Neuroimaging and Biosample Collection in the Toronto Adolescent and Youth Cohort Study: Rationale, Methods, and Early Data.

BACKGROUND: The Toronto Adolescent and Youth (TAY) Cohort Study will characterize the neurobiological trajectories of psychosis spectrum symptoms, functioning, and suicidality (i.e., suicidal thoughts and behaviors) in youth seeking mental health care. Here, we present the neuroimaging and biosample component of the protocol. We also present feasibility and quality control metrics for the baseline sample collected thus far. METHODS: The current study includes youths (ages 11-24 years) who were referred to child and youth mental health services within a large tertiary care center in Toronto, Ontario, Canada, with target recruitment of 1500 participants. Participants were offered the opportunity to provide any or all of the following: 1) 1-hour magnetic resonance imaging (MRI) scan (electroencephalography if ineligible for or declined MRI), 2) blood sample for genomic and proteomic data (or saliva if blood collection was declined or not feasible) and urine sample, and 3) heart rate recording to assess respiratory sinus arrhythmia. RESULTS: Of the first 417 participants who consented to participate between May 4, 2021, and February 2, 2023, 412 agreed to participate in the imaging and biosample protocol. Of these, 334 completed imaging, 341 provided a biosample, 338 completed respiratory sinus arrhythmia, and 316 completed all 3. Following quality control, data usability was high (MRI: T1-weighted 99%, diffusion-weighted imaging 99%, arterial spin labeling 90%, resting-state functional MRI 95%, task functional MRI 90%; electroencephalography: 83%; respiratory sinus arrhythmia: 99%). CONCLUSIONS: The high consent rates, good completion rates, and high data usability reported here demonstrate the feasibility of collecting and using brain imaging and biosamples in a large clinical cohort of youths seeking mental health care.

Interactions between genetic risk for 21 neurodevelopmental and psychiatric disorders and sport activity on youth mental health.

Childhood is a sensitive period where behavioral disturbances, determined by genetics and environmental factors including sport activity, may emerge and impact risk of mental illness in adulthood. We aimed to determine if participation in sports can mitigate genetic risk for neurodevelopmental and psychiatric disorders in youth. We analyzed 4975 unrelated European youth (ages 9-10) from the Adolescent Brain Cognitive Development Study. Our outcomes were eight Child Behavior Checklist (CBCL) scores, measured annually. Polygenic risk scores (PRSs) were calculated for 21 disorders, and sport frequency and type were summarized. PRSs and sport variables were tested for main effects and interactions against CBCL outcomes using linear models. Cross-sectionally, PRSs for attention-deficit/hyperactivity disorder and major depressive disorder were associated with increases in multiple CBCL outcomes. Participation in non-contact or team sports, as well as more frequent sport participation reduced all cross-sectional CBCL outcomes, whereas involvement in contact sports increased attention problems and rule-breaking behavior. Interactions revealed that more frequent exercise was significantly associated with less rule breaking behavior in individuals with high genetic risk for obsessive compulsive disorder. Associations with longitudinal CBCL outcomes demonstrated weaker effects. We highlight the importance of genetic context when considering sports as an intervention for early life behavioural problems.

Anti-Vegf therapy leads to an improvement in grade of retinal pigment epithelium alterations on single layer retinal pigment epithelium map in diabetic macular edema.

PURPOSE: In bovine retinal pigment epithelium (RPE) cells, increased secretion of vascular endothelial growth factor (VEGF) has a positive linear association with proliferation of RPE. Spectral domain optical coherence tomography (SD-OCT) based improvement in grades of topographic retinal pigment epithelium alterations (RPE-A), were evaluated after intravitreal anti-VEGF therapy, in diabetic macular edema (DME), for the first time. METHODS: A tertiary care center-based, prospective study. Forty-four consecutive patients, 40-65 years of age with type 2 diabetes mellitus (DM) with DME, were administered three doses of anti-VEGF therapy at monthly intervals. Pre- and post-intervention SD-OCT was done and central sub field thickness (CST), cube average thickness (CAT) and topographic grades of RPE-A were assessed using single layer RPE map (SL-RPE) as; Grade 0: No alterations, Grade 1: Alteration in two quadrants, Grade 2: Alteration in more than two quadrants. RESULTS: CST decreased from 354.2 ± 16.0 µm pre-intervention to 233.2 ± 7.9 µm post-intervention. CAT reduced from 340.6 ± 6.5 µm pre-intervention to 274.1 ± 5.1 µm post-intervention. Significant improvement in grades of RPE-A pre- v/s post-intervention were observed. (Grade 0: 0 v/s 39; Grade 1: 17 v/s 3; Grade 2: 27 v/s 2) (p < 0.001). CONCLUSION: Anti-VEGF therapy is associated with an improvement in grades of RPE-A in DME.The study was registered with the Clinical Trial Registry of India (CTRI/2019/03/018135).

Serum cortisol is a biomolecular biomarker for severity of diabetic retinopathy.

Purpose: Cortisol and prolactin are multifunctional hormones essential for various metabolic processes in the human body. This study evaluated for the first time the association between serum cortisol and prolactin levels and severity of diabetic retinopathy (DR) and their role as biomolecular biomarkers for disease progression. Methods: A tertiary care center-based cross-sectional study was conducted. Forty-six consecutive cases of type 2 diabetes mellitus (DM) were included. Retinopathy was graded according to the Early Treatment Diabetic Retinopathy Study (ETDRS) classification: diabetes with no retinopathy (NoDR, n = 15), nonproliferative DR (NPDR, n = 16), and proliferative DR (PDR, n = 15). Healthy controls (n = 15) were also included. All study participants underwent complete ophthalmological evaluations. Serum levels of cortisol and prolactin were analyzed using the chemiluminescence microparticle assay method. Statistical analysis was performed using ANOVA, univariate and multivariate ordinal logistic regression, and receiver operating characteristics (ROC) area under the curve (AUC). Results: The mean serum cortisol levels (µg/dl) were 10.25±1.380 for the NoDR group, 12.00±2.540 for the NPDR group, 13.19±2.170 for the PDR group, and 8.22±2.97 for the control group. The mean serum prolactin levels (ng/ml) were13.13±1.97 for the NoDR group, 11.04±2.59 for the NPDR group, 7.84±1.17 for the PDR group, and 7.38±3.34 for the control group. ANOVA showed a statistically significant increase in serum cortisol levels (F = 12.87, p<0.001) and a decrease in serum prolactin levels (F = 19.31, p<0.001) with severity of DR. However, the multivariate ordinal logistic regression analysis showed serum cortisol is a statistically significant independent predictor for severity of DR (odds ratio (OR) = 0.49, 95% confidence interval (CI) = 0.36-0.68, p<0.001). The AUC analysis of the serum cortisol levels to discriminate between severity of DR showed statistically significant diagnostic accuracy (NoDR group: AUC = 0.787, p<0.001; NPDR group: AUC = 0.852, p<0.001; PDR group: AUC = 0.887, p<0.001). Serum cortisol levels of >9.5 µg/dl and >10.2 µg/dl were found to be statistically significantly associated with occurrence of NPDR and PDR, respectively. Conclusions: Statistically significantly elevated serum cortisol levels are observed before development of signs of DR. Serum cortisol levels are statistically significantly associated with severity of DR and serve as a sensitive and specific biomolecular biomarker for disease progression.

Increased serum cortisol is associated with alterations in cross-sectional and topographic OCT parameters in diabetic retinopathy: a preliminary study.

PURPOSE: Cortisol, a steroid hormone, plays an essential role in metabolic processes of diabetes mellitus. This study for the first time evaluated the association of serum cortisol with spectral domain optical coherence tomography (SD-OCT)-based cross-sectional and topographic parameters with severity of diabetic retinopathy (DR). METHODS: A tertiary care center-based preliminary study was undertaken. Fourteen consecutive cases of DR and fifteen healthy controls were included. Cases were graded according to ETDRS classification: non-proliferative DR (NPDR, n = 8) and proliferative DR (PDR, n = 6). All study subjects underwent complete ophthalmological evaluation. Serum cortisol was analyzed using chemiluminescence microparticle assay method. Central subfield thickness (CST), cube average thickness (CAT), cube volume (CV), retinal nerve fiber layer (RNFL) thickness, disorganization of inner retinal layers (DRIL), grade of retinal photoreceptor ellipsoid zone (EZ) disruption and grade of retinal pigment epithelium (RPE) alterations were evaluated using SD-OCT. Statistical analysis was done using ANOVA and Pearson's correlation analysis. RESULTS: Mean serum cortisol levels (µg/dL) were NPDR = 11.59 ± 0.42, PDR = 14.50 ± 0.26 and controls = 8.22 ± 0.77. With increasing severity of DR, mean CST, CAT, CV showed positive correlation, whereas mean RNFL thickness showed negative correlation with serum cortisol levels (p < 0.01). DRIL, EZ disruption and RPE alterations showed positive correlation with serum cortisol levels (p < 0.001). CONCLUSION: Serum cortisol levels are significantly associated with severity of DR and correlate positively with CST, CAT, CV, DRIL, EZ disruption and RPE alterations and negatively with RNFL thickness.

Evaluation of accuracy and reliability of OneCeph digital cephalometric analysis in comparison with manual cephalometric analysis-a cross-sectional study.

INTRODUCTION: Lateral cephalometric analysis continues to be one of the gold standard diagnostic aids in orthodontics, with various software available to enhance this. AIM: This study was done to evaluate the accuracy and reliability of linear and angular measurements obtained from OneCeph digital cephalometric tracing and manual tracings in lateral cephalometry. METHODOLOGY: This is a cross-sectional study done on twenty pre-treatment lateral cephalometric radiographs of subjects who reported to the postgraduate orthodontic clinic for orthodontic treatment over one month. Cephalometric tracings were done using OneCeph digital software and manual tracing method to evaluate nine parameters of Steiner's cephalometric analysis. An Independent T-sample test was done between the mean values of manual and OneCeph tracing. Intra operator reliability was evaluated by paired T-test after a week. RESULTS: No significant statistical difference was observed as the p-value was greater than 0.05 for all the parameters in the two groups. CONCLUSION: The reliability and accuracy of OneCeph software application was found to be at par with manual cephalometric tracing.

Public Policy in a Time of Crisis: A Framework for Evaluating Canada's COVID-19 Income Support Programs.

Income support programs introduced for workers during the first wave of coronavirus disease 2019 (COVID-19) lockdowns faced criticism for their negative labour supply effects. We propose that these concerns about work disincentives are embedded in restrictive assumptions about work and led to suboptimal design of crisis support policies. We describe a framework for analyzing alternative crisis income support programs predicated on more realistic assumptions of labour markets and human motivation. Our framework proposes that balancing efficiency, equity, and voice objectives should be the goal of crisis labour market policies. We argue that adoption of a basic income targeted toward low-income workers, in combination with Canada's pre-existing Employment Insurance program, would have balanced efficiency, equity, and voice better than the combination of the Canada Emergency Response Benefit and Canada Emergency Wage Subsidy. A targeted basic income would also have been more effective at achieving stated public health objectives.

Les programmes de soutien du revenu mis en place à l'intention des travailleurs au cours de la première vague de confinements visant à contrer la maladie provoquée par le coronavirus (COVID­19) ont soulevé la critique en raison de leurs possibles répercussions négatives sur l'offre de travail. Selon nous, ces craintes qu'ils freinent le travail découlent d'hypothèses restrictives quant au travail et ont abouti à une conception sous-optimale des politiques de soutien en période de crise. Nous proposons un cadre de référence pour l'analyse d'autres options en matière de programmes de soutien du revenu en temps de crise, basées sur des hypothèses plus réalistes quant au fonctionnement des marchés du travail et aux mécanismes de la motivation humaine. Ce cadre de référence repose sur le principe selon lequel la mise en équilibre des objectifs d'efficience, d'équité et de droit de parole devrait être le but visé par les politiques de gestion du marché du travail en situation de crise. Nous sommes d'avis que l'adoption d'un revenu de base visant les travailleurs à faible revenu, en conjugaison avec le programme canadien existant d'assurance emploi, permettrait la mise en équilibre de l'efficience, de l'équité et du droit de parole de manière plus efficace que la combinaison de la Prestation canadienne d'urgence et de la Subvention salariale d'urgence du Canada. Un revenu de base ciblé aurait en outre été plus efficace dans l'atteinte des objectifs énoncés en matière de santé publique.

An Ex Vivo Evaluation of Antimicrobial Efficacy of Root Canal Preparation With Hand K-Files, Hand Pro Taper, and Pro Taper Rotary Files.

BACKGROUND: Microorganisms are considered to be the primary cause behind persistent pulpoperiapical pathologies as well as endodontic failures. It has been found that Enterococcus faecalis is one of the most commonly isolated organisms in failed endodontic treatment. Proper and appropriate mechanical instrumentation is necessary to eradicate these microorganisms. AIMS AND OBJECTIVES: The aim of this study was to compare antimicrobial efficacy of various root canal instrumentation techniques. This study was designed to compare antimicrobial efficacy of root canal preparation using hand K-files, hand Pro Taper files, and Pro Taper rotary files. MATERIALS AND METHODS: Forty intact maxillary premolars extracted for orthodontic reasons were used. After extirpation of pulp, teeth are decoronated and autoclaved. Then the root canals were infected with E. faecalis suspension and the teeth were incubated at 37°C for 24 h. Thereafter the teeth were divided into five groups and were prepared using the following instruments: group 1 (hand K-files), group 2 (hand Pro Taper files), group 3 (Pro Taper rotary files), group 4 (Control I; treatment consists of irrigation with 1 mL of sterile physiological saline with no instrumentation), and group 5 (Control II; teeth received no treatment at all). Before and after treatments, samples were taken from the root canals for culture and were transferred to physiological saline. Results were evaluated after 24-h incubation in selective culture medium. RESULTS: The results showed that the teeth prepared with Pro Taper rotary files showed significant reduction in number of bacteria from the root canals.

QuantifyMe: An Open-Source Automated Single-Case Experimental Design Platform.

Smartphones and wearable sensors have enabled unprecedented data collection, with many products now providing feedback to users about recommended step counts or sleep durations. However, these recommendations do not provide personalized insights that have been shown to be best suited for a specific individual. A scientific way to find individualized recommendations and causal links is to conduct experiments using single-case experimental design; however, properly designed single-case experiments are not easy to conduct on oneself. We designed, developed, and evaluated a novel platform, QuantifyMe, for novice self-experimenters to conduct proper-methodology single-case self-experiments in an automated and scientific manner using their smartphones. We provide software for the platform that we used (available for free on GitHub), which provides the methodological elements to run many kinds of customized studies. In this work, we evaluate its use with four different kinds of personalized investigations, examining how variables such as sleep duration and regularity, activity, and leisure time affect personal happiness, stress, productivity, and sleep efficiency. We conducted a six-week pilot study (N = 13) to evaluate QuantifyMe. We describe the lessons learned developing the platform and recommendations for its improvement, as well as its potential for enabling personalized insights to be scientifically evaluated in many individuals, reducing the high administrative cost for advancing human health and wellbeing.

Sensible organizations: technology and methodology for automatically measuring organizational behavior.

We present the design, implementation, and deployment of a wearable computing platform for measuring and analyzing human behavior in organizational settings. We propose the use of wearable electronic badges capable of automatically measuring the amount of face-to-face interaction, conversational time, physical proximity to other people, and physical activity levels in order to capture individual and collective patterns of behavior. Our goal is to be able to understand how patterns of behavior shape individuals and organizations. By using on-body sensors in large groups of people for extended periods of time in naturalistic settings, we have been able to identify, measure, and quantify social interactions, group behavior, and organizational dynamics. We deployed this wearable computing platform in a group of 22 employees working in a real organization over a period of one month. Using these automatic measurements, we were able to predict employees' self-assessments of job satisfaction and their own perceptions of group interaction quality by combining data collected with our platform and e-mail communication data. In particular, the total amount of communication was predictive of both of these assessments, and betweenness in the social network exhibited a high negative correlation with group interaction satisfaction. We also found that physical proximity and e-mail exchange had a negative correlation of r = -0.55 (p 0.01), which has far-reaching implications for past and future research on social networks.

Health0: a new health and lifestyle management paradigm.

The paper describes Health0: an innovative healthcare and lifestyle management wearable system that aims to bring an individual focused approach to healthcare. A modular architecture is proposed that combines a Linux-based PDA with a distributed wireless sensor-network and innovative bandage-sized (2.5 cm2) sensor hardware. Real-world scenarios that can use the Health0 system are discussed.