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Katarina Dedovic,1,2 Janice Ngiam3 1Department of Psychiatry, Douglas Hospital Research Centre, Montreal, QC, Canada; 2Social and Affective Neuroscience Laboratory, University of California, Los Angeles, CA, USA; 3Department of Psychology, McGill University, Montreal, QC, Canada Abstract: A vast body of literature has revealed that dysregulation of the hypothalamic–pituitary–adrenal (HPA) stress axis is associated with etiology of major depressive disorder (MDD). There are many ways that the dysregulation of the HPA axis can be assessed: by sampling diurnal basal secretion and/or in response to a stress task, pharmacological challenge, and awakening. Here, we focus on the association between cortisol awakening response (CAR), as one index of HPA axis function, and MDD, given that the nature of this association is particularly unclear. Indeed, in the following selective review, we attempt to reconcile sometimes-divergent evidence of the role of CAR in the pathway to depression. We first examine association of CAR with psychological factors that have been linked with increased vulnerability to develop depression. Then, we summarize the findings regarding the CAR profile in those with current depression, and evaluate evidence for the role of CAR following depression resolution and continued vulnerability. Finally, we showcase longitudinal studies showing the role of CAR in predicting depression onset and recurrence. Overall, the studies reveal an important, but complex, association between CAR and vulnerability to depression. Keywords: HPA axis, MDD, SCN, daily hassles, genetic influence, environmental factors

Background Transient hyperglycaemia in the context of illness with or without known diabetes has been termed as 'stress hyperglycaemia'. Stress hyperglycaemia can result in poor functional outcomes in patients with acute ischaemic stroke (AIS) who underwent mechanical thrombectomy. We investigated the association between stress hyperglycaemia and clinical outcomes in AIS patients undergoing intravenous thrombolysis (IVT). Methods We examined 666 consecutive patients with AIS who underwent IVT from 2006 to 2018. All patients had a glycated haemoglobin level (HbA1c) and fasting venous blood glucose measured within 24 h of admission. Stress hyperglycaemia ratio (SHR) was defined as the ratio of the fasting glucose to the HbA1c. Univariate and multivariate analyses were employed to identify predictors of poor functional outcomes (modified Rankin Scale 3–6 at 3 months) after IVT. Results Three-hundred and sixty-one patients (54.2%) had good functional outcomes. These patients tended to be younger (60.7 ± 12.7 vs. 70 ± 14.4 years, P  < 0.001), male (70.7% vs. 51.5%, P  < 0.001), had lower prevalence of atrial fibrillation (13.0% vs. 20.7%, P  = 0.008) and lower SHR (0.88 ± 0.20 vs. 0.99 ± 26, P  < 0.001). Patients with high SHR (≥0.97) were slightly older than those with low SHR (<0.97) and were more likely to have diabetes mellitus. On multivariate analysis, higher SHR was independently associated with poor functional outcomes (adjusted odds ratio 3.85, 95% confidence interval 1.59–9.09, P  = 0.003). Conclusion SHR appears to be an important predictor of functional outcomes in patients with AIS undergoing IVT. This may have important implications on the role of glycaemic control in the acute management of ischaemic stroke. [ABSTRACT FROM AUTHOR]

In the present study, Salmonella spp. was successfully isolated from Asian clam Corbicula fluminea by using Xylose Lysine Deoxycholate (XLD) selective agar. A total of 200 bacterial colonies from live Asian clams were isolated and subjected to antimicrobial sensitivity test by using disc diffusion method. A total of 18 antibiotics was applied in the present study, namely oxolinic acid, nalidixic acid, erythromycin, tetracycline, doxycycline, oleandomycin, oxytetracycline, spiramycin, ampicillin, kanamycin, fosfomycin, florfenicol, lincomycin, novobiocin, chloramphenicol, amoxycillin, flumequine and sulphamethoxazole. The findings of the present study showed that total antibiotic sensitive case for Salmonella spp. isolated from C. fluminea sample was 50% or 1800 cases. This was followed by antibiotic resistance case 45% or 1620 cases and intermediary antibiotic sensitive case (5% or 180 cases). Based on the results of the present study, tetracycline, doxycycline, oxytetracycline and flumequine showed the highest inhibition of isolated Salmonella spp. The multiple antibiotic resistance (MAR) index was 0.36, indicating the sampled clams were highly exposed to the tested antibiotics.

Study Objectives: To characterize how mandibular advancement enlarges the upper airway via posterior tongue advancement in people with obstructive sleep apnea (OSA) and whether this is associated with mandibular advancement splint (MAS) treatment outcome., Methods: One-hundred and one untreated people with OSA underwent a 3T magnetic resonance (MRI) scan. Dynamic mid-sagittal posterior tongue and mandible movements during passive jaw advancement were measured with tagged MRI. Upper airway cross-sectional areas were measured with the mandible in a neutral position and advanced to 70% of maximum advancement. Treatment outcome was determined after a minimum of 9 weeks of therapy., Results: Seventy-one participants completed the study: 33 were responders (AHI<5 or AHI≤10 events/hr with >50% AHI reduction), 11 were partial responders (>50% AHI reduction but AHI>10 events/hr), and 27 nonresponders (AHI reduction<50% and AHI≥10 events/hr). Responders had the greatest naso- and oropharyngeal tongue anterior movement (0.40 ± 0.08 and 0.47 ± 0.13 mm, respectively) and oropharyngeal cross-sectional area enlargement (6.41 ± 2.12%) per millimeter of mandibular advancement. A multivariate model that included tongue movement and percentage of airway enlargement per millimeter of mandibular advancement along with baseline AHI correctly classified 69.2% (5-fold cross-validated 62.5%, n = 39) of participants in response categories when the jaw was advanced in the range that would usually be regarded as sufficient for clinical efficacy (> 4 mm). In comparison, a model using only baseline AHI correctly classified 50.0% of patients (5-fold cross-validated 52.5%, n = 40)., Conclusions: Tongue advancement and upper airway enlargement with mandibular advancement in conjunction with baseline AHI improve treatment response categorization to a satisfactory level (69.2%, 5-fold cross-validated 62.5%)., (© The Author(s) 2022. Published by Oxford University Press on behalf of Sleep Research Society. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Additive engineering is emerging as a powerful strategy to further enhance the performance of perovskite solar cells (PSCs), with the incorporation of bulky cations and amino acid (AA) derivatives being shown as a promising strategy for enhanced device stability. However, the incorporation of such additives typically results in photocurrent losses owing to their saturated carbon backbones, hindering charge transport and collection. Here, we investigate the use of AAs with varying carbon chain lengths as zwitterionic additives to enhance the PSC device stability, in air and nitrogen, under illumination. We, however, discovered that the device stability is insensitive to the chain length as the anticipated photocurrent drops as the chain length increases. Using glycine as an additive results in an improvement in the open circuit voltage from 1.10 to 1.14 V and a resulting power conversion efficiency of 20.2% (20.1% stabilized). Using time-of-flight secondary ion mass spectrometry, we confirm that the AAs reside at the surfaces and interfaces of our perovskite films and propose the mechanisms by which stability is enhanced. We highlight this with glycine as an additive, whereby an 8-fold increase in the device lifetime in ambient air at 1 sun illumination is recorded. Short-circuit photoluminescence quenching of complete devices is reported, which reveals that the loss in photocurrent density observed with longer carbon chain AAs results from the inefficient charge extraction from the perovskite absorber layer. These combined results demonstrate new fundamental understandings about the photophysical processes of additive engineering using AAs and provide a significant step forward in improving the stability of high-performance PSCs.

Study Objectives: Oral appliance (OA) therapy usage can be objectively measured through temperature-sensing data chips embedded in the appliance. Initial reports of group data for short-term treatment usage suggest good nightly hours of usage. However, individual variability in treatment usage patterns has not been assessed. We aimed to identify OA treatment usage subtypes in the first 60 days and the earliest predictors of these usage patterns., Methods: OSA patients were recruited for a study of OA therapy with an embedded compliance chip (DentiTrac, Braebon, Canada). Fifty-eight participants with 60 days of downloadable treatment usage data (5-minute readings) were analyzed. A hierarchical cluster analysis was used to group participants with similar usage patterns. A random forest classification model was used to identify the minimum number of days to predict usage subtype., Results: Three user groups were identified and named: "Consistent Users" (48.3%), "Inconsistent Users," (32.8%) and "Non-Users" (19.0%). The first 20 days provided optimal data to predict the treatment usage group a patient would belong to at 60 days (90% accuracy). The strongest predictors of user group were downloaded usage data, average wear time, and number of days missed., Conclusions: Granular analysis of OA usage data suggests the existence of treatment user subtypes (Consistent, Inconsistent, and Non-Users). Our data suggest that 60-day usage patterns can be identified in the first 20 days of treatment using downloaded treatment usage data. Understanding initial treatment usage patterns provide an opportunity for early intervention to improve long-term usage and outcomes., Citation: Sutherland K, Almeida FR, Kim T, et al. Treatment usage patterns of oral appliances for obstructive sleep apnea over the first 60 days: a cluster analysis. J Clin Sleep Med . 2021;17(9):1785-1792., (© 2021 American Academy of Sleep Medicine.)

Study Objectives: To investigate whether the presence of tendinous PMR could predict treatment outcome and how it affects lateral wall mechanical properties. Mandibular advancement increases the lateral dimensions of the nasopharyngeal airway via a direct connection from the airway to the ramus of the mandible. The anatomical structure in this region is the pterygomandibular raphe (PMR), but a tendinous component is not always present. Whether tendon presence influences treatment outcome is unknown., Methods: In total, 105 participants with obstructive sleep apnea completed detailed anatomical magnetic resonance imaging with and without mandibular advancement. The study design was case-control. Variables were compared between participants with and without the tendon present., Results: The amount of maximum mandibular advancement decreased when pterygomandibular tendon was present (4.0 ± 1.2 mm present versus 4.6 ± 1.4 mm absent, p = 0.04). PMR tendon-absent participants had a lower posttreatment apnea hypopnea index (16 ± 12 events/hour tendon present versus 9 ± 9 events/hour absent, p = 0.007) and were more likely to have complete response (63% versus 36%, p = 0.02). However, tendon-absent participants were more likely to not complete the study (χ 2 (3) = 10.578, p = 0.014). Tendon-absent participants had a greater increase in midline anteroposterior airway diameter (1.6 ± 1.7 mm versus 0.6 ± 2.3 mm, p = 0.04)., Conclusion: When PMR tendon is absent, treatment response and amount of maximum advancement improve, possibly at the expense of reduced splint tolerability. Tendon presence may help predict a group less likely to respond to mandibular advancement splint therapy., (© Sleep Research Society 2020. Published by Oxford University Press on behalf of the Sleep Research Society. All rights reserved. For permissions, please e-mail journals.permissions@oup.com.)

Study Objectives: To characterize how mandibular advancement splint (MAS) alters inspiratory tongue movement in people with obstructive sleep apnea (OSA) during wakefulness and whether this is associated with MAS treatment outcome., Methods: A total of 87 untreated OSA participants (20 women, apnea-hypopnea index (AHI) 7-102 events/h, aged 19-76 years) underwent a 3T MRI with a MAS in situ. Mid-sagittal tagged images quantified inspiratory tongue movement with the mandible in a neutral position and advanced to 70% of the maximum. Movement was quantified with harmonic phase methods. Treatment outcome was determined after at least 9 weeks of therapy., Results: A total of 72 participants completed the study: 34 were responders (AHI < 5 or AHI ≤ 10events/h with >50% reduction in AHI), 9 were partial responders (>50% reduction in AHI but AHI > 10 events/h), and 29 nonresponders (change in AHI <50% and AHI ≥ 10 events/h). About 62% (45/72) of participants had minimal inspiratory tongue movement (<1 mm) in the neutral position, and this increased to 72% (52/72) after advancing the mandible. Mandibular advancement altered inspiratory tongue movement pattern for 40% (29/72) of participants. When tongue dilatory patterns altered with advancement, 80% (4/5) of those who changed to a counterproductive movement pattern (posterior movement >1 mm) were nonresponders and 71% (5/7) of those who changed to beneficial (anterior movement >1 mm) were partial or complete responders., Conclusions: The mandibular advancement action on upper airway dilator muscles differs between individuals. When mandibular advancement alters inspiratory tongue movement, therapeutic response to MAS therapy was more common among those who convert to a beneficial movement pattern., (© Sleep Research Society 2020. Published by Oxford University Press on behalf of the Sleep Research Society. All rights reserved. For permissions, please e-mail journals.permissions@oup.com.)

Background: Implementation of mandibular advancement splint (MAS) therapy as first-line treatment for obstructive sleep apnoea (OSA) is hindered by inter-individual variability of treatment outcomes and lack of robust patient selection methods. Optimal continuous positive airway pressure (CPAP) requirement provides an estimate of airway collapsibility severity, and high CPAP requirements predict MAS therapy failure in retrospective studies. Thus, understanding the effects of mandibular advancement on optimal CPAP requirements may enhance optimisation of patient selection for MAS therapy., Objective: This study aims to determine dose-dependent effects of mandibular advancement on optimal CPAP requirements in OSA., Methods: Prior to MAS therapy initiation, participants with OSA (apnoea-hypopnea index (AHI) > 10 events/h) underwent a research polysomnogram in which a remotely controlled mandibular positioner (RCMP) was used to determine dose-response effects of varying mandibular advancement positions (0% 'habitual bite' and 25, 50, 75 and 100% of maximum mandibular advancement, in random order) on optimal CPAP requirements. A separate polysomnography determined treatment outcome. Data are presented as mean ± SD or median (1st-3rd quartiles)., Results: Seventeen participants (age = 47 ± 9 years, body mass index = 26 kg/m 2 (23-27), apnoea-hypopnea index = 18 events/h (14-44) and minimal oxygen saturation = 84 ± 7%) were studied. Optimal CPAP requirements were reduced with mandibular advancement in a dose-dependent manner (8.9 ± 2.4 vs. 7.9 ± 2.8, 6.4 ± 1.8, 5.7 ± 1.9 and 4.9 ± 1.8 cmH 2 O; respectively, p < 0.0001). Compared with non-responders, responders to MAS therapy had lower AHI, lower arousal index and greater MinSaO 2 at baseline. Optimal CPAP requirements at 0% mandibular advancement (or other positions) were not different between groups., Conclusions: Increasing mandibular advancement lowers optimal CPAP requirements in a dose-dependent manner. This supports prior work indicating a beneficial effect of MAS on upper airway collapsibility.

Study Objectives: Mandibular advancement splints (MAS) are the leading treatment alternative to continuous positive airway pressure (CPAP) for obstructive sleep apnea (OSA). However, not all patients experience clinical benefit and treatment prediction remains challenging. Understanding the effects of mandibular advancement on pharyngeal collapsibility and muscle function may provide valuable information on the mechanisms of MAS, and thereby help to develop novel approaches for patient selection. Thus, we aimed to determine dose-dependent effects of mandibular advancement on pharyngeal collapsibility and muscle function concurrently in OSA patients undergoing MAS therapy., Methods: Twelve (11 male) MAS-naïve patients underwent a detailed physiology sleep study (polysomnography) to quantify pharyngeal collapsibility (PCRIT), pharyngeal muscle responsiveness to negative pharyngeal pressure (via genioglossus intramuscular electromyography and an epiglottic pressure sensor) and effectiveness to restore airflow and minute ventilation (Vi) after 1-minute transient CPAP reductions (induced airflow-limitation) at three mandibular advancement positions: 0% (habitual bite), 50% and 100% of the maximum comfortable mandibular advancement. Standard clinical polysomnography after MAS therapy optimization was performed to determine treatment outcome., Results: Overall, participants were obese with severe OSA (mean ± SD: BMI = 31 ± 4 kg/m2, apnea-hypopnea index [AHI] = 33 ± 14 events/hour). PCRIT decreased with mandibular advancement in a dose-dependent manner (1.8 ± 3.9 vs. -0.9 ± 2.9 vs. -4.0 ± 3.6 cmH2O; p < 0.001). There was no systematic change in genioglossus muscle responsiveness (p = 0.09) or effectiveness to restore peak airflow (p = 0.4) or Vi (p = 0.7) with mandibular advancement., Conclusions: Mandibular advancement reduces pharyngeal collapsibility in a dose-dependent manner without systematically changing genioglossus muscle function in a predominantly obese and severe OSA population. This indicates that the primary mode of action of MAS therapy is via improvement in passive pharyngeal anatomy., (© Sleep Research Society 2019. Published by Oxford University Press on behalf of the Sleep Research Society. All rights reserved. For permissions, please e-mail journals.permissions@oup.com.)

Purpose: Clinical methods to identify responders to oral appliance (OA) therapy for obstructive sleep apnoea (OSA) are needed. Awake nasopharyngoscopy during mandibular advancement, with image capture and subsequent processing and analysis, may predict treatment response. A qualitative assessment of awake nasopharyngoscopy would be simpler for clinical practice. We aimed to determine if a qualitative classification system of nasopharyngoscopic observations reflects treatment response., Methods: OSA patients were recruited for treatment with a customised two-piece OA. A custom scoring sheet was used to record observations of the pharyngeal airway (velopharynx, oropharynx, hypopharynx) during supine nasopharyngoscopy in response to mandibular advancement and performance of the Müller manoeuvre. Qualitative scores for degree (< 25%, 25-50%, 50-75%, > 75%), collapse pattern (concentric, anteroposterior, lateral) and diameter change (uniform, anteroposterior, lateral) were recorded. Treatment outcome was confirmed by polysomnography after a titration period of 14.6 ± 9.8 weeks. Treatment response was defined as (1) Treatment AHI < 5, (2) Treatment AHI < 10 plus > 50% AHI reduction and (3) > 50% AHI reduction., Results: Eighty OSA patients (53.8% male) underwent nasopharyngoscopy. The most common naspharyngoscopic observation with mandibular advancement was a small (< 50%) increase in velopharyngeal lateral diameter (37.5%). The majority of subjects (72.5%) were recorded as having > 75% velopharyngeal collapse on performance of the Müller manoeuvre. Mandibular advancement reduced the observed level of pharyngeal collapse at all three pharyngeal regions (p < 0.001). None of the nasopharyngoscopic qualitative scores differed between responder and non-responder groups., Conclusion: Qualitative assessment of awake nasopharyngoscopy appears useful for assessing the effect of mandibular advancement on upper airway collapsibility. However, it is not sensitive enough to predict oral appliance treatment outcome.

Study Objectives: An oral appliance (OA) is a validated treatment for obstructive sleep apnea (OSA). However, therapeutic response is not certain in any individual and is a clinical barrier to implementing this form of therapy. Therefore, accurate and clinically applicable prediction methods are needed. The goal of this study was to derive prediction models based on multiple awake assessments capturing different aspects of the pharyngeal response to mandibular advancement. We hypothesized that a multimodal model would provide robust prediction., Methods: Patients with OSA (apnea-hypopnea index [AHI] > 10 events/h) were recruited for treatment with a customized OA (n = 142, 59% male). Participants underwent facial photography (craniofacial structure), spirometry (mid-inspiratory flow at 50% vital capacity [MIF 50 ] and mid-expiratory flow at 50% vital capacity [MEF 50 ] and the ratio MEF 50 /MIF 50 ) and nasopharyngoscopy (velopharyngeal collapse with Mueller maneuver and mandibular advancement). Treatment response was defined by 3 criteria: (1) AHI < 5 events/h plus ≥ 50% reduction, (2) AHI < 10 events/h plus ≥ 50% reduction, (3) ≥ 50% AHI reduction. Multivariable regression models were used to assess predictive utility of phenotypic assessments compared to clinical characteristics alone (age, sex, obesity, baseline AHI)., Results: Craniofacial structure and flow-volume loops predicted treatment response. Accuracy of the prediction models (area under the receiver operating characteristic curve) for each criterion were 0.90 (criterion 1), 0.79 (criterion 2), and 0.78 (criterion 3). However, these prediction models including phenotypic assessments did not provide a statistically significant improvement over clinical predictors only., Conclusions: Multimodal awake phenotyping does not enhance OA treatment outcome prediction. These office-based, awake assessments have limited utility for robust clinical prediction models. Future work should focus on sleep-related assessments., Commentary: A commentary on this article appears in this issue on page 1837., Clinical Trial Registration: Registry: Australian New Zealand Clinical Trials Registry, Title: Multimodal phenotyping for the prediction of oral appliance treatment outcome in obstructive sleep apnoea, Identifier: ACTRN12611000409976, URL: https://www.anzctr.org.au/Trial/Registration/TrialReview.aspx?id=336663., (© 2018 American Academy of Sleep Medicine.)

Study Objectives: Mandibular protrusion during sleep monitoring has been proposed as a method to predict oral appliance treatment outcome. A commercial remotely controlled mandibular protrusion (RCMP) device has become available for this purpose with predictive accuracy demonstrated in an initial study. Our aim was to validate this RCMP method for oral appliance treatment outcome prediction in a clinical sleep laboratory setting., Methods: Forty-two obstructive sleep apnea (OSA) patients (apnea-hypopnea index [AHI] > 10 events/h) were recruited to undergo a RCMP sleep study before commencing oral appliance treatment. The RCMP study was used to make a prediction of treatment "Success" or "Failure" based on a rule of ≤ 1 respiratory event per 5 min supine rapid eye movement sleep. Oral appliance treatment response was verified by polysomonography and defined as treatment AHI < 10 events/h with 50% reduction., Results: Participants were on average middle-aged (57.1 ± 11.6 y) and overweight (29.6 ± 4.5 kg/m 2 ) with baseline AHI 31.5 ± 20.5 events/h, 39% severe OSA (AHI > 30 events/h). Two participants (5%) were not able to tolerate the RCMP study. Oral appliance treatment outcome was verified in 33 participants (RCMP results: "Success" n = 10, "Failure" n = 15, "Inconclusive" n = 8). In those with a treatment outcome prediction (n = 25) the diagnostic characteristics of the RCMP test were sensitivity 81.8%, specificity 92.9%, positive predictive value 90%, and negative predictive value 86.7% (n = 3 misclassified)., Conclusions: The RCMP device was well tolerated by patients and successfully used to perform mandibular protrusion sleep studies in our sleep laboratory. The RCMP sleep study showed good accuracy as a prediction technique for oral appliance treatment outcome, although there was a high rate of inconclusive tests., (© 2017 American Academy of Sleep Medicine)

Paediatric obstructive sleep apnea (OSA) is common and its prevalence is expected to increase due to the rise in childhood obesity. Recent research has shown that many children, both syndromic and non-syndromic, who exhibit mouth breathing as a result of upper airway obstruction, may also exhibit dentofacial anomalies. Although adenotonsillectomy and continuous positive airway pressure have been classically proposed as the primary treatment modalities for paediatric OSA, there are significant limitations to both therapies. Therefore newer treatment modalities are needed. Current research has focused on emerging dental treatment options for paediatric OSA, such as rapid maxillary expansion, oral appliances and distraction osteogenesis. However, there are few randomized trials assessing the effectiveness of these novel dental therapies for paediatric OSA, and hence further research is required to advance the field., (Copyright © 2014 Elsevier Ltd. All rights reserved.)

Objective: To investigate the efficacy of orthodontic microimplant-based mandibular advancement therapies for the treatment of snoring and obstructive sleep apnea (OSA) in adult patients., Materials and Methods: Ten adult OSA patients (seven men, three women; mean age 60.00 ± 9.25 years) were each treated with two mandibular orthodontic microimplants attached to a customized reverse face mask for mandibular advancement. Pretreatment and posttreatment outcome measures of microimplant mobility, apnea-hypopnea index, snoring, respiratory movement, and Epworth sleepiness scores were evaluated after 6 months., Results: Highly significant reductions in the apnea-hypopnea index, snoring, and sleep variables were observed. Sixteen of the 20 (80%) microimplants were stable and showed no mobility, and four (20%) demonstrated grade 1 or 2 mobility and required removal and reinsertion of a new microimplant., Conclusions: Favorable reductions in sleep variables highlight the potential of microimplant-based mandibular advancement therapy as an alternative treatment modality for OSA patients who cannot tolerate continuous positive airway pressure and oral appliance therapy.