Associations of sleep disorders with serum neurofilament light chain levels in Parkinson's disease.

BACKGROUND: Sleep disorders are a prevalent non-motor symptom of Parkinson's disease (PD), although reliable biological markers are presently lacking. OBJECTIVES: To explore the associations between sleep disorders and serum neurofilament light chain (NfL) levels in individuals with prodromal and early PD. METHODS: The study contained 1113 participants, including 585 early PD individuals, 353 prodromal PD individuals, and 175 healthy controls (HCs). The correlations between sleep disorders (including rapid eye movement sleep behavior disorder (RBD) and excessive daytime sleepiness (EDS)) and serum NfL levels were researched using multiple linear regression models and linear mixed-effects models. We further investigated the correlations between the rates of changes in daytime sleepiness and serum NfL levels using multiple linear regression models. RESULTS: In baseline analysis, early and prodromal PD individuals who manifested specific behaviors of RBD showed significantly higher levels of serum NfL. Specifically, early PD individuals who experienced nocturnal dream behaviors (ß = 0.033; P = 0.042) and movements of arms or legs during sleep (ß = 0.027; P = 0.049) showed significantly higher serum NfL levels. For prodromal PD individuals, serum NfL levels were significantly higher in individuals suffering from disturbed sleep (ß = 0.038; P = 0.026). Our longitudinal findings support these baseline associations. Serum NfL levels showed an upward trend in early PD individuals who had a higher total RBDSQ score (ß = 0.002; P = 0.011) or who were considered as probable RBD (ß = 0.012; P = 0.009) or who exhibited behaviors on several sub-items of the RBDSQ. In addition, early PD individuals who had a high total ESS score (ß = 0.001; P = 0.012) or who were regarded to have EDS (ß = 0.013; P = 0.007) or who exhibited daytime sleepiness in several conditions had a trend toward higher serum NfL levels. CONCLUSION: Sleep disorders correlate with higher serum NfL, suggesting a link to PD neuronal damage. Early identification of sleep disorders and NfL monitoring are pivotal in detecting at-risk PD patients promptly, allowing for timely intervention. Regular monitoring of NfL levels holds promise for tracking both sleep disorders and disease progression, potentially emerging as a biomarker for evaluating treatment outcomes.

Orexin and Sleep Disturbances in Alpha-Synucleinopathies: a Systematic Review.

PURPOSE OF REVIEW: Sleep disturbances are amongst most frequent non-motor symptoms of Parkinson's Disease (PD), and they are similarly frequently reported in other alpha-syncleinopathies, such as Dementia with Lewy Bodies (DLB) and Multiple System Atrophy (MSA). More recently, the orexin system has been implicated in control of arousal based on salient environmental set points, and its dysregulation in sleep issues in alpha-synucleinopathies suggested by the findings from the translational animal models. However, its role in the patients with alpha-synucleinopathies remains unclear. We thus set to systematically review, and to critically assess, contemporary evidence on the association of the orexinergic system and sleep disturbances in alpha-synucleinopathies. In this systematic review, studies investigating orexin and sleep in alpha-synucleinopathies (Rapid Eye Movement (REM) Behaviour Disorder (RBD), Parkinson's Disease (PD), Dementia with Lewy Bodies (DLB), Multiple System Atrophy (MSA)) were identified using electronic database searches of PubMed, Web of Science and PsychINFO using MeSH terms, keywords, and title words such as "Alpha-synucleinopathies" AND "Orexin" AND "Sleep Disturbances". RECENT FINDINGS: 17 studies were included in this systemic review, of which 2 studies on RBD, 10 on PD, 4 on DLB, and 1 on MSA patients. Taken together, RBD and PD studies suggest a potential adaptive increase in orexin levels in early stages of the neurodegenerative process, with reduced levels more often reported for later, more advanced stages of illness. To date, no differences in orexin levels were demonstrated between MSA patients and healthy controls. There is a dearth of studies on the role of orexin levels in alpha-synucleinopathies. Moreover, significant methodologic limitations in the current body of work, including use of non-standardised research protocols and lack of prospective, multi-centre studies, disallow for any finite conclusion in regards to underlying pathomechanisms. Nonetheless, a picture of a complex, multifaceted relationship between the dysregulation of the orexinergic pathway and sleep disturbances in alpha-synucleinopathies is emerging. Hence, future studies disentangling orexinergic pathomechanisms of alpha-syncleinopathies are urgently needed to obtain a more comprehensive account of the role of orexinergic pathway in alpha-synucleinopathies. Pharmacological manipulations of orexins may have multiple therapeutic applications in treatment strategies, disease diagnosis, and might be effective for treating both motor and non-motor symptoms.

Eating habits and sleep quality in individuals with type 1 diabetes on continuous glucose monitoring and insulin pump.

BACKGROUND AND AIMS: Sleep disorders are bidirectionally linked with eating behaviors and glucose metabolism, which could be clinically relevant in type 1 diabetes (T1D). We investigated the relationship between dietary habits and sleep quality in individuals with T1D on insulin pumps and continuous glucose monitoring (CGM). METHODS AND RESULTS: In a cross-sectional study, dietary habits (7-day food diary, EPIC questionnaire) and sleep quality (Pittsburgh Sleep Quality Index questionnaire) were assessed in 59 men and 58 women with T1D, aged 19-79 years, using CGM and insulin pump. Differences in dietary habits and blood glucose after dinner (6 h) between participants differing in sleep quality, sleep duration, and sleep onset latency were evaluated. Bad Sleepers (n = 81) were twice as prevalent as Good Sleepers (n = 36) and had a significantly higher intake of fat than Good Sleepers (dinner: 30.7 ± 10.7 vs. 24.0 ± 10.5 g, p = 0.004). Short sleepers had a significantly higher usual intake (g/1000 kcal) of coffee and tea (90.4 ± 71.7 vs. 62.0 ± 35.6), alcoholic (47.8 ± 51.1 vs. 28.9 ± 31.5) and carbonated beverages (21.8 ± 38.1 vs. 9.3 ± 17.2) (p < 0.05 for all) than Long Sleepers. Long Sleep Onset Latency was associated with a significantly higher fat intake at dinner (41.8 ± 7.4 vs. 38.1 ± 9.1 % total energy, p = 0.029) than Short Sleep Onset Latency. No significant differences in post-dinner blood glucose levels were detected between participants with good or bad sleep quality. CONCLUSION: Sleep disruption is common in T1D and is associated with unhealthy dietary choices, especially at dinner, independently of post-dinner blood glucose control.

Targeted metabolomics-based understanding of the sleep disturbances in drug-naïve patients with schizophrenia.

BACKGROUND: Sleep disturbances are a common occurrence in patients with schizophrenia, yet the underlying pathogenesis remain poorly understood. Here, we performed a targeted metabolomics-based approach to explore the potential biological mechanisms contributing to sleep disturbances in schizophrenia. METHODS: Plasma samples from 59 drug-naïve patients with schizophrenia and 36 healthy controls were subjected to liquid chromatography-mass spectrometry (LC-MS) targeted metabolomics analysis, allowing for the quantification and profiling of 271 metabolites. Sleep quality and clinical symptoms were assessed using the Pittsburgh Sleep Quality Index (PSQI) and the Positive and Negative Symptom Scale (PANSS), respectively. Partial correlation analysis and orthogonal partial least squares discriminant analysis (OPLS-DA) model were used to identify metabolites specifically associated with sleep disturbances in drug-naïve schizophrenia. RESULTS: 16 characteristic metabolites were observed significantly associated with sleep disturbances in drug-naïve patients with schizophrenia. Furthermore, the glycerophospholipid metabolism (Impact: 0.138, p<0.001), the butanoate metabolism (Impact: 0.032, p=0.008), and the sphingolipid metabolism (Impact: 0.270, p=0.104) were identified as metabolic pathways associated with sleep disturbances in drug-naïve patients with schizophrenia. CONCLUSIONS: Our study identified 16 characteristic metabolites (mainly lipids) and 3 metabolic pathways related to sleep disturbances in drug-naïve schizophrenia. The detection of these distinct metabolites provide valuable insights into the underlying biological mechanisms associated with sleep disturbances in schizophrenia.

Sleep and nighttime behavior disorders in older adults: associations with hypercholesterolemia and hypertriglyceridemia at baseline, and a predictive analysis of incident cases at 12 months follow-up.

INTRODUCTION: Sleep disorders, particularly insomnia and obstructive sleep apnea, are associated with dyslipidemia in the general population. The study's aim was to explore the association between pathological Cholesterol and Triglyceride levels, and sleep and nighttime behavior disorders (SNBD) in older adults, whether they might predict SNBD onset, and to emphasize the role of body mass index (BMI) in this association. METHODS: Alzheimer's Disease Neuroimaging Initiative (ADNI) population with complete Cholesterol, Triglyceride, SNBD, and neurocognitive data were included. Logistic regression was performed to study the association between hypercholesterolemia, hypertriglyceridemia, and SNBD at baseline and at 12 months. Relevant confounders, particularly BMI, were adjusted for. RESULTS: Among the 2,216 included cases, 1,045 (47%) were females, and the median age was 73 years (IQR: 68, 78). At baseline, 357 (16%) had SNBD and 327 (18%) at 12 months; 187 of them were incident cases. There were more cases of baseline SNBD in the hypertriglyceridemia group than in those without (19% vs. 14%, P-value = 0.003). Similarly, more follow-up SNBD cases had hypertriglyceridemia at baseline (21% vs. 16%, P-value = 0.025). SNBD cases at baseline had significantly higher serum Triglyceride levels than those without (132 vs. 118mg/dL, P-value < 0.001). Only hypertriglyceridemia was significantly associated with baseline SNBD (crude OR = 1.43, 95%CI: 1.13,1.80, P-value = 0.003), even after adjustment for confounding factors (adj. OR = 1.36, 95%CI: 1.06,1.74, P-value = 0.016) and (BMI-adj. OR = 1.29, 95%CI: 1.00,1.66, P-value = 0.048). None of the dyslipidemia forms did predict incident cases at 12 months. CONCLUSIONS: Hypertriglyceridemia, but not hypercholesterolemia, was associated with higher odds of SNBD. The association was independent of BMI. None of the dyslipidemia forms did predict incident SNBD over 12 months. Sleep disorders should motivate a systematic screening of dyslipidemia in older adults and vice versa.

Serum vitamin D concentrations and sleep disorders: insights from NHANES 2011-2016 and Mendelian Randomization analysis.

OBJECTIVE: This investigation seeks to examine the association between serum vitamin D concentrations and the prevalence of sleep disorders, additionally elucidating the causal relationship via Mendelian Randomization (MR) analysis. MATERIALS AND METHODS: This research employed data from the National Health and Nutrition Examination Survey (NHANES) 2011-2016, focusing on adults aged 20-50 years reporting sleep disorders. The research encompassed 4913 American adults. Weighted multivariable logistic regression models and cubic spline analyses were utilized to evaluate the association between serum vitamin D concentrations and the incidence of sleep disorders. Additionally, a two-sample Mendelian Randomization analysis was performed to evaluate the potential causal link between serum vitamin D concentrations and the risk of sleep disorders. RESULTS: Within the 2011-2016 NHANES cohort of the U.S. population, a notable inverse association was detected between serum vitamin D concentrations and sleep disorders (ß = - 3.81, 95% CI: - 6.10 to - 1.52, p = 0.003). After multivariate adjustments, a higher incidence of sleep disorders was associated with lower vitamin D Concentrations (OR 1.52, 95% CI 1.10-2.10, trend p = 0.014). Restricted cubic spline regression analysis indicated a linear association between serum vitamin D concentrations and sleep disorders(non-linearity p > 0.05). Lastly, the two-sample MR analysis yielded evidence supporting a potential causal connection between serum vitamin D concentrations and sleep disorders, with each unit increase in genetically predicted serum vitamin D reducing the odds ratio to 0.78 (95% CI 0.61-0.99, p = 0.044). CONCLUSIONS: These results imply that lower vitamin D concentrations in the population might correlate with a heightened risk of sleep disorders, suggesting the importance of considering vitamin D supplementation when treating sleep disorders.

Relationship between longer sleep and serum neurofilament light chain in american adults: evidence from the 2013-2014 US national health and nutrition examination survey.

BACKGROUND: Sleep disturbance is linked to neurodegenerative diseases and the related brain pathophysiology. Serum neurofilament light chain (NfL) is a reliable biomarker for neurological disorders. This study examined the association between sleep characteristics and serum NfL levels in American adults. METHODS: In this cross-sectional study, data from the 2013-2014 US National Health and Nutrition Examination Survey were utilized. Participants were categorized into short (≤ 6 h), normal (7-8 h), and long (≥ 9 h) sleep groups based on their self-reported sleep durations. Sleep duration, trouble sleeping, and diagnosed sleep disorders were queried, forming "sleep pattern (healthy, moderate, and poor)." The association between sleep characteristics and serum NfL levels was assessed using multivariate linear regression models. Stratification and sensitivity analyses were conducted to determine the stability of results. RESULTS: Overall, 1637 participants were included; among them, 48.2% were male and 51.8% were female (mean ± SD, age: 46.9 ± 15.5 years) and 38.8% reported sleeping for ≤ 6 h, 54.4% for 7-8 h, and 6.8% for ≥ 9 h. Participants with longer sleep duration, poor sleep pattern, diagnosed sleep disorders, or trouble sleeping exhibited higher serum NfL levels. A positive correlation was found between extended sleep and elevated serum NfL levels (Adjusted ß = 4.82, 95%CI: 2.2, 7.44, P < 0.001), with no significant correlation observed in the short-sleep group or those with poor sleep pattern. Stratified and sensitivity analyses confirmed the robustness of the relationship between longer sleep and elevated serum NfL levels. CONCLUSIONS: A long sleep duration is associated with higher serum NfL levels than a normal sleep duration in American adults.

Association between sleep patterns and galectin-3 in a Chinese community population.

BACKGROUND: Irregular sleep patterns have been associated with inflammation. Galectin-3, a novel biomarker, plays an important role in inflammation. We investigated the relationship between sleep patterns and galectin-3 in a Chinese population. METHODS: A total of 1,058 participants from the Shenzhen-Hong Kong United Network on Cardiovascular Disease study were included in the analysis. Age and sex-adjusted linear regression models were employed to investigate the relationship between galectin-3 level and traditional metabolic biomarkers. Logistic regression models were used to estimate the association among sleep disturbance, nighttime sleep duration, and daytime napping duration and elevated galectin-3, with elevated galectin-3 defined as galectin-3 level > 65.1 ng/ml. RESULTS: Of study participants, the mean age was 45.3 years and 54.3% were women. Waist circumference, natural logarithm (ln)-transformed triglyceride, and ln-transformed high sensitivity C-reactive protein were positively associated with galectin-3 level (age and sex-adjusted standardized ß [95% confidence interval (CI)], 0.12 [0.04, 0.21], 0.11 [0.05, 0.17], and 0.08 [0.02, 0.14], respectively). Sleep disturbance was associated with elevated galectin-3 (odds ratio [95% CI], 1.68 [1.05, 2.68], compared to those without sleep disturbance) after adjusting for traditional metabolic biomarkers. No interaction was observed between galectin-3 and age, sex, obesity, hypertension, and diabetes on sleep disturbance. No association was found between nighttime sleep duration or daytime napping duration and elevated galectin-3. CONCLUSIONS: Our study provides evidence of a significant association between sleep disturbance and elevated galectin-3 level, independent of traditional metabolic biomarkers. Screening and interventions on galectin-3 could assist in preventing sleep disturbance-induced inflammatory disease.

The Role of the Lipid Profile and Oxidative Stress in Fatigue, Sleep Disorders and Cognitive Impairment in Patients with Multiple Sclerosis.

The aim of this study is to investigate the relationship of the lipid profile, dysfunctional high-density lipoprotein, ischaemia-modified albumin and thiol-disulfide homeostasis with cognitive impairment, fatigue and sleep disorders in patients with multiple sclerosis. The cognitive functions of patients were evaluated with the Brief International Cognitive Assessment for Multiple Sclerosis battery. Fatigue was evaluated with the Fatigue Severity Scale and the Fatigue Impact Scale. The Pittsburgh Sleep Quality Index and the Epworth Sleepiness Scale were used to assess patients' sleep disturbance. Peripheral blood samples were collected, and lipid levels and myeloperoxidase and paraoxonase activity were measured. The myeloperoxidase/paraoxonase ratio, which indicates dysfunctional high-density lipoprotein, was calculated. Thiol-disulfide homeostasis and ischaemia-modified albumin were measured.
We did not identify any relationship between dysfunctional high-density lipoprotein and the physical disability, cognitive decline, fatigue and sleep problems of multiple sclerosis. Thiol-disulfide homeostasis was associated with cognitive scores. The shift of the balance towards disulfide was accompanied by a decrease in cognitive scores. On the other hand, we did not detect any relationship between fatigue and sleep disorders and thiol-disulfide homeostasis. Our findings revealed a possible correlation between cognitive dysfunction and thiol-disulfide homeostasis in multiple sclerosis patients.

Altered sleep and diurnal consequences in women with dysmenorrhea: study from the EPISONO database.

PURPOSE: Our study aimed to identify alterations in sleep, inflammatory mediators, fatigue and quality of life in women with dysmenorrhea and compare them to women without dysmenorrhea. METHODS: The sample comprised 328 women from a Brazilian cross-sectional sleep study, EPISONO (2007), who had undergone 1-night polysomnography (PSG) type I and completed questionnaires related to sleep quality, daytime sleepiness, insomnia, fatigue, anxiety, depression, and quality of life. Blood samples were used to assess levels of interleukin 6 (IL-6), tumor necrosis factor-alpha (TNF-alpha), and C-reactive protein (CRP). The 2 groups were distributed based on the presence or absence of dysmenorrhea symptoms. RESULTS: Sleep efficiency was significantly lower in the group of women with dysmenorrhea (82.5% ± 13.8) compared to the non-dysmenorrhea group (86.2% ± 10.9). Dysmenorrhea was associated with significantly higher scores of fatigue and worse scores in the physical quality of life. No statistical differences were detected in inflammatory markers between the 2 groups. DISCUSSION: Fatigue and physical quality of life were presented in women with dysmenorrhea, as was reduced sleep efficiency, although no alteration on inflammatory markers were observed. CONCLUSION: These findings show that dysmenorrhea can have a deleterious effect on women's sleep, with repercussions on daily routines and quality of life.

Melatonin hormone level in nurses and factors affecting it; Investigation according to shift working pattern.

This study aimed to determine the relationship between melatonin hormone levels, sleep, and factors affecting sleep, psychological resilience, and depression in nurses working with a shift work system. Conducted between February 5-12, 2021, at the Training and Research Hospital in Agri province, the descriptive study included 41 night shift nurses and 35 day shift nurses, totaling 76 participants. Blood samples for melatonin analysis were collected and data were gathered using the Sociodemographic Information Form, Epworth Sleepiness Scale, Sleep Disorder Scale Short Form, Brief Psychological Resilience Scale, and Beck Depression Scale Short Form. Melatonin analysis was performed using the ELISA method. Statistical significance was set at p < 0.05. Results showed that sleep disorders were present in all nurses with <7 h of daily sleep. Factors such as the use of sleeping pills, marital status, age, and gender affected sleep disorders. Mean scores for melatonin levels were 67.82 ± 40.20 for night shift nurses and 68.08 ± 39.62 for day shift nurses, with no significant difference between shifts. Similarly, no significant differences were found in daytime sleepiness (7.49 ± 4.47 vs. 7.51 ± 4.65), sleep disturbance (24.71 ± 7.33 vs. 25.23 ± 6.64), psychological resilience (18.42 ± 4.19 vs. 17.89 ± 4.74), or depression (3.22 ± 2.60 vs. 3.49 ± 3.35). Nurses exhibited mild sleep disturbances, low depression tendencies, and moderate psychological resilience. Increased daytime sleepiness and sleep disorders correlated with higher depression tendencies and lower psychological resilience. Hospital management and education units are recommended to conduct interventions on sleep quality, depression, and psychological resilience to raise awareness among nurses.

Mean Oxygen Saturation during Sleep Is Related to Specific Brain Atrophy Pattern.

OBJECTIVE: There is much controversy about the neurobiological mechanisms underlying the effects of sleep-disordered breathing on the brain. The aim of this study was to investigate the association between markers of sleep-related hypoxemia and brain anatomy. METHODS: We used data from a large-scale cohort from the general population (n = 775, 50.6% males, age range = 45-86 years, mean age = 60.3 ± 9.9) that underwent full polysomnography and brain magnetic resonance imaging to correlate respiratory variables with regional brain volume estimates. RESULTS: After adjusting for age, gender, and cardiovascular risk factors, only mean oxygen saturation during sleep was associated with bilateral volume of hippocampus (right: p = 0.001; left: p < 0.001), thalamus (right: p < 0.001; left: p < 0.001), putamen (right: p = 0.001; left: p = 0.001), and angular gyrus (right: p = 0.011; left: p = 0.001). We observed the same relationship in left hemispheric amygdala (p = 0.010), caudate (p = 0.008), inferior frontal gyrus (p = 0.004), and supramarginal gyrus (p = 0.003). The other respiratory variables-lowest oxygen saturation, percentage of sleep time with oxygen saturation < 90%, apnea-hypopnea index, and oxygen desaturation index-did not show any significant association with brain volumes. INTERPRETATION: Lower mean oxygen saturation during sleep was associated with atrophy of cortical and subcortical brain areas known for high sensitivity to oxygen supply. Their vulnerability to hypoxemia may contribute to behavioral phenotype and cognitive decline in patients with sleep-disordered breathing. ANN NEUROL 2020;87:921-930.

Sleep disturbance in adults with chronic pruritic dermatoses is associated with increased C-reactive protein levels.

BACKGROUND: Pruritus is a common symptom that can significantly reduce quality of life through sleep disruption. OBJECTIVE: To examine features of disturbed sleep in patients with chronic pruritic dermatoses and test the hypothesis that systemic inflammation may serve as a biomarker for impaired sleep in these patients. METHODS: Cross-sectional analysis of the National Health and Nutrition Examination Survey investigating systemic inflammation using C-reactive protein (CRP) levels. Logistic regression was used to compare patients with and without sleep disturbances, adjusting for demographics (model 1) and medical comorbidities (model 2). RESULTS: Chronic pruritic dermatoses were associated with multiple sleep disturbances, including nighttime awakenings (model 1: odds ratio [OR], 1.646; 95% confidence interval [CI], 1.031-2.627; model 2: OR, 1.329; 95% CI, 0.888-1.989) and early morning awakening (model 1: OR, 1.669, 95% CI, 1.118-2.493; model 2: OR, 1.582; 95% CI, 1.008-2.481). Mean CRP levels were 52.8% higher among patients with pruritic dermatoses reporting trouble sleeping compared with those who did not (0.663 vs 0.434 mg/dL; P = .034). Trouble sleeping was also positively correlated with CRP levels (ß = 0.142, P = .025). LIMITATIONS: Potential recall bias among participants. CONCLUSIONS: In addition to confirming sleep disturbances with pruritic dermatoses, we found these disturbances are more likely to present with elevated CRP levels. Clinicians should consider the potential risk for sleep-related and cardiac comorbidities in patients diagnosed with itchy skin conditions.

Levels of trace blood elements associated with severe sleep disturbance in maintenance hemodialysis patients.

PURPOSE: Sleep disturbance is frequently observed in patients on maintenance hemodialysis (MHD), and this population usually presents imbalances in trace elements. We investigated the association between blood trace element levels and sleep quality in patients on MHD. METHODS: This cross-sectional and single-center study was performed in September 2019. Patients regularly undergoing hemodialysis for > 3 months at our center were recruited, and demographic, clinical, and laboratory parameters were recorded. The Pittsburgh Sleep Quality Index (PSQI) was applied to define sleep disturbance. Blood trace element (zinc, manganese, copper, selenium, and lead) levels were measured using an inductively coupled plasma mass spectrometer. RESULTS: In total, 121 patients on MHD (male/female = 68:53) were enrolled in the study (mean age 63.7 ± 13.9 years, median dialysis vintage 38.0 [20.0, 60.0] months). According to PSQI, 56 (46%) patients experienced severe sleep disturbance. These patients were characterized by older age, higher serum parathyroid hormone levels, and lower blood selenium levels (all P < 0.05). No significant differences in blood zinc, manganese, copper, and lead levels were observed between groups. Univariate binary logistic regression showed that lower blood selenium levels were associated with severe sleep disturbance (odds ratio = 0.976, 95% confidence interval: 0.954-0.999, P = 0.038). Multivariate analyses also confirmed the results after adjusting for confounding factors. CONCLUSION: Our study indicated an association between lower blood selenium levels and the occurrence of severe sleep disturbances in patients on MHD. However, a prospective study with a larger sample size and assessing the importance of selenium supplementation are needed to confirm the results.

Symptom cluster profiles following traumatic orthopedic injuries: A protocol.

Traumatic injuries affect millions of Americans annually, resulting in $671 billion in healthcare costs and lost productivity. Postinjury symptoms, like pain, sleep disturbance, anxiety, depression, and stressor-related disorders are highly prevalent following traumatic orthopedic injuries (TOI) and may contribute to negative long-term outcomes. Symptoms rarely present in isolation, but in clusters of two or more symptoms that co-occur to affect health in aggregate. Identifying symptom cluster profiles following TOI may identify those at highest risk for negative outcomes. Dysregulation of brain-derived neurotrophic factor (BDNF) is a potential biological mechanism responsible for symptom cluster profile membership after TOI and may be targeted in future precision-health applications. The purpose of this paper is to present the protocol of a cross-sectional study designed to identify symptom cluster profiles and measure the extent to which the BDNF val66met mutation and serum concentration of BDNF are associated with membership in symptom cluster profiles. We plan to recruit 150 TOI survivors within the first 72 h of injury. The study aims are to (1) describe TOI survivors' membership in symptom cluster profiles, indicated by pain, sleep disturbance, and symptoms of anxiety, depression, and stressor-related disorders, immediately following a TOI; (2) examine associations between demographic and clinical factors and symptom cluster profile membership among TOI survivors; (3) test the hypothesis that low serum concentrations of BDNF are associated with membership among symptom cluster profiles following TOI; and (4) test the hypothesis that the presence of the val66met mutation on one or both alleles of the BDNF gene is associated with membership among symptom cluster profiles following TOI.

Serotonin variations and sleep disorders among shift workers. A cross-sectional study.

Sleep disorders are prevalent occupational health problems among shift workers, especially healthcare workers with long shifts. Serotonin is a neurotransmitter related to circadian variations accompanied by shift work. A cross-sectional study was performed on 73 nurses at a tertiary hospital in Cairo, Egypt, to assess sleep quality among shift work nurses (SWNs), to determine blood serotonin level, and its relation to shift work and sleep quality. A demographic and occupational history questionnaire, Pittsburgh Sleep Quality Index (PSQI) questionnaire, and measurement of blood serotonin were carried out to the studied group. The data were analyzed using SPSS 25, and descriptive statistics, unpaired t-test, ANOVA, Kruskal-Wallis Test, Chi-square, Spearman correlation, and multivariate regression analysis were utilized. The results showed that the mean PSQI global score was significantly higher among SWNs than non-shift work nurses (NSWNs) and was the highest (10.32 ± 3.56 and 10.22 ± 2.4, respectively) among rotatory and fixed night shift nurses. Blood serotonin showed highly significant differences between SWNs over NSWNs (p = 0.001), and mostly reduced among rotatory and fixed night shift nurses (66.7% and 65%, respectively). Moreover, there were highly significant differences in serotonin levels between poor and good sleep quality nurses (p < 0.001), and most of the poor sleep quality nurses (62.7%) had low serotonin levels. Abnormal serotonin level (odds = 246.5) and working years (odds = 1.2) were statistically significant predictors of poor sleep quality. In conclusion, SWNs, especially rotating and night shift nurses, suffer from poor sleep quality associated with abnormal levels of blood serotonin.

Impact of COVID-19 on serum melatonin levels and sleep parameters in children

Background/aim: This study aimed to analyze the serum melatonin levels and changes in sleep patterns in pediatric patients with coronavirus disease 2019 (COVID-19). Materials and methods: This study was designed as a descriptive, cross-sectional study. Serum melatonin levels and sleep parameters of children with the diagnosis of COVID-19 who had mild and moderate disease (i.e., COVID-19 group) were compared with those of children admitted with non-COVID-19 nonspecific upper respiratory tract infection (i.e., control group). The sleep disturbance scale for children (SDSC) questionnaire was applied to the participants> primary caregivers to analyze their sleep patterns at present and six months before symptom onset and to investigate the impact of COVID-19 on sleep patterns. Results: The entire study cohort consisted of 106 patients. The COVID-19 group included 80 patients, while the control group consisted of 26 patients. The mean serum melatonin levels were 136.72 pg/mL and 172.63 pg/mL in the COVID-19 and control groups, respectively (p = 0.16). There was no significant difference between the groups in terms of 6 subcategories of the SDSC questionnaire regarding the present time and 6 months before symptom onset. The total SDSC scores were also similar in two different evaluation time points described above (p = 0.99) Conclusions: We conclude that COVID-19 did not impact the sleep parameters of children. Serum melatonin levels of all patients were higher than the reference range; however, they were higher in the non-COVID-19 patient group than the COVID-19 group. Since serum melatonin levels were higher than the reference values in children with COVID-19, and this disease is significantly less morbid in children, melatonin may have protective effects against COVID-19.

Sleep disorders and vascular responsiveness in patients with rheumatoid arthritis.

BACKGROUND: Rheumatoid arthritis (RA) is the most common systemic autoimmune disease characterized by chronic systemic inflammation. Half of the deaths of patients with RA are due to cardiovascular diseases (CVD), considered to be 1.5 to -2.0-fold that in the general population. Patients with RA also experience poor sleep, which by itself is associated with endothelial dysfunction, CVD events and sudden death. Our aim was to study the mechanistic pathways and the correlations between sleep efficiency and vascular reactivity of patients with RA. METHODS AND RESULTS: A prospective study that evaluated quality of sleep using ACTi Graphs, vascular inflammation and endothelial function of 18 patients with RA. Inflammation was studied by levels of E-selectin, intercellular adhesion molecule 1 (ICAM-1) and NO in serum. Endothelial function was studied using the brachial artery plethysmography method. Eighteen RA patients (aged 57.56 ± 13.55 years; 16 women) with a long-standing active RA: Eight patients had impaired sleep efficiency and 10 had a good sleep efficiency. Those who had an impaired sleep had larger baseline diameters of the brachial artery (0.39 ± 0.08 cm vs. 0.32 ± 0.04 cm; P = 0.02). Negative correlations were found between baseline brachial artery diameter and sleep efficiency (P = 0.01), and with NO level (P = 0.04). Stepwise regression found that brachial artery diameter at baseline and NO level could predict sleep efficiency (r2  = 0.543, P = 0.01). CONCLUSION: Vascular reactivity could predict quality of sleep in patients with RA. Quality of sleep may serve as an independent CVD risk factor in patients with RA.

Angelman syndrome and melatonin: What can they teach us about sleep regulation.

In 1965, Dr Harry Angelman reported a neurodevelopmental disorder affecting three unrelated children who had similar symptoms: brachycephaly, mental retardation, ataxia, seizures, protruding tongues, and remarkable paroxysms of laughter. Over the past 50 years, the disorder became Angelman's namesake and symptomology was expanded to include hyper-activity, stereotypies, and severe sleep disturbances. The sleep disorders in many Angelman syndrome (AS) patients are broadly characterized by difficulty falling and staying asleep at night. Some of these patients sleep less than 4 hours a night and, in most cases, do not make up this lost sleep during the day-leading to the speculation that AS patients may "need" less sleep. Most AS patients also have severely reduced levels of melatonin, a hormone produced by the pineal gland exclusively at night. This nightly pattern of melatonin production is thought to help synchronize internal circadian rhythms and promote nighttime sleep in humans and other diurnal species. It has been proposed that reduced melatonin levels contribute to the sleep problems in AS patients. Indeed, emerging evidence suggests melatonin replacement therapy can improve sleep in many AS patients. However, AS mice show sleep problems that are arguably similar to those in humans despite being on genetic backgrounds that do not make melatonin. This suggests the hypothesis that the change in nighttime melatonin may be a secondary factor rather than the root cause of the sleeping disorder. The goals of this review article are to revisit the sleep and melatonin findings in both AS patients and animal models of AS and discuss what AS may tell us about the underlying mechanisms of, and interplay between, melatonin and sleep.

Circadian rhythm abnormalities in patients with inflammatory bowel disease - association with adipokine profile.

Background: The role of sleep disturbances in patients with inflammatory bowel disease (IBD) remained relatively unknown. The aim of this study was to identify the adipokine profile in the patients with IBD and its relationship with the circadian rhythm disorders.Methods: Prospective, observational cohort study was performed. In all the enrolled adult IBD patients, the disease activity was assessed by using Crohn's Disease Activity Index (CDAI) for Crohn's disease (CD) and Partial Mayo Score for ulcerative colitis (UC), respectively. All patients were also asked to respond to a questionnaire to define Pittsburgh Quality Sleep Index (PSQI). From all the enrolled patients, 15 mL venous blood was taken to determine adipokine levels and perform standard laboratory tests.Results: Sixty-five IBD patients were enrolled in our study: 30 with CD and 35 with UC. Poor sleep was noted in 69.2% patients with clinically active and in 7.7% patients with inactive disease (p = .0023). In the group of IBD patients with poor sleep, the significantly higher level of serum resistin (p = .0458), and lower level of serum adiponectin and leptin (p = .0215, p = .0201; respectively) were observed. In the IBD patients with exacerbation, the significantly higher level of serum resistin (p = .0396), significantly lower serum level of leptin (p = .0453) and tendency to lower serum level of adiponectin (p = .1214) were recorded.Conclusions: The relationship between circadian rhythm abnormalities and specific adipokine profile may show us a risk factor of developing inflammatory intestinal lesions in IBD patients. This knowledge may allow the treatment of sleep disturbances, body weight-control and dietary habits become new targets in IBD therapy.