Sleep Dysfunction Research Articles

Sleep dysfunction in aspirin exacerbated respiratory disease: A prospective cohort study

AbstractObjectiveStudies have described sleep dysfunction (SD) in patients with chronic rhinosinusitis (CRS). However, there is a paucity of literature describing sleep dysfunction in the context of aspirin‐exacerbated respiratory disease (AERD). The purpose of this study was to evaluate the prevalence and severity of SD in patients with AERD relative to CRS.MethodsThis study is a prospective cohort study. Patients diagnosed with CRS without polyposis (CRSsNP, n = 206), CRS with nasal polyposis (CRSwNP, n = 38), and AERD (n = 28) were recruited prospectively in academic center rhinology clinic. SD was assessed using the Neuro‐QOL Short Form v1.0‐Sleep Disturbance (sleep‐QOL), for which severe SD is defined as a score >2.0 standard deviations from the normalized mean. Demographic and patient‐reported outcome measures (including SNOT‐22 and PHQ‐2) were collected to adjust for sleep confounders. Comparisons were made between groups using univariate and multivariate analyses.ResultsThe prevalence of severe SD was significantly higher in AERD (57.1%) than in CRSsNP (32.5%) or CRSwNP (34.2%), p = 0.038. After adjusting for sleep confounders, the risk of sleep dysfunction remained higher among patients with AERD (odds ratio [OR] = 2.72 vs. CRSsNP, 95% confidence interval [CI] = 1.18–6.27, p = 0.02; OR = 3.06 vs. CRSwNP, 95% CI = 1.06–8.82, p = 0.04). SNOT‐22 total score and the sleep subdomain showed no correlation with sleep‐QOL score.ConclusionsThe frequency and severity of SD are greater in AERD patients than in patients with CRS with or without nasal polyposis, independent of confounders of sleep quality. While the putative link between AERD and SD remains elusive, this study suggests that SD in AERD may be greater than previously recognized.

Mitochondrial antioxidant elamipretide improves learning and memory impairment induced by chronic sleep deprivation in mice.

The inflammation and synaptic dysfunction induced by mitochondrial dysfunction play essential roles in the learning and memory impairment associated with sleep dysfunction. Elamipretide (SS-31), a novel mitochondrion-targeted antioxidant, was proven to improve mitochondrial dysfunction, the inflammatory response, synaptic dysfunction, and cognitive impairment in models of cerebral ischemia, sepsis, and type 2 diabetes. However, the potential for SS-31 to improve the cognitive impairment induced by chronic sleep deprivation (CSD) and its underlying mechanisms is unknown. Adult c57BL/6J mice were subjected to CSD for 21 days using an activity wheel accompanied by daily intraperitoneal injection of SS-31 (5mg/kg). The novel object recognition and Morris water maze test were used to evaluate hippocampus-dependent cognitive function. Western blotting and reverse transcription-quantitative polymerase chain reaction assays were used to determine the effects of CSD and SS-31 on markers of mitochondria, inflammation response, and synaptic function. Enzyme-linked immunosorbent assays were used to examine the levels of proinflammatory cytokines. SS-31 could improve the cognitive impairment induced by CSD. In particular, SS-31 treatment restored the CSD-induced decrease in sirtuin 1 (SIRT1) and peroxisome proliferator-activated receptor γ coactivator alpha levels and the increase in levels nuclear factor kappa-B and inflammatory cytokines, including interleukin (IL)-1β, IL-6, and tumor necrosis factor-alpha. Furthermore, SS-31 significantly increased the levels of brain-derived neurotrophic factor, postsynaptic density protein-95, and synaptophysin in CSD mice. Taken together, these results suggest that SS-31 could improve CSD-induced mitochondrial biogenesis dysfunction, inflammatory response, synaptic dysfunction, and cognitive impairment by increasing SIRT1 expression levels.

1039 Diffusion Imaging Markers of Glymphatic Function in Veterans with Sleep Dysfunction and Mild Traumatic Brain Injury

1039 Diffusion Imaging Markers of Glymphatic Function in Veterans with Sleep Dysfunction and Mild Traumatic Brain Injury

Acupuncture for reducing the south to reinforce the north on executive function and sleep structure in patients with chronic insomnia disorder of heart-kidney disharmony.

To observe the efficacy of acupuncture for reducing the south to reinforce the north on executive function, sleep structure and sleep quality in patients with chronic insomnia disorder of heart-kidney disharmony. A total of 100 patients with chronic insomnia disorder of heart-kidney disharmony were randomized into an acupuncture group (50 cases, 1 case dropped out) and a western medication group (50 cases, 2 cases dropped out). Acupuncture for reducing the south to reinforce the north was applied at Baihui (GV 20) and bilateral Shenmen (HT 7), Sanyinjiao (SP 6), Shenmai (BL 62), Zhaohai (KI 6), Xinshu (BL 15), Shenshu (BL 23) in the acupuncture group, once a day, 5 days a week. Lorazepam tablet was given orally in the western medication group, 0.5-1 mg a time, once a day. Both groups were treated for 4 weeks. The Stroop color-word test (SCWT) indexes (the time consuming and the correct number of card A, B, C and the Stroop interference effect [SIE]), sleep structure indexes (total sleep time [TST], sleep latency [SL], wake after sleep onset [WASO], sleep efficiency [SE], non-rapid eye movement period 1 [N1], non-rapid eye movement period 2 [N2], non-rapid eye movement period 3 [N3], rapid eye movement period [REM]) and Pittsburgh sleep quality index (PSQI) score were observed before and after treatment in the two groups. After treatment, the time consuming of card B and C, the time consuming and the correct number of SIE, SL, WASO, N1, N2, as well as the sub-item scores and total score of PSQI were decreased (P<0.05, P<0.01), the correct number of card A, B and C, TST, SE, N3 and REM were increased (P<0.01) compared with those before treatment in the acupuncture group; the time consuming of card C and SIE, the correct number of card A and SIE, TST, SE, REM were increased (P<0.05, P<0.01), SL, WASO, N1, as well as the sub-item scores of sleep quality, sleep latency, sleep duration, sleep efficiency, daytime function and total score of PSQI were decreased (P<0.01) compared with those before treatment in the western medication group. After treatment, in the acupuncture group, the time consuming of card C, the time consuming and the correct number of SIE, N1, N2, as well as the sub-item scores of sleep quality, sleep dysfunction, daytime function and total score of PSQI were lower than those in the western medication group (P<0.01), the correct number of card B and C, N3, REM were higher than those in the western medication group (P<0.01). Acupuncture for reducing the south to reinforce the north can improve the executive function of patients with chronic insomnia disorder of heart-kidney disharmony, adjust the sleep structure, and improve the night sleep quality and daytime body function.

Effects of dopaminergic therapy on sleep quality in fluctuating Parkinson's disease patients.

Sleep disorders negatively impact quality of life in Parkinson's disease (PD), yet the role of antiparkinsonian drugs on sleep quality is still unclear. We aimed to explore the correlation between sleep dysfunction and dopaminergic therapy in a large cohort of advanced PD patients. Patients consecutively evaluated for device-aided therapies eligibility were evaluated by means of the PD Sleep Scale (PDSS-2; score ≥ 18 indicates poor sleep quality), and the Epworth Sleepiness Scale (ESS score ≥ 10 indicates excessive daytime sleepiness-EDS). Binary logistic regression analysis, adjusting for age, sex, disease duration, motor impairment, and sleep drugs, was employed to evaluate the association between dopaminergic therapy and PDSS-2 and ESS scores. Analysis of covariance assessed differences in PDSS-2 and ESS scores between patients without DA, and between patients treated with low or high doses of DA (cut-off: DA-LEDD = 180mg). In a cohort of 281 patients, 66.2% reported poor sleep quality, and 34.5% reported EDS. DA treatment demonstrated twofold lower odds of reporting relevant sleep disturbances (OR 0.498; p = 0.035), while DA-LEDD, levodopa-LEDD, total LEDD, and extended-release levodopa were not associated with disturbed sleep. EDS was not influenced by dopaminergic therapy. Patients with DA intake reported significant lower PDSS-2 total score (p = 0.027) and "motor symptoms at night" domain score (p = 0.044). Patients with higher doses of DA showed lower PDSS-2 total score (p = 0.043). Our study highlights the positive influence of DA add-on treatment on sleep quality in this group of advanced fluctuating PD patients.

Effects of Continuous Subcutaneous Infusion of Foslevodopa/Foscarbidopa on Sleep Dysfunction in People with Parkinson’s (P9-3.005)

Effects of Continuous Subcutaneous Infusion of Foslevodopa/Foscarbidopa on Sleep Dysfunction in People with Parkinson’s (P9-3.005)

Ozone rectal insufflation mitigates chronic rapid eye movement sleep deprivation-induced cognitive impairment through inflammation alleviation and gut microbiota regulation in mice

A range of sleep disorders has the potential to adversely affect cognitive function. This study was undertaken with the objective of investigating the effects of ozone rectal insufflation (O3-RI) on cognitive dysfunction induced by chronic REM sleep deprivation, as well as elucidating possible underlying mechanisms. O3-RI ameliorated cognitive dysfunction in chronic REM sleep deprived mice, improved the neuronal damage in the hippocampus region and decreased neuronal loss. Administration of O3-RI may protect against chronic REM sleep deprivation induced cognitive dysfunction by reversing the abnormal expression of Occludin and leucine-rich repeat and pyrin domain-containing protein 3 inflammasome as well as interleukin-1β in the hippocampus and colon tissues. Moreover, the microbiota diversity and composition of sleep deprivation mice were significantly affected by O3-RI intervention, as evidenced by the reversal of the Firmicutes/Bacteroidetes abundance ratio and the relative abundance of the Bacteroides genus. In particular, the relative abundance of the Bacteroides genus demonstrated a pronounced correlation with cognitive impairment and inflammation. Our findings suggested that O3-RI can improve cognitive dysfunction in sleep deprivation mice, and its mechanisms may be related to regulating gut microbiota and alleviating inflammation and damage in the hippocampus and colon.

Meal related symptoms in youth with chronic abdominal pain: Relationship to anxiety, depression, and sleep dysfunction.

The objective of the current study was to describe meal-related symptoms in youth with chronic abdominal pain fulfilling criteria for a disorder of gut-brain interaction (DGBI) and their associations with anxiety, depression, and sleep disturbances. This was a retrospective evaluation of 226 consecutive patients diagnosed with an abdominal pain-associated DGBI. As part of routine care, all had completed a standardized symptom history, the Sleep Disturbances Scale for Children (utilized to assess for disorders of initiation and maintenance of sleep and excessive daytime somnolence) and the Behavior Assessment System for Children-Third Edition (utilized to assess for anxiety and depression). Four meal related symptoms were assessed: early satiety, postprandial bloating, postprandial abdominal pain, and postprandial nausea. Overall, 87.6% of patients reported at least one meal related symptom and the majority reported at least three symptoms. All meal related symptoms were significantly related to each other. Postprandial pain and nausea were more often reported by females. Early satiety, postprandial bloating, and postprandial nausea, but not postprandial pain demonstrated significant though variable associations with anxiety, depression, disorders of initiation and maintenance of sleep, and disorders of excessive somnolence, but only in adolescents. Meal related symptoms are very common in youth with abdominal pain-associated DGBIs. Early satiety, bloating, and postprandial nausea demonstrate variable associations with anxiety, depression, and disordered sleep while increased postprandial pain was not associated with psychologic or sleep dysfunction, suggesting a different pathway for symptom generation.

Resveratrol prevents cognitive deficits induced by sleep deprivation via modulating sirtuin 1 associated pathways in the hippocampus.

Accumulating evidence confirms that sleep insufficiency is a high risk factor for cognitive impairment, which involves inflammation and synaptic dysfunction. Resveratrol, an agonist of the Sirt1, has demonstrated anti-inflammation and neuroprotective effects in models of Alzheimer's disease, Parkinson's disease, and schizophrenia. However, the beneficial effects of resveratrol on sleep deprivation-induced cognitive deficits and its underlying molecular mechanisms are unclear. In the present study, thirty-two male C57BL/6 J mice were randomly divided into a Control+DMSO group, Control+Resveratrol group, SD+DMSO group, and SD+Resveratrol group. The mice in the SD+Resveratrol group underwent 5 days of sleep deprivation after pretreatment with resveratrol (50 mg/kg) for 2 weeks, while the mice in the SD+DMSO group only underwent sleep deprivation. After sleep deprivation, we evaluated spatial learning and memory function using the Morris water maze test. We used general molecular biology techniques to detect changes in levels of pro-inflammatory cytokines and Sirt1/miR-134 pathway-related synaptic plasticity proteins. We found that resveratrol significantly reversed sleep deprivation-induced learning and memory impairment, elevated interleukin-1β, interleukin-6, and tumor necrosis factor-α levels, and decreased brain-derived neurotrophic factor, tyrosine kinase receptor B, postsynaptic density protein-95, and synaptophysin levels by activating the Sirt1/miR-134 pathway. In conclusion, resveratrol is a promising agent for preventing sleep deprivation-induced cognitive dysfunction by reducing pro-inflammatory cytokines and improving synaptic function via the Sirt1/miR-134 pathway.

Healthy couple, better sleep: Exploring connections and changes in couple relationship education participants.

Considerable evidence suggests couple relationship education (CRE) programs are effective in improving couples' relationship functioning, yet few studies have examined the implications of CRE programs on indicators of physical health despite substantial research supporting links between relational and physical health. This study utilized a sample of 308 couples randomly assigned to a CRE curriculum to explore the dyadic links between conflict management and self-care skills (emphasized in CRE), stress, and sleep dysfunction concurrently. We prospectively tested whether changes in skills drove changes in sleep dysfunction or vice versa, for both self and partner. Results from a series of structural equation models indicated indirect links for men and women between conflict management and self-care skills and sleep dysfunction through lower stress level at program start. Dyadically, men's and women's better conflict management skills were associated with partners' lower stress, which was in turn associated with partners' lower sleep dysfunction. Men's better self-care skills were linked with partners' lower stress levels, which were linked with partners' lower sleep dysfunction. Tests of dyadic prospective cross-lagged effects among changes in sleep and changes in skills indicated that initial improvements in both partners' sleep predicted improvements in their own conflict management skills 1 year later. Initial improvements in women's conflict management skills predicted reduced sleep dysfunction for themselves. Additionally, for both partners, early changes in self-care predicted later reductions in sleep dysfunction. Dyadically, immediate improvements in men's self-care predicted reduced sleep dysfunction for their partner a year later. Implications for research and practice are discussed.

Sleep, Glial Function, and the Endocannabinoid System: Implications for Neuroinflammation and Sleep Disorders.

The relationship between sleep, glial cells, and the endocannabinoid system represents a multifaceted regulatory network with profound implications for neuroinflammation and cognitive function. The molecular underpinnings of sleep modulation by the endocannabinoid system and its influence on glial cell activity are discussed, shedding light on the reciprocal relationships that govern these processes. Emphasis is placed on understanding the role of glial cells in mediating neuroinflammatory responses and their modulation by sleep patterns. Additionally, this review examines how the endocannabinoid system interfaces with glia-immune signaling to regulate inflammatory cascades within the central nervous system. Notably, the cognitive consequences of disrupted sleep, neuroinflammation, and glial dysfunction are addressed, encompassing implications for neurodegenerative disorders, mood disturbances, and cognitive decline. Insights into the bidirectional modulation of cognitive function by the endocannabinoid system in the context of sleep and glial activity are explored, providing a comprehensive perspective on the potential mechanisms underlying cognitive impairments associated with sleep disturbances. Furthermore, this review examines potential therapeutic avenues targeting the endocannabinoid system to mitigate neuroinflammation, restore glial homeostasis, and normalize sleep patterns. The identification of novel therapeutic targets within this intricate regulatory network holds promise for addressing conditions characterized by disrupted sleep, neuroinflammation, and cognitive dysfunction. This work aims to examine the complexities of neural regulation and identify potential avenues for therapeutic intervention.

Associations between disturbed sleep and attenuated psychotic experiences in people at clinical high risk for psychosis.

Pre-diagnostic stages of psychotic illnesses, including 'clinical high risk' (CHR), are marked by sleep disturbances. These sleep disturbances appear to represent a key aspect in the etiology and maintenance of psychotic disorders. We aimed to examine the relationship between self-reported sleep dysfunction and attenuated psychotic symptoms (APS) on a day-to-day basis. Seventy-six CHR young people completed the Experience Sampling Methodology (ESM) component of the European Union Gene-Environment Interaction Study, collected through PsyMate® devices, prompting sleep and symptom questionnaires 10 times daily for 6 days. Bayesian multilevel mixed linear regression analyses were performed on time-variant ESM data using the brms package in R. We investigated the day-to-day associations between sleep and psychotic experiences bidirectionally on an item level. Sleep items included sleep onset latency, fragmentation, and quality. Psychosis items assessed a range of perceptual, cognitive, and bizarre thought content common in the CHR population. Two of the seven psychosis variables were unidirectionally predicted by previous night's number of awakenings: every unit increase in number of nightly awakenings predicted a 0.27 and 0.28 unit increase in feeling unreal or paranoid the next day, respectively. No other sleep variables credibly predicted next-day psychotic symptoms or vice-versa. In this study, the relationship between sleep disturbance and APS appears specific to the item in question. However, some APS, including perceptual disturbances, had low levels of endorsement amongst this sample. Nonetheless, these results provide evidence for a unidirectional relationship between sleep and some APS in this population.

Sleep Physiology and Neurocognition Among Adolescents With Attention-Deficit/Hyperactivity Disorder

Few studies have characterized the nature of sleep problems among adolescents with attention-deficit/hyperactivity disorder (ADHD) using polysomnography (PSG). Additionally, although adolescents with ADHD and adolescents with sleep disturbances display similar neurocognitive deficits, the role of sleep in contributing to neurocognitive impairment in adolescent ADHD is unknown. This study investigated differences in PSG-measured sleep among adolescents with ADHD compared with non-psychiatric controls and associations with neurocognition. Medication-free adolescents aged 13 to 17 (N= 62, n= 31 with ADHD; mean age= 15.3 years; 50% female) completed a diagnostic evaluation, 3 nights of ambulatory PSG, the Cambridge Neuropsychological Test Automated Battery, and subjective reports of sleep and executive functioning. Linear regressions covarying for age, sex, and pubertal status examined group differences in sleep indices, and partial Pearson correlations assessed relations between sleep and neurocognition. Although adolescents with ADHD did not exhibit differences in PSG-measured sleep duration, awakenings, or latency (ps > .05) compared with non-psychiatric controls, they displayed lower slow wave sleep percentage (β=-.40) and non-rapid eye movement (NREM) electroencephalogram (EEG) delta power (β=-.29). They also exhibited greater stage 2 percentage (β= .41), NREM EEG sigma power (β= .41), and elevated self-reported sleep disturbances (ps< .05). Lower NREM EEG delta power, increased high-frequency power, and slower decline in NREM EEG delta power overnight were associated with poorer neurocognition among adolescents with ADHD. Adolescents with ADHD reported more sleep disturbances than non-psychiatric controls and exhibited differences in sleep stage distribution and NREM sleep EEG frequency. Sleep-EEG spectral indices were associated with impaired neurocognition, suggesting that physiological sleep processes may underlie neurocognitive deficits in ADHD. Future studies may clarify whether sleep plays a causal role in neurocognitive impairments in adolescent ADHD and whether interventions normalizing sleep improve neurocognition. Sleep Dysfunction and Neurocognitive Outcomes in Adolescent ADHD; https://clinicaltrials.gov/; NCT02897362. We worked to ensure sex and gender balance in the recruitment of human participants. We worked to ensure race, ethnic, and/or other types of diversity in the recruitment of human participants. We worked to ensure that the study questionnaires were prepared in an inclusive way. One or more of the authors of this paper self-identifies as a member of one or more historically underrepresented sexual and/or gender groups in science. We actively worked to promote sex and gender balance in our author group. While citing references scientifically relevant for this work, we also actively worked to promote sex and gender balance in our reference list.

HLA-DQB1*05 subtypes and not DRB1*10:01 mediates risk in anti-IgLON5 disease.

Anti-IgLON5 disease is a rare and likely underdiagnosed subtype of autoimmune encephalitis. The disease displays a heterogeneous phenotype that includes sleep, movement, and bulbar-associated dysfunction. Presence of IgLON5-antibodies in CSF/serum, together with a strong association with HLA-DRB1*10:01∼DQB1*05:01, support an autoimmune basis. In this study, a multicentric HLA study of 87 anti-IgLON5 patients revealed a stronger association with HLA-DQ than HLA-DR. Specifically, we identified a predisposing rank-wise association with HLA-DQA1*01:05∼DQB1*05:01, HLA-DQA1*01:01∼DQB1*05:01 and HLA-DQA1*01:04∼DQB1*05:03 in 85% of patients. HLA sequences and binding cores for these three DQ heterodimers were similar, unlike those of linked DRB1 alleles, supporting a causal link to HLA-DQ. This association was further reflected in an increasingly later age of onset across each genotype group, with a delay of up to 11 years, while HLA-DQ-dosage dependent effects were also suggested by reduced risk in the presence of non-predisposing DQ1 alleles. The functional relevance of the observed HLA-DQ molecules was studied with competition binding assays. These proof-of-concept experiments revealed preferential binding of IgLON5 in a post-translationally modified, but not native, state to all three risk-associated HLA-DQ receptors. Further, a deamidated peptide from the Ig2-domain of IgLON5 activated T cells in two patients, compared to one control carrying HLA-DQA1*01:05∼DQB1*05:01. Taken together, these data support a HLA-DQ-mediated T cell response to IgLON5 as a potentially key step in the initiation of autoimmunity in this disease.

State of the Science: The Transdiagnostic Intervention for Sleep and Circadian Dysfunction

State of the Science: The Transdiagnostic Intervention for Sleep and Circadian Dysfunction

Multi-night cortico-basal recordings reveal mechanisms of NREM slow-wave suppression and spontaneous awakenings in Parkinson's disease.

Sleep disturbance is a prevalent and disabling comorbidity in Parkinson's disease (PD). We performed multi-night (n = 57) at-home intracranial recordings from electrocorticography and subcortical electrodes using sensing-enabled Deep Brain Stimulation (DBS), paired with portable polysomnography in four PD participants and one with cervical dystonia (clinical trial: NCT03582891). Cortico-basal activity in delta increased and in beta decreased during NREM (N2 + N3) versus wakefulness in PD. DBS caused further elevation in cortical delta and decrease in alpha and low-beta compared to DBS OFF state. Our primary outcome demonstrated an inverse interaction between subcortical beta and cortical slow-wave during NREM. Our secondary outcome revealed subcortical beta increases prior to spontaneous awakenings in PD. We classified NREM vs. wakefulness with high accuracy in both traditional (30 s: 92.6 ± 1.7%) and rapid (5 s: 88.3 ± 2.1%) data epochs of intracranial signals. Our findings elucidate sleep neurophysiology and impacts of DBS on sleep in PD informing adaptive DBS for sleep dysfunction.

Slow-wave sleep dysfunction in mild parkinsonism is associated with excessive beta and reduced delta oscillations in motor cortex.

Increasing evidence suggests slow-wave sleep (SWS) dysfunction in Parkinson's disease (PD) is associated with faster disease progression, cognitive impairment, and excessive daytime sleepiness. Beta oscillations (8-35 Hz) in the basal ganglia thalamocortical (BGTC) network are thought to play a role in the development of cardinal motor signs of PD. The role cortical beta oscillations play in SWS dysfunction in the early stage of parkinsonism is not understood, however. To address this question, we used a within-subject design in a nonhuman primate (NHP) model of PD to record local field potentials from the primary motor cortex (MC) during sleep across normal and mild parkinsonian states. The MC is a critical node in the BGTC network, exhibits pathological oscillations with depletion in dopamine tone, and displays high amplitude slow oscillations during SWS. The MC is therefore an appropriate recording site to understand the neurophysiology of SWS dysfunction in parkinsonism. We observed a reduction in SWS quantity (p = 0.027) in the parkinsonian state compared to normal. The cortical delta (0.5-3 Hz) power was reduced (p = 0.038) whereas beta (8-35 Hz) power was elevated (p = 0.001) during SWS in the parkinsonian state compared to normal. Furthermore, SWS quantity positively correlated with delta power (r = 0.43, p = 0.037) and negatively correlated with beta power (r = -0.65, p < 0.001). Our findings support excessive beta oscillations as a mechanism for SWS dysfunction in mild parkinsonism and could inform the development of neuromodulation therapies for enhancing SWS in people with PD.

Influences of Genetic and Environmental Factors on Chronic Migraine: A Narrative Review.

In this narrative review, we aim to summarize recent insights into the complex interplay between environmental and genetic factors affecting the etiology, development, and progression of chronic migraine (CM). Environmental factors such as stress, sleep dysfunction, fasting, hormonal changes, weather patterns, dietary compounds, and sensory stimuli are critical triggers that can contribute to the evolution of episodic migraine into CM. These triggers are particularly influential in genetically predisposed individuals. Concurrently, genome-wide association studies (GWAS) have revealed over 100 genetic loci linked to migraine, emphasizing a significant genetic basis for migraine susceptibility. In CM, environmental and genetic factors are of equal importance and contribute to the pathophysiology of the condition. Understanding the bidirectional interactions between these elements is crucial for advancing therapeutic approaches and preventive strategies. This balanced perspective encourages continued research into the complex gene-environment nexus to improve our understanding and management of CM.

Patient perspectives on chronic rhinosinusitis in cystic fibrosis: Symptom prioritization in the era of highly effective modulator therapy.

Chronic rhinosinusitis (CRS) is common in people with cystic fibrosis (PwCF). Rhinologic symptom prioritization and areas that influence CRS treatment choices, including pursuing endoscopic sinus surgery (ESS), remain understudied. Adult PwCF+CRS were enrolled at eight centers into a prospective, observational study (2019-2023). Participants were administered the 22-SinoNasal Outcome Test (SNOT-22) survey and a modified SNOT-22 instrument examining symptom importance. We determined importance rankings for individual symptoms and SNOT-22 symptom importance subdomains in two sets of subgroups-those pursuing ESS versus continuing medical management (CMT), and those on elexacaftor/tezacaftor/ivacaftor (ETI) versus not on ETI. Among 69 participants, the highest priorities were nasal congestion (n=48, 69.6% important), post-nasal discharge (32, 46.4%), facial pain (29, 43.3%), waking up tired (27, 39.1%), and fatigue (26, 37.7%). Those electing surgery (n=23) prioritized sleep and psychological dysfunction symptoms compared to those pursuing CMT (n=49) (sleep median score=19.0 [interquartile range: 12.0, 25.0] vs. 4.5 [0.0, 12.8]; p<0.0001; psychological=17.0 [7.0, 26.0] vs. 7.0 [0.0, 15.8]; p=0.002). ETI users had comparable SNOT-22 total symptom importance scores to non-ETI users (p=0.14). Non-ETI users (n=34) showed a trend toward prioritizing sleep symptoms compared to ETI users (n=35) (13.0 [2.8, 22.3] vs. 6.0 [2.0, 17.0]; p=0.055). Nasal congestion and post-nasal discharge were top priorities reported by PwCF+CRS. Those electing surgery prioritized sleep and psychological symptoms, highlighting their importance in pre-operative discussions. Non-ETI users' prioritization of sleep improvement may highlight their unique disease impact and therapeutic needs; however, additional investigation is required.

Association of subjective and objective sleep disturbance with the spectrum of gastroesophageal reflux disease.

The relationship between obstructive sleep apnea (OSA) and gastroesophageal reflux disease (GERD) is complex. We aim to determine the association of subjective and objective sleep parameters with diverse manifestations of the GERD spectrum. We prospectively recruited 561 subjects who underwent an electrocardiogram-based cardiopulmonary coupling (CPC) for OSA screening during a health check-up. All subjects received the Reflux Disease Questionnaire (RDQ) and an upper endoscopy to determine the presence of troublesome reflux symptoms and erosive esophagitis (EE). Sleep quality was evaluated by the Pittsburgh Sleep Quality Index (PSQI) and sleep dysfunction was defined as a PSQI > 5. OSA was defined as a CPC-derived apnea/hypopnea index exceeding 15 events per hour. Comparisons were made between subjects on the GERD spectrum with respect to their various subjective and objective sleep parameters. Among the 277 subjects with GERD (49.4%), 198 (35.3%) had EE. Subjects with GERD had higher scores of PSQI (6.99 ± 3.97 vs. 6.07 ± 3.73, P = 0.005) and a higher prevalence of sleep dysfunction (60.6% vs. 49.6%, P = 0.009). Subjects with EE had a higher prevalence of OSA (42.9% vs. 33.9%, P = 0.034). Along the GERD spectrum, symptomatic EE subjects had the highest PSQI scores and prevalence of sleep dysfunction (70.7%), while asymptomatic EE subjects had the highest prevalence of OSA (44%). Our findings indicate a high prevalence of sleep dysfunction among individuals with GERD. Furthermore, patients on the GERD spectrum are prone to experiencing a range of subjective and objective sleep disturbances.