A Deep Transfer Learning Approach for Sleep Stage Classification and Sleep Apnea Detection Using Wrist-Worn Consumer Sleep Technologies.

Obstructive sleep apnea (OSA) is a common, underdiagnosed sleep-related breathing disorder with serious health implications Objective - We propose a deep transfer learning approach for sleep stage classification and sleep apnea (SA) detection using wrist-worn consumer sleep technologies (CST). Methods - Our model is based on a deep convolutional neural network (DNN) utilizing accelerometers and photo-plethysmography signals from nocturnal recordings. The DNN was trained and tested on internal datasets that include raw data from clinical and wrist-worn devices; external validation was performed on a hold-out test dataset containing raw data from a wrist-worn CST. Results - Training on clinical data improves performance significantly, and feature enrichment through a sleep stage stream gives only minor improvements. Raw data input outperforms feature-based input in CST datasets. The system generalizes well but performs slightly worse on wearable device data compared to clinical data. However, it excels in detecting events during REM sleep and is associated with arousal and oxygen desaturation. We found; cases that were significantly underestimated were characterized by fewer of such event associations. Conclusion - This study showcases the potential of using CSTs as alternate screening solution for undiagnosed cases of OSA. Significance - This work is significant for its development of a deep transfer learning approach using wrist-worn consumer sleep technologies, offering comprehensive validation for data utilization, and learning techniques, ultimately improving sleep apnea detection across diverse devices.

A Virus-like Particle-Based F4 Enterotoxigenic Escherichia coli Vaccine Is Inhibited by Maternally Derived Antibodies in Piglets but Generates Robust Responses in Sows.

F4-positive enterotoxigenic Escherichia coli is associated with diarrhea and poor growth outcomes in neonatal and newly weaned piglets and is thus a major economic and welfare burden in the swine industry. Vaccination of sows with F4 fimbriae protects against the neonatal disease via passive transfer of maternal immunity. However, this strategy does not protect against infection post-weaning. Consequently, prevention and treatment methods in weaner pigs heavily rely on the use of antimicrobials. Therefore, in order to reduce antimicrobial consumption, more effective prophylactic alternatives are needed. In this study, we describe the development of a capsid virus-like particle (cVLP)-based vaccine targeting the major F4 fimbriae subunit and adhesion molecule, FaeG, and evaluate its immunogenicity in mice, piglets, and sows. cVLP-display significantly increased systemic and mucosal antibody responses towards the recombinant FaeG antigen in mice models. However, in piglets, the presence of anti-F4 maternally derived antibodies severely inhibited the induction of active humoral responses towards the FaeG antigen. This inhibition could not be overcome, even with the enhanced immunogenicity achieved via cVLP display. However, in sows, intramuscular vaccination with the FaeG.cVLP vaccine was able to generate robust IgG and IgA responses that were comparable with a commercial fimbriae-based vaccine, and which were effectively transferred to piglets via colostrum intake. These results demonstrate that cVLP display has the potential to improve the systemic humoral responses elicited against low-immunogenic antigens in pigs; however, this effect is dependent on the use of antigens, which are not the targets of pre-existing maternal immunity.

Validation of the newly developed Sleep Screening Questionnaire Children and Adolescents (SSQ-CA) with objective sleep measures.

OBJECTIVES: Objectively validated pediatric sleep questionnaires covering a broader age range and different sleep disturbances are lacking, therefore we developed the Sleep Screening Questionnaire Children and Adolescents (SSQ-CA) and compared it with objective sleep parameters. METHODS: This child-reported questionnaire was developed by a multidisciplinary panel and face validated. In a cross-sectional prospective design, participants aged 6-17, answered the questionnaire twice with 21-28 days in between, wore actigraphy (AG) and kept a sleep diary for seven nights and home-polysomnography (PSG) for one of these nights. Exploratory factor analyses (EFA), reliability and validity assessments were performed. RESULTS: Of the 139 participants, 128 (F:47.7%, AG: n = 128, PSG: n = 59), were included in the analyses. Mean age: 11.3 years (SD: 2.9). EFA revealed 11 factors and 40 items loading above r = 0.4. Subscale internal consistency: 0.54-0.92. Subscale test-retest reliability: r = 0.71-0.87. Total sleep time (TST) from SSQ-CA on weekdays correlated with PSG (r = 0.48, p = 0.001) and with AG (r = 0.75, p < 0.001). The subscale total score for "Sleep duration and latency" correlated with TST from AG (r = -0.19, p = 0.03) and sleep latency (r = 0.31, p < 0.001), but not for PSG variables. The subscale "Awakenings" showed no correlation with objective measures whereas "Circadian rhythm" correlated to AG-derived mid-sleep time (r = 0.34, p < 0.001). CONCLUSIONS: The SSQ-CA shows adequate reliability for the 6-17-year-olds and acceptable criterion validity for two subscales. It appears to be a useful tool for screening for sleep disturbances in combination with objective tools as the subjective and objective parameters seem to uncover different aspects of sleep.

Digital media use and sleep in late adolescence and young adulthood: A systematic review.

Despite much attention on digital media use and young peoples' sleep, the literature on digital media and its impact on sleep in older adolescents and young adults remains to be synthesized. We conducted a systematic review of studies including young people aged 16-25 years. We searched Medline, Web of Science, and CINAHL for observational studies, identifying 60 studies. These studies were assessed for methodological quality. Only studies rated as moderate or high-quality studies were included (n = 42). A narrative synthesis summarized the impact of digital media use on eight sleep outcomes: Bedtime; Sleep onset latency or problems falling asleep; Sleep duration; Early awakening; Sleep disturbance; Daytime tiredness and function; Sleep deficits; Sleep quality. In summary, digital media use was associated to shorter sleep duration and poorer sleep quality. These associations were found for general screen use and use of mobile phone, computer, internet, and social media, but not for television, game console, and tablet use. Most studies investigating bedtime or nighttime use found associations to poor sleep outcomes. Later bedtime and daytime tiredness were associated with mobile phone use at night. Additional research is warranted to draw solid conclusions about the causal direction and to understand the underlying mechanisms.

A Flexible Deep Learning Architecture for Temporal Sleep Stage Classification Using Accelerometry and Photoplethysmography.

Wrist-worn consumer sleep technologies (CST) that contain accelerometers (ACC) and photoplethysmography (PPG) are increasingly common and hold great potential to function as out-of-clinic (OOC) sleep monitoring systems. However, very few validation studies exist because raw data from CSTs are rarely made accessible for external use. We present a deep neural network (DNN) with a strong temporal core, inspired by U-Net, that can process multivariate time series inputs with different dimensionality to predict sleep stages (wake, light-, deep-, and REM sleep) using ACC and PPG signals from nocturnal recordings. The DNN was trained and tested on 3 internal datasets, comprising raw data both from clinical and wrist-worn devices from 301 recordings (PSG-PPG: 266, Wrist-worn PPG: 35). External validation was performed on a hold-out test dataset containing 35 recordings comprising only raw data from a wrist-worn CST. An accuracy = 0.71 ± 0.09, 0.76 ± 0.07, 0.73 ± 0.06, and κ = 0.58 ± 0.13, 0.64 ± 0.09, 0.59 ± 0.09 was achieved on the internal test sets. Our experiments show that spectral preprocessing yields superior performance when compared to surrogate-, feature-, raw data-based preparation. Combining both modalities produce the overall best performance, although PPG proved to be the most impactful and was the only modality capable of detecting REM sleep well. Including ACC improved model precision to wake and sleep metric estimation. Increasing input segment size improved performance consistently; the best performance was achieved using 1024 epochs (∼8.5 hrs.). An accuracy = 0.69 ± 0.13 and κ = 0.58 ± 0.18 was achieved on the hold-out test dataset, proving the generalizability and robustness of our approach to raw data collected with a wrist-worn CST.

The effect of group-based cognitive behavioural therapy for insomnia in patients with rheumatoid arthritis: a randomized controlled trial.

OBJECTIVES: The primary objective was to compare the effect of cognitive behavioural therapy for insomnia (CBT-I) to usual care on sleep efficiency, measured by polysomnography (PSG) immediately after the intervention at week 7. Secondary objectives included comparing the longer-term effect on sleep- and RA-related outcomes at week 26. METHODS: In a randomized controlled trial using a parallel group design, the experimental intervention was 6 weeks' nurse-led group-based CBT-I; the comparator was usual care. Analyses were based on the intention-to-treat (ITT) principle; missing data were statistically modelled using repeated-measures linear mixed effects models adjusted for the level at baseline. RESULTS: The ITT population consisted of 62 patients (89% women), with an average age of 58 years and an average sleep efficiency of 83.1%. At primary end point, sleep efficiency was 88.7% in the CBT-I group, compared with 83.7% in the control group (difference: 5.03 [95% CI -0.37, 10.43]; P = 0.068) measured by PSG at week 7. Key secondary outcomes measured with PSG had not improved at week 26. However, for all the patient-reported key secondary sleep- and RA-related outcomes, there were statistically highly significant differences between CBT-I and usual care (P < 0.0001), e.g. insomnia (Insomnia Severity Index: -9.85 [95% CI -11.77, -7.92]) and the RA impact of disease (RAID: -1.36 [95% CI -1.92, -0.80]) at week 26. CONCLUSION: Nurse-led group-based CBT-I did not lead to an effect on sleep efficiency objectively measured with PSG. However, CBT-I showed improvement on all patient-reported key secondary sleep- and RA-related outcomes measured at week 26. TRIAL REGISTRATION: ClinicalTrials.gov, https://clinicaltrials.gov, NCT03766100.

White matter microstructure and sleep-wake disturbances in individuals at ultra-high risk of psychosis.

Aim: White matter changes in individuals at ultra-high risk for psychosis (UHR) may be involved in the transition to psychosis. Sleep-wake disturbances commonly precede the first psychotic episode and predict development of psychosis. We examined associations between white matter microstructure and sleep-wake disturbances in UHR individuals compared to healthy controls (HC), as well as explored the confounding effect of medication, substance use, and level of psychopathology. Methods: Sixty-four UHR individuals and 35 HC underwent clinical interviews and diffusion weighted imaging. Group differences on global and callosal mean fractional anisotropy (FA) was tested using general linear modeling. Sleep-wake disturbances were evaluated using the subjective measures disturbed sleep index (DSI) and disturbed awakening index (AWI) from the Karolinska Sleep Questionnaire, supported by objective sleep measures from one-night actigraphy. The primary analyses comprised partial correlation analyses between global FA/callosal FA and sleep-wake measures. Secondary analyses investigated multivariate patterns of covariance between measures of sleep-wake disturbances and FA in 48 white matter regions of interest using partial least square correlations. Results: Ultra-high risk for psychosis individuals displayed lower global FA (F = 14.56, p < 0.001) and lower callosal FA (F = 11.34, p = 0.001) compared to HC. Subjective sleep-wake disturbances were significantly higher among the UHR individuals (DSI: F = 27.59, p < 0.001, AWI: F = 36.42, p < 0.001). Lower callosal FA was correlated with increased wake after sleep onset (r = -0.34, p = 0.011) and increased sleep fragmentation index (r = -0.31, p = 0.019) in UHR individuals. Multivariate analyses identified a pattern of covariance in regional FA which were associated with DSI and AWI in UHR individuals (p = 0.028), but not in HC. Substance use, sleep medication and antipsychotic medication did not significantly confound these associations. The association with objective sleep-wake measures was sustained when controlling for level of depressive and UHR symptoms, but symptom level confounded the covariation between FA and subjective sleep-wake measures in the multivariate analyses. Conclusion: Compromised callosal microstructure in UHR individuals was related to objectively observed disruptions in sleep-wake functioning. Lower FA in ventrally located regions was associated with subjectively measured sleep-wake disturbances and was partly explained by psychopathology. These findings call for further investigation of sleep disturbances as a potential treatment target.

[Migration of the Tips of Metal Implants during Treatment of Coxa Vara Adolescentium (Slipped Capital Femoral Epiphysis)]. / Migrace spicek kovových implantátu v prubehu lécby u coxa vara adolescentium.

PURPOSE OF THE STUDY This paper aims to detect, through a retrospective study, the migration of the tips of used metal implants (K-wires or a screw) in the direction out from the proximal femoral epiphysis as a part of studied basic radiometric characteristics of the cohort, with no intention of the authors to evaluate the therapy outcomes. MATERIAL AND METHODS It was a retrospective multicentre study including patients of two orthopaedic clinics and one department of orthopaedics treated in the period 2005-2018. The same treatment procedure was used in all three centres. The "in situ" fixation was indicated in patients, in whom the Southwick angle in anteroposterior and Lauenstein views was not much greater than 30°, whether primarily due to a mild slip or thanks to careful reduction either in acute or acute-on-chronic forms. All X-rays were measured by a single author (M.S.). In AP and Lauenstein view, overlap of the implant tip (K-wire or a screw) above the subcapital growth plate, the height of epiphysis and Southwick angle are measured at the beginning and at the end of treatment. In a smaller group of patients, also the inter-observer error (M.S. and J.P.) was identified. RESULTS K-wire transfixation was used in 43 patients (50 joints), with the mean age of 11.7 years and the mean duration of transfixation of 18.2 months. The slip of the implant tip out of the head, assessed separately for each introduced K-wire and then averaged, was in both views considered statistically significant (in AP view the level of significance was 5% (p-value = 1.393 x 10^(-6) < 0.05) , in Lauenstein view the level of significance was also 5% (p-value = 0.0001652 < 0.05)). The Wilcoxon signed rank test with continuity correction was used. Transfixation by screw alternatively with one K-wire was used in 23 patients (28 joints), with the mean age of 12.4 years and the mean duration of transfixation of 14.4 months. The slip of the screw tip outside the head was assessed as significant (in AP view at the level of significance of 5% (p-value = 9.41 x 10^(-5) < 0.05), in Lauenstein view at the level of significance of 5% (p-value = 0.003557 < 0.05)). The Wilcoxon signed rank test with continuity correction was used. DISCUSSION This paper aims to detect, through a retrospective study, the so-called migration of the tips of used metal implants (K-wires or a screw) outside the femoral head. Smooth and thin implants such as Kirschner wires should not compromise the continuing growth from subcapital growth plate contrary to the AO screw with threads in the femoral head, the screw head rested against the lateral cortical bone and the screw inserted as a compression one. Nonetheless, with some exceptions, the literature confirms the continued growth of the femoral neck even in the case of screws. In general, implants that do not compromise femoral neck growth provide an opportunity to remodel the anterolateral prominence of the femoral metaphysis, especially in younger patients. In agreement with other authors, the data from our study confirmed, even after a short period of time, a certain degree of proximal femoral remodelling expressed by changes in the Southwick angle. CONCLUSIONS Our study confirmed that in the case of "smooth" K-wires as well as cannulated screws the tips of both implants migrate outside the head. The differences were statistically significant. Therefore, the introduction of a conventional cannulated screw cannot be claimed to immediately produce the effect of epiphyseodesis. Yet, smooth implants less compromise the growth of the femoral neck, which is why they have recently been preferred. Key words: coxa vara adolescentium, metal implants, migration.

Is the TOAST Classification Suitable for Use in Personalized Medicine in Ischemic Stroke?

Pathophysiologic classification of ischemic stroke is essential to a personalized approach to stroke treatment. The Trial of Org 101072 in Acute Stroke Treatment (TOAST) classification is the most frequently used tool to classify index ischemic strokes. We aimed to assess presence of small and large vessel disease markers across the TOAST groups. In an observational study, 99 ischemic stroke patients were consecutively included and classified according to TOAST. The assessment was supplemented with cerebral small vessel disease (SVD) score, based on Magnetic Resonance Imaging (MRI), and tests for carotid atherosclerosis, ankle−brachial index (ABI), estimated glomerular filtration rate (eGFR), and peripheral reactive hyperemia index (RHI). Markers of small and large vessel disease were present in all TOAST groups. Carotid stenosis and atrial fibrillation were associated with their respective TOAST groups (p = 0.023 and p < 0.001, respectively). We found no association between the SVD score and the small vessel occlusion TOAST group (p = 0.59), and carotid atherosclerosis (p = 0.35), RHI (p = 0.39), ABI (p = 0.20), and eGFR (p = 0.79) were not associated with TOAST groups. The TOAST classification does not provide differential information on the pathophysiologies of the ischemic stroke. An operational classification that contains quantification of each vascular pathophysiology in the individual patient is pivotal for future research and development of personalized medicine.

Impact of Nonpharmacologic Interventions Targeting Sleep Disturbances or Disorders in Patients With Inflammatory Arthritis: A Systematic Review and Meta-Analysis of Randomized Trials.

OBJECTIVE: Patients with inflammatory arthritis have a high risk of sleep disturbances and disorders. The objective was to evaluate the evidence of nonpharmacologic interventions targeting sleep disturbances or disorders in patients with inflammatory arthritis. METHODS: A systematic search was undertaken from inception to September 8, 2020. We included randomized trials concerning nonpharmacologic interventions applied in adults with inflammatory arthritis and concomitant sleep disturbances or disorders. The primary outcome was the sleep domain, while secondary outcomes were core outcome domains for inflammatory arthritis trials and harms. The Cochrane Risk of Bias tool was applied, and the overall quality of the evidence was assessed using Grading of Recommendations Assessment, Development and Evaluation criteria. Effect sizes for continuous outcomes were based on the standardized mean difference, combined using random-effects meta-analysis. RESULTS: Six trials (308 patients) were included in the quantitative synthesis; 3 of these reported improvement in sleep in favor of the nonpharmacologic interventions. The meta-analysis of the sleep domains indicated a large clinical effect of -0.80 (95% confidence interval -1.33, -0.28) in favor of nonpharmacologic interventions targeting sleep disturbances or disorders. The estimate was rated down twice for risk of bias and unexplained inconsistency; this risk was assessed as corresponding to low-quality evidence. None of the secondary core outcomes used in contemporary inflammatory arthritis trials indicated a clinical benefit in favor of nonpharmacologic interventions targeting sleep. CONCLUSION: Nonpharmacologic interventions targeting sleep disturbances/disorders in patients with inflammatory arthritis indicated a promising effect on sleep outcomes, but not yet with convincing evidence.

Brain tumours result in sleep disorders in children and adolescents.

BACKGROUND AND OBJECTIVES: Sleep disturbances are frequently reported in children with brain tumours. The objective of our cross-sectional study was to systematically examine sleep in these children. We hypothesised that children with tumours involving the sleep-wake-regulatory areas have an altered sleep-wake-regulation. METHODS: Sixty-one patients aged 0-18 years and with a diagnosis of a primary brain or cervical medullary tumour were included. They were categorised based upon tumour location into two groups - those affecting the sleep-wake regulatory regions, i.e. brain stem, basal forebrain, hypothalamus, thalamus, and posterior fossa compressing the brain stem and those that did not. Sleep history, questionnaire surveys, polysomnography, and multiple sleep latency test were used, as indicated clinically. Surveys included Pediatric Daytime Sleepiness Scale, Children's Sleep Habits Questionnaire, Strengths and Difficulties Questionnaire, and Pediatric Quality of Life Inventory, Multidimensional Fatigue Scale and Generic Core Scale. RESULTS: Patients with tumours involving the sleep-wake regulatory areas were sleepier/more fatigued (p = 0.03). Sleep apnoea was observed in 86% of all the patients and comorbid narcolepsy in 8%, without group differences (p ≥ 0.12). Patients with tumours involving the sleep-wake-regulatory areas had more emotional problems (p = 0.04), were more affected by mental health problems (p < 0.001), and had poorer quality of life (p ≤ 0.03). CONCLUSIONS: Many children with brain tumours suffer from disturbed sleep, poor mental health, and low quality of life. We recommend that systematic sleep evaluation is included in their routine care along with psychological and social support.

Impact of COVID-19 Pandemic on Sleep Quality, Stress Level and Health-Related Quality of Life-A Large Prospective Cohort Study on Adult Danes.

The everyday lives of Danish inhabitants have been affected by the COVID-19 pandemic, e.g., by social distancing, which was employed by the government in March 2020 to prevent the spread of SARS-CoV-2. Moreover, the pandemic has entailed economic consequences for many people. This study aims to assess changes in physical and mental health-related quality of life (MCS, PCS), in stress levels, and quality of sleep during the COVID-19 pandemic and to identify factors that impact such changes, using a prospective national cohort study including 26,453 participants from the Danish Blood Donor Study who answered a health questionnaire before the pandemic and during the pandemic. Descriptive statistics, multivariable linear and multinomial logistic regression analyses were applied. A worsening of MCS and quality of sleep was found, and an overall decrease in stress levels was observed. PCS was decreased in men and slightly increased in women. The extent of health changes was mainly affected by changes in job situation, type of job, previous use of anti-depressive medication and the participants' level of personal stamina. Thus, living under the unusual circumstances that persisted during the COVID-19 pandemic has had a negative impact on the health of the general population. This may, in time, constitute a public health problem.

Effect of a dynamic lighting intervention on circadian rest-activity disturbances in cognitively impaired, older adults living in a nursing home: A proof-of-concept study.

Development of non-pharmacological interventions to improve disrupted rest-activity patterns and disturbed behavior in people with dementia is an important research goal. Here we report a proof-of-concept study which evaluates the effect and applicability of a dynamic light intervention to improve rest-activity patterns in cognitively impaired, institutionalized, older adults. The study was a randomized, open-label, proof-of-concept trial of limited sample size conducted at a nursing home for older adults in a non-metropolitan area in Denmark. Participants were 24 older nursing home residents with cognitive deficiencies. Equipment for delivery of a specialized dynamic light intervention was installed in the private apartments (within the nursing home) of the residents in the experimental group (N = 12). Study duration was four weeks. The control group (N = 12) was exposed to conventional lighting. We measured activity and rest using actigraphy, functional disability, behavioral disturbances, and time in bed We performed regression analyses to examine differences between the intervention groups. Participants in the experimental group partially improved on one of three diurnal rhythm variables, but otherwise no differences were observed between the two intervention groups. The improvement was found for the intradaily variability during the first part of the intervention period indicating a more stable and less fragmented 24-h rest-activity rhythm. However, availability of staff assistance in response to impaired physical mobility of the residents seemed to be a stronger determinant of activity level and pattern. The examined intervention showed promising results but did not consistently alter circadian rest-activity patterns in older nursing home residents given the current sample size. Future studies in the field need to consider real-life applicability of the experimental intervention and the interaction and importance of other important zeitgebers than light.

[Simultaneous Bilateral Femoral Osteotomies in Neurogenic Hip Instability: a Feasibility Study]. / Simultánní oboustranné femorální osteotomie u neurogenních kycelních instabilit: studie proveditelnosti.

PURPOSE OF THE STUDY The study aimed to evaluate the intraoperative and early postoperative response to simultaneous bilateral femoral osteotomy usually accompanied by soft tissue release of hip joints, or open reduction, capsuloplasty, pelvic osteotomy or extraarticular shelf procedure. MATERIAL AND METHODS A bilateral surgery was performed in 16 children. Twelve children suffered from (spastic) cerebral palsy and there was one case of paralytic dislocation in a patient with myelomeningocele, while the remaining patients suffered from chromosome I aberrations, Dandy-Walker syndrome and merosin-deficient muscular dystrophy. GMFCS Level IV and V prevailed. The patients with femoral head deformity or severe adduction contracture were removed from the study group. In all cases the LCP Pediatric Hip Plate 3.5 or 5.0 (Synthes) was used for osteosynthesis. The postoperative fixation by a hip spica cast was applied for 6 weeks, after which in most cases SWASH orthosis was used at night. The age of the patient, the hip joint finding, the GMFCS level and the type of procedure were recorded. RESULTS The evaluation took into account the use of general anaesthesia only or a combination of general and epidural anaesthesia, most often through caudal block, duration of surgery, time when blood transfusion was necessary and the volumes of blood needed, duration of stay in the Anaesthesiology and Resuscitation Unit, or Intensive Care Unit. As a response to surgery, the changes in haemoglobin levels in g/l and VAS pain score were studied. In four patients only the operative time exceeded 3 hours. Blood transfusion was necessary in 13 patients, with one blood unit being always sufficient. Two patients were admitted to the Anaesthesiology and Resuscitation Unit, the remaining patients spent 1-3 days after surgery in the ICU. The average length of hospital stay did not exceed a week. The postoperative decrease in haemoglobin levels quickly improved. The pain intensity was regularly recorded postoperatively and on day 3-4 it was evaluated as moderate, with patients responding well to common analgesics (VAS 4-7). DISCUSSION The evaluation of duration of simultaneous bilateral procedure, postoperative recovery based on the need for blood transfusion, changes in blood count and VAS scores indicated that the procedure performed on both hip joints simultaneously does not significantly exceed the reasonable limits in terms of the patient s burden. In literature, we found only a single article on a topic of this sort, the conclusions of which are very similar. CONCLUSIONS The simultaneous bilateral femoral osteotomy can be considered a fairly safe procedure. Key words: hip joint instability, simultaneous femoral osteotomy, cerebral palsy.

Pre-treatment of blood samples reveal normal blood hypocretin/orexin signal in narcolepsy type 1.

The hypocretin/orexin system regulates arousal through central nervous system mechanisms and plays an important role in sleep, wakefulness and energy homeostasis. It is unclear whether hypocretin peptides are also present in blood due to difficulties in measuring reliable and reproducible levels of the peptides in blood samples. Lack of hypocretin signalling causes the sleep disorder narcolepsy type 1, and low concentration of cerebrospinal fluid hypocretin-1/orexin-A peptide is a hallmark of the disease. This measurement has high diagnostic value, but performing a lumbar puncture is not without discomfort and possible complications for the patient. A blood-based test to assess hypocretin-1 deficiency would therefore be of obvious benefit. We here demonstrate that heating plasma or serum samples to 65°C for 30 min at pH 8 significantly increases hypocretin-1 immunoreactivity enabling stable and reproducible measurement of hypocretin-1 in blood samples. Specificity of the signal was verified by high-performance liquid chromatography and by measuring blood samples from mice lacking hypocretin. Unspecific background signal in the assay was high. Using our method, we show that hypocretin-1 immunoreactivity in blood samples from narcolepsy type 1 patients does not differ from the levels detected in control samples. The data presented here suggest that hypocretin-1 is present in the blood stream in the low picograms per millilitres range and that peripheral hypocretin-1 concentrations are unchanged in narcolepsy type 1.

Sleep in hospitalized children and adolescents: A scoping review.

Hospitalized children and adolescents are at risk of short sleep and subsequent adverse health effects, but little is known about actual sleep duration, the factors that cause sleep disturbances in an inpatient pediatric setting, and what has been done to promote sleep in this population. The aim of this review was to systematically identify, categorize, and synthesize the literature on sleep in children and adolescents in an inpatient setting. We searched five electronic databases (PubMed, CENTRAL, CINAHL, PsycINFO, and Scopus) and of the 3770 references identified, 28 were eligible for inclusion. From studies reporting age-specific sleep durations, we found that four out of nineteen fell within the National Sleep Foundations recommendations for age-specific sleep durations. Reported causes of sleep disturbances were primarily related to modifiable, external factors, e.g., nursing care activities and noise from equipment and other patients. Sleep-promoting interventions seemed acceptable to patients, parents, and healthcare professionals. However, the literature in this area is heterogeneous regarding methodology, reporting, and population characteristics. Our findings underline the importance of prioritizing and optimizing sleep in hospitalized pediatric patients and highlight the need for standardization in the planning and reporting of studies within this field.

Serum melatonin concentration in critically ill patients randomized to sedation or non-sedation.

BACKGROUND: Abolished circadian rhythm is associated with altered cognitive function, delirium, and as a result increased mortality in critically ill patients, especially in those who are mechanically ventilated. The causes are multifactorial, of which changes in circadian rhythmicity may play a role. Melatonin plays a crucial role as part of the circadian and sleep/wake cycle. Whether sedation effects circadian regulation is unknown. Hence, the objective of this study was to evaluate the melatonin concentration in critically ill patients randomized to sedation or non-sedation and to investigate the correlation with delirium. METHODS: All patients were included and randomized at the intensive care unit at the hospital of southwest Jutland, Denmark. Seventy-nine patients completed the study (41 sedated and 38 non-sedated). S-melatonin was measured 3 times per day, (03.00, 14.00, and 22.00), for 4 consecutive days in total, starting on the second day upon randomization/intubation. The study was conducted as a sub-study to the NON-SEDA study in which one hundred consecutive patients were randomized to sedation or non-sedation with a daily wake-up call (50 in each arm). PRIMARY OUTCOME: melatonin concentration in sedated vs. non-sedated patients (analyzed using linear regression). Secondary outcome: risk of developing delirium or non-medically induced (NMI) coma in sedated vs. non-sedated patients, assessed by CAM-ICU (Confusion Assessment Method for the Intensive Care Unit) analyzed using logistic regression. RESULTS: Melatonin concentration was suppressed in sedated patients compared to the non-sedated. All patients experienced an elevated peak melatonin level early on in the course of their critical illness (p = 0.01). The risk of delirium or coma (NMI) was significantly lower in the non-sedated group (OR 0.42 CI 0.27; 0.66 p < 0.0001). No significant relationship between delirium development and suppressed melatonin concentration was established in this study (OR 1.004 p = 0.29 95% CI 0.997; 1.010). CONCLUSION: Melatonin concentration was suppressed in sedated, critically ill patients, when compared to non-sedated controls and the frequency of delirium was elevated in sedated patients. Trail registration Clinicaltrials.gov (NCT01967680) on October 23, 2013.

Large genome-wide association study identifies three novel risk variants for restless legs syndrome.

Restless legs syndrome (RLS) is a common neurological sensorimotor disorder often described as an unpleasant sensation associated with an urge to move the legs. Here we report findings from a meta-analysis of genome-wide association studies of RLS including 480,982 Caucasians (cases = 10,257) and a follow up sample of 24,977 (cases = 6,651). We confirm 19 of the 20 previously reported RLS sequence variants at 19 loci and report three novel RLS associations; rs112716420-G (OR = 1.25, P = 1.5 × 10-18), rs10068599-T (OR = 1.09, P = 6.9 × 10-10) and rs10769894-A (OR = 0.90, P = 9.4 × 10-14). At four of the 22 RLS loci, cis-eQTL analysis indicates a causal impact on gene expression. Through polygenic risk score for RLS we extended prior epidemiological findings implicating obesity, smoking and high alcohol intake as risk factors for RLS. To improve our understanding, with the purpose of seeking better treatments, more genetics studies yielding deeper insights into the disease biology are needed.

Diagnosis of central disorders of hypersomnolence: A reappraisal by European experts.

The aim of this European initiative is to facilitate a structured discussion to improve the next edition of the International Classification of Sleep Disorders (ICSD), particularly the chapter on central disorders of hypersomnolence. The ultimate goal for a sleep disorders classification is to be based on the underlying neurobiological causes of the disorders with clear implication for treatment or, ideally, prevention and or healing. The current ICSD classification, published in 2014, inevitably has important shortcomings, largely reflecting the lack of knowledge about the precise neurobiological mechanisms underlying the majority of sleep disorders we currently delineate. Despite a clear rationale for the present structure, there remain important limitations that make it difficult to apply in routine clinical practice. Moreover, there are indications that the current structure may even prevent us from gaining relevant new knowledge to better understand certain sleep disorders and their neurobiological causes. We suggest the creation of a new consistent, complaint driven, hierarchical classification for central disorders of hypersomnolence; containing levels of certainty, and giving diagnostic tests, particularly the MSLT, a weighting based on its specificity and sensitivity in the diagnostic context. We propose and define three diagnostic categories (with levels of certainty): 1/"Narcolepsy" 2/"Idiopathic hypersomnia", 3/"Idiopathic excessive sleepiness" (with subtypes).

Soluble HLA-G and TGF-ß in couples attending assisted reproduction - A possible role of TGF-ß isoforms in semen?

Soluble isoforms of the non-classical Human Leukocyte Antigen (HLA)-G as well as Transforming Growth Factor (TGF)-ß is expressed in seminal plasma possibly influencing the pregnancy potential. We wanted to examine the association of seminal plasma sHLA-G, TGF-ß1, TGF-ß2 and TGFß3 with pregnancy success in a cohort of 127 couples and 4 single women attending fertility treatment with the use of assisted reproduction technologies (ART). Soluble HLA-G, TGF-ß1, TGF-ß2 and TGF-ß3 in seminal plasma did not fluctuate significantly over time. We did not find any impact of seminal plasma sHLA-G, TGF-ß1, TGF-ß2 and TGF-ß3 on time-to-pregnancy measured as number of treatment cycles. There was a significant association between concentrations of seminal plasma sHLA-G and HLA-G variations in the 3'untranslated region (3'UTR) of the HLA-G gene, supporting and extending previous findings. Furthermore, by comparing seminal plasma concentrations of sHLA-G, TGF-ß1, TGF-ß2 and TGF-ß3 in male subjects with reduced semen quality, male subjects with normal semen quality, and sperm donors, we found that TGF-ß2 was significantly lower, and TGF-ß3 was significantly higher, in seminal plasma from sperm donors. These findings suggest that TGF-ß isoforms may influence semen quality and fertility.