth sleepiness scale (ESS). The median ISI was reduced significantly 3 months after HGNS activation (preoperative: 19; postoperative: 14; p < 0.01). Significant correlations emerged between preoperative ISI and postoperative AHI (apnea/hypopnea index; Spearman's rho = 0.4, p < 0.05), ∆ AHI (r = −0.51, p < 0.01) and ∆ ODI (oxygen desaturation index; r = −0.48, p < 0.05). ISI correlated strongly with EES both preoperatively (r = 0.46; p < 0.02) and postoperatively (r = 0.79; p < 0.001). Therefore, HGNS therapy is associated with a significant reduction of insomnia-related symptoms, in addition to the improvement in respiratory metrics in OSA. Nonetheless, the preoperative severity of patient-reported insomnia symptoms was inversely correlated with the respiratory PSG-outcomes after HGNS. Insomnia should be considered in studies of EDS in OSA patients, especially those treated with HGNS.

Short-Term Outcome of Unilateral Inspiration-Coupled Hypoglossal Nerve Stimulation in Patients with Obstructive Sleep Apnea.

Hypoglossal nerve stimulation (HGNS) is a therapeutic option for patients with obstructive sleep apnea (OSA) and intolerance of positive airway pressure (PAP) therapy. Most reported data are based on multicentre pivotal trials with selected baseline core clinical features. Our aim was to investigate polysomnography (PSG)-based outcomes of HGNS-therapy in a patient cohort with higher average AHI and BMI than previously reported. Data of 29 consecutive patients (nine female; mean age: 55.52 ± 8.6 years, mean BMI 30.13 ± 3.93 kg/m2) were retrospectively evaluated. Numerical values of PSG- based metrics were compared before and after intervention using Wilcoxon's rank-sum test. AHI (38.57/h ± 12.71, 24.43/h ± 13.3, p < 0.001), hypopnea index (24.05/h ± 9.4, 15.27/h ± 8.23, p < 0.001), apnea index (14.5/h ± 12.05, 9.17/h ± 10.86, p < 0.01), snoring index (262.68/h ± 170.35, 143.48/h ± 162.79, p < 0.001), cortical arousal index (20.8/h ± 10.34 vs. 14.9/h ± 8.36, p < 0.01) and cumulative duration of apnea and hypopnea during sleep (79.79 min ± 40.32 vs. 48.62 min ± 30.56, p < 0.001) were significantly lower after HGNS. HGNS provides an effective therapy option for selected patients not tolerating PAP-therapy with higher average AHI and BMI than usually reported. HGNS-therapy appears to suppress central nervous system arousal circuits while not eliciting peripheral autonomous sympathetic activation. Such metrics as the snoring index and the cumulative duration of respiratory events during sleep may be considered in future HGNS studies.

Obstructive Sleep Apnea Disrupts Glycemic Control in Obese Individuals.

The link between obstructive sleep apnea (OSA) and obesity, and their common comorbidities such as diabetes mellitus (DM) or cardiovascular diseases, is not fully understood. The aim of this study was to investigate the possible association of OSA severity in obese individuals with polysomnography-based sleep parameters, as well as C-reactive protein (CRP) and glycated hemoglobin (HbA1c) serum levels. Polysomnographic recordings and blood samples were retrospectively compared between a group of 23 adult obese individuals with mild OSA (apnea-hypopnea index (AHI) = 7.5 (5.5-12.5)/h, age = 42.57 ± 11.44 years, 16 male, 7 female, body mass index (BMI) = 37.35 ± 3.88 kg/m²) and an age-, sex-, and BMI-matched group of individuals with moderate or severe OSA (AHI 41.5 (25.7-71.8)/h, age = 43.43 ± 11.96 years, 16 male, 7 female, BMI = 37.87 ± 4.74 kg/m²). All respiratory sleep-associated parameters were significantly higher in individuals with moderate and severe OSA compared to those with mild OSA. CRP levels did not differ between the two OSA severity groups. However, serum levels of HbA1c were significantly higher in the moderate/severe OSA group. Therefore, OSA severity may have a significant impact on glycemic control in obese individuals. Additionally, OSA severity did not appear to be further associated with systemic inflammation in obese individuals. Obese individuals may benefit not only from lifestyle modification, but also from OSA screening and treatment, particularly to prevent DM-associated disorders and conditions.

A Novel Quantitative Arousal-Associated EEG-Metric to Predict Severity of Respiratory Distress in Obstructive Sleep Apnea Patients.

Respiratory arousals (RA) on polysomnography (PSG) are an important predictor of obstructive sleep apnea (OSA) disease severity. Additionally, recent reports suggest that more global indices of desaturation such as the hypoxic burden, namely the area under the curve (AUC) of the oxygen saturation (SaO2) PSG trace may better depict the desaturation burden in OSA. Here we investigated possible associations between a new metric, namely the AUC of the respiratory arousal electroencephalographic (EEG) recording, and already established parameters as the apnea/hypopnea index (AHI), arousal index and hypoxic burden in patients with OSA. In this data-driven study, polysomnographic data from 102 patients with OSAS were assessed (32 female; 70 male; mean value of age: 52 years; mean value of Body-Mass-Index-BMI: 31 kg/m2). The marked arousals from the pooled EEG signal (C3 and C4) were smoothed and the AUC was estimated. We used a support vector regressor (SVR) analysis to predict AHI, arousal index and hypoxic burden as captured by the PSG. The SVR with the arousal-AUC metric could quite reliably predict the AHI with a high correlation coefficient (0,58 in the training set, 0,65 in the testing set and 0,64 overall), as well as the hypoxic burden (0,62 in the training set, 0,58 in the testing set and 0,59 overall) and the arousal index (0,58 in the training set, 0,67 in the testing set and 0,66 overall). This novel arousal-AUC metric may predict AHI, hypoxic burden and arousal index with a quite high correlation coefficient and therefore could be used as an additional quantitative surrogate marker in the description of obstructive sleep apnea disease severity.

Cellular Immune Dysfunction in Obstructive Sleep Apnea.

Obstructive sleep apnea (OSA) is the most common sleep-related breathing disorder. Repetitive pauses in breathing during sleep cause a brief but recurrent decrease in oxygen saturation in organs and tissues (chronic intermittent tissue hypoxia). Many studies have proven a pro-inflammatory status in OSA patients. However, few reports are available on the effects of OSA on the cellular immune system, mostly focusing on single immune cell types and their subtypes. The aim of this Mini-Review is to summarize these reports, as OSA is associated with a high prevalence and comorbidities such as atherosclerosis, which are known to involve the cellular immune system.

Reduced Cross-Frequency Coupling and Daytime Sleepiness in Obstructive Sleep Apnea Patients.

Obstructive sleep apnea (OSA) is associated with sleep-stage- and respiratory-event-specific sensorimotor cortico-muscular disconnection. The modulation of phase−amplitude cross-frequency coupling (PACFC) may influence information processing throughout the brain. We investigated whether sleep-stage-specific PACFC is impaired at the sensorimotor areas in OSA patients. C3 and C4 electrode EEG polysomnography recordings of 170 participants were evaluated. Different frequency band combinations were used to compute CFC modulation index (MI) to assess if MI differs between OSA and non-significant OSA patients in distinct sleep stages. We tested if the CFC-MI could predict daytime sleepiness in OSA. Theta−gamma CFC-MI at cortical sensorimotor areas was significantly reduced during all sleep stages; the delta−alpha CFC-MI was significantly reduced during REM and N1 while increasing during N2 in patients with respiratory disturbance index (RDI) > 15/h compared to those with RDI ≤ 15/h. A sleep stage classification using MI values was achieved in both patient groups. Theta−gamma MI during N2 and N3 could predict RDI and Epworth Sleepiness Scale, while delta−alpha MI during REM predicted RDI. This increase in disconnection at the cortical sensorimotor areas with increasing respiratory distress during sleep supports a cortical motor dysfunction in OSA patients. The MI provides an objective marker to quantify subjective sleepiness and respiratory distress in OSA.

Accumulating Comorbidities May Promote Increasing Severity of Obstructive Sleep Apnea with Aging in Males but Not in Females.

Evidence suggests an increasing apnea−hypopnea index (AHI) with aging. However, the effect of aging on sleep-related metrics, especially AHI, has been less frequently investigated within different gender-specific subpopulations by taking prominent confounding factors, e.g., obstructive sleep apnea (OSA)-related comorbidities and body mass index (BMI) into account. Therefore, we retrospectively analyzed 186 first-time polysomnographic (PSG) recordings and medical files of all patients presented to a tertiary university sleep center during a 1-year period. Six groups were formed based on age (over vs. under 55 years) and gender: PSG-related parameters (AHI, apnea-index, and hypopnea-index) were significantly higher in the older mixed-gender cohort (p = 0.0001, p = 0.0011, and p = 0.0015, respectively), and the older female cohort (p = 0.0005, p = 0.0027, and p = 0.001, respectively). Within the older male cohort, the AHI and apnea-index were significantly higher (p = 0.0067, and p = 0.0135, respectively). Inter-group comparison of the BMI showed no significant difference in any subpopulation. Within the older male cohort there were significantly more patients with arterial hypertension, diabetes mellitus, cardiovascular diseases, and chronic mental health disorders (p < 0.0001, p = 0.001, p = 0.0181, and p = 0.0454, respectively). Contrarily, within the female subpopulation there were no significant differences for the aforementioned comorbidities. In conclusion, all investigated sleep PSG-parameters increased among the older subpopulations. We suggest that Osa severity may increase with age due to the increasing accumulation of comorbidities in males, but not in females.