Publications by authors named "Forson Chan"

4 Publications

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Prenatal alcohol exposure and sleep-wake behaviors: exploratory and naturalistic observations in the clinical setting and in an animal model.

Sleep Med 2019 02 25;54:101-112. Epub 2018 Oct 25.

Department of Cellular & Physiological Sciences, Faculty of Medicine, University of British Columbia, Vancouver, BC, Canada.

Introduction: Clinical research and studies using animal models have revealed a complex and relatively under-explored interaction between prenatal alcohol exposure (PAE) and alterations in sleep-wake behaviors.

Objectives: To utilize a structured naturalistic observation-based methodology, consisting of descriptive elements, to provide insight into possible links between altered sleep and disruptive daytime presentations in children and adolescents with fetal alcohol spectrum disorder (FASD). To apply a similar structured behavioral observation protocol in a PAE animal model to compare outcomes from the experimental and clinical studies utilizing naturalistic observational methodology.

Methods: Forty pediatric patients with FASD (1.8-17.5 yrs, median age 9.4 yrs) and chronic sleep problems were assessed. In the PAE animal model, male offspring from PAE, Pair-Fed (PF), and ad libitum-fed Control (C) groups (n = 8/group) were assessed in the juvenile/preadolescent (23-25 days of age) and adolescent/pubertal (35-36 days of age) periods.

Results: In the clinical setting, we found that 95% of children with FASD showed disruptive or externalizing behaviors, 73% showed internalizing behaviors, 93% had circadian rhythm sleep disorders, all had chronic insomnia, and 85% had restless sleep, often with tossing/turning/kicking movements indicative of non-restorative sleep with hypermotor events. In the daytime, individuals showed excessive daytime sleepiness as well as hyperactive/hyperkinetic behaviors, an urge-to-move, and involuntary movements suggestive of hyperarousability. Alterations in sleep/wake behaviors in the PAE animal model paralleled the clinical data in many aspects, demonstrating greater sleep latencies, less total time asleep, more total time awake and longer awake bouts, more position changes, more time in transition, and longer transition bouts in PAE compared to PF and/or control animals.

Conclusions: Thus, our findings provide support for the power and validity of naturalistic observational paradigms in revealing dysregulated sleep-wake behaviors and their association and/or exacerbating relationship with day and nighttime behavioral problems, such as disruptive behaviors, externalizing and internalizing disorders, and daytime sleepiness.
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http://dx.doi.org/10.1016/j.sleep.2018.10.006DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7343292PMC
February 2019

A diagnosis of Stevens-Johnson Syndrome (SJS) in a patient presenting with superficial keratitis.

Am J Ophthalmol Case Rep 2018 Sep 19;11:167-169. Epub 2018 Jun 19.

Department of Ophthalmology and Visual Sciences, University of Alberta, 10240 Kingsway Avenue, Edmonton, T5H 3V9, AB, Canada.

Purpose: To describe a case of Stevens-Johnson syndrome (SJS) diagnosed in a patient presenting with primarily ocular findings where SJS had not been initially suspected.

Observations: A 23-year-old female presented with a 2 day history of bilateral eye pain, conjunctival injection, decreased visual acuity, and photophobia in the context of a 4 day history of fever, headache, and sore throat. She was found to have bilateral superficial keratitis and treated for suspected early infectious keratitis secondary to extended contact lens wear. She returned the next day with worsening visual symptoms, a new macular rash over her upper torso, and new ulcerating lesions over her buccal and perioral tissue. The patient was diagnosed with SJS. She was successfully treated using systemic cyclosporine with antibiotics and steroid eye drops.

Conclusions And Importance: Ophthalmologists may be the first physicians to diagnose SJS, a life-threatening condition that can initially present with non-specific viral prodromal symptoms and ocular signs alone. This case emphasizes the importance of considering a patient's entire clinical history, especially when the presentation is atypical and the diagnosis is not obviously apparent.
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http://dx.doi.org/10.1016/j.ajoc.2018.06.004DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6098186PMC
September 2018

High-content screening identifies a role for Na(+) channels in insulin production.

R Soc Open Sci 2015 Dec 2;2(12):150306. Epub 2015 Dec 2.

Department of Cellular and Physiological Sciences University of British Columbia Life Sciences Centre, 2350 Health Sciences Mall, Vancouver, British Columbia, Canada V6T 1Z3.

Insulin production is the central feature of functionally mature and differentiated pancreatic β-cells. Reduced insulin transcription and dedifferentiation have been implicated in type 2 diabetes, making drugs that could reverse these processes potentially useful. We have previously established ratiometric live-cell imaging tools to identify factors that increase insulin promoter activity and promote β-cell differentiation. Here, we present a single vector imaging tool with eGFP and mRFP, driven by the Pdx1 and Ins1 promoters, respectively, targeted to the nucleus to enhance identification of individual cells in a high-throughput manner. Using this new approach, we screened 1120 off-patent drugs for factors that regulate Ins1 and Pdx1 promoter activity in MIN6 β-cells. We identified a number of compounds that positively modulate Ins1 promoter activity, including several drugs known to modulate ion channels. Carbamazepine was selected for extended follow-up, as our previous screen also identified this use-dependent sodium channel inhibitor as a positive modulator of β-cell survival. Indeed, carbamazepine increased Ins1 and Ins2 mRNA in primary mouse islets at lower doses than were required to protect β-cells. We validated the role of sodium channels in insulin production by examining Nav1.7 (Scn9a) knockout mice and remarkably islets from these animals had dramatically elevated insulin content relative to wild-type controls. Collectively, our experiments provide a starting point for additional studies aimed to identify drugs and molecular pathways that control insulin production and β-cell differentiation status. In particular, our unbiased screen identified a novel role for a β-cell sodium channel gene in insulin production.
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http://dx.doi.org/10.1098/rsos.150306DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4807443PMC
December 2015

"Diagnosis by behavioral observation" home-videosomnography - a rigorous ethnographic approach to sleep of children with neurodevelopmental conditions.

Front Psychiatry 2015 17;6:39. Epub 2015 Mar 17.

Department of Linguistics, University of British Columbia , Vancouver, BC , Canada.

Introduction: Advanced video technology is available for sleep-laboratories. However, low-cost equipment for screening in the home setting has not been identified and tested, nor has a methodology for analysis of video recordings been suggested.

Methods: We investigated different combinations of hardware/software for home-videosomnography (HVS) and established a process for qualitative and quantitative analysis of HVS-recordings. A case vignette (HVS analysis for a 5.5-year-old girl with major insomnia and several co-morbidities) demonstrates how methodological considerations were addressed and how HVS added value to clinical assessment.

Results: We suggest an "ideal set of hardware/software" that is reliable, affordable (∼$500) and portable (=2.8 kg) to conduct non-invasive HVS, which allows time-lapse analyses. The equipment consists of a net-book, a camera with infrared optics, and a video capture device. (1) We present an HVS-analysis protocol consisting of three steps of analysis at varying replay speeds: (a) basic overview and classification at 16× normal speed; (b) second viewing and detailed descriptions at 4-8× normal speed, and (c) viewing, listening, and in-depth descriptions at real-time speed. (2) We also present a custom software program that facilitates video analysis and note-taking (Annotator(©)), and Optical Flow software that automatically quantifies movement for internal quality control of the HVS-recording. The case vignette demonstrates how the HVS-recordings revealed the dimension of insomnia caused by restless legs syndrome, and illustrated the cascade of symptoms, challenging behaviors, and resulting medications.

Conclusion: The strategy of using HVS, although requiring validation and reliability testing, opens the floor for a new "observational sleep medicine," which has been useful in describing discomfort-related behavioral movement patterns in patients with communication difficulties presenting with challenging/disruptive sleep/wake behaviors.
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http://dx.doi.org/10.3389/fpsyt.2015.00039DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4362082PMC
April 2015