Negative childhood experiences alter a prefrontal-insular-motor cortical network in healthy adults: A preliminary multimodal rsfMRI-fMRI-MRS-dMRI study.

Research in humans and animals has shown that negative childhood experiences (NCE) can have long-term effects on the structure and function of the brain. Alterations have been noted in grey and white matter, in the brain's resting state, on the glutamatergic system, and on neural and behavioural responses to aversive stimuli. These effects can be linked to psychiatric disorder such as depression and anxiety disorders that are influenced by excessive exposure to early life stressors. The aim of the current study was to investigate the effect of NCEs on these systems. Resting state functional MRI (rsfMRI), aversion task fMRI, glutamate magnetic resonance spectroscopy (MRS), and diffusion magnetic resonance imaging (dMRI) were combined with the Childhood Trauma Questionnaire (CTQ) in healthy subjects to examine the impact of NCEs on the brain. Low CTQ scores, a measure of NCEs, were related to higher resting state glutamate levels and higher resting state entropy in the medial prefrontal cortex (mPFC). CTQ scores, mPFC glutamate and entropy, correlated with neural BOLD responses to the anticipation of aversive stimuli in regions throughout the aversion-related network, with strong correlations between all measures in the motor cortex and left insula. Structural connectivity strength, measured using mean fractional anisotropy, between the mPFC and left insula correlated to aversion-related signal changes in the motor cortex. These findings highlight the impact of NCEs on multiple inter-related brain systems. In particular, they highlight the role of a prefrontal-insular-motor cortical network in the processing and responsivity to aversive stimuli and its potential adaptability by NCEs.

Access to pyridyl-substituted 1,3,5-triazines from 4H-pyrido[1,3]oxazin-4-ones via a cyclocondensation process.

Pyridyl-substituted 1,3,5-triazines were synthesized in good to excellent yields via an unprecedented one-step cyclocondensation of 4H-pyrido[1,3]oxazin-4-ones with amidines at room temperature or under microwave irradiations. The broad applicability was demonstrated by 33 examples with a variety of amidines and three different 4H-pyrido[1,3]oxazin-4-one chemical series. In addition, a one-pot process from 4H-pyrido[1,3]oxazin-4-one precursors (imide sodium salts) was developed and led to the desired triazines compounds, thus allowing a one-step economy in their global synthetic preparation. This approach provides rapid access to pyridyl (or pyridone)-substituted 1,3,5-triazines with high potential in various fields of application.

Synthesis of bridgehead-substituted azabicyclo[2.2.1]heptane and -[3.3.1]nonane derivatives for the elaboration of α7 nicotinic ligands.

Azabicyclo[2.2.1]heptane and -[3.3.1]nonane scaffolds (X = Cl, Br) containing a pyridinyl substituent at the bridgehead position were prepared via two complementary chemical pathways, either by the transformation of a methoxy group into a synthetically valuable chlorine atom at the C-6 position of the pyridine moiety or by means of a regioselective C-6 deprotonation/halogenation process of the pyridine moiety exemplified by chlorination or bromination. These newly generated scaffolds were then engaged in Suzuki-Miyaura coupling reactions to provide α7 nicotinic ligands. Both chemical series were evaluated in vitro for their affinity at α7 nicotinic receptors, revealing nanomolar potency with significant selectivity over the α4ß2 nicotinic subtype. These approaches offer a general access to these α7 nicotinic scaffolds and ligands.

Validity, reliability and accuracy of inertial measurement units (IMUs) to measure angles: application in swimming.

The first objective was to test the validity, reliability and accuracy of paired inertial measurement units (IMUs) to assess absolute angles relative to Vicon and OptiTrack systems. The potential impacts of slow vs. rapid and intermittent vs. continuous movements were tested during 2D laboratory analyses and 3D ecological context analysis. The second objective was to test the IMUs alone in an ecological activity (i.e., front crawl) that encompassed the previous independent variables to quantify inter-cyclic variability. Slow and intermittent motion ensured high to reasonable validity, reliability and accuracy. Rapid motion revealed an out-of-phase pattern for temporal reliability and lower validity, which was also visible in 3D. Also, spatial reliability and accuracy decreased in 3D, mainly due to discrepancies in local maximums, whereas temporal reliability remained in-phase. For the second objective, inter-cyclic variability did not exceed 12° based on root mean square error (RMSE). Therefore, IMUs should be considered valuable supplements to optoelectronic systems if users carefully position the sensors in rigid clusters and calibrate them to integrate potential offsets. Drift correction by spline interpolation or normalisation of the absolute data should also be considered as additional techniques that increase IMU performance in ecological contexts of performance.

Lessons Learned in a Physician Referral to Pediatric Telemental Health Services Program.

BACKGROUND: This study explores the physician referral and engagement process of a pediatric telemental health program based in a large urban teaching children's hospital, and identifies the processes, strengths and challenges from the perspectives of Primary Care Physicians (PCPs) and telepsychiatrist consultants. METHODS: A mixed methods approach was used. This included an online survey completed by 43 PCPs in Ontario rural communities who had referred patients to the telemental health program. Qualitative interviews were conducted with 11 child/adolescent telepsychiatrists who provide consultations via teleconferencing. RESULTS: The majority of PCPs (61%) reported somewhat to moderate satisfaction with referral experiences. Challenges identified by physicians were related to communication and administration issues including: lack of timely follow-up appointments and continuity of care; lengthy referral forms; and recommendations for mental health services not accessible in their communities. Similarly, psychiatrist consultants expressed frustration with the sparse information they received from referring physicians and most significantly, the absence of appropriate service providers/professionals during the consultation to provide collateral information and ensure uptake of recommendations. CONCLUSION: Telemental health programs provide a valuable service to PCPs and their child and youth clients that could be significantly enhanced with a different consultation model. Such models of service delivery require protocols to educate PCPs, improve communication and information sharing and establish clear expectations between PCPs and telepsychiatry consultants.

CONTEXTE: Cette étude explore l'aiguillage d'un médecin et le processus de participation à un programme de télésanté mentale pédiatrique situé dans un vaste hôpital universitaire pour enfants en milieu urbain, et mentionne les processus, les forces et les difficultés du point de vue des médecins des soins de première ligne (MPL) et des télépsychiatres consultants. MÉTHODES: Une approche de méthodes mixtes a été utilisée, ce qui comprenait un sondage en ligne auquel ont répondu 43 MPL des communautés rurales de l'Ontario qui avaient aiguillé des patients au programme de télésanté mentale. Des entrevues qualitatives ont été menées auprès de 11 télépsychiatres de l'enfant et de l'adolescent qui offrent des consultations par téléconférence. RÉSULTATS: La majorité des MPL (61 %) ont déclaré une satisfaction de passable à modérée à l'égard des expériences d'aiguillage. Les difficultés identifiées par les médecins étaient liées aux enjeux de communication et d'administration, notamment l'absence de rendez-vous de suivi ponctuels et de continuité des soins; les formulaires d'aiguillage fastidieux; et les recommandations de services de santé mentale qui ne sont pas offerts dans leur communauté. De même, les psychiatres consultants ont exprimé leur frustration quant à l'information insuffisante reçue des médecins de l'aiguillage et surtout, en raison de l'absence de prestataires/professionnels appropriés durant la consultation qui apporteraient l'information collatérale et assureraient l'adoption des recommandations. CONCLUSION: Les programmes de télésanté mentale fournissent un service valable aux MPL et à leurs clients pédiatriques, mais ils pourraient être améliorés significativement par un modèle de consultation différent. Ces modèles de prestation des services exigent des protocoles pour éduquer les MPL, améliorer l'échange de communication et d'information, et établir des attentes bien définies entre MPL et consultants en télépsychiatrie.

Perception and action in swimming: Effects of aquatic environment on upper limb inter-segmental coordination.

This study assessed perception-action coupling in expert swimmers by focusing on their upper limb inter-segmental coordination in front crawl. To characterize this coupling, we manipulated the fluid flow and compared trials performed in a swimming pool and a swimming flume, both at a speed of 1.35ms-1. The temporal structure of the stroke cycle and the spatial coordination and its variability for both hand/lower arm and lower arm/upper arm couplings of the right body side were analyzed as a function of fluid flow using inertial sensors positioned on the corresponding segments. Swimmers' perceptions in both environments were assessed using the Borg rating of perceived exertion scale. Results showed that manipulating the swimming environment impacts low-order (e.g., temporal, position, velocity or acceleration parameters) and high-order (i.e., spatial-temporal coordination) variables. The average stroke cycle duration and the relative duration of the catch and glide phases were reduced in the flume trial, which was perceived as very intense, whereas the pull and push phases were longer. Of the four coordination patterns (in-phase, anti-phase, proximal and distal: when the appropriate segment is leading the coordination of the other), flume swimming demonstrated more in-phase coordination for the catch and glide (between hand and lower arm) and recovery (hand/lower arm and lower arm/upper arm couplings). Conversely, the variability of the spatial coordination was not significantly different between the two environments, implying that expert swimmers maintain consistent and stable coordination despite constraints and whatever the swimming resistances. Investigations over a wider range of velocities are needed to better understand coordination dynamics when the aquatic environment is modified by a swimming flume. Since the design of flumes impacts significantly the hydrodynamics and turbulences of the fluid flow, previous results are mainly related to the characteristics of the flume used in the present study (or a similar one), and generalization is subject to additional investigations.

Expeditive access to 2-substituted 4H-pyrido[1,3]oxazin-4-ones via an intramolecular O-arylation.

Unreported 2-substituted 4H-pyrido[e][1,3]oxazin-4-ones are synthesized via an unprecedented intramolecular O-arylation of N-aroyl- and N-heteroaroyl-(iso)nicotinamides under microwave irradiations, in good to excellent yields. The broad applicability was demonstrated by 24 examples with a variety of substituents at the 2-position of the final compounds and 3 possible positions for the nitrogen atom of the pyridine ring. In addition, transformation of one of these compounds into 2-hydroxypyridyl-substituted 1,2,4-triazole and 1,2,4-oxazinone was realized. This approach opens a rapid access to a new bicyclic heteroaromatic chemical series with high potential in medicinal chemistry.

Synthesis of new bridgehead substituted azabicyclo-[2.2.1]heptane and -[3.3.1]nonane derivatives as potent and selective α7 nicotinic ligands.

New azabicyclo[2.2.1]heptane and -[3.3.1]nonane derivatives containing a pyridinyl substituent at the bridgehead position have been synthesized via an efficient ten chemical steps pathway. Both chemical series were then evaluated in vitro for their affinity at α7 nicotinic receptors revealing nanomolar potency with notably excellent selectivity over the α4ß2 nicotinic subtype.