ORCID Profile
0000-0003-3924-9199
Current Organisation
University of Kansas Medical Center
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Publisher: Cold Spring Harbor Laboratory
Date: 19-04-2018
DOI: 10.1101/303941
Abstract: Using genome-wide data from 697,828 research participants from 23andMe and UK Biobank, we increase the number of identified loci associated with being a morning person, a behavioural indicator of a person’s underlying circadian rhythm, from 24 to 351. Using data from 85,760 in iduals with activity-monitor derived measures of sleep timing we show that the chronotype loci influence sleep timing: the mean sleep timing of the 5% of in iduals carrying the most “morningness” alleles was 25 minutes earlier than the 5% carrying the fewest. The loci were enriched for genes involved in circadian regulation, cAMP, glutamate and insulin signalling pathways, and those expressed in the retina, hindbrain, hypothalamus, and pituitary. We provide evidence that being a morning person is causally associated with better mental health but does not appear to affect BMI or Type 2 diabetes. This study offers new insights into the biology of circadian rhythms and links to disease in humans.
Publisher: Oxford University Press (OUP)
Date: 05-11-2021
Abstract: Randomized controlled trials (RCTs) have shown no reduction in adverse cardiovascular (CV) events in patients randomized to continuous positive airway pressure (CPAP) therapy for obstructive sleep apnea (OSA). This study examined whether randomized study populations were representative of OSA patients attending a sleep clinic. Sleep clinic patients were 3,965 consecutive adults diagnosed with OSA by in-laboratory polysomnography from 2006 to 2010 at a tertiary hospital sleep clinic. Characteristics of these patients were compared with participants of five recent RCTs examining the effect of CPAP on adverse CV events in OSA. The percentage of patients with severe (apnea-hypopnea index, [AHI] ≥ 30 events/h) or any OSA (AHI ≥ 5 events/h) who met the eligibility criteria of each RCT was determined, and those criteria that excluded the most patients identified. Compared to RCT participants, sleep clinic OSA patients were younger, sleepier, more likely to be female and less likely to have established CV disease. The percentage of patients with severe or any OSA who met the RCT eligibility criteria ranged from 1.2% to 20.9% and 0.8% to 21.9%, respectively. The eligibility criteria that excluded most patients were preexisting CV disease, symptoms of excessive sleepiness, nocturnal hypoxemia and co-morbidities. A minority of sleep clinic patients diagnosed with OSA meet the eligibility criteria of RCTs of CPAP on adverse CV events in OSA. OSA populations in these RCTs differ considerably from typical sleep clinic OSA patients. This suggests that the findings of such OSA treatment-related RCTs are not generalizable to sleep clinic OSA patients. Randomized Intervention with Continuous Positive Airway Pressure in CAD and OSA (RICCADSA) trial, t2/show/NCT00519597, ClinicalTrials.gov number, NCT00519597. Usefulness of Nasal Continuous Positive Airway Pressure (CPAP) Treatment in Patients with a First Ever Stroke and Sleep Apnea Syndrome, t2/show/NCT00202501, ClinicalTrials.gov number, NCT00202501. Effect of Continuous Positive Airway Pressure (CPAP) on Hypertension and Cardiovascular Morbidity-Mortality in Patients with Sleep Apnea and no Daytime Sleepiness, t2/show/NCT00127348, ClinicalTrials.gov number, NCT00127348. Continuous Positive Airway Pressure (CPAP) in Patients with Acute Coronary Syndrome and Obstructive Sleep Apnea (OSA) (ISAACC), t2/show/NCT01335087, ClinicalTrials.gov number, NCT01335087.
Publisher: Elsevier BV
Date: 02-2011
DOI: 10.1016/J.FERTNSTERT.2010.10.012
Abstract: To evaluate a potential association among the hormonal profile, PROGINS polymorphism, and erectile dysfunction (ED) complaints in a large population-based s le in Sao Paulo, Brazil. Population-based questionnaire study. Interviews, sleep recording, and blood s le were conducted in a sleep institute. The total study participants included 467 men. General information was obtained through interviews, and a blood s le was collected for hormone levels, DNA extraction, and PROGINS genotyping. The effect of progesterone and the PROGINS polymorphism on the risk of developing ED were measured by questionnaire and blood s le. Progesterone, prolactin, testosterone, and estradiol levels did not differ between the genotype groups (T1/T1 and T1/T2+T2/T2). No significant genotypic or allelic differences were found between in iduals with ED complaints and controls. Multivariate logistic regression analyses including age, body mass index, hypertension, diabetes, apnea-hypopnea index, and genetic ancestry estimation, as well as the PROGINS polymorphism, confirmed the lack of association between the T2 allele carriers and the risk of ED (odds ratio = 0.80 95% confidence interval = 0.40-1.62). This is the first study to demonstrate the genotypic and allelic frequencies of the PROGINS polymorphism in a large population-based s le of men. The results do not support a direct role for the PROGINS polymorphism in the risk of developing ED however, further examination of other variants within PR gene will be necessary to completely rule out an effect.
Publisher: Elsevier BV
Date: 12-2013
DOI: 10.1016/J.RESP.2013.08.012
Abstract: In this study, our goal was to identify the key genes that are associated with obstructive sleep apnea (OSA). Thirty-five volunteers underwent full in-lab polysomnography and, according to the sleep apnea hypopnea index (AHI), were classified into control, mild-to-moderate OSA and severe OSA groups. Severe OSA patients were assigned to participate in a continuous positive airway pressure (CPAP) protocol for 6 months. Blood was collected and the expression of 84 genes analyzed using the RT(2) Profiler™ PCR array. Mild-to-moderate OSA patients demonstrated down-regulation of 2 genes associated with induction of apoptosis, while a total of 13 genes were identified in severe OSA patients. After controlling for body mass index, PRPF40A and PLOD3 gene expressions were strongly and independently associated with AHI scores. This research protocol highlights a number of molecular targets that might help the development of novel therapeutic strategies.
Publisher: Frontiers Media SA
Date: 24-06-2014
Publisher: Elsevier BV
Date: 05-2018
DOI: 10.1016/J.APERGO.2018.01.012
Abstract: Process control environments are characterised by rapid changes in work demands, the successful response to which is dependent upon the availability of cognitive resources. Since high cue utilisation is associated with a reduction in cognitive load and a consequent release of residual resources, it was hypothesised that participants with high cue utilisation would experience lower subjective arousal and lower physiological effort in response to increases in the work demands associated with a simulated rail control task. A total of 41 participants completed a 10 min, low work demand period, followed by a 10 min, high work demand condition. High cue utilisation was associated with a reduction in systolic blood pressure and the maintenance of sustained, superior performance in response to high work demands. However, an increase in subjective arousal was also evident. The outcomes have implications for the selection and assessment of operators of high reliability, dynamic, process control environments.
Publisher: Wiley
Date: 09-11-2012
DOI: 10.1111/JSR.12005
Abstract: Human leucocyte antigen (HLA) DQB1*0602 allele, a well-known genetic risk factor for narcolepsy, has been associated with sleep parameters in healthy subjects. We aimed to assess the association of this allele with daytime sleepiness and altered sleep electroencephalogram characteristics in the general population and in patients with obstructive sleep apnoea syndrome (OSAS). Eight hundred and ninety-four in iduals from the Epidemiologic Study of Sleep were genotyped for the HLA DQB1*0602 allele. Full-night polysomnography was performed, and daytime sleepiness was analysed according to the Epworth Sleepiness Scale. HLA-DQB1*0602 allele-positive and -negative subjects in the general population, as well as in patients with OSAS, exhibited similar sleep parameters and levels of daytime sleepiness. However, spectral analysis showed that allele-positive in iduals with OSAS exhibited higher theta power during sleep Stage 1 (P < 0.05) in occipital derivations, and lower delta power during sleep Stages 1 and 2 (P < 0.01) compared with in iduals negative for the allele, even after correction for potential confounders as age, sex, body mass index and European ancestry. No significant differences in the electroencephalogram variables were found in in iduals without OSAS. The data highlight the HLA-DQB1*0602 as a potential genetic factor influencing sleep physiology in in iduals diagnosed with OSAS.
Publisher: Wiley
Date: 10-08-2021
DOI: 10.1111/JSR.13441
Abstract: Intermittent hypoxaemia is a risk factor for numerous diseases. However, the reverse pathway remains unclear. Therefore, we investigated whether pre‐existing hypertension, diabetes or cardiovascular diseases are associated with the worsening of intermittent hypoxaemia. Among the included 2,535 Sleep Heart Health Study participants, hypertension ( n = 1,164), diabetes ( n = 170) and cardiovascular diseases ( n = 265) were frequently present at baseline. All participants had undergone two polysomnographic recordings approximately 5.2 years apart. Covariate‐adjusted linear regression analyses were utilized to investigate the difference in the severity of intermittent hypoxaemia at baseline between each comorbidity group and the group of participants free from all comorbidities ( n = 1,264). Similarly, we investigated whether the pre‐existing comorbidities are associated with the progression of intermittent hypoxaemia. Significantly higher oxygen desaturation index (β = 1.77 [95% confidence interval: 0.41–3.13], p = 0.011), desaturation severity (β = 0.07 [95% confidence interval: 0.00–0.14], p = 0.048) and desaturation duration (β = 1.50 [95% confidence interval: 0.31–2.69], p = 0.013) were observed in participants with pre‐existing cardiovascular diseases at baseline. Furthermore, the increase in oxygen desaturation index (β = 3.59 [95% confidence interval: 1.78–5.39], p 0.001), desaturation severity (β = 0.08 [95% confidence interval: 0.02–0.14], p = 0.015) and desaturation duration (β = 2.60 [95% confidence interval: 1.22–3.98], p 0.001) during the follow‐up were higher among participants with diabetes. Similarly, the increase in oxygen desaturation index (β = 2.73 [95% confidence interval: 1.15–4.32], p = 0.001) and desaturation duration (β = 1.85 [95% confidence interval: 0.62–3.08], p = 0.003) were higher among participants with cardiovascular diseases. These results suggest that patients with pre‐existing diabetes or cardiovascular diseases are at increased risk for an expedited worsening of intermittent hypoxaemia. As intermittent hypoxaemia is an essential feature of sleep apnea, these patients could benefit from the screening and follow‐up monitoring of sleep apnea.
Publisher: Elsevier BV
Date: 11-2011
DOI: 10.1016/J.CCA.2011.08.007
Abstract: The purpose of this study was to evaluate the influence of polymorphism on sleep parameters of Obstructive Sleep Apnea Syndrome (OSAS) patients. Patients were genotyped after a full-night polysomnography using the large Epidemiologic Sleep Study of São Paulo population-based s le. In iduals who carry the APOE ε2 allele showed longer sleep latency, lower sleep efficiency and higher numbers of arousals/hour, when compared to ε3 allele homozygous and carriers of ε4 allele (p<0.05). These findings remained significant even after correction for potential confounders, such as sex, age and African genetic ancestry. The APOE polymorphisms may modulate the effects of intermittent hypoxia and sleep fragmentation in the sleep architecture of OSAS patients, and that the presence of the ε2 allele may serve as a biological marker for the identification of a subgroup of patients who are more likely to suffer with OSAS detrimental effects on sleep, impacting not only the daily functioning, but also their quality of life.
Publisher: Oxford University Press (OUP)
Date: 2023
DOI: 10.1093/SLEEPADVANCES/ZPAD028
Abstract: Comparisons of actigraphy findings between studies are challenging given differences between brand-specific algorithms. This issue may be minimized by using open-source algorithms. However, the accuracy of actigraphy-derived sleep parameters processed in open-source software needs to be assessed against polysomnography (PSG). Middle-aged adults from the Raine Study (n = 835 F 58% Age 56.7 ± 5.6 years) completed one night of in-laboratory PSG and concurrent actigraphy (GT3X+ ActiGraph). Actigraphic measures of total sleep time (TST) were analyzed and processed using the open-source R-package GENEActiv and GENEA data in R (GGIR) with and without a sleep diary and additionally processed using proprietary software, ActiLife, for comparison. Bias and agreement (intraclass correlation coefficient) between actigraphy and PSG were examined. Common PSG and sleep health variables associated with the discrepancy between actigraphy, and PSG TST were examined using linear regression. Actigraphy, assessed in GGIR, with and without a sleep diary overestimated PSG TST by (mean ± SD) 31.0 ± 50.0 and 26.4 ± 69.0 minutes, respectively. This overestimation was greater (46.8 ± 50.4 minutes) when actigraphy was analyzed in ActiLife. Agreement between actigraphy and PSG TST was poor (ICC = 0.27–0.44) across all three methods of actigraphy analysis. Longer sleep onset latency and longer wakefulness after sleep onset were associated with overestimation of PSG TST. Open-source processing of actigraphy in a middle-aged community population, agreed poorly with PSG and, on average, overestimated TST. TST overestimation increased with increasing wakefulness overnight. Processing of actigraphy without a diary in GGIR was comparable to when a sleep diary was used and comparable to actigraphy processed with proprietary algorithms in ActiLife.
Publisher: American Academy of Sleep Medicine (AASM)
Date: 15-04-2019
DOI: 10.5664/JCSM.7730
Publisher: Wiley
Date: 03-04-2014
DOI: 10.1002/JNR.23380
Abstract: Previous studies have suggested that brain-derived neurotrophic factor (BDNF) participates in the homeostatic regulation of sleep. The objective of this study was to investigate the influence of the Val66Met functional polymorphism of the BDNF gene on sleep and sleep EEG parameters in a large population-based s le. In total 337 in iduals participating in the São Paulo Epidemiologic Sleep Study were selected for analysis. None of the participants had indications of a sleep disorder, as measured by full-night polysomnography and questionnaire. Spectral analysis of the EEG was carried out in all in iduals using fast Fourier transformation of the oscillatory signals for each EEG electrode. Sleep and sleep EEG parameters in in iduals with the Val/Val genotype were compared with those in Met carriers (Val/Met and Met/Met genotypes). After correction for multiple comparisons and for potential confounding factors, Met carriers showed decreased spectral power in the alpha band in stage one and decreased theta power in stages two and three of nonrapid-eye-movement sleep, at the central recording electrode. No significant influence on sleep macrostructure was observed among the genotype groups. Thus, the Val66Met polymorphism seems to modulate the electrical activity of the brain, predicting interin idual variation of sleep EEG parameters. Further studies of this and other polymorphic variants in potential candidate genes will help the characterization of the molecular basis of sleep.
Publisher: Public Library of Science (PLoS)
Date: 29-04-2002
Publisher: Elsevier BV
Date: 06-2014
DOI: 10.1016/J.PNPBP.2014.02.001
Abstract: Epilepsy is a neurological disorder with significant prevalence and the in iduals affected by this disease have a great probability of occurrence of a lethal phenomenon known as Sudden Unexpected Death in Epilepsy (SUDEP). SUDEP occurs mainly during the night and probably during sleep. The pathophysiological mechanisms involved in this lethal phenomenon are still obscure and new evidences that could corroborate in this area are warranted. Thus, the aim of the present study was to evaluate the effect of sleep deprivation in the expression of microRNA (miRNA) in the frontal cortex and heart tissues of adult male rats after 50days of saline (SAL) or pilocarpine-induced status epilepticus (PILO). Initially 389 miRNA expressions were evaluated between SAL and PILO groups by microarray. Subsequently, 3 differentially expressed miRNAs of each tissue were investigated after total sleep deprivation (TSD 6h) and paradoxical sleep deprivation (PSD 24h). Still, it was analyzed that the effects of sleep rebound with equivalent duration of PSD and TSD. There was a significant increase of miR-146a expression, an important inflammatory modulator in the frontal cortex of PILO rats when compared to SAL animals. Animals treated with pilocarpine were affected by TSD (through overexpression of miRNAs related to inflammatory process) and these changes were maintained even after a sleep window of 6h. In contrast, miRNAs associated with heart diseases were down-regulated in PSD rebound, suggesting a possible restoration of homeostasis in cardiovascular system of SAL and PILO groups.
Publisher: Springer Science and Business Media LLC
Date: 29-01-2019
DOI: 10.1038/S41467-018-08259-7
Abstract: Being a morning person is a behavioural indicator of a person’s underlying circadian rhythm. Using genome-wide data from 697,828 UK Biobank and 23andMe participants we increase the number of genetic loci associated with being a morning person from 24 to 351. Using data from 85,760 in iduals with activity-monitor derived measures of sleep timing we find that the chronotype loci associate with sleep timing: the mean sleep timing of the 5% of in iduals carrying the most morningness alleles is 25 min earlier than the 5% carrying the fewest. The loci are enriched for genes involved in circadian regulation, cAMP, glutamate and insulin signalling pathways, and those expressed in the retina, hindbrain, hypothalamus, and pituitary. Using Mendelian Randomisation, we show that being a morning person is causally associated with better mental health but does not affect BMI or risk of Type 2 diabetes. This study offers insights into circadian biology and its links to disease in humans.
Publisher: Elsevier BV
Date: 06-2012
DOI: 10.1016/J.SLEEP.2012.02.009
Abstract: Although it is well recognized that the prevalence of sleep complaints increases with age, estimates in developing countries are still unknown. The present study aims to estimate the prevalence and prevalence ratios of the correlates of sleep complaints in a large population of older adults from low and middle income countries (LAMICs). A cross-sectional survey was performed in 16,680 65 year-old or older residents in catchment areas of Cuba, the Dominican Republic, Peru, Venezuela, Mexico, China, India, and Puerto Rico (10/66 Dementia Research Group study). Information about socio-demographic factors, lifestyle, health, and sleep complaints was obtained. Results were standardized by age, sex, household clustering, and residence site (urban or rural). Prevalence ratios were derived for each country and fixed effects meta-analyses were used to combine them. The standardized prevalence of sleep complaints varied from 9.1% (China) to 37.7% (India). The meta-analysis showed that female gender, urban residence, low educational level, low physical activity status, high pain scores, poor health, higher memory impairment score, presence of major depression, mild cognitive impairment, and high number of co-morbidities were associated with sleep complaints. This study robustly characterized the prevalence of sleep complaints in large s les of the elderly in LAMICs and identified potential risk factors that may be specific to these populations. This approach can help to direct health-care efforts related to sleep disturbances in these countries.
Publisher: Springer Science and Business Media LLC
Date: 28-08-2018
DOI: 10.1038/S41598-018-31266-Z
Abstract: Wrist worn raw-data accelerometers are used increasingly in large-scale population research. We examined whether sleep parameters can be estimated from these data in the absence of sleep diaries. Our heuristic algorithm uses the variance in estimated z-axis angle and makes basic assumptions about sleep interruptions. Detected sleep period time window (SPT-window) was compared against sleep diary in 3752 participants (range = 60–82 years) and polysomnography in sleep clinic patients (N = 28) and in healthy good sleepers (N = 22). The SPT-window derived from the algorithm was 10.9 and 2.9 minutes longer compared with sleep diary in men and women, respectively. Mean C-statistic to detect the SPT-window compared to polysomnography was 0.86 and 0.83 in clinic-based and healthy sleepers, respectively. We demonstrated the accuracy of our algorithm to detect the SPT-window. The value of this algorithm lies in studies such as UK Biobank where a sleep diary was not used.
Publisher: Public Library of Science (PLoS)
Date: 29-08-2012
Publisher: Oxford University Press (OUP)
Date: 03-2011
Location: United States of America
Location: United States of America
No related grants have been discovered for Diego R. Mazzotti, Ph.D..