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Opstrukcijska apneja tijekom spavanja (OSA) obilježena je razdobljima kolapsa gornjih dišnih putova praćenih ponavljanim epizodama hipoksije. U pokusnih životinja akutne ponavljane hipoksije (AIH) mogu dovesti do dugotrajne pojačane aktivnosti freničkoga živca, poznate kao dugoročna facilitacija freničkoga živca (pLTF). Taj oblik fiziološke kompenzacije mogao bi doprinositi stabilizaciji disanja, smanjujući pojavnost apneja i/ili hipopneja u pacijenata oboljelih od OSA-e. Pokazano je da serotonin modulira neuralnu kontrolu disanja, vjerojatno putem projekcija koje kreću iz rafe jezgara. Cilj disertacije bio je istražiti važnost pravovremene aktivacije 5-HT1A receptora u nastanku i očuvanju pLTF-a. Uloga aktivacije 5- HT1A receptora ispitana je u dvije različite vremenske točke, prije izlaganja AIH protokolu i nakon što je pLTF nastao. Nadalje, cilj disertacija bio je i proučiti učinke blokiranja 5-HT1A receptora u kaudalnom rafe području na pLTF izazvan AIH protokolom. Kako bi se istražila važnost pravovremene aktivacije 5-HT1A receptora u nastanku i očuvanju pLTF-a, odrasli mužjaci Sprague–Dawley štakora, anestezirani uretanom, vagotomizirani, paralizirani i mehanički ventilirani izloženi su AIH protokolu. Jedna skupina životinja je intravenski primila selektivni antagonist 5-HT1A receptora WAY- 100635 prije početka AIH protokola (skupina WAY0, n=7), a druga skupina nakon što se pLTF razvio (skupina WAY60, n=7). Kontrolna skupina (n=7) nije primila WAY-100635, nego je samo bila izložena AIH protokolu. Vršna aktivnost freničkoga živca (pPNA), frekvencija disanja i parametri ritma disanja analizirani su tijekom pet hipoksijskih epizoda, te 15, 30 i 60 minuta nakon kraja posljednje hipoksije. U kontrolnoj skupini 60 minuta nakon kraja posljednje hipoksije razvio se pLTF, koji se manifestirao kao povećanje pPNA (povećanje za 121, 6±7, 3%, P

Objectives: Osteogenesis imperfecta (OI) is a rare genetic disease characterized by disruption of normal collagen formation leading to skeletal vulnerability and consequent frequent skeletal fractures, ligamentous laxity, and scleral discoloration. However, beside the robust symptoms associated with locomotor system, OI might have detrimental effects on quality of life and sleep quality and promote development of various sleep disorders. One of the most common sleep disorders is obstructive sleep apnea (OSA), characterized by repetitive cessations of breathing during sleep and is associated with excessive daytime sleepiness and an increased risk for a number of cardiovascular and metabolic disorders. Recent research and data suggest a bidirectional causality between sleep apnea and disorders of bone metabolism, and a high frequency of sleep apnea has been reported in this population. Such comorbidities, along with pain and fatigue, might contribute to the low sleep quality of OI patients. Thus, our aim was to assess the sleep quality, daytime sleepiness, and risk for OSA among patients with OI. We hypothesized that patients with OI have poor sleep quality, excessive daytime sleepiness and increased risk for OSA. Methods: A total of 20 patients (11 males, 9 females) with OI participated in this research, diagnosed with type 1 (25%), type 3 (40%), and type 4 (30%) OI, and a missing data regarding the type for 1 respondent. The average age of the patients was 26.4±19.4 years. To assess sleep quality, we used Pittsburgh Sleep Quality Index (PSQI), Epworth Sleepiness Scale (ESS) was used to assess daytime sleepiness, and STOP and STOP-Bang questionnaires were used for assessment of the risk for OSA. All questionnaires were distributed to OI patients via social networks in an online format. Results: The risk for OSA, according to STOP questionnaire, was reported in 5 (25%) patients, whereas STOP-Bang revealed a risk for OSA in 8 (40%) of patients. Patients reported an average sleep quality PSQI value of 6.1±2.8, with 55% of patients reporting values of PSQI>5, indicating low sleep quality. Average daytime sleepiness assessment showed rather low values of 3.3±2.8, with just one patient reporting excessive daytime sleepiness. Conclusion: In this group of OI patients, STOP- Bang questionnaire more frequently recognized the risk for OSA than the STOP questionnaire. The frequency of this risk was slightly higher when compared to our previously reported values in the general population of similar age. Furthermore, in this group of OI patients, low sleep quality was reported by majority of respondents, which was not the case with excessive daytime sleepiness. Future research should aim to conduct a similar study on a larger group of patients preferably as case control comparisons addressing the postulated reduced sleep quality and elevated risk for OSA in the patients with OI.

The study investigated the role of alpha2-adrenergic receptors of the caudal raphe region in the sympathetic and cardiovascular responses to the acute intermittent hypercapnia (AIHc). Urethane-anesthetized, vagotomized, mechanically ventilated Sprague-Dawley rats (n=38) were exposed to the AIHc protocol (5×3 min, 15 % CO2+50 % O2) in hyperoxic background (50 % O2). alpha2-adrenergic receptor antagonist-yohimbine was applied intravenously (1 mg/kg, n=9) or microinjected into the caudal raphe region (2 mM, n=12) prior to exposure to AIHc. Control groups of animals received saline intravenously (n=7) or into the caudal raphe region (n=10) prior to exposure to AIHc. Renal sympathetic nerve activity (RSNA), mean arterial pressure (MAP) and heart rate (HR) were monitored before exposure to the AIHc protocol (T0), during five hypercapnic episodes (THc1-5) and at 15 min following the end of the last hypercapnic episode (T15). Following intravenous administration of yohimbine, RSNA was significantly greater during THc1-5 and at T15 than in the control group (P0.05). When yohimbine was microinjected into the caudal raphe region, AIHc elicited greater increases in RSNA during THc1-5 when compared to the controls (THc1: 138.0+/-4.0 % vs. 123.7+/-4.8 %, P=0.032; THc2: 137.1+/-5.0 % vs. 124.1+/-4.5 %, P=0.071; THc3: 143.1+/-6.4 % vs. 122.0±4.8 %, P=0.020; THc4: 146.1+/-6.2 % vs. 120.7+/-5.7 %, P=0.007 and THc5: 143.2+/-7.7 % vs. 119.2+/-7.2 %, P=0.038). During THc1-5, significant decreases in HR from T0 were observed in all groups, while changes in MAP were observed in the group that received yohimbine intravenously. These findings suggest that blockade of the alpha2-adrenegic receptors in the caudal raphe region might have an important role in sympathetic responses to AIHc.

Objectives/Introduction Our group previously reported that excluding item assessing tiredness (T) might improve the overall predictive value of STOP-Bang in one population. The current research is aimed to investigate the role of the aforementioned item T of the STOP-Bang questionnaire among populations in different European geographic regions, while considering the possible moderating role of age and gender. Methods A study has been conducted in 3 European Sleep medicine centers - in Split, Croatia ; Thessaloniki, Greece ; and Izmir, Turkey. A total of 9154 respondents were included, of whom 2364 in Greece, 3638 in Turkey and 3152 in Croatia. Among them, 6345 respondents (69.4%) were men. 1351 respondents were younger than 40 years, with 6684 respondents aged 40 to 69 years, and 1014 respondents were older than 70 years of age. All patients in Greece were assessed with the use of polygraphy, all patients in Turkey were assessed with full-night polysomnography, and Croatian patients were assessed with polysomnography (n=1043) or polygraphy (n=2109). Results Specifically, among Greek patients, the exclusion of item T resulted in a decrease of STOP-Bang sensitivity from 97.6% to 94.2%, and an increase in specificity from 20.6% to 34.7%. Among patients in Turkey, the exclusion of the item T resulted in decreased sensitivity from 98.2% to 93.4%, while increasing specificity from 12.9% to 32.3%. In Croatian respondents, the exclusion of item T resulted in decreased sensitivity from 92.4% to 86.7% and increased specificity from 46.6% to 63.7%. Change in sensitivity and specificity was recognized in respondents below 40 years of age, 40 to 69 years of age and in groups of respondents older than 70 years. In all three investigated populations, a larger decrease in the sensitivity of the STOP-Bang questionnaire was recognized among female respondents when item T was excluded from the final sum, whereas the specificity increased. Conclusions The exclusion of item T in the final sum of the STOP-Bang questionnaire decreased the sensitivity of questionnaire in the recognition of OSA in all three investigated populations, but enabled an overall larger increase in the specificity. The change in sensitivity was more pronounced in female respondents.

Objectives/Introduction The search for factors predisposing to continuous positive airway pressure (CPAP) adherence remains inconsistent. Therefore, we aimed to investigate the role of oxygen desaturation severity expressed as the slope of the oxygen desaturation curve (Slope Index, SI) in short-term CPAP adherence prediction and possible cut-off values of SI in distinguishing good and poor CPAP adherers. Methods A retrospective study was performed on 70 CPAP-treated patients with severe obstructive sleep apnea (OSA). SI was calculated as the averaged quotient of difference between blood oxygen saturation level before and after the obstructive apnea and the event duration throughout the night. Apnea-Hypopnea Index (AHI) was defined as a sum of apneas and hypopneas per hour of sleep. Good short-term CPAP adherence was defined as CPAP usage for ≥4 hours/night on ≥70% of nights during first three months of therapy. Results Following logistic regression (R2=16.7% ; p=0.010), a lower SI was a predictor of good CPAP adherence during first three months of CPAP therapy (OR=0.004 ; p=0.019). As a predictor of good CPAP adherence during initial therapy, SI achieved AUC value of 0.650 (p=0.032) with the highest predictive value based on Youden index for 0.465 cut-off. The AUC value for AHI in the prediction of good CPAP adherence was not significant (p=0.228). Using the cut-off SI value of 0.465, patients were classified into the group with SI below (n=51) and above 0.465 (n=19). During first three months of CPAP therapy, average CPAP usage hours, percentage of nights with CPAP usage and nights with CPAP usage ≥4 hours were significantly higher in the group with SI below 0.465 (p

The aim of this study is to establish the changes of the salivary parameters in CPAP- treated OSA patients.CPAP treatment was associated with lower salivary calcium and lower ratio of salivary calcium and phosphate levels. Although there was no significant change in salivary flow rate, subjective assessment of dry mouth appears to be lower after CPAP treatment.

Introduction: Numerous studies have supported the idea that sleep has an important role in regulation of cognitive and affective brain functions. Even though the overall sleep quality contributes to cognitive performance, distinction of various components of subjective sleep quality might provide more precise insight into the aforementioned association, specifically in student population. The aim of this study was to elucidate the relationship between components of sleep quality and reaction times in solving simple and complex cognitive and psychomotor tasks in medical students. We hypothesized that sleep quality components are more precise indicators of sleep than general subjective sleep quality in students and that poor sleep can be detected even by subtle deteriorations in cognitive performance. Methods: A total of 164 students (49 men) enrolled in the Basic neuroscience course at the University of Split School of medicine, participated in the study. All subjects completed Pittsburgh Sleep Quality Index (PSQI), a self-reported general measure of sleep quality and disturbances over the past one-month period. From the 19 items of the PSQI questionnaire, 7 components are created indicating subjective sleep quality, sleep latency, sleep duration, habitual sleep efficiency, sleep disturbances, use of sleeping medications, and daytime dysfunction. Cognitive and psychomotor abilities were assessed using Complex Reactionmeter Drenovac (CRD-series), a battery of computer supported neuropsychological tests, measuring reaction times and speed of information processing. Three CRD-series test were used: CRD11, assessing solving simple arithmetic operations, CRD311, assessing discrimination of the light signal position, and CRD411, assessing complex psychomotor coordination of limbs. In each single test, several variables were analyzed: total test solving time (TTST), minimum single task solving time (MinT), maximum single task solving time (MaxT) and start to end ballast ratio (SB/EB). Results: There was no significant correlation between TTST and MinT with the total PSQI score on CRD11 (P=0.633 and P=0.881), CRD311 (P=0.446 and P=0.951) and CRD411 tests (P=0.464 and P=0.412). However, SB/EB ratio was correlated with total PSQI score on the CRD311 test (r=0.201, P=0.01). Regression analysis using 7 components of the PSQI questionnaire as predictors revealed that there was an association between use of sleeping medication and MaxT on CRD11 test (β=0.167, P=0.037). On CRD311 test, prolonged MaxT was associated with increased sleep latency (β=0.379, P

This study aims to investigate the relationship of oxygen desaturation and apnea severity expressed as apnea-hypopnea index (AHI) with CPAP adherence in severe OSA patients. A retrospective study was performed on 70 severe OSA patients, with Slope Index (SI) calculated as the averaged quotient of difference between the blood oxygen saturation level before and after the obstructive event (ΔSpO2) and the duration of the obstructive event throughout the night. CPAP usage for ≥4 hours/night on ≥70% of nights was defined as good CPAP adherence. Increased SI was associated with decreased percentage of nights with CPAP usage ≥4 hours during first three months of CPAP usage (r=-0.314 ; p=0.008), whereas not significantly during the first month of CPAP usage (r=-0.225 ; p=0.062) No significant correlation was observed between AHI and percentage of nights with CPAP usage ≥4 hours during initial therapy periods. The SI was significantly higher in patients with poor adherence during both observed periods of CPAP usage in comparison to patients with good adherence (p=0.011 and p=0.005, respectively). No difference in AHI was recognized between patients with good and poor adherence during both time spans of CPAP usage. When logistic regression analyses were performed, a lower SI was a predictor of good CPAP adherence during the first month and first three months of CPAP therapy (ß=0.018 ; p=0.039 ; R2=12.2% ; p=0.035 and ß=0.004 ; p=0.019 ; R2=16.6% ; p=0.010, respectively). Patients with a greater slope of the oxygen desaturation curve were recognized as less likely to have good CPAP adherence following therapy onset. This novel parameter might give an insight on the impact of desaturation severity on CPAP adherence and might be valuable in recognizing patients with severe OSA at risk for poor CPAP adherence.

The aim of this study was to investigate the correlations between IQ test scores obtained using the Raven’s Advanced Progressive Matrices (APM) and psychomotor testing using the Complex Reactionmeter Drenovac (CRD) test battery. In the period 2017-2019, 224 medical students at the University of Split School of Medicine studying in the English and the Croatian programs were recruited for this study. The IQ scores of the students were assessed using Raven’s APM where students had to complete 36 items of the abstract reasoning test. The computerized test of CRD- series was used for testing reaction times of light stimulus perception (CRD311), operative thinking through complex psychomotor limb coordination (CRD411) and convergent thinking through solving simple arithmetic operations (CRD11). The total test solving time (TTST) and the minimum single task solving time (MinT) were analyzed. On the CRD11 test, task-solving times were significantly shorter in students with higher APM scores (r=-0.48 for TTST and r=-0.44 for MinT ; P

Long-term home confinement and measures of social distancing and lockdown have influenced daytime routines. To evaluate effects of the COVID-19 lockdown on sleep habits, we performed a study on 1173 participants of general population in Croatia which revealed a strong negative impact of home confinement on sleep. We found that sleep latency prolonged from 10 (5-20) to 15 (10-30) minutes during COVID-19 lockdown (P

Aim: To determine whether there were changes in behavior, mood and sleep habits during the lockdown caused by the SARS-CoV-2 virus depending on age and sex, and to analyze attitudes toward vaccination. Subjects and methods: During the two months (February 26 - April 26, 2021) of the COVID-19 pandemic, 636 people (74% women) completed an online questionnaire sent via social media, using a snowball method. Most respondents were resided in Croatia (62.26%), Bosnia and Herzegovina (29.72%) and Germany (6.92%). Demographic data, data on attitudes toward vaccination, and data on changes in behavior, mood and sleep habits before and during lockdown were collected. Results: Overall respondents reported to exercise less and spend more time on social media during pandemic (P

Detecting OSA early might contribute to a decreased public health economic burden. Especially when limited resources are available, low specificity might lead to unnecessary full- night recordings in healthy patients. The current study aimed to investigate predictive contribution of each item of the STOP-BANG questionnaire and pulse oximetry in OSA. Additionally, the role of older age was assessed. The study included 3128 participants admitted to Split Sleep Medicine Center, referred for polygraphy or polysomnography and assessed with STOP-BANG and Pittsburgh Sleep Quality Index (PSQI). Full-night polysomnography was conducted in-laboratory and full-night polygraphy was performed unattended. Following sleep assessment, 467 participants had no OSA and 2661 had mild to severe OSA. When only STOP-BANG variables were included in a model predicting confirmed OSA diagnosis, the largest amount of variability was explained in respondents 65 year old respondents, lower predictive value was achieved in both models (R2=19, 9% and R2=23, 5% ; p

The aim of the study was to investigate the effects of lockdown on sleep habits during the COVID-19 epidemic in the Croatian general population and to explore potential influence factors. Using an online cross-sectional survey, 1173 subjects from the general population (male=288, female=809) completed a self-reported questionnaire assessing demographic data, sleep habits and mood changes prior to and during lockdown. Results indicated a postponed bedtime (from 23:11±1:07 to 23:49±1:32 h, p

We aimed to investigate and compare differences and changes in sleep and lifestyle habits as well a mood of Croatian medical (MS) and non-medical students (NMS) during the COVID-19 lockdown. A cross-sectional study included 1163 participants (21.6% male) with median age 22 (IQR 20-23) whose demographics, teaching modes, lifestyle and sleep habits and mood before and during the COVID-19 lockdown were assessed with an online, self- reported questionnaire. Significant shifts toward later bedtimes and wake- times were reported in both MS and NMS (P

Linda Lusic Kalcina, Ivana Pavlinac Dodig, Renata Pecotic, Maja Valic, Zoran Dogas Department of Neuroscience, Split Sleep Medicine Center, University of Split School of Medicine, Split, CroatiaCorrespondence: Zoran DogasDepartment of Neuroscience, Split Sleep Medicine Center, University of Split School of Medicine, Soltanska 2, Split 21000, CroatiaTel +38521557905Fax +38521557955Email zdogas@mefst.hrPurpose: Determinants of obstructive sleep apnea (OSA) are hypoxemia and hypercapnia, as well as (micro) arousals from sleep, resulting in chronic sleep fragmentation, sleep deprivation, and excessive daytime sleepiness (EDS). All of the above-mentioned factors might contribute to psychomotor impairment seen in OSA patients. Additionally, this study aimed to assess the contribution of BMI, age, EDS assessed with Epworth sleepiness scale (ESS), and severity of OSA assessed with apnea-hypopnea index (AHI) to the reaction time on chronometric tests in OSA patients and controls. It is hypothesized that moderate and severe OSA have adverse effects on reaction time of perception to visual stimulus, of solving simple arithmetic operations, and of psychomotor limbs coordination assessed by chronometric psychodiagnostic test battery.Patients and Methods: This study was conducted on 206 male participants; 103 of them had moderate or severe OSA diagnosed by whole-night polysomnography/polygraphy. Control participants (N=103), matched to patients with OSA by age and BMI, had no reported OSA in their medical history, no increased risk for OSA, nor EDS. All participants were assessed with three chronometric psychodiagnostic tests, measuring thereaction time of perception to visual stimulus, of solving simple arithmetic operations, and of psychomotor limbs coordination.Results: Participants from theOSA group achieved impaired results compared to control participants in minimum single task solving time in speed of solving simple arithmetic operations (3± 0.9 and 2.6± 0.6, P< 0.001), and in minimum solving time of a single task in complex psychomotor limbs coordination (0.69± 0.2 and 0.61± 0.1, P=0.007). Regression analysis revealed no significant contribution of daytime sleepiness to the results achieved in each of the tests.Conclusion: It is concluded that severe OSA impaired speed of perception, convergent, and operative thinking. Moreover, it is suggested that EDS did not contribute to poor psychomotor outcome in patients with OSA in thisstudy, when age was controlled for.Keywords: obstructive sleep apnea syndrome, overnight polysomnography, psychomotor performance, psychodiagnostic test, daytime sleepiness

According to PG/PSG, 474 participants had no OSA and 2658 had mild to severe OSA. The sensitivity of the STOP was 86, 5% with the specificity of 45, 3%, whereas for the STOP-BANG there was a 92, 4% sensitivity with specificity of 45, 8%. In conclusion, our findings have indicated STOP bang screening performance as extremely low in subjects older than 60 years of age, reporting very low specificity for STOP and extremely low specificity for STOP BANG questionnaire.

Objectives/Introduction: Numerous epidemiological studies have shown the varying prevalence of obstructive sleep apnea (OSA) among different age groups of the general population, with an in- creased prevalence in the elderly. Considering the expensive and time-consuming OSA diagnostic procedures, appropriate assess-ment of the OSA risk with reliable screening tools is essential. However, age-related effects on the risk for OSA and one of its hall-mark features, excessive daytime sleepiness, remain controversial. Therefore, the aim of this study was to assess the risk for OSA and daytime sleepiness in a large population sample, with regard to age and gender. Methods: A large population sample included 14606 respondents (45.32% men) from Western Herzegovina, with the median age of 32 (IQR 21–53). The respondents completed STOP questionnaire for OSA risk assessment and Epworth sleepiness scale for daytime sleepiness evaluation. Results: A total of 4273 (29%) respondents had increased risk for OSA. The risk for OSA increased with age (χ2=78 . 3 5 , p < 0.001). Male respondents had a higher risk for OSA compared to female respond-ents in younger age groups (up to 70 years) (χ2 = 11.940, p = 0.018), whereas no difference was found in advanced age group (>70 years). The proportion of respondents with excessive daytime sleepiness was significantly higher in participants with increased OSA risk com-pared to those not at risk, in all age groups (χ2 = 998.36, p < 0.001). Furthermore, a positive correlation was found between age and day-time sleepiness in the male respondents (r = 0.042, p < 0.001), but not in female respondents. Conclusions: This study performed on a large population sample demonstrated that the risk for OSA increases with advanced age. Male respondents had a significantly greater risk than females in all ages, until the age of 70. Daytime sleepiness was a prominent symp-tom among subjects with increased OSA risk in all age groups, but less pronounced in females, emphasizing the influence of gender on OSA risk and symptomatology.

OBJECTIVE The aim of this cross-sectional study was to examine the influence of age and gender on cognitive and psychomotor abilities measured by tests of the Complex Reactionmeter Drenovac (CRD- series). SUBJECTS AND METHODS A total of 3421 subjects (1427 men) solved three representative CRD-series tests based on chronometry, from the simplest to the most complex one: CRD311 (discrimination of the light signal position), CRD411 (complex psychomotor coordination), and CRD11 (simple arithmetic operations). The total test solving time (TTST), minimum single task solving time (MinT), number of errors, initial dissociation (D1), start (SB), end (EB), and total (TB) ballasts, as measures of wasted time at the first half, second half, and the total test time, respectively, were analyzed. RESULTS On CRD11 test, men had shorter TTST than women (134.47±56.43 s vs. 139.17±57.60 s, p=0.021), shorter SB, EB, and TB (p

Increased respiratory drive suppresses renal sympathetic nerve activity in rats exposed to acute intermittent hypoxia.

Polysomnography parameters and sleep architecture: the role in daytime sleepiness and sleep quality of OSA patients

OBJECTIVES The aim of this study is to elucidate the relationship between sleep, anxiety, and reaction times and information processing in solving simple and complex cognitive and psychomotor tasks of the electronic psychodiagnostic test battery, Complex Reactionmeter Drenovac (CRD-series) in medical students. SUBJECTS AND METHODS A total of 168 students (49 men) from School of medicine, University of Split, completed following questionnaires: Sleep Habits questionnaire (SH), Epworth Sleepiness Scale (ESS) assessing daytime sleepiness, Pittsburgh Sleep Quality Index (PSQI) assessing subjective sleep quality, and State- Trait Anxiety Inventory (STAI) assessing anxiety. Cognitive and psychomotor abilities were measured by CRD-series tests: CRD311 (discrimination of the light signal position), CRD411 (complex psychomotor coordination), and CRD11 (simple arithmetic operations), in the sequence from the easiest to the most difficult. In each single test total test solving time (TTST) and minimum single task solving time (MinT) were analyzed. Statistical analysis of the data was performed in MedCalc for Windows, version 11.5.1.0 (MedCalc Software, Mariakerke, Belgium), and significance was considered at p

The aim of this study was to investigate the relationships between SI and AHI with daytime sleepiness, sleep efficiency and comorbidity presence in severe OSA patients. A total of 111 patients who underwent whole-night polysomnography (PSG) at the Split Sleep Medicine Centre with severe OSA (AHI≥30) were included. Among PSG parameters AHI and sleep efficiency were analyzed. Daytime sleepiness was assessed by Epworth Sleepiness Scale (ESS). Arterial hypertension, diabetes mellitus type 2 (DM2) and depression were self-reported. The SI was calculated as the averaged quotient of the difference between the blood oxygen saturation before and after the obstructive apnea episode and the duration of the episode throughout the night. Both indices, SI and AHI, predicted daytime sleepiness in severe OSA patients without comorbidities. SI better predicted sleep efficiency in severe OSA patients with hypertension, as well as in the patients without depression. The slope of the oxygen desaturation curve index, as a novel OSA severity index, could help in understanding the impact of hypoxia in different OSA phenotypes.

Salivary parameters may offer a noninvasive and easy sampling alternative in diagnosis and monitoring high risk behaviour and disease progresion. The aim of this study is to establish association of salivary flow rate, salivary pH, salivary calcium, phosphate and magnesium levels with the severity of obstructive sleep apnea (OSA). Materials and methods: The study involved 138 subject who were grouped according to the severity of OSA: 10 subject served as controls, 78 subjects had mild to moderate OSA and 50 had severe OSA. Unstimulated saliva was collected from all subjects and they had completed a questionnaire for evaluating the subjective assessment of dry mouth. Salivary pH was measured immediately after collection with pH tester of ±0.01accuracy. Ca, P, Mg levels were measured with inductively coupled plasma mass spectrometry (ICP-MS). Results: There was significant correlation between salivary flow rate and the severity of OSA. The subject with severe OSA had higher salivary flow rate than subjects with mild to moderate OSA (3, 97±2, 59 vs 4, 95±2, 83, p=0, 046). Furthermore, the prevalence of subjective assessment of dry mouth upon awakening was higher in subjects with severe OSA than in subjects with mild to moderate OSA (p=0, 023). There were no significant differences in salivary calcium, phosphate and magnesium levels between subject groups. Conlusion: Based on the study results indicate that severe OSA subjects had higher salivary flow rate compared to mild and moderate OSA subjects. However, subjective assessment of dry mouth upon awakening appears to be significantly associated with severe OSA.

Obstructive sleep apnoea (OSA) is characterized by repetitive transient obstructions of the upper airway, which result in cessations of the airflow and consequently lead to hypoxemia and hypercapnia. Apart from the hypoxemia, each obstructive event in apnoeic patients is also accompanied by (micro) arousals from sleep, resulting in chronic sleep fragmentation, sleep deprivation and consequent excessive daytime sleepiness (EDS). All of the above mentioned factors might be proposed as mechanisms underlying cognitive impairment seen in OSA patients, mostly in areas of general intellectual functioning, memory, reasoning, executive and motor functioning, psychomotor speed, visuospatial functions, attention and vigilance, concept formation, construction, perception, attention and alertness. We hypothesize that moderate and severe OSA have adverse effects on reaction times on visual stimuli, simple arithmetic tasks, and complex psychomotor limbs coordination assessed by the computer-based psychomotor CRD-series tests. This study was conducted on 206 male subjects ; 103 of them had moderate or severe OSA diagnosed by whole-night polysomnography/polygraphy. Control subjects (N=103), matched to OSA subjects by gender, age and BMI, had no recorded OSA in their medical history, no increased risk for OSA measured by STOP and STOP-BANG questionnaires, nor ESD measured by Epworth Sleepiness Scale (ESS) score. All subjects in a random order solved three tests from CRD-series, which measured speed of visual perception (CRD311), convergent thinking during solving simple arithmetic operations (CRD11), and operative thinking during tasks that required complex psychomotor limbs coordination (CRD411). In each of the applied tests total test solving time (TTST), minimum (best) single task solving time (MinT), and median time for task solving (MedT) were recorded. We conclude that moderate and severe OSA impaired reaction times of visual perception, convergent thinking during solving simple arithmetic operations, and operative thinking during tasks that required complex psychomotor limbs coordination. Moreover, we propose that EDS was not the underlying mechanism by which OSA produced these negative effects on cognitive outcome in our study.

Introduction: Previous studies showed that intermittent hypercapnia may evoke phrenic long-term depression (pLTD), which manifests as prolonged depression of phrenic nerve activity. Adrenergic receptors have been shown to modulate pLTD, but the precise site of action has not been revealed. The present study investigated the role of alpha-2 adrenergic receptors in caudal raphe region in pLTD. Our hypothesis was that microinjections of alpha-2 adrenergic antagonist yohimbine into the caudal raphe nucleus could attenuate phrenic LTD after exposure to acute intermittent hypercapnia (AIHc). Materials and methods: Adult, male, urethane- anesthetized, vagotomized, paralyzed, and mechanically ventilated Sprague-Dawley rats were exposed to AIHc protocol. Experimental group of animals (n=9) received microinjection of yohimbine (1 mM, 20±5 nl) into the caudal raphe region, whereas control group (n=7) received microinjection of 0.9% saline (20±5 nl) into the same region. Peak phrenic nerve activity (pPNA) and burst frequency (f) were analyzed during five hypercapnic episodes (THc1-5) and at 15, 30, and 60 minutes after the end of the last hypercapnia. Results: In the control group, pPNA decreased by 43.3±14.3 % at 60 minutes after the end of the last hypercapnic episode compared to baseline values, i.e. pLTD developed (P=0.023). Microinjections of yohimbine into the caudal raphe region prior to hypercapnic stimulation attenuated pLTD at one hour post-hypercapnia (pPNA increased by 35.5±46.7%, P>0.05). Conclusions: Microinjection of alpha-2 adrenergic receptors antagonist yohimbine into the caudal raphe nuclei attenuated pLTD following acute intermittent hypercapnia, suggesting that alpha-2 adrenergic receptors in the caudal raphe region are important for induction of pLTD.

What is the central question of this study? Intermittent hypercapnia is a concomitant feature of breathing disorders. Hypercapnic stimuli evoke a form of respiratory plasticity known as phrenic long-term depression in experimental animals. This study was performed to investigate the putative role of serotonin receptors in the initiation of phrenic long- term depression in anaesthetized rats. What is the main finding and its importance? Phrenic nerve long-term depression was revealed in animals pretreated with the serotonin broad- spectrum antagonist, methysergide. This study highlights that serotonin receptors modulate respiratory plasticity evoked by acute intermittent hypercapnia in anaesthetized rats. This study was performed to test the hypothesis that intermittent hypercapnia can evoke a form of respiratory plasticity known as long-term depression of the phrenic nerve (pLTD) and that 5- HT receptors play a role in the initiation of pLTD. Adult male urethane-anaesthetized, vagotomized, paralysed, mechanically ventilated Sprague-Dawley rats were exposed to an acute intermittent hypercapnia protocol. One group received i.v. injection of the non-selective 5- HT receptor antagonist methysergide and another group received i.v. injection of the selective 5-HT1A receptor antagonist WAY-100635 20 min before exposure to intermittent hypercapnia. A control group received i.v. injection of saline. Peak phrenic nerve activity and respiratory rhythm parameters were analysed at baseline (T0), during each of five hypercapnic episodes, and 15, 30 and 60 min (T60) after the last hypercapnia. Intravenous injection of methysergide before exposure to acute intermittent hypercapnia induced development of amplitude pLTD at T60 (decreased by 46.1 ± 6.9%, P = 0.003). Conversely, in control and WAY-100635-pretreated animals, exposure to acute intermittent hypercapnia did not evoke amplitude pLTD. However, a long-term decrease in phrenic nerve frequency was evoked both in control (42 ± 4 breaths min(-1) at T0 versus 32 ± 5 breaths min(-1) at T60 ; P = 0.036) and in methysergide-pretreated animals (42 ± 2 breaths min(-1) at T0 versus 32 ± 3 breaths min(-1) at T60 ; P = 0.028). In WAY-100635 pretreated animals, frequency pLTD was prevented. These results suggest that 5-HT receptors modulate respiratory plasticity induced by acute intermittent hypercapnia in anaesthetized rats.

Plasticity is a key property of neural systems, manifested as a persistent change in the neural control system based on a prior experience. It includes the respiratory control system, and promotes effective homeostatic regulation. Acute intermittent hypoxia can evoke long-lasting increase of phrenic nerve activity known as phrenic long-term facilitation (pLTF). On the other hand, it has been shown that acute intermittent hypercapnia can evoke long-lasting decrease of phrenic nerve activity, known as phrenic long-term depression (pLTD) in anesthetized rats. This study was performed to investigate the effects of acute intermittent hypoxia and acute intermittent hypercapnia, as well as combined acute intermittent hypoxic and hypercapnic stimulus on phrenic nerve activity. Adult male urethane-anesthetized, vagotomized, paralyzed, mechanically ventilated Sprague-Dawley rats were exposed to: acute intermittent hypoxia (AIH), acute intermittent hypercapnia (AIHc), or combined intermittent hypercapnia and hypoxia (AIHcH). Peak phrenic nerve activity (pPNA) and burst frequency were analyzed during baseline (T0), hypercapnia or hypoxia exposures at 15, 30, and 60 minutes (T60) after the end of the stimulus. Exposure to AIH elicited increase of pPNA at T60 to 241.0±28.2% compared to baseline (P=0.015), i.e., phrenic long-term facilitation was induced. Exposure to AIHc elicited decrease of phrenic nerve frequency from 44.25±4.06 at T0 to 35.29±5.21 at T60 (P=0.038), i.e., frequency phrenic long-term depression was induced. Exposure to AIHcH protocol failed to induce long-term plasticity of the phrenic nerve. Phrenic nerve frequency was 40.5±2.2 breaths/min at T0 and 38.14±1.82 breaths/min at T60 (P>0.05) and pPNA was 172.6±38.4%, (P>0.05) 60 min after the last combined stimulus compared to baseline values. Thus, we conclude that combined intermittent hypercapnic and hypoxic stimulus might be responsible for maintenance of breathing stability.

Previous studies aimed to determine if Pittsburgh sleep quality index was a valid screening instrument for obstructive sleep apnea (OSA), indicated its’ disadvantages. However, the rationale of Pittsburgh sleep quality index use in sleep clinics is not the screening, but the assessment of sleep quality itself. Therefore, the aim of this study was to investigate the sleep quality in OSA patients and to identify the cut- off point for differentiation of „good” and „poor” sleepers among them. We constructed the Croatian version of the Pittsburgh sleep quality index (PSQI) questionnaire and assessed its’ psychometric properties. The protocol of the study included the assessment of sleep quality using the constructed and validated Croatian PSQI questionnaire in 130 OSA patients and 75 healthy control subjects. All subjects completed the Croatian version of PSQI, and the patients underwent overnight polysomnography screening. OSA patients had higher values of the global PSQI component score, indicating lower sleep quality, compared to a healthy control group (P

The aims were to investigate the role of 5-HT1A receptor activation in induction and preservation of phrenic long term facilitation (pLTF) at two different time points, before exposures to acute intermittent hypoxia (AIH) and after pLTF was induced and to examine the effects of 5-HT1A receptors blockade by selective antagonist WAY- 100635 into the caudal raphe region on pLTF elicited by AIH. We found that 5-HT1A receptor activation plays a significant role in both induction and preservation of pLTF. Furthermore, activation of the 5-HT1A receptors at supraspinal level is important for induction of pLTF.

Obstructive sleep apnea syndrome (OSAS) is sleep- related breathing disorder characterized by repetitive cessations of breathing during sleep. The apnea-hypopnea index (AHI), represented by the number of apneas and hypopneas per hour of sleep, is a measure used to indicate the severity of OSAS. In numerous studies, it has been shown that OSAS patients have poor cognitive outcomes in areas of general intellectual functioning, memory, attention and alertness. We hypothesize that Complex Reactionmeter Drenovac (CRD-series), a computerized psychodiagnostic test battery, can measure adverse effects of OSAS on cognitive functions. Our aim was to evaluate the influence of the OSAS on reaction time and information processing in solving simple and complex psychomotor and cognitive tasks of the CRD-series. A total of 204 male subjects were studied ; 102 of them had OSAS, diagnosed by the whole-night polysomnography, and 102 were control subjects with no recorded OSAS in their medical history, matched to OSAS subjects by age and BMI. Three representative tests from CRD-series were applied to measure solving simple arithmetic operations (CRD11), simple light signal position discrimination (CRD311), and complex psychomotor coordination (CRD411). Five parameters were recorded: total test solving time (TTST), minimum (best) single task solving time (MinT), median time for task solving (MedT), number of errors (Err), and average error time (ErrT). Subjects from OSAS group had longer TTST on CRD11 test compared to control group (186.0±67.03s vs. 174.44±65.27s, P=0.047). Moreover, OSAS group had longer MinT on CRD411 test in comparison to control group (0.68±0.23s vs. 0.63±0.14s, P=0.041). There were no significant differences in performance on CRD311 test between two groups. However, a positive correlation was found between AHI and MedT on CRD311 test in OSAS group (r=0.213, P=0.032). In conclusion, all cognitive and psychomotor performance tests used in this study showed reduced values in OSAS patients compared with matched controls. Solving simple and complex psychomotor and cognitive tasks of the CRD-series could be used in evaluation of cognitive impairment in OSAS patients.

In experimental animals repeated bouts of hypercapnia may evoke sustained depression of phrenic nerve activity, known as phrenic long-term depression (pLTD). Serotonin (5-HT) has been shown to modulate respiratory neuronal activity, possibly via projections originating in the raphe nuclei. The present study was performed to investigate the role of 5-HT1A receptors in the caudal raphe region in pLTD development. Our hypothesis was that microinjections of selective 5-HT1A receptor agonist 8-OH-DPAT into the caudal raphe nucleus could modulate pLTD after exposure to acute intermittent hypercapnia (AIHc). Adult male urethane-anesthetized, vagotomized, paralyzed, and mechanically ventilated Sprague- Dawley rats were exposed to AIHc protocol. Experimental group of animals (n=7) received microinjections of 8-OH-DPAT (0.02 M, 20±5 nl) into the caudal raphe region (midline, 2.5 mm deep, 0.2 mm rostral to the obex) whereas control group (n=6) received microinjections of 0.9% saline (20±5 nl) into the same site. Peak phrenic nerve activity (pPNA), burst frequency (f), and respiratory rhythm parameters were analyzed at baseline (T0), during five hypercapnic episodes (THc1-5), as well as at 15 (T15), 30 (T30), and 60 (T60) minutes after the end of the last hypercapnic episode. Peak phrenic nerve activity one hour post-hypercapnia decreased to 56.5±16.1% compared to baseline (P=0.04) in control group, and to 62.7±10.0% in 8-OH-DPAT group (P=0.01). In group of animals that received microinjections of 8-OH-DPAT into the caudal raphe region prior to hypercapnic stimulation respiratory frequency decreased from 45.9±2.0 breaths/min at T0 to 37.0±3.8 at T60 (P=0.04). In the control group, respiratory frequency was 41.0±3.1 breaths/min at T0 and 43.0±5.1 breaths/min at T60 (P>0.05). These data suggest that pLTD elicited by exposure to intermittent hypercapnia is mediated via 5-HT1A receptors in the caudal raphe region, indicating that 5-HT receptor activation at supraspinal level is important for induction of pLTD.