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Islay Pittaway,1 Anna Ishkova,1 Helena Bean,1 Stephanie McCarthy,1 Isabella Lay,1 Joanne Avraam,1 Andrew Dawson,1 Therese Thornton,1 Christian L Nicholas,1,2 John Trinder,1 Fergal J O’Donoghue,2,3 Melinda L Jackson,2,4 Amy S Jordan1,2 1Melbourne School of Psychological Sciences, The University of Melbourne, Parkville, VIC 3010, Australia; 2Institute for Breathing and Sleep, Austin Health, Heidelberg, VIC 3084, Australia; 3Department of Medicine, The University of Melbourne, Austin Hospital, Heidelberg, VIC 3084, Australia; 4Turner Institute for Brain and Mental Health, School of Psychological Sciences, Monash University, Clayton, VIC 3164, AustraliaCorrespondence: Amy S Jordan Tel +61 3 8344 6357Email ajordan@unimelb.edu.auPurpose: Obstructive sleep apnea (OSA) is less prevalent among women and is associated with different symptoms and consequences to OSA in men. The reasons for these differences are unknown and difficult to tease apart in clinical populations. If OSA could be temporarily induced in healthy men and women, the causes of some of these differences could be investigated. Nasal blocking has been used to induce OSA in healthy men but its effect in women has not been reported.Patients and Methods: A total of 14 healthy individuals (10 women) underwent in-laboratory diagnostic sleep studies on two occasions separated by a week. On one occasion, the nasal passages were blocked, whereas on the other occasion, participants slept naturally. In both conditions, a full-face mask was used to monitor respiratory events. Participants’ self-reported sleepiness, mood and performance on a motor learning task were assessed in the evening and morning of both sleep studies. Furthermore, endothelial function and self-reported sleep quality were assessed in the morning following each study.Results: Nasal blockage induced OSA in healthy young (age=22± 3 years) and slim (BMI=22.2± 3.2 kg/m2) women (control AHI=2.0± 2.6, blocked AHI=33.1± 36.7 events/hr, p=0.02). One night of OSA was associated with poorer self-reported sleep quality (p< 0.001) and increased self-reported snoring (p< 0.04), choking and gasping during sleep (p< 0.001) but was not associated with alterations in mood, neurocognitive or endothelial function on the following morning.Conclusion: Nasal blockage induces OSA in healthy, young, and normal weight women. However, whether the induced OSA is representative of naturally occurring OSA and the technique useful for future studies is unclear.Keywords: pathophysiology, upper airway collapse, sex, breathing route, obstructive sleep apnea, nasal blockage, female

High activity of upper airway dilator muscles is thought to be critical in preventing sleep-related upper airway collapse. To date, most of the research regarding upper airway dilator muscles has focused on the genioglossus muscle, which protrudes the tongue and opens the retroglossal airway. However, collapse commonly occurs in the retropalatal region. We, therefore, aimed to examine the motor control of the palatoglossus muscle as well as investigate breathing route-related changes in genioglossus and palatoglossus motor units. Single motor unit recordings of the genioglossus and palatoglossus were made simultaneously in healthy individuals during wakefulness while breathing through the nose with the mouth closed (NMC), nose with mouth open (NMO), or orally (OMO). The palatoglossus was found to have all five motor unit firing patterns that have been observed in other upper airway dilator muscles, but during nasal breathing had a higher proportion of tonically active but inspiratory modulated motor units as compared with the genioglossus (67% vs. 30%). When still breathing nasally but with the mouth open, the units with an expiratory firing pattern in genioglossus, and all firing patterns in palatoglossus, increased their firing rates compared with nasal breathing with the mouth closed [genioglossus (GG): 17.8 ± 4.9 vs. 23.1 ± 4.8 Hz, palatoglossus (PG): 17.0 ± 4.0 vs. 19.3 ± 4.0 Hz]. Finally, oral breathing resulted in dramatic reductions in the number of palatoglossal motor units that were firing (35 units vs. 92 during nasal breathing). Palatoglossal activity may contribute importantly to airway collapsibility and may provide an alternate pathway for preventing sleep-related airway collapse. NEW & NOTEWORTHY The firing patterns of motor units in the palatoglossus have until now not been investigated, and how they and motor units in the genioglossus change with breathing route alteration was not known. This study has shown that the palatoglossus contains motor units with all the firing patterns observed in the genioglossus but in different proportions. Furthermore, breathing route changes alter units with different firing patterns differentially in the two muscles.

Objectives: Perfectionism is an important factor in insomnia development and maintenance. Previous studies exploring the relationship between perfectionism and insomnia have predominantly relied on self-reported sleep measures. Therefore, this study sought to assess whether actigraphy-measured sleep parameters were associated with perfectionism., Methods: Sixty adults (85% females, mean age 30.18 ± 11.01 years) were sampled from the Australian general population. Actigraphy-derived objective sleep measures, subjective sleep diary measures, the Frost Multidimensional Perfectionism Scale (FMPS), Hewitt-Flett Multidimensional Perfectionism Scale (HFMPS) and Depression, Anxiety and Stress Scale 21 (DASS-21) were collected., Results: High perfectionism levels were associated with poor sleep, but these relationships differed between objective and subjective measures. Perfectionism via FMPS total score and subscales of Concern over Mistakes, Doubts about Actions, Personal Standards and Self-oriented Perfectionism correlated with subjective sleep onset latency and sleep efficiency with moderate effects ( r  = .26 to .88). In contrast, perfectionism via HFMPS total score and subscales of Socially Prescribed Perfectionism and Parental Expectations predicted objective sleep onset latency and sleep efficiency. Additionally, stress mediated the relationships between objective sleep efficiency and Concern over Mistakes and Doubts about Actions., Conclusions: Perfectionism demonstrated stronger associations with subjective than objective sleep measures. Higher Parental Expectations and Socially Prescribed Perfectionism may increase one's vulnerability to objectively measured poor sleep. Therefore, perfectionism may be important in preventing and treating insomnia.

Study Objectives: Transient arousal from sleep has been shown to elicit a prolonged increase in genioglossus muscle activity that persists following the return to sleep and which may protect against subsequent airway collapse. We hypothesized that this increased genioglossal activity following return to sleep after an arousal is due to persistent firing of inspiratory-modulated motor units (MUs) that are recruited during the arousal., Methods: Thirty-four healthy participants were studied overnight while wearing a nasal mask with pneumotachograph to measure ventilation and with 4 intramuscular genioglossus EMG electrodes. During stable N2 and N3 sleep, auditory tones were played to induce brief (3-15s) AASM arousals. Ventilation and genioglossus MUs were quantified before the tone, during the arousal and for 10 breaths after the return to sleep., Results: A total of 1089 auditory tones were played and gave rise to 239 MUs recorded across arousal and the return to sleep in 20 participants (aged 23 ± 4.2 years and BMI 22.5 ± 2.2 kg/m2). Ventilation was elevated above baseline during arousal and the first post-arousal breath (p < .001). Genioglossal activity was elevated for five breaths following the return to sleep, due to increased firing rate and recruitment of inspiratory modulated MUs, as well as a small increase in tonic MU firing frequency., Conclusions: The sustained increase in genioglossal activity that occurs on return to sleep after arousal is primarily a result of persistent activity of inspiratory-modulated MUs, with a slight contribution from tonic units. Harnessing genioglossal activation following arousal may potentially be useful for preventing obstructive respiratory events., (© The Author(s) 2023. Published by Oxford University Press on behalf of Sleep Research Society.)

Objective: During embryogenesis of mandible, the initial ossification centre begins at the bifurcation of the inferior alveolar (IA) and the mental nerves. Additionally, in congenital anomalies like craniofacial microsomia (CFM), the IA canal is completely absent on the microsomic side. These observations led us to hypothesise that there may be a morphological integration between these structures - the IA nerve and the mandibular shapes. Therefore, the primary objective of this study was to test for morphological integration between these structures and the secondary objective was to determine if there were shape variations in these structures among skeletal Classes I, II and III subjects., Setting and Sample Population: The sample size of the study is 80 full-head cone-beam computed tomography (CBCT) scans (age 16-56 years)., Methods: We retrieved CBCT scans from our archived database using specific inclusion/exclusion criteria. In the de-identified CBCT scans, traditional coordinate landmarks and sliding semi-landmarks were placed on the mandible and the IA canal (proxy for IA nerve). Using geometric morphometric analyses, we tested integration between the IA canal and the mandibular shapes. We used Procrustes ANOVA to test for overall shape variations among the three skeletal classes (Classes I, II and III)., Results: The IA canal and posterior/inferior border of mandible showed strong integration (r-PLS = .845, P = .001). Similar strong integration was also observed between the IA canal and the overall shape of the mandible (r-PLS = .866, P = .001). Additionally, there was a statistically significant variation in overall shape between skeletal Class I and Class II (P = .008) and Class II and Class III (P = .001)., Conclusions: The strong integration between two structures suggests that the IA nerve may play a role in establishing mandibular shape early in development. We posit this may be important in driving mandibular defects seen in CFM, which warrants further investigation., (© 2023 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

Introduction: The dentition is one of the most accurate features for age estimation in children. However, there is some evidence that timing of dental development varies across populations. Recent research suggests that dental development may also be susceptible to influence by environmental factors, such as obesity. Given that there are also population differences in average body mass, it is possible that this may be a confounding variable that was not accounted for in prior work. We aim to compare the relative association between body mass index (BMI) and ancestry with timing of dental development., Methods: A retrospective cross-sectional chart review was undertaken using panoramic radiographs of 6- to 12-year-olds (n = 281). Age, ancestry, sex, height, and weight were obtained. Dental development was assessed using the Demirjian method, and chronological age was subtracted from estimated dental age to determine relative timing of dental development (ΔAge). BMI was calculated based upon recorded height/weight within 6 months of time of radiograph., Results: We found no difference in timing of dental development (accelerated/delayed) across ancestry groups (African-American, Euro-American, Hispanic, Asian; P = .15). Overweight/obese subjects had statistically significantly advanced (precocious) dental development (P < .001). Compared to normal-weight subjects, children who were overweight's age were overestimated by 5.76 months (0.48 years) and children with obesity by 5.97 months (0.49 years) on average., Conclusions: BMI appears to have a greater impact on relative timing of dental development than ancestry in this population. Our results support other findings that obesity results in accelerated growth and development., (© 2023 The Authors. Orthodontics & Craniofacial Research published by John Wiley & Sons Ltd.)

New Findings: What is the central question of this study? How does alcohol intake, which worsens obstructive sleep apnoea, alter motor control of the genioglossus muscle, an upper airway dilator, in healthy awake human volunteers, and does alcohol alter genioglossus muscle afterdischarge? What is the main finding and its importance? Alcohol consumption had a very minor effect on the activity of the genioglossus in healthy young individuals studied during wakefulness and did not alter afterdischarge, leaving open the possibility that alcohol worsens obstructive sleep apnoea via other mechanisms., Abstract: Alcohol worsens obstructive sleep apnoea (OSA). This effect is thought to be due to alcohol's depressant effect on upper airway dilator muscles such as the genioglossus, but how alcohol reduces genioglossal activity is unknown. The aim of this study was to investigate the effect of alcohol consumption on genioglossus muscle single motor units (MUs). Sixteen healthy individuals were studied on two occasions (alcohol: breath alcohol concentration ∼0.07% and placebo). They were instrumented with a nasal mask, four intramuscular genioglossal EMG electrodes, and an ear oximeter. They were exposed to 8-12 hypoxia trials (45-60 s of 10% O 2 followed by one breath of 100% O 2 ) while awake. MUs were sorted according to their firing patterns and quantified during baseline, hypoxia and recovery. For the alcohol and placebo conditions, global muscle activity (mean ± SD peak inspiratory EMG = 119.3 ± 44.1 and 126.5 ± 51.9 μV, respectively, P = 0.53) and total number of MUs recorded at baseline (68 and 67, respectively) were similar. Likewise, the peak discharge frequency did not differ between conditions (21.2 ± 4.28 vs. 22.4 ± 4.08 Hz, P = 0.09). There was no difference between conditions in the number (101 vs. 88, respectively) and distribution of MU classes during hypoxia, and afterdischarge duration was also similar. In this study, alcohol had a very minor effect on genioglossal activity and afterdischarge in these otherwise healthy young individuals studied while awake. If similar effects are observed during sleep, it would suggest that the worsening of OSA following alcohol may be related to increased upper airway resistance/nasal congestion or arousal threshold changes., (© 2022 The Authors. Experimental Physiology published by John Wiley & Sons Ltd on behalf of The Physiological Society.)

Background: Disrupted sleep and post-traumatic stress disorder (PTSD) are bi-directionally linked and have been found to mutually reinforce each other on a day-to-day basis. However, most of the previous research has focused on subjective measures of sleep only., Objective: Here, we investigated the temporal relationship between sleep and PTSD symptoms using both subjective (sleep diary) and objective measures of sleep (actigraphy)., Methods: Forty-one non-treatment seeking, trauma exposed young adults (age M  = 24.68, SD  = 8.15) with a range of PTSD symptom severities (PTSS, 0-53 on PCL-5) were recruited. Participants completed two surveys per day over four weeks to measure day-time PTSD symptoms (i.e. PTSS and number of intrusions) and night-time sleep subjectively, while wearing an actigraphy watch to measure sleep objectively., Results: Linear mixed models revealed that subjectively reported sleep disruptions were associated with elevated next-day PTSS and increasing number of intrusive memories both within and between participants. Similar results were found for daytime PTSD symptoms on night-time sleep. However, these associations were not found using objective sleep data. Exploratory moderator analyses including sex (male vs. female) found that these associations differed in strength between sexes but were generally in the same direction., Discussion: These results were in line with our hypothesis with regards to the sleep diary (subjective sleep), but not actigraphy (objective sleep). Several factors which have implications on both PTSD and sleep, such as the COVID-19 pandemic and/ or sleep-state misperception, may be potential reasons behind those discrepancies. However, this study had limited power and needs to be replicated in larger samples. Nonetheless, these results add to the current literature about the bi-directional relationship between sleep and PTSD and have clinical implications for treatment strategies.

Human remains from forensic and bioarcheological contexts are often fragmentary, requiring methods for estimating a forensic profile that are based upon limited skeletal features. In 2017, Berg and Keryhercz created an online application, (hu)MANid, that provides sex and ancestry estimation from mandibular morphoscopic traits and linear measurements. In this study, we examine the utility of the (hu)MANid application in a diverse, urban US adult sample (aged 20-45; n = 143) derived from computed tomography (CT) scans. We secondarily conduct a preliminary analysis of the program's utility in a sample of adolescents (aged 15-17; n = 40). Six morphoscopic, and eleven morphometric traits were recorded as directed by the literature associated with the (hu)MANid program. Percent correct classification and posterior predictive values were calculated for the sex and ancestry estimations output by the program; chi-squared tests were employed to compare self-reported and predicted ancestry. In the adult sample, sex was accurately predicted for 75.52% of the sample. Ancestry prediction, however, was less favorable ranging from 19.3% to 50% correct. For the adolescent sample, correct sex estimation (45%) did not surpass what could occur by chance alone, though ancestry prediction fared better than in the larger adult sample (percent correct prediction overall average: 47.5%, range 35.71%-71.43%). The (hu)MANid application shows utility for use with CT scan-derived adult samples for sex estimation, but caution is warranted for ancestry estimation and use with samples that may not have reached full adult maturity., (© 2022 The Authors. Journal of Forensic Sciences published by Wiley Periodicals LLC on behalf of American Academy of Forensic Sciences.)

Sleep has been found to play a key role in fear conditioning, extinction learning and extinction recall, and sleep disturbances are linked to many mental disorders including post-traumatic stress disorder (PTSD). Previous studies examining associations between sleep and fear or extinction processes primarily focused on objectively measured sleep architecture. Little research has so far focused on subjective sleep measures and particularly in clinical populations, which often experience subjectively poor sleep, including PTSD. Here we investigated whether subjective sleep disturbance, sleep onset latency, wake after sleep onset or sleep efficiency were related to fear conditioning, extinction learning or extinction recall in a large sample of individuals with a range of PTSD symptom severity (n = 248). Overall, we did not find that subjective sleep was associated with fear conditioning or extinction processes. However, exploratory analyses examining the moderating effect of sex found that shorter sleep onset latency and greater sleep efficiency were associated with improved extinction recall in women with higher PTSD symptom severity. This suggests that less time falling asleep and longer time asleep while in bed may be protective in highly symptomatic women against the commonly observed impaired extinction recall in PTSD. More studies are needed to explore sex-specific effects further., Competing Interests: Declaration of competing interest The authors have no conflict of interest to declare., (Copyright © 2022 Elsevier Ltd. All rights reserved.)

Objective: To assess longitudinal variation in patterns of retromolar space growth, with regard to sex and cervical vertebrae maturation., Design: We utilized serial lateral cephalograms from three craniofacial growth studies (Denver, Iowa, Oregon), measuring retromolar space and cervical vertebrae maturation in 99 subjects (56% male) from 8 to 18 years of age for each subject. Repeated measures ANOVA and a linear mixed effects model were used to assess retromolar space growth through time., Results: Our analyses revealed an average increase in retromolar space of 8.73 mm from 8 to 18 years. While t-tests failed to find differences in retromolar space growth between males and females at the measured age points, repeated measures ANOVA and linear mixed effects models revealed modest differences in growth trends between sexes, with females having more growth earlier but a younger age of deceleration of growth (between 12 and 14 years of age)., Conclusions: Our results confirm large increases in retromolar space through growth, reaching an average of 1.38 mm/year around puberty. Importantly, we add to the conversation regarding sex differences, showing differences in timing of growth. This highlights the importance of using longitudinal data and analytical approaches to address questions of this nature., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2022 Elsevier Ltd. All rights reserved.)

Internal nasal cavity morphology has long been thought to reflect respiratory pressures related to heating and humidifying inspired air. Yet, despite the widely recognized importance of ontogeny in understanding climatic and thermoregulatory adaptations, most research on nasal variation in modern and fossil humans focuses on static adult morphology. This study utilizes cross-sectional CT data of three morphologically distinct samples (African, European, Arctic) spanning from infancy to adulthood (total n = 321). Eighteen landmarks capturing external and internal regions of the face and nose were subjected to generalized Procrustes and form-space principal component analyses (separately conducted on global and individual samples) to ascertain when adult-specific nasal morphology emerges during ontogeny. Across the global sample, PC1 (67.18% of the variation) tracks age-related size changes regardless of ancestry, while PC2 (6.86%) differentiates between the ancestral groups irrespective of age. Growth curves tracking morphological changes by age-in-years indicate comparable growth trajectories across all three samples, with the majority of nasal size and shape established early in ontogeny (<5 years of age). Sex-based trends are also evident, with females exhibiting a more truncated growth period than males, particularly for nasal height dimensions. Differences are also evident between the anterior and posterior nose, with the height and breadth dimensions of the anterior nasal aperture and nasal cavity showing differential ontogenetic patterns compared to the choanae. Cumulatively, these results suggest that multiple selective pressures influence human nasal morphology through ontogenetic processes, including metabolic demands for sufficient oxygen intake and climatic demands for adequate intranasal air conditioning., (© 2021 American Association for Anatomy.)

Introduction: An association between the increased risk of late stillbirth and the maternal supine sleeping position has been recently established. The risk of stillbirth following supine sleep has been suspected to occur as a result of aortocaval compression by the gravid uterus. A number of studies conducted during wakefulness have reported compromised cardiovascular function during supine rest, as demonstrated by reductions in cardiac output, blood pressure and utero-placental blood flow. It remains unclear whether similar effects are also present during sleep, due to the presence of key sleep-specific changes in cardiovascular function., Objective: To investigate the changes in maternal cardiovascular function between the supine and left-lateral positions during wakefulness and non-rapid eye movement (NREM) sleep in late pregnancy., Methods: Twenty-nine women with a singleton pregnancy between 24.7 and 36.7 weeks' gestation participated in a single overnight sleep study. Physiological measures (blood pressure, heart rate, heart rate variability - HRV, and pulse arrival time - PAT) were measured and recorded throughout the night using standard polysomnography equipment and the Portapres Model-2 device. As the present study evaluated cardiovascular changes during natural rest and sleep in pregnancy, participants were not given explicit instructions on which position to adopt. Body position was continuously recorded using a position monitor and verified with video recording., Results: No changes in systolic, diastolic or mean arterial blood pressure were observed between the left-lateral and supine positions during wakefulness or sleep. However, heart rate was significantly higher in the supine position compared to the left during wakefulness ( p= .03), with a similar trend present during sleep ( p = .11). A significantly shorter PAT was measured in the supine position (compared to the left) during wakefulness ( p= .01) and sleep ( p= .01). No change in HRV measures was observed between the left and supine positions in either state., Conclusion: Blood pressure did not appear to differ significantly between the left-lateral and supine positions during wakefulness and sleep. The lack of blood pressure differences may reflect elevated sympathetic activity during rest and sleep in the supine position (compared to the left), suggesting that some degree of compensation for aortocaval compression may still be possible during sleep.

Demonstrating inter-device reliability is essential to use devices interchangeably, and accurately integrate, interpret, or compare data from different actigraphs. Despite this, there is a paucity of comparative literature over a timeframe exceeding one night. The aims of this study were to determine an optimal wake threshold for GENEActiv and to evaluate the concordance between Actiwatch-2 and GENEActiv using a common algorithm (Phillips Respironics). Data were collected from 33 individuals (20 female) aged 20-35 years ( M = 25.33, SD = 4.69) across a total 213 nights. Participants wore both devices simultaneously and continuously for seven days. The sleep parameters of interest were: total sleep time, sleep efficiency, sleep onset latency, and wake after sleep onset. Exploratory analyses of sensitivity, specificity, overall accuracy, mean bias, and paired samples t-tests indicated an optimal wake threshold of 115 for GENEActiv, compared with Actiwatch-2 at the 40 (medium, default) threshold. Using these thresholds, sensitivity, and overall accuracy of GENEActiv were both good (86% and 78%, respectively), however specificity was relatively low (40%). There were no significant inter-device differences for any sleep parameters, and all absolute mean biases were small. Overall, the findings from this study provide the first empirical evidence to support the reliability of GENEActiv against Actiwatch-2 over multiple nights using a common algorithm with device-specific wake thresholds.

Objectives: Childhood obesity is a systemic disease with multiple downstream consequences, including shifts in timing of growth and development. It has been documented that children with high body mass index (BMI) show accelerated timing of dental development, but the mechanism for this acceleration is unknown. Prior work has suggested that inflammation and/or nutrition may play a role. We investigate the potential association between diet (caloric intake, macronutrients), obesity, and accelerated dental development., Methods: Children and adolescents (age 10-15; n = 112) were recruited from dental clinics at the University of Illinois Chicago. We collected subjects' height, weight, panoramic radiographic records, and each subject filled out a Block Food Frequency Questionnaire., Results: The only macronutrient level associated with BMI was a negative correlation to Total Fat consumption (p = .01), though this relationship was not significant in the path analysis (p > .05). Regression analyses indicated that BMI (p = .003) and total caloric intake (controlling for BMI; rho = 0.19; p = .04) were both significantly correlated with timing of dental development. However, when a path analysis was conducted, it was revealed that only BMI was statistically significant (p = .008)., Conclusions: Body mass index percentile, regardless of caloric intake, is positively associated with accelerated dental development. While it is possible that excess caloric intake itself plays a minor role in timing of dental development, we do not see unambiguous evidence for this in our sample. We posit that another mechanism, such as inflammation, may be the link between obesity status and dental development., (© 2022 Wiley Periodicals LLC.)

Characterising sleep in young people (aged 15-25 years) with borderline personality disorder (BPD) features is crucial given the association between BPD features and sleep disturbance, negative consequences of poor sleep, and normative developmental sleep changes that occur in this age group. The present study aimed to characterise the sleep profile of young people with BPD to determine whether this profile is non-normative and specific to BPD. Participants were 96 young people (40 with BPD features, 38 healthy individuals, and 18 young people seeking help for mental health difficulties without BPD). Sleep was measured subjectively (self-report questionnaires) and objectively (10 days of actigraphy). Young people with BPD features reported poorer subjective sleep quality, greater insomnia symptoms and later chronotype than same-age healthy and clinical comparison groups. Young people with BPD features also displayed irregular sleep timing, later rise times, greater time in bed and longer sleep durations than healthy young people. Those with BPD features had superior sleep quality (greater sleep efficiency, less wake after sleep onset) and longer sleep durations than the clinical comparison group. Sleep profiles were similar across young people with BPD features with and without co-occurring depression. Overall, the findings revealed a subjective-objective sleep discrepancy and suggest that sleep-improvement interventions might be beneficial to improve subjective sleep in young people with BPD features., (© 2021 European Sleep Research Society.)

Background: Sleep disturbance is common among young people (15-25 years) with features of borderline personality disorder (BPD). However, the mechanisms underlying sleep disturbance in BPD remain unknown. Understanding these underlying processes is essential to guide the development of sleep-improvement interventions and to optimise their efficacy through identifying beneficial treatment targets. This exploratory study aimed to investigate potential underlying mechanisms to inform future hypotheses, research development, and provide insight into potential treatment targets to improve sleep in young people with BPD. This study explored the indirect roles of emotion regulation difficulties, depression, anxiety and stress in the relationship between BPD features and sleep disturbance in young people., Methods: Sleep was measured subjectively (self-report questionnaires) and objectively (10 days wrist actigraphy) in 40 young people with BPD features and 38 healthy young people. Participants also completed the Difficulties in Emotion Regulation Scale and the Depression, Anxiety and Stress Scale., Results: Mediation analyses revealed that impulse control difficulties, limited emotion regulation strategies and anxiety indirectly affected the relationship between group (BPD vs. healthy) and subjective sleep disturbance in young people. Lack of emotional awareness and anxiety contributed to associations between group and objectively longer time in bed and bedtime variability, respectively., Conclusions: These preliminary findings suggest that targeting emotional dysregulation (impulse control, strategies, emotional awareness) and anxiety might be beneficial for improving sleep in this population., (© 2022. The Author(s).)

Sleep disturbance is commonly reported in young people with features of borderline personality disorder (BPD). Examining sleep quality and sleep-wake patterns in young people with features of BPD is essential to inform the development of sleep-improvement interventions. A scoping review was conducted according to the Joanna Briggs Institute methodology. The objectives were to map the literature regarding sleep in young people with features of BPD, highlight areas for further investigation, and provide methodological recommendations for future research. Seven data sets were included in the review. Young people with features of BPD had poorer objective and subjective sleep quality, disturbed sleep architecture (particularly rapid-eye-movement sleep), an increased vulnerability to delayed sleep phase syndrome, and more nightmares and dream anxiety, compared with healthy individuals. Future research should use both objective and subjective sleep measures, include clinical comparison groups, and focus specifically on young people with BPD.

OBJECTIVES: Airline cabin crew experience high levels of fatigue and sleepiness. Whether these are solely related to their work schedules/jetlag or are in part related to individual factors is unknown. The COVID-19 pandemic has significantly disrupted the aviation industry and many cabin crew have been grounded. This provides a unique opportunity to assess the causes of fatigue and sleepiness in this population. METHODS: An online anonymous survey was distributed in April-June 2020 to cabin crew who were 1) flying, 2) grounded but doing alternative work, and 3) grounded, not working, or unemployed. The survey measured fatigue, sleepiness, and mental health. It also screened their risk for insomnia, depression, and shift work disorder and assessed drug and caffeine use. RESULTS: Collected were 409 valid responses: 45 currently flying; 35 grounded but doing alternate work; and 329 not working. On average, all three groups experienced normal levels of fatigue and sleepiness. The risk for major depressive disorder was 27.4%, with 59.5% of individuals reporting abnormal levels of anxiety. Caffeine intake and the use of drugs and alcohol to facilitate sleep were common, although not different between those currently flying vs. grounded. CONCLUSIONS: With reduced workloads or not flying, cabin crew reported lowered fatigue and sleepiness compared to prepandemic findings, along with reduced risk for major depressive disorder. However, a high occurrence of negative emotional states were reported, potentially related to the uncertainty surrounding the pandemic. This study suggests fatigue and sleepiness is primarily related to airline operational rather than personal variables. Wen CC-Y, Nicholas CL, Howard ME, Trinder J, Jordan AS. Understanding sleepiness and fatigue in cabin crew using COVID-19 to dissociate causative factors . Aerosp Med Hum Perform. 2022; 93(1):50-53.

Sleep may contribute to the long-lasting consolidation and processing of emotional memories. Experimental fear conditioning and extinction paradigms model the development, maintenance, and treatment of anxiety disorders. The literature provides compelling evidence for the involvement of rapid eye movement (REM) sleep in the consolidation of such memories. This meta-analysis correlated polysomnographic sleep findings with psychophysiological reactivity to the danger (CS+) and safety stimuli (CS-), to clarify the specific role of sleep stages before and after fear conditioning, extinction learning and extinction recall. Overall, there was evidence that more pre-learning sleep stage two and less slow wave sleep was associated with higher psychophysiological reactivity to the safety stimulus during extinction learning. Preliminary evidence found here support the role of REM sleep during the post-extinction consolidation sleep phase in clinical populations with disrupted sleep, but not in healthy controls. Furthermore, the meta-regressions found that sex moderated the associations between sleep and psychophysiological reactivity throughout the paradigm providing evidence for diverging correlations in male and females. Specifically, increased post-extinction REM was associated with poorer extinction and safety recall in females while the opposite was found in males. These results have implications for future research in the role of sleep in emotional memory processing., Competing Interests: Conflicts of interest Maya Schenker was funded by the Melbourne Graduate Research Scholarship. The authors have no other conflict of interest to disclose., (Copyright © 2021 Elsevier Ltd. All rights reserved.)

Study Objectives: Genioglossus (GG) after-discharge is thought to protect against pharyngeal collapse by minimizing periods of low upper airway muscle activity. How GG after-discharge occurs and which single motor units (SMUs) are responsible for the phenomenon are unknown. The aim of this study was to investigate genioglossal after-discharge., Methods: During wakefulness, after-discharge was elicited 8-12 times in healthy individuals with brief isocapnic hypoxia (45-60 s of 10% O2 in N2) terminated by a single breath of 100% O2. GG SMUs were designated as firing solely, or at increased rate, during inspiration (Inspiratory phasic [IP] and inspiratory tonic [IT], respectively); solely, or at increased rate, during expiration (Expiratory phasic [EP] or expiratory tonic [ET], respectively) or firing constantly without respiratory modulation (Tonic). SMUs were quantified at baseline, the end of hypoxia, the hyperoxic breath, and the following eight normoxic breaths., Results: A total of 210 SMUs were identified in 17 participants. GG muscle activity was elevated above baseline for seven breaths after hyperoxia (p < 0.001), indicating a strong after-discharge effect. After-discharge occurred due to persistent firing of IP and IT units that were recruited during hypoxia, with minimal changes in ET, EP, or Tonic SMUs. The firing frequency of units that were already active changed minimally during hypoxia or the afterdischarge period (p > 0.05)., Conclusion: That genioglossal after-discharge is almost entirely due to persistent firing of previously silent inspiratory SMUs provides insight into the mechanisms responsible for the phenomenon and supports the hypothesis that the inspiratory and expiratory/tonic motor units within the muscle have idiosyncratic functions., (© Sleep Research Society 2021. Published by Oxford University Press on behalf of the Sleep Research Society. All rights reserved. For permissions, please email: journals.permissions@oup.com.)

The level of expression of programmed cell death-1 (PD-1)/programmed death ligand-1 (PD-L1) is a predictive biomarker for cancer immunotherapy, however, its detection remains challenging due to tumour heterogeneity and the influence from the binding of therapeutic agents. We recently developed [ 99m Tc]-NM-01 as a companion diagnostic imaging agent for non-invasive molecular imaging of PD-L1 by single-photon emission computed tomography (SPECT). The aim of the study was to evaluate the [ 99m Tc] radiolabelling of GMP graded NM-01 and its pharmacology, pharmacokinetics and toxicology. NM-01 bound specifically to human PD-L1 (K d =0.8 nM) and did not interfere with the binding of the anti-PD-L1 antibody atezolizumab. NM-01 can bind various PD-L1-positive cancer cell lines and only interact with PD-L1 expressed on the cell surface. In SPECT/CT imaging, high [ 99m Tc]-NM-01 accumulation was observed in the HCC827 mouse xenografted tumour model (30-min: 1.50 ± 0.27 %ID/g; 90-min: 1.23 ± 0.18 %ID/g), demonstrated a predominantly renal elimination (high uptake in bladder and kidney), while activity in the blood pool and other major organs remained low. The tumour-to-muscle and tumour-to-blood ratios were comparable with/without atezolizumab (P<0.04) but were significantly lowered when co-injected with excess NM-01 (P=0.04 and P=0.01, respectively.) The blood clearance of [ 99m Tc]-NM-01 is bi-phasic; consisting of an initial fast washout phase with half-life of 2.1 min and a slower clearance phase with half-life of 25.4 min. In an intravenous extended single-dose toxicity study, no treatment-related changes were observed and the maximum tolerated dose of [ 99m Tc]-NM-01 was 2.58 mg/kg. [ 99m Tc]-NM-01 has suitable properties as a potential candidate for SPECT/CT imaging of PD-L1 assessment in cancer patients., Competing Interests: N.C.L.W., Y.C., L.K.M. and H.H.T. are employees of NanoMab Technology Ltd. H.J.B. is an advisor for NanoMab Technology Ltd. G.J.R.C. is a consultant and receive research support for NanoMab Technology Ltd, Theragnostics Ltd and Serac Healthcare Ltd. F. M. M is on the advisory board of Advanced Accelerator Applications GmbH and has received institutional grants from GE Healthcare, Siemens, and NanoMab Technology Ltd., (AJNMMI Copyright © 2021.)

Background: The extracellular matrix (ECM) is a fundamental component of multicellular organisms that orchestrates developmental processes and controls cell and tissue organization. We previously identified the novel ECM protein SNED1 as a promoter of breast cancer metastasis and showed that its level of expression negatively correlated with breast cancer patient survival. Here, we sought to identify the roles of SNED1 during murine development., Results: We generated two novel Sned1 knockout mouse strains and showed that Sned1 is essential since homozygous ablation of the gene led to early neonatal lethality. Phenotypic analysis of the surviving knockout mice revealed a role for SNED1 in the development of craniofacial and skeletal structures since Sned1 knockout resulted in growth defects, nasal cavity occlusion, and craniofacial malformations. Sned1 is widely expressed in embryos, notably by cell populations undergoing epithelial-to-mesenchymal transition, such as the neural crest cells. We further show that mice with a neural-crest-cell-specific deletion of Sned1 survive, but display facial anomalies partly phenocopying the global knockout mice., Conclusions: Our results demonstrate requisite roles for SNED1 during development and neonatal survival. Importantly, the deletion of 2q37.3 in humans, a region that includes the SNED1 locus, has been associated with facial dysmorphism and short stature., (© 2020 American Association of Anatomists.)

Objective: We hypothesize that childhood obesity influences both facial and mandibular size and form in children and adolescents., Design: Pre-treatment records of patients (n = 181; 86 males, 95 females) from the Department of Orthodontics at the University of Illinois at Chicago representing six different ancestry groups (Asian, African-American, Caucasian Non-Hispanic, Hispanic, Multiracial, Unknown) were reviewed retrospectively. Body mass index (BMI) scores and categories were calculated using the Center for Disease Control and Prevention (CDC) guidelines. Twenty-two landmarks were collected on lateral cephalometric radiographs. The landmark dataset was analyzed as a whole (facial shape) and a subset of landmarks was also used to study mandibular shape in isolation., Results: Evidence of allometry (size related shape differences) was detected. Principal Component Analyses (PCA) were performed on the allometric regression residuals. Overall facial shape did not correlate with BMI. A series of one-way ANOVA tests on PC1-6 on a mandible-only subset of the landmarks using BMI category (normal, overweight, obese) showed PC5 and PC6 were significant (p = 0.003; p = 0.027). Centroid size was positively correlated with BMI when controlling for age (facial: p = 0.011, r = 0.196; mandibular: p < 0.001, r = 0.256)., Conclusions: Our results mostly did not support a relationship between high BMI and facial shape. However, we found larger facial skeletal sizes in high BMI children, providing tentative evidence that childhood obesity may lead to accelerated timing of facial growth., (Copyright © 2020 Elsevier Ltd. All rights reserved.)

Background: Aviation pilots and cabin crew regularly undertake shift work, and may experience circadian disruption, restricted sleep, sleepiness and impaired health. Research on aviation fatigue and sleepiness has focused on pilots, with less being known about cabin crew. This study aimed to identify likely predictors of fatigue, sleepiness, shift work disorder (SWD) and depression in cabin crew., Methods: An online anonymous survey was distributed to active cabin crew around the world. It measured sleepiness, fatigue, and screened for insomnia, depression and SWD. Information on individuals' habits and work schedules were collected., Results: 930 valid responses were analysed. 63.5% of the sample had abnormal levels of fatigue and 46.9% experienced excessive daytime sleepiness. 68.0% were at risk for SWD, 57.7% screened positive for insomnia, and 40.0% for depression. Caffeine and use of alcohol and drugs for sleep were independently associated with insomnia and SWD ( p < 0.05), whereas, type of route (international, domestic, both) and number of duty days per week predicted fatigue ( p < 0.05)., Conclusions: Cabin crew had a high prevalence of fatigue, sleepiness and elevated risk for SWD, insomnia and depression. Many cabin crew engaged in behaviours detrimental to good sleep hygiene, highlighting targets for future interventional studies.

Objective: This study assessed the consequences of childhood traumatic brain injury (TBI) on sleep, fatigue, depression, and quality of life (QoL) outcomes and explored the relationships between these variables at 20 years following childhood TBI., Participants: We followed up 54 young adults with mild, moderate, and severe TBI, and 13 typically developing control (TDC) participants, recruited at the time of TBI., Methods: Sleep was assessed with the Pittsburgh Sleep Quality Index and actigraphy., Results: At 20 years postinjury, results showed no significant difference between whole TBI group and TDC participants on subjective sleep quality; however, the moderate TBI group reported significantly poorer subjective sleep quality compared to those with severe TBI. Poorer subjective sleep was associated with increased symptoms of fatigue, depression, and poorer perceptions of General Health in the TBI group. Actigraphic sleep efficiency, fatigue, depression, and QoL outcomes were not significantly different between TBI and TDC or among TBI severity groups., Conclusions: These preliminary findings underscore associations between subjective sleep disturbance, fatigue, depression, and QoL in this TBI sample, and mostly comparable outcomes in sleep, fatigue, depression, and QoL between the TBI and TDC groups. Further research is required to clarify these findings.