The immune response in patients with sleep apnea syndrome

Background:Obstructive Sleep Apnea Syndrome (OSAS) may be associated with elevated plasma levels of IL-6 and TNF-α. We hypothesized that plasma levels of IL-6 and TNF-a are increased during the night in OSAS patients secondary to the intermittent strenuous diaphragmatic contractions and the episodes of hypoxia-reoxygenation associated with the obstuctive apneas-hypopneas.Furthermore, monocytes and diaphragm myocytes are the source of increased circulating cytokines during the night and oxidative stress is the stimulus for cytokine upregulation in OSAS.Methods:28 patients diagnosed with OSAS ( 21 M; AHI: 37.8, Age: 49.8) and 11 healthy ( AHI<5) were studied. OSAS Patients underwent 4 overnight PSG (polysomnographic) sleep studies: i)Standard PSG study which is a repeat study of their initial diagnostic PSG study, with an indwelling i.v. catheter in place for blood sample collection,ii) Oxygen supplemmentation study during which patients were supplemented with oxygen via a non-rebreathing mask to prevent (to the extent possible) oxygen desaturation iii) a continuous positive airway pressure PSG study to prevent obstructive apnea-hypopnea induced strenuous diaphragmatic contractions,iv) antioxidants supplementation study which was a repeat standard PSG study after patients will receive a previously described antioxidant regime for 2 months. IL-6 & TNF-α plasma levels were measured at baseline, every 20 minutes intervals and 30 minutes past morning arousal,using ELISA comercially available kits. Circulating monocytes intracellular cytokine concetration was determined using Flow Cytometry with a previously described method. Known Il-6 promoter gene polymorphisms frequencies were identified in our OSAS and control cohort.Results: OSAS patients exhibit higher plasma il- 6 levels compared with non OSAS controls p<0.02. The il-6 variation is predicted independently by the duration of the apnoeic episodes and the average oxygen saturation. The nocturnal IL-6 response to OSAS is not uniform across our cohort but exhibits individual variation classifiable in an IL-6 raising and a non raising group. The different response between the two groups cannot be attributed to il-6 gene promoter polymorphism. The IL-6 raising group exhibited worse oxygen saturation p<0.01 and less total hypopneas duration p<0.01. Oxygen supplementation and nCPAP treatment reduce the nocturnal il-6 variation-loading in the il-6 raising individuals only p<0.005, compared with the standard study. Mononuclear cells are not the source of circulating il-6 in our cohort of OSAS patients and normal subjects. Antioxidant administration does not attenuate the IL-6. No difference was identified in TNF-α plasma levels between OSAS and control individuals.Conclusions: Establishing an individual inflammatory response within OSAS patients may have implications on OSAS related clinical sequalae, and thus merits further investigation. Though the stimulus and source or even the presence of raised IL-6 levels remain elusive, the results of this work render our original hypothesis more plausible.Εισαγωγή: Το Σύνδρομο Απνοιών Υποπνοιών Ύπνου ( ΣΑΥΥ) ενδέχεται να συνδέεται με αυξημένα επίπεδα IL-6 και TNF-α στο πλάσμα. Υποθέσαμε πως τα επίπεδα πλάσματος IL-6 και TNF-α αύξανονται κατά τη διάρκεια της νύχτας σε ασθενείς με ΣΑΥΥ, ως αποτέλεσμα διαλείποντων, έντονων συσπάσεων του διαφράγματος και των επεισοδίων υποξαιμίας που προκαλούν οι αποφρακτικές άπνοιες και υπόπνοιες. Επιπρόσθετα, τα μονοκύτταρα και τα μυοκύτταρα του διαφράγματος είναι η πηγή των αυξημένων κυκλοφορούντων κυτταροκινών και το οξειδωτικό stress συνιστά το ερέθισμα.Μέθοδοι: Μελετήσαμε 28 ασθενείς διεγνωσμένους με ΣΑΥΥ και 11 υγιείς μάρτυρες.Οι ασθενέις με ΣΑΥΥ υπεβλήθησαν σε 4 πολυσωματοκαταγραφικές (ΠΣΚ) μελέτες ύπνου. Πρότυπη μελέτη, η οποία συνιστούσε επανάληψη της αρχικής διαγνωστικής μελέτης.Κατά τη δεύτερη μελέτη, έγινε χορήγηση οξυγόνου (Fi02 85-90%) μέσω μάσκας χωρίς επανεισπνοή. Κατά την τρίτη συνεδρία, χορηγήθηκε συνεχής θετική πίεση αεραγωγών (CPAP) με ρινική μάσκα. Η τέταρτη συνεδρία ήταν μία πρότυπη ΠΣΚ μελέτη, αφού χορηγήθηκε αντιοξειδωτική αγωγή για 2 μήνες.Τα υγιή άτομα που αποτέλεσαν την ομάδα μαρτύρων υποβλήθηκαν σε μία και μοναδική πρότυπη ΠΣΚ μελέτη. Έγινε λήψη δειγμάτων περιφερικού αίματος των συμμετεχόντων κατά την αρχική αξιολόγηση, ανά 20 λεπτά και 30 λεπτά μετά την τελική πρωινή αφύπνιση.Τα επίπεδα πλάσματος της ιντερλευκίνης-6 (IL-6) και του παράγοντα νέκρωσης όγκων-α (TNF-α) μετρήθηκαν με χρήση κιτ ELISAΗ ανίχνευση κυτταροκινών με κυτταρομετρία ροής πραγματοποιήθηκε όπως έχει περιγραφεί. Η συχνότητα των δύο συχνότερων πολυμορφισμών του γονιδίου προαγωγέα της IL-6 μελετήθηκαν στον πληθυσμό ΣΑΥΥ και τους υγιείς μάρτυρεςΑποτελέσματα: Άτομα που πάσχουν από σοβαρό ΣΑΥΑ παρουσιάζουν υψηλότερα επίπεδα της IL-6 στο πλάσμα από τους υγιείς μάρτυρες.. Η διακύμανση της IL-6 προβλέφθηκε ανεξάρτητα, από τη διάρκεια των απνοϊκών επεισοδίων και τον μέσο κορεσμό οξυγόνου Η φλεγμονώδης απόκριση στο ΣΑΥΑ δεν είναι ομοιόμορφη στο σύνολο της κοόρτης μας αλλά διακυμένεται μεταξύ μίας ομάδας που εμφανίζει αύξηση της IL-6 στο πλάσμα και σε μία άλλη που δεν εμφανίζει. Η διαφορετική απόκριση μεταξύ των δύο ομάδων δεν μπορεί να αποδοθεί σε πολυμορφισμό του υποκινητή του γονιδίου της IL-6. Οι δύο ομάδες εμφανίζουν διαφορετικούς τύπους υπνικών επεισοδίων. Η συμπληρωματική χορήγηση οξυγόνου και η χορήγηση θεραπείας με ρινική μάσκα CPAP μειώνουν τη νυκτερινή φόρτιση με IL-6 στα άτομα με αύξηση της IL-6, σε σύγκριση με την πρότυπη μελέτη. Τα μονοκύτταρα δεν είναι η πηγή της αυξημένης κυκλοφορούσας IL-6 στην κοόρτη ασθενών με ΣΑΥΑ. Η χορήγηση αντιοξειδωτικής θεραπείας δε μειώνει τα επίπεδα IL-6. Τα αποτελέσματα αυτά δεν παρατηρήθηκαν σε σχέση με τα επίπεδα TNF-a στο πλάσμα.Το έυρημα της ανομοιομορφίας στην ανοσολογική απόκριση των ασθενών με ΣΑΥΥ μπορεί να έχει σημαντικές επιπτώσεις σε ότι αφορά τις καρδιοαγγειακές συνέπειες του συνδρομου και άρα χρήζει περαιτέρω διερεύνησης. Παρ ‘όλο που το ερέθισμα και η πηγή των κυτταροκινών συνεχίζει να είναι αδιευκρίνιστη, τα αποτελέσματα αυτής της εργασίας κάνουν την αρχική μας υπόθεση πιο πίθανη

Regulation of breathing pattern by IL-10

Proinflammatory cytokines like interleukin-1 beta (IL-1 beta) affect the control of breathing. Our aim is to determine the effect of the anti-inflammatory cytokine IL-10 on the control of breathing. IL-10 knockout mice (IL-10(-/-), n = 10) and wild-type mice (IL-10(+/+), n = 10) were exposed to the following test gases: hyperoxic hypercapnia 7% CO2-93% O-2, normoxic hypercapnia 7% CO2-21% O-2, hypoxic hypercapnia 7% CO2-10% O-2, and hypoxic normocapnia 3% CO2-10% O-2. The ventilatory function was assessed using whole body plethysmography. Recombinant mouse IL-10 (rIL-10; 10 mu/kg) was administered intraperitoneally to wild-type mice (n = 10) 30 min before the onset of gas challenge. IL-10 was administered in neonatal medullary slices (10-30 ng/ml, n = 8). We found that IL-10(-/-) mice exhibited consistently increased frequency and reduced tidal volume compared with IL-10(+/+) mice during room air breathing and in all test gases (by 23.62 to 33.2%, P &lt; 0.05 and -36.23 to -41.69%, P &lt; 0.05, respectively). In all inspired gases, the minute ventilation of IL-10(-/-) mice was lower than IL-10(+/+) (by -15.67 to -22.74%, P &lt; 0.05). The rapid shallow breathing index was higher in IL-10(-/-) mice compared with IL-10(+/+) mice in all inspired gases (by 50.25 to 57.5%, P &lt; 0.05). The intraperitoneal injection of rIL-10 caused reduction of the respiratory rate and augmentation of the tidal volume in room air and also in all inspired gases (by -12.22 to -29.53 and 32.18 to 45.11%, P &lt; 0.05, respectively). IL-10 administration in neonatal rat (n = 8) in vitro rhythmically active medullary slice preparations did not affect either rhythmicity or peak amplitude of hypoglossal nerve discharge. In conclusion, IL-10 may induce a slower and deeper pattern of breathing

COVID-19 Outbreak on a Passenger Ship and Assessment of Response Measures, Greece, 2020

We describe response measures to an outbreak involving 128 (33.4%) coronavirus disease cases (46.1% asymptomatic) among 383 persons onboard a passenger ship. Multivariate analysis indicated that dining in certain rooms and bar areas, nationality, working department (for crew members), and quarantining onboard the ship were significantly associated with infection

Privacy Regulations, Context aware services,

middleware Recent advances in mobile communications, location/sensing technologies and data processing are boosting the deployment of context-aware services and smart spaces creation. This is reflected in urban environments by the smart-city vision, a city with advanced ICT and surveillance infrastructures offering to citizens a diversity of services. Nevertheless, privacy risks and threats ambush, since collection and process of large amount of personal data occur. Although technology enables the collection of data, its protection against abuse is left to data protection legislation. However, privacy terms to be regarded as legislature issues, should be brought down in the technological reality and carefully accounted for in devising technical solutions. In order to limit the disclosure and misuse of citizens ’ personal data, this report introduces a distributed unit o

COVID-19 Outbreak on a Passenger Ship and Assessment of Response Measures, Greece, 2020

We describe response measures to an outbreak involving 128 (33.4%) coronavirus disease cases (46.1% asymptomatic) among 383 persons onboard a passenger ship. Multivariate analysis indicated that dining in certain rooms and bar areas, nationality, working department (for crew members), and quarantining onboard the ship were significantly associated with infection

Molecular Epidemiology of SARS-CoV-2 in Greece Reveals Low Rates of Onward Virus Transmission after Lifting of Travel Restrictions Based on Risk Assessment during Summer 2020.

The novel coronavirus severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) spread rapidly during the first months of 2020 and continues to expand in multiple areas across the globe. Molecular epidemiology has provided an added value to traditional public health tools by identifying SARS-CoV-2 clusters or providing evidence that clusters based on virus sequences and contact tracing are highly concordant. Our aim was to infer the levels of virus importation and to estimate the impact of public health measures related to travel restrictions to local transmission in Greece. Our phylogenetic and phylogeographic analyses included 389 full-genome SARS-CoV-2 sequences collected during the first 7 months of the pandemic in Greece and a random collection in five replicates of 3,000 sequences sampled globally, as well as the best hits to our data set identified by BLAST. Phylogenetic trees were reconstructed by the maximum likelihood method, and the putative source of SARS-CoV-2 infections was inferred by phylogeographic analysis. Phylogenetic analyses revealed the presence of 89 genetically distinct viruses identified as independent introductions into Greece. The proportion of imported strains was 41%, 11.5%, and 8.8% during the three periods of sampling, namely, March (no travel restrictions), April to June (strict travel restrictions), and July to September (lifting of travel restrictions based on thorough risk assessment), respectively. The results of phylogeographic analysis were confirmed by a Bayesian approach. Our findings reveal low levels of onward transmission from imported cases during summer and underscore the importance of targeted public health measures that can increase the safety of international travel during a pandemic. IMPORTANCE Our study based on current state-of-the-art molecular epidemiology methods suggests that virus screening and public health measures after the lifting of travel restrictions prevented SARS-CoV-2 onward transmission from imported cases during summer 2020 in Greece. These findings provide important data on the efficacy of targeted public health measures and have important implications regarding the safety of international travel during a pandemic. Our results can provide a roadmap about prevention policy in the future regarding the reopening of borders in the presence of differences in vaccination coverage, the circulation of the virus, and the presence of newly emergent variants across the globe

Molecular Epidemiology of SARS-CoV-2 in Greece Reveals Low Rates of Onward Virus Transmission after Lifting of Travel Restrictions Based on Risk Assessment during Summer 2020

The novel coronavirus severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) spread rapidly during the first months of 2020 and continues to expand in multiple areas across the globe. Molecular epidemiology has provided an added value to traditional public health tools by identifying SARS-CoV-2 clusters or providing evidence that clusters based on virus sequences and contact tracing are highly concordant. Our aim was to infer the levels of virus importation and to esti-mate the impact of public health measures related to travel restrictions to local transmission in Greece. Our phylogenetic and phylogeographic analyses included 389 full-genome SARS-CoV-2 sequences collected during the first 7 months of the pandemic in Greece and a random collection in five replicates of 3,000 sequences sampled globally, as well as the best hits to our data set identified by BLAST. Phylogenetic trees were reconstructed by the maximum likelihood method, and the putative source of SARS-CoV-2 infections was inferred by phylogeographic analysis. Phylogenetic analyses revealed the presence of 89 genetically distinct viruses identified as independent introductions into Greece. The proportion of imported strains was 41%, 11.5%, and 8.8% during the three periods of sampling, namely, March (no travel restrictions), April to June (strict travel restrictions), and July to September (lifting of travel restrictions based on thorough risk assessment), respectively. The results of phylogeographic analysis were confirmed by a Bayesian approach. Our findings reveal low levels of onward transmission from imported cases during summer and underscore the importance of targeted public health measures that can increase the safety of international travel during a pandemic. IMPORTANCE Our study based on current state-of-the-art molecular epidemiology methods suggests that virus screening and public health measures after the lifting of travel restrictions prevented SARS-CoV-2 onward transmission from imported cases during summer 2020 in Greece. These findings provide important data on the efficacy of targeted public health measures and have important implications regarding the safety of international travel during a pandemic. Our results can provide a roadmap about prevention policy in the future regarding the reopening of borders in the presence of differences in vaccination coverage, the circulation of the virus, and the presence of newly emergent variants across the globe

Nationwide Survey in Greece about Knowledge, Risk Perceptions, and Preventive Behaviors for COVID-19 during the General Lockdown in April 2020

Background: The aim of this study was to investigate the knowledge, attitudes, and practices of the Greek general population toward coronavirus disease 2019 (COVID-19) during the lockdown period in April 2020, to examine factors associated with misperceptions and to determine behavioral patterns that may require interventions. Methods: A cross-sectional study of the general Greek population (N = 1858) was conducted. A geographically stratified cluster sampling was implemented. A questionnaire was composed consisting of 35 questions. Data collection took place from 15 April to 2 May 2020. A random-digit dialing survey was conducted by 29 interviewers. Results: The majority of respondents (62.7%) answered &ge;12/17 questions correctly. Participants aged 18&ndash;44 years, male gender, specific occupations (freelancer, unemployed, housewife, retiree) and those who sought information about COVID-19 from less than two sources received lower aggregated scores on knowledge questions. Regarding attitudes toward future vaccination, 18.9% declared that were against it, while 81.1% that they may consider or will be vaccinated. About 40% were not using a face mask and only 42% washed their hands appropriately. Conclusion: Adjusting information campaigns targeting especially people below 45 years of age can help to sensitize them and realise their role to control the spread. Further targeted surveys are needed to adjust/design prevention campaigns