Publications by authors named "Nathan Chan"

24 Publications

  • Page 1 of 1

Prevalence and Disease Spectrum of Extracoronary Arterial Abnormalities in Spontaneous Coronary Artery Dissection.

JAMA Cardiol 2021 Nov 24. Epub 2021 Nov 24.

Department of Cardiovascular Sciences, University of Leicester, NIHR Leicester Biomedical Research Centre, Glenfield Hospital, Leicester, United Kingdom.

Importance: Spontaneous coronary artery dissection (SCAD) has been associated with fibromuscular dysplasia (FMD) and other extracoronary arterial abnormalities. However, the prevalence, severity, and clinical relevance of these abnormalities remain unclear.

Objective: To assess the prevalence and spectrum of FMD and other extracoronary arterial abnormalities in patients with SCAD vs controls.

Design, Setting, And Participants: This case series included 173 patients with angiographically confirmed SCAD enrolled between January 1, 2015, and December 31, 2019. Imaging of extracoronary arterial beds was performed by magnetic resonance angiography (MRA). Forty-one healthy individuals were recruited to serve as controls for blinded interpretation of MRA findings. Patients were recruited from the UK national SCAD registry, which enrolls throughout the UK by referral from the primary care physician or patient self-referral through an online portal. Participants attended the national SCAD referral center for assessment and MRA.

Exposures: Both patients with SCAD and healthy controls underwent head-to-pelvis MRA (median time between SCAD event and MRA, 1 [IQR, 1-3] year).

Main Outcome And Measures: The diagnosis of FMD, arterial dissections, and aneurysms was established according to the International FMD Consensus. Arterial tortuosity was assessed both qualitatively (presence or absence of an S curve) and quantitatively (number of curves ≥45%; tortuosity index).

Results: Of the 173 patients with SCAD, 167 were women (96.5%); mean (SD) age at diagnosis was 44.5 (7.9) years. The prevalence of FMD was 31.8% (55 patients); 16 patients (29.1% of patients with FMD) had involvement of multiple vascular beds. Thirteen patients (7.5%) had extracoronary aneurysms and 3 patients (1.7%) had dissections. The prevalence and degree of arterial tortuosity were similar in patients and controls. In 43 patients imaged with both computed tomographic angiography and MRA, the identification of clinically significant remote arteriopathies was similar. Over a median 5-year follow-up, there were 2 noncardiovascular-associated deaths and 35 recurrent myocardial infarctions, but there were no primary extracoronary vascular events.

Conclusions And Relevance: In this case series with blinded analysis of patients with SCAD, severe multivessel FMD, aneurysms, and dissections were infrequent. The findings of this study suggest that, although brain-to-pelvis imaging allows detection of remote arteriopathies that may require follow-up, extracoronary vascular events appear to be rare.
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http://dx.doi.org/10.1001/jamacardio.2021.4690DOI Listing
November 2021

From Inter-Racial Solidarity to Action: Minority Linked Fate and African American, Latina/o, and Asian American Political Participation.

Polit Behav 2021 Sep 25:1-23. Epub 2021 Sep 25.

University of California Irvine, Irvine, USA.

Recent literature in race, ethnicity, and politics has assessed how minority linked fate, defined as "the idea that ethnoracial minorities might share a sense of commonality that extends beyond their particular ethnoracial group to other ethnoracial groups (Gershon et al., in Politics Groups Identities 7(3):642-653, 2019)," shapes attitudes toward descriptive representation and support for coalition building. However, scholarship has yet to examine the influence of minority linked fate on political participation. We argue that similar to those who view the interests of co-ethnics as a proxy for their individual interests, Latina/os, Asian Americans, and African Americans who express linked fate with a more expansive minority community are more likely to take political action. This political participation results from senses of obligation to and solidarity with other racial minorities outside of their own. Results from the 2016 Collaborative Multiracial Post-Election Survey show that controlling for conventional measures of linked fate, minority linked fate is associated primarily with more system-challenging modes of political activity for Latina/os, Asian Americans, and African Americans. We conclude by positioning minority linked fate as a complementary heuristic to traditional notions of intra-racial linked fate and note how shared inter-racial linked fate informs our understanding of recent political activism among people of color.

Supplementary Information: The online version contains supplementary material available at 10.1007/s11109-021-09750-6.
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http://dx.doi.org/10.1007/s11109-021-09750-6DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8475384PMC
September 2021

Risks and benefits of percutaneous coronary intervention in spontaneous coronary artery dissection.

Heart 2021 Sep 18;107(17):1398-1406. Epub 2021 May 18.

Department of Cardiovascular Sciences and NIHR Biomedical Research Centre, University of Leicester, Leicester, Leicestershire, UK

Objective: To investigate percutaneous coronary intervention (PCI) practice in an international cohort of patients with spontaneous coronary artery dissection (SCAD). To explore factors associated with complications and study angiographic and longer term outcomes.

Methods: SCAD patients (n=215, 94% female) who underwent PCI from three national cohort studies were investigated and compared with a matched cohort of conservatively managed SCAD patients (n=221).

Results: SCAD-PCI patients were high risk at presentation with only 8.8% undergoing PCI outside the context of ST-elevation myocardial infarction/cardiac arrest, thrombolysis in myocardial infarction (TIMI) 0/1 flow or proximal dissections. PCI complications occurred in 38.6% (83/215), with 13.0% (28/215) serious complications. PCI-related complications were associated with more extensive dissections (multiple vs single American Heart Association coronary segments, OR 1.9 (95% CI: 1.06-3.39),p=0.030), more proximal dissections (proximal diameter per mm, OR 2.25 (1.38-3.67), p=0.001) and dissections with no contrast penetration of the false lumen (Yip-Saw 2 versus 1, OR 2.89 (1.12-7.43), p=0.028). SCAD-PCI involved long lengths of stent (median 46mm, IQR: 29-61mm). Despite these risks, SCAD-PCI led to angiographic improvements in those with reduced TIMI flow in 84.3% (118/140). Worsening TIMI flow was only seen in 7.0% (15/215) of SCAD-PCI patients. Post-PCI major adverse cardiovascular and cerebrovascular events (MACCE) and left ventricular function outcomes were favourable.

Conclusion: While a conservative approach to revascularisation is favoured, SCAD cases with higher risk presentations may require PCI. SCAD-PCI is associated with longer stent lengths and a higher risk of complications but leads to overall improvements in coronary flow and good medium-term outcomes in patients.
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http://dx.doi.org/10.1136/heartjnl-2020-318914DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8372386PMC
September 2021

Aortic stenosis in the time of COVID-19: Development and outcomes of a rapid turnaround TAVI service.

Catheter Cardiovasc Interv 2021 09 10;98(3):E478-E482. Epub 2021 Feb 10.

Glenfield Hospital, University Hospitals, Leicester, Leicester, UK.

The COVID-19 pandemic has resulted in the cancellation of many elective surgical procedures. This has led to reports of an increase in mortality for patients with non-Covid health conditions due to delayed definitive management. Patients with severe aortic stenosis have a high annual mortality if left untreated. These patients are at risk due to the reduced number of surgical aortic valve replacements and competition for intensive care facilities during the COVID-19 pandemic. This case series suggests that the minimally invasive transcatheter aortic valve implantation is safe to continue during the COVID-19 pandemic with adjustments to the patient pathway to minimize hospital stay and to reduce patient and staff exposure. This helps to reduce the delay of definitive treatment for patients with severe aortic stenosis.
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http://dx.doi.org/10.1002/ccd.29550DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8014719PMC
September 2021

Structural Brain Differences Between Cognitively Impaired Patients With and Without Apathy.

Am J Geriatr Psychiatry 2021 04 13;29(4):319-332. Epub 2020 Dec 13.

Centre for Addiction and Mental Health (CAMH), Toronto, Ontario, Canada; Institute of Medical Science, University of Toronto, Toronto, Ontario, Canada; Department of Psychiatry, University of Toronto, Toronto, Ontario, Canada; Geriatric Mental Health Division, CAMH, University of Toronto, Toronto, Ontario, Canada; Campbell Family Mental Health Research Institute, CAMH, University of Toronto, Toronto, Ontario, Canada. Electronic address:

Objective: Since apathy increases in prevalence with severity of dementia pathology, we sought to distinguish concomitant neurodegenerative processes from brain differences associated with apathy in persons with mild cognitive impairment (MCI) and Alzheimer's Disease (AD). We examined relative structural brain differences between case-control matched cognitively impaired patients with and without apathy.

Design: Cross-sectional case-control study.

Setting: Fifty-eight clinical sites in phase 2 of the AD Neuroimaging Initiative across the United States and Canada.

Participants: The ≥ 55 years of age with MCI or AD dementia and no major neurological disorders aside from suspected incipient AD dementia. Participants with apathy (n=69) were age-, sex-, apolipoprotein E ε4 allele carrier status-, Mini-Mental State Exam score-, and MCI or AD dementia diagnosis-matched to participants without apathy (n=149).

Interventions: The 3-tesla T1-weighted MRI scan and neurocognitive assessments. Using the Neuropsychiatric Inventory apathy domain scores, participants were dichotomized into a with-apathy group (score ≥ 1) and a without-apathy group (score = 0).

Measurements: Cortical thicknesses from 24 a priori regions of interest involved in frontostriatal circuits and frontotemporal association areas.

Results: False-discovery rate adjusted within-group comparisons between participants with apathy and participants without apathy showed thinner right medial orbitofrontal (mOFC; meandifference(MD)±standarderrorofMD(SE)=-0.0879±0.0257mm; standardizedMD(d)=-0.4456) and left rostral anterior cingulate (rACC; MD±SE=-0.0905±0.0325mm; d=-0.3574) cortices and thicker left middle temporal cortices (MTC; MD±SE=0.0688±0.0239mm; d=0.3311) in those with apathy.

Conclusion: Atrophy of the right mOFC and left rACC and sparing of atrophy in the left MTC are associated with apathy in cognitively impaired persons.
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http://dx.doi.org/10.1016/j.jagp.2020.12.008DOI Listing
April 2021

Inhibiting α5 Subunit-Containing γ-Aminobutyric Acid Type A Receptors Attenuates Cognitive Deficits After Traumatic Brain Injury.

Crit Care Med 2020 04;48(4):533-544

Department of Physiology, University of Toronto, Toronto, ON, Canada.

Objectives: Cognitive deficits after traumatic brain injury are a leading cause of disability worldwide, yet no effective pharmacologic treatments exist to improve cognition. Traumatic brain injury increases proinflammatory cytokines, which trigger excess function of α5 subunit-containing γ-aminobutyric acid type A receptors. In several models of brain injury, drugs that inhibit α5 subunit-containing γ-aminobutyric acid type A receptor function improve cognitive performance. Thus, we postulated that inhibiting α5 subunit-containing γ-aminobutyric acid type A receptors would improve cognitive performance after traumatic brain injury. In addition, because traumatic brain injury reduces long-term potentiation in the hippocampus, a cellular correlate of memory, we studied whether inhibition of α5 subunit-containing γ-aminobutyric acid type A receptors attenuated deficits in long-term potentiation after traumatic brain injury.

Design: Experimental animal study.

Setting: Research laboratory.

Subjects: Adult male mice and hippocampal brain slices.

Interventions: Anesthetized mice were subjected to traumatic brain injury with a closed-head, free-weight drop method. One week later, the mice were treated with L-655,708 (0.5 mg/kg), an inhibitor that is selective for α5 subunit-containing γ-aminobutyric acid type A receptors, 30 minutes before undergoing behavioral testing. Problem-solving abilities were assessed using the puzzle box assay, and memory performance was studied with novel object recognition and object place recognition assays. In addition, hippocampal slices were prepared 1 week after traumatic brain injury, and long-term potentiation was studied using field recordings in the cornu Ammonis 1 region of slices that were perfused with L-655,708 (100 nM).

Measurements And Main Results: Traumatic brain injury increased the time required to solve difficult but not simple tasks in the puzzle box assay and impaired memory in the novel object recognition and object place recognition assays. L-655,708 improved both problem solving and memory in the traumatic brain injury mice. Traumatic brain injury reduced long-term potentiation in the hippocampal slices, and L-655,708 attenuated this reduction.

Conclusions: Pharmacologic inhibition of α5 subunit-containing γ-aminobutyric acid type A receptors attenuated cognitive deficits after traumatic brain injury and enhanced synaptic plasticity in hippocampal slices. Collectively, these results suggest that α5 subunit-containing γ-aminobutyric acid type A receptors are novel targets for pharmacologic treatment of traumatic brain injury-induced persistent cognitive deficits.
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http://dx.doi.org/10.1097/CCM.0000000000004161DOI Listing
April 2020

Glutamatergic neurometabolites and cortical thickness in treatment-resistant schizophrenia: Implications for glutamate-mediated excitotoxicity.

J Psychiatr Res 2020 05 5;124:151-158. Epub 2020 Mar 5.

Multimodal Imaging Group, Research Imaging Centre, Centre for Addiction and Mental Health (CAMH), Toronto, Ontario, Canada; Institute of Medical Science, University of Toronto, Toronto, Ontario, Canada; Department of Psychiatry, University of Toronto, Toronto, Ontario, Canada; Geriatric Mental Health Division, CAMH, University of Toronto, Toronto, Ontario, Canada; Campbell Family Mental Health Research Institute, CAMH, University of Toronto, Toronto, Ontario, Canada. Electronic address:

Treatment-resistant schizophrenia may be related to structural brain alterations. However, the mechanisms underlying these changes remain unclear. The present study had two main aims: (1) to explore differences in cortical thickness between patients with treatment-resistant schizophrenia non-responsive to clozapine (ultra-treatment-resistant schizophrenia, UTRS), patients with treatment-resistant schizophrenia responsive to clozapine (Cloz-Resp), patients responsive to first-line non-clozapine antipsychotics (FL-Resp), and healthy controls (HCs); and (2) to test our hypothesis of structural compromise as a manifestation of neurotoxic effects from elevated glutamate (Glu) (i.e. glutamate-mediated excitotoxicity) by examining the relationships between glutamatergic neurometabolite levels (Glu and glutamate + glutamine (Glx)) in the dorsal anterior cingulate cortex (dACC) and cortical thickness. T1-weighted images and H-MRS data were obtained from UTRS (n = 24), Cloz-Resp (n = 25), FL-Resp (n = 19), and HCs (n = 26). Vertex-wise analyses showed that patients with UTRS had widespread cortical thinning in the bilateral frontal, temporal, parietal, and occipital gyri compared to HCs and FL-Resp patients. In the patient group, negative associations were found between dACC Glx levels and cortical thickness in the right dorsolateral prefrontal cortex after correcting for multiple comparisons and controlling for age, sex, antipsychotic dose, and illness severity. In conclusion, glutamate-mediated excitotoxicity may be one of the mechanisms underlying structural compromise seen in treatment-resistant schizophrenia. Future studies should longitudinally examine the associations between glutamatergic neurometabolite levels and cortical thickness in the context of treatment and illness progression.
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http://dx.doi.org/10.1016/j.jpsychires.2020.02.032DOI Listing
May 2020

Anomalous origin of the three coronary arteries with separate ostia from right sinus of Valsalva in a young patient presenting with myocarditis: a very rare congenital anomaly.

Eur Heart J Case Rep 2019 Dec 22;3(4):1-2. Epub 2019 Oct 22.

Cardiology Department, Kettering General Hospital, Rothwell Road, Kettering, Northamptonshire NN168UZ, UK.

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http://dx.doi.org/10.1093/ehjcr/ytz186DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7042133PMC
December 2019

Isolated caecal necrosis-a case study.

BJR Case Rep 2019 Jun 13;5(2):20180089. Epub 2018 Nov 13.

Department of Radiology, Norfolk and Norwich University Hospitals NHS Foundation Trust, Norwich, UK.

A patient with right iliac fossa pain underwent CT angiography which demonstrated isolated caecal necrosis with associated superior mesenteric artery (SMA) stenosis. This was supported by colonoscopic findings and histopathological analysis. Isolated caecal necrosis is a rare presentation of ischaemic colitis.. Clinical and imaging findings of ischaemic colitis may mimic other pathologies. To improve diagnostic accuracy both referrers and radiologists should be aware of risk factors associated with ischaemic colitis. Isolated bowel wall thickening and pneumatosis of a colonic segment on CT are suggestive of focal bowel ischaemia, in the right clinical context.
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http://dx.doi.org/10.1259/bjrcr.20180089DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6726176PMC
June 2019

Resting-state functional connectivity in treatment response and resistance in schizophrenia: A systematic review.

Schizophr Res 2019 09 19;211:10-20. Epub 2019 Jul 19.

Multimodal Imaging Group, Research Imaging Centre, Centre for Addiction and Mental Health (CAMH), Toronto, Ontario, Canada; Institute of Medical Science, University of Toronto, Toronto, Ontario, Canada; Department of Psychiatry, University of Toronto, Toronto, Ontario, Canada; Geriatric Mental Health Division, CAMH, University of Toronto, Toronto, Ontario, Canada; Campbell Family Mental Health Research Institute, CAMH, University of Toronto, Toronto, Ontario, Canada. Electronic address:

Background: Treatment-resistant schizophrenia (TRS) and treatment-responsive schizophrenia may exhibit distinct pathophysiology. Several functional magnetic resonance imaging (fMRI) studies have used resting-state functional connectivity analyses (rs-FC) in TRS patients to identify markers of treatment resistance. However, to date, existing findings have not been systematically evaluated.

Methods: A systematic literature search using Embase, MEDLINE, PsycINFO, ProQuest, PUBMED, and Scopus was performed. The query sought fMRI articles investigating rs-FC in treatment response or resistance in patients with schizophrenia. Only studies that examined treatment response, operationalized as the explicit categorization of patients by their response to antipsychotic medication, were considered eligible. Pairwise comparisons between patient groups and controls were extracted from each study.

Results: The search query identified 159 records. Ten studies met inclusion criteria. Five studies examined not TRS (NTRS), and 8 studies examined TRS. Differences in rs-FC analysis methodology precluded direct comparisons between studies. However, disruptions in areas involved in visual and auditory information processing were implicated in both patients with TRS and NTRS. Changes in connectivity with sensorimotor network areas tended to appear in the context of TRS but not NTRS. Moreover, there was some indication that this connectivity could be affected by clozapine.

Conclusions: Functional connectivity may provide clinically meaningful biomarkers of treatment response and resistance in schizophrenia. Studies generally identified similar areas of disruption, though methodological differences largely precluded direct comparison between disruption effects. Implementing data sharing as standard practice will allow future reviews and meta-analyses to identify rs-FC correlates of TRS.
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http://dx.doi.org/10.1016/j.schres.2019.07.020DOI Listing
September 2019

3D printed coaxial nozzles for the extrusion of hydrogel tubes toward modeling vascular endothelium.

Biofabrication 2019 07 12;11(4):045009. Epub 2019 Jul 12.

Department of Chemistry, University of Washington, Seattle, WA, United States of America.

Engineered tubular constructs made from soft biomaterials are employed in a myriad of applications in biomedical science. Potential uses of these constructs range from vascular grafts to conduits for enabling perfusion of engineered tissues and organs. The fabrication of standalone tubes or complex perfusable constructs from biofunctional materials, including hydrogels, via rapid and readily accessible routes is desirable. Here we report a methodology in which customized coaxial nozzles are 3D printed using commercially available stereolithography (SLA) 3D printers. These nozzles can be used for the fabrication of hydrogel tubes via coextrusion of two shear-thinning hydrogels: an unmodified Pluronic F-127 (F127) hydrogel and an F127-bisurethane methacrylate (F127-BUM) hydrogel. We demonstrate that different nozzle geometries can be modeled via computer-aided design and 3D printed in order to generate tubes or coaxial filaments with different cross-sectional geometries. We were able to fabricate tubes with luminal diameters or wall thicknesses as small as ∼150 μm. Finally, we show that these tubes can be functionalized with collagen I to enable cell adhesion, and human umbilical vein endothelial cells can be cultured on the luminal surfaces of these tubes to yield tubular endothelial monolayers. Our approach could enable the rapid fabrication of biofunctional hydrogel conduits which can ultimately be utilized for engineering in vitro models of tubular biological structures.
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http://dx.doi.org/10.1088/1758-5090/ab2b4dDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7350911PMC
July 2019

Alterations in body mass index and waist-to-hip ratio in never and minimally treated patients with psychosis: A systematic review and meta-analysis.

Schizophr Res 2019 06 23;208:420-429. Epub 2019 Jan 23.

Multimodal Imaging Group, Research Imaging Centre, Centre for Addiction and Mental Health (CAMH), Toronto, Ontario, Canada; Institute of Medical Science, University of Toronto, Toronto, Ontario, Canada; Department of Psychiatry, University of Toronto, Toronto, Ontario, Canada; Geriatric Mental Health Division, CAMH, University of Toronto, Toronto, Ontario, Canada; Campbell Family Mental Health Research Institute, CAMH, University of Toronto, Toronto, Ontario, Canada. Electronic address:

Background: Obesity is up to 4 times higher in patients with schizophrenia than in the general population. However, the link between obesity and schizophrenia in the absence of antipsychotic use is unclear. Therefore, we aimed to examine differences in obesity measures (body mass index (BMI), waist circumference (WC), and waist-to-hip ratio (WHR)) in antipsychotic-naive and minimally treated (up to 2 weeks of lifetime antipsychotic exposure) patients with psychosis compared to healthy controls (HCs).

Methods: A systematic search was conducted using Ovid Medline®, PsycINFO, and Embase. Standardized mean differences (SMDs) in obesity measures between groups were calculated. Separate sensitivity analyses were performed to examine the effects of age, sex, and ethnicity; antipsychotic exposure; and schizophrenia-related psychosis on SMDs.

Results: A total of 23 studies were included in the meta-analysis (BMI = 23, WC = 9, WHR = 5). BMI was lower (SMD = -0.19, 95% CI = -0.34 to -0.05, P = 0.009) and WHR was elevated (SMD = 0.34, 95% CI = 0.14 to 0.55, P = 0.001) in patients. These differences remained after analyses were restricted to patients matched with HCs for age, sex, and ethnicity; to antipsychotic-naive patients; and to patients with schizophrenia-related diagnoses.

Conclusions: Differences in BMI and WHR were observed in never and minimally treated patients with psychosis compared to HCs. Future research is warranted to understand these alterations in the context of body fat biomarkers and neuropathology of psychiatric disorders, independent of the effects of antipsychotics.
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http://dx.doi.org/10.1016/j.schres.2019.01.005DOI Listing
June 2019

Implanted Nanosensors in Marine Organisms for Physiological Biologging: Design, Feasibility, and Species Variability.

ACS Sens 2019 01 11;4(1):32-43. Epub 2018 Dec 11.

Red Sea Research Center, Division of Biological and Environmental Sciences and Engineering , King Abdullah University of Science and Technology , Thuwal 23955-6900 , Saudi Arabia.

In recent decades, biologists have sought to tag animals with various sensors to study aspects of their behavior otherwise inaccessible from controlled laboratory experiments. Despite this, chemical information, both environmental and physiological, remains challenging to collect despite its tremendous potential to elucidate a wide range of animal behaviors. In this work, we explore the design, feasibility, and data collection constraints of implantable, near-infrared fluorescent nanosensors based on DNA-wrapped single-wall carbon nanotubes (SWNT) embedded within a biocompatible poly(ethylene glycol) diacrylate (PEGDA) hydrogel. These sensors are enabled by Corona Phase Molecular Recognition (CoPhMoRe) to provide selective chemical detection for marine organism biologging. Riboflavin, a key nutrient in oxidative phosphorylation, is utilized as a model analyte in in vitro and ex vivo tissue measurements. Nine species of bony fish, sharks, eels, and turtles were utilized on site at Oceanogràfic in Valencia, Spain to investigate sensor design parameters, including implantation depth, sensor imaging and detection limits, fluence, and stability, as well as acute and long-term biocompatibility. Hydrogels were implanted subcutaneously and imaged using a customized, field-portable Raspberry Pi camera system. Hydrogels could be detected up to depths of 7 mm in the skin and muscle tissue of deceased teleost fish ( Sparus aurata and Stenotomus chrysops) and a deceased catshark ( Galeus melastomus). The effects of tissue heterogeneity on hydrogel delivery and fluorescence visibility were explored, with darker tissues masking hydrogel fluorescence. Hydrogels were implanted into a living eastern river cooter ( Pseudemys concinna), a European eel ( Anguilla anguilla), and a second species of catshark ( Scyliorhinus stellaris). The animals displayed no observable changes in movement and feeding patterns. Imaging by high-resolution ultrasound indicated no changes in tissue structure in the eel and catshark. In the turtle, some tissue reaction was detected upon dissection and histopathology. Analysis of movement patterns in sarasa comet goldfish ( Carassius auratus) indicated that the hydrogel implants did not affect swimming patterns. Taken together, these results indicate that this implantable form factor is a promising technique for biologging using aquatic vertebrates with further development. Future work will tune the sensor detection range to the physiological range of riboflavin, develop strategies to normalize sensor signal to account for the optical heterogeneity of animal tissues, and design a flexible, wearable device incorporating optoelectronic components that will enable sensor measurements in moving animals. This work advances the application of nanosensors to organisms beyond the commonly used rodent and zebrafish models and is an important step toward the physiological biologging of aquatic organisms.
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http://dx.doi.org/10.1021/acssensors.8b00538DOI Listing
January 2019

Dexmedetomidine Prevents Excessive γ-Aminobutyric Acid Type A Receptor Function after Anesthesia.

Anesthesiology 2018 09;129(3):477-489

From the Departments of Physiology (D.-S.W., K.K., G.L., F.M., J.W., I.L., Y.-F.X., N.K.C., A.F.-E., A.J.R., B.A.O.) Anesthesia (A.S., B.A.O.) Pharmacology and Toxicology (A.J.R.) Ophthalmology and Vision Science (J.M.S.) the Leslie Dan Faculty of Pharmacy (Y.-F.X., R.P.B.) University of Toronto, Toronto, Ontario, Canada; the Department of Anesthesia, Sunnybrook Health Sciences Centre, Toronto, Ontario, Canada (S.A., B.A.O.) the Center for Neuroscience and Connectomics, Korea Institute of Science and Technology, Seoul, Korea (J.W., C.J.L.) the Division of Vision Sciences, Krembil Research Institute, University Health Network, Toronto, Ontario, Canada (D.C., J.M.S.).

What We Already Know About This Topic: WHAT THIS ARTICLE TELLS US THAT IS NEW: BACKGROUND:: Postoperative delirium is associated with poor long-term outcomes and increased mortality. General anesthetic drugs may contribute to delirium because they increase cell-surface expression and function of α5 subunit-containing γ-aminobutyric acid type A receptors, an effect that persists long after the drugs have been eliminated. Dexmedetomidine, an α2 adrenergic receptor agonist, prevents delirium in patients and reduces cognitive deficits in animals. Thus, it was postulated that dexmedetomidine prevents excessive function of α5 γ-aminobutyric acid type A receptors.

Methods: Injectable (etomidate) and inhaled (sevoflurane) anesthetic drugs were studied using cultured murine hippocampal neurons, cultured murine and human cortical astrocytes, and ex vivo murine hippocampal slices. γ-Aminobutyric acid type A receptor function and cell-signaling pathways were studied using electrophysiologic and biochemical methods. Memory and problem-solving behaviors were also studied.

Results: The etomidate-induced sustained increase in α5 γ-aminobutyric acid type A receptor cell-surface expression was reduced by dexmedetomidine (mean ± SD, etomidate: 146.4 ± 51.6% vs. etomidate + dexmedetomidine: 118.4 ± 39.1% of control, n = 8 each). Dexmedetomidine also reduced the persistent increase in tonic inhibitory current in hippocampal neurons (etomidate: 1.44 ± 0.33 pA/pF, n = 10; etomidate + dexmedetomidine: 1.01 ± 0.45 pA/pF, n = 9). Similarly, dexmedetomidine prevented a sevoflurane-induced increase in the tonic current. Dexmedetomidine stimulated astrocytes to release brain-derived neurotrophic factor, which acted as a paracrine factor to reduce excessive α5 γ-aminobutyric acid type A receptor function in neurons. Finally, dexmedetomidine attenuated memory and problem-solving deficits after anesthesia.

Conclusions: Dexmedetomidine prevented excessive α5 γ-aminobutyric acid type A receptor function after anesthesia. This novel α2 adrenergic receptor- and brain-derived neurotrophic factor-dependent pathway may be targeted to prevent delirium.
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http://dx.doi.org/10.1097/ALN.0000000000002311DOI Listing
September 2018

Duodenal Cannulation in Pigs () as a Drug Delivery Method.

Comp Med 2018 02;68(1):48-55

Surgical and Interventional Research Laboratories of Tufts Medical Center and Division of Laboratory Animal Medicine, Tufts University, Boston, Massachusetts.

Currently available animal models for delivery of drug capsules and pharmacokinetic testing are limited by either intersubject variability in gastric emptying time or the need to sedate animals when using targeted delivery methods of drug capsules. With the increasing development of large-molecule biologics, better in vivo models for testing the pharmacokinetics of capsule-delivered drugs are urgently needed. To this end, we made engineering modifications to an existing bovine surgical cannula device, successfully implanted this modified cannula into pigs, and delivered drug capsules directly to the proximal duodenum. In our porcine model, capsule insertion and serial blood samples were all acquired without the use of sedatives. Furthermore, we were able to maintain cannulated pigs for weekly pharmacokinetic testing for more than 18 mo, with minimal postoperative complications. This study demonstrates a novel and effective porcine model of sedation-free drug delivery and blood collection that eliminates inconsistencies associated with models that require either gastric emptying or animal sedation.
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http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5824139PMC
February 2018

Age-specific trends of atrial fibrillation-related ischaemic stroke and transient ischaemic attack, anticoagulant use and risk factor profile in Chinese population: a 15-year study.

J Neurol Neurosurg Psychiatry 2017 09 26;88(9):744-748. Epub 2017 May 26.

Department of Medicine and Therapeutics, Prince of Wales Hospital, The Chinese University of Hong Kong, Hong Kong.

Background: Prevalence of atrial fibrillation (AF) is increasing globally, and the fivefold increase in stroke risk constitutes significant healthcare burden.

Aims: We aim to evaluate the trends of AF-related stroke and transient ischaemic attack (AF-stroke/TIA), prior anticoagulant use and their risk factors in different age groups in Chinese population.

Methods: Data were retrieved from the stroke registry at Prince of Wales Hospital. We compared the data at 5-year intervals over a 15-year period (years 1999, 2004, 2009 and 2014).

Results: A total of 3894 patients were included, 712 patients had AF-stroke/TIA. Over the 15 years, the total number of ischaemic stroke/TIA fluctuated slightly during the period from year 1999 to 2009, and increased by 21.5% in the year 2014. While AF-stroke/TIA increased continuously with time by 282.1%. Increasing trend of AF-stroke/TIA was observed in all age groups. Absolute growth was highest in patients aged ≥80 years; relative growth was most pronounced in those between 65 and 72 years (>3.5 fold increase). Throughout the 15 years, >70% of AF-stroke/TIA occurred in non-anticoagulated patients, and this proportion increased with age. Increasing trends in both hypertension and ischaemic heart disease were also observed in patients with AF aged ≥73 years.

Conclusion: AF-stroke/TIA has increased continuously by >2.5 fold in Chinese population over a 15-year period, with the majority of AF-stroke/TIA occurring in non-anticoagulated patients. Strategic planning is needed to optimise anticoagulant use, particularly non-vitamin K antagonist oral anticoagulants in elderly patients, low-income group and those with ischaemic heart disease requiring concomitant antiplatelet therapy.
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http://dx.doi.org/10.1136/jnnp-2017-315735DOI Listing
September 2017

A rare case of a chest wall abscess caused by a migrating oesophageal stent. An iatrogenic gastrocutaneous fistula.

BJR Case Rep 2017 30;3(3):20160138. Epub 2017 Mar 30.

Department of Radiology and General Surgical , Epsom and St Helier's NHS Trust, Epsom, England, UK.

We report the case of a 65-year-old male, who presented with septicaemia and a chest wall mass on a background of oesophageal carcinoma. This chest wall mass measured 10 cm by 10 cm, was fluctuant, and was situated on the anterior chest wall. Owing to local erythema and surgical emphysema, necrotising fasciitis was suspected and thus intravenous antibiotic and fluid therapy were instituted. Following a chest radiograph, which confirmed the presence of subcutaneous gas, the patient underwent thoraco-abdomino-pelvic CT, which demonstrated oesophageal stent migration through the gastric fundus to the chest wall, between the 10th and 11th left ribs. Through this migration tract, the chest wall was contaminated with gastric contents, accounting for the mass and sepsis. The patient underwent endoscopic stent removal, and incision and drainage to create a gastrocutaneous fistula. Additionally, a nasojejunal tube and intravenous line were sited for jejunal and total parenteral nutrition, respectively, in order to promote healing of the fistula.
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http://dx.doi.org/10.1259/bjrcr.20160138DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6159195PMC
March 2017

Hypoglossal dural arteriovenous fistula: a rare cause of unilateral hypoglossal nerve palsy.

BJR Case Rep 2017 10;3(3):20160144. Epub 2017 Mar 10.

Department of Anatomy and Human Sciences, King's College, University of London, London, UK.

Ms Y, a 57-year-old female presented with a 1-week history of tongue deviation. The history of the presenting complaint also included minor dysarthria, dysphagia for solids and liquids as well as a 2- to 3-month history of pulsatile tinnitus affecting the right ear. Examination of the cranial and peripheral nerves revealed a right hypoglossal nerve lower motor neurone palsy. MRI demonstrated a dural arteriovenous fistula (DAVF) in the region of the right hypoglossal canal. She underwent a cerebral angiogram, which confirmed a hypoglossal DAVF with predominant supply from the neuromeningeal branches of the right ascending pharyngeal artery. She has been able to cope with her symptoms and remains on active surveillance. Hypoglossal nerve palsy is uncommon, causes may be classified according to location. DAVFs are a rare cause of hypoglossal nerve palsy. DAVFs can be graded according to their pattern of venous drainage. This case illustrates the complex venous anatomy of the craniocervical junction, which enables postural-dependent drainage through the internal jugular and vertebral venous systems. This network of veins is encountered during interventional radiology procedures and neurosurgical skull base approaches.
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http://dx.doi.org/10.1259/bjrcr.20160144DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6159185PMC
March 2017

Colonoscopy after CT-diagnosed acute diverticulitis: Is it really necessary?

Can J Surg 2015 Aug;58(4):226-31

From the Department of Medicine, Division of Gastroenterology (Ou, Rosenfield, Bressler) and the Department of Radiology (Brown), St. Paul's Hospital, University of British Columbia, Vancouver, BC; the Department of Medicine, Vancouver General Hospital, University of British Columbia, Vancouver, BC (Chan); the Department of Family Medicine, University of Calgary, Calgary, Alta (Hong); and the Department of Medical Oncology, British Columbia Cancer Agency, University of British Columbia, Vancouver, BC (Lim).

Background: Computed tomography (CT) scans are commonly used to diagnose acute diverticulitis, but there are overlapping features between diverticulitis and colorectal cancer (CRC) on imaging studies. Hence, colonoscopy is typically recommended after an episode of acute diverticulitis to rule out underlying malignancy. Currently, 64-slice multidetector CT scanners are capable of providing higher-resolution images and may be able to distinguish malignancy from diverticular inflammation. We aimed to determine the prevalence of CRC among patients with CT-diagnosed acute diverticulitis.

Methods: We performed a retrospective study of patients with acute diverticulitis diagnosed on CT scan between December 2005 and December 2010 at St. Paul's Hospital, Vancouver, BC. Nonresidents were excluded. We reviewed CT scan reports that included the term "diverticulitis," reports of follow-up colonic evaluation within 1 year of diagnosis and pathology results. We queried the provincial cancer registry to ensure no cases of CRC were missed.

Results: A total of 293 patients had acute diverticulitis diagnosed on CT scan, but 8 were nonresidents and were excluded. Of the 285 included in the analysis, the mean age was 59.4 ± 15.1 years, and 167 (58.6%) were men. Among the 114 patients who underwent follow-up evaluation, malignancy was diagnosed in 4 (3.5%). The overall prevalence of malignancy among patients with CT-diagnosed diverticulitis was 1.4%.

Conclusion: Routine endoscopic evaluation after an episode of diverticulitis diagnosed with high-resolution CT scan does not appear to be necessary. Selective approach in patients with protracted clinical course or those with mass lesion/obstruction on CT scan may be of benefit.
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http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4512863PMC
http://dx.doi.org/10.1503/cjs.014514DOI Listing
August 2015

Moyamoya disease in a patient with neuromyelitis optica.

Oxf Med Case Reports 2014 Apr 8;2014(1):13-5. Epub 2014 Apr 8.

Department of Medicine & Therapeutics , Chinese University of Hong Kong, Prince of Wales Hospital , Shatin , Hong Kong.

Moyamoya disease can be associated with autoimmune disease such as thyrotoxicosis, but there has been only one report of association with neuromyelitis optica (NMO). We report another case of this combination with the presence of anti-SSA antibody in addition to the NMO-immunoglobulin G. The patient presented limb weakness along with unsteady gait and numbness. A magnetic resonance imaging (MRI) of the spine showed extensive intramedullary hyperintense signals at C2 to T3 levels. On the other hand, no lesions were found on the MRI of the brain. The patient tested positive for anti-aquaporin-4 antibody and anti-SSA antibody which confirms the diagnosis of NMO. A magnetic resonance angiography scan of the brain revealed a bilateral distal occlusion of the internal carotid arteries (ICAs) as well as occlusions of the middle cerebral arteries (MCAs) with fine collaterals in the region which confirms the diagnosis of moyamoya disease. This report suggests that autoimmunity may be an important factor in the pathogenesis of moyamoya disease in some patients.
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http://dx.doi.org/10.1093/omcr/omu006DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4369969PMC
April 2014

A urea channel from Bacillus cereus reveals a novel hexameric structure.

Biochem J 2012 Jul;445(2):157-66

Astbury Centre for Structural Molecular Biology, Institute of Membrane and Systems Biology, University of Leeds, Leeds LS2 9JT, U.K.

Urea is exploited as a nitrogen source by bacteria, and its breakdown products, ammonia and bicarbonate, are employed to counteract stomach acidity in pathogens such as Helicobacter pylori. Uptake in the latter is mediated by UreI, a UAC (urea amide channel) family member. In the present paper, we describe the structure and function of UACBc, a homologue from Bacillus cereus. The purified channel was found to be permeable not only to urea, but also to other small amides. CD and IR spectroscopy revealed a structure comprising mainly α-helices, oriented approximately perpendicular to the membrane. Consistent with this finding, site-directed fluorescent labelling indicated the presence of seven TM (transmembrane) helices, with a cytoplasmic C-terminus. In detergent, UACBc exists largely as a hexamer, as demonstrated by both cross-linking and size-exclusion chromatography. A 9 Å (1 Å=0.1 nm) resolution projection map obtained by cryo-electron microscopy of two-dimensional crystals shows that the six protomers are arranged in a planar hexameric ring. Each exhibits six density features attributable to TM helices, surrounding a putative central channel, while an additional helix is peripherally located. Bioinformatic analyses allowed individual TM regions to be tentatively assigned to the density features, with the resultant model enabling identification of residues likely to contribute to channel function.
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http://dx.doi.org/10.1042/BJ20120169DOI Listing
July 2012

Prevalence of primary and revision total hip and knee arthroplasty in the United States from 1990 through 2002.

J Bone Joint Surg Am 2005 Jul;87(7):1487-97

Exponent Inc., 3401 Market Street, Suite 300, Philadelphia, PA 19104, USA.

Background: The purpose of this study was to quantify the procedural rate and revision burden of total hip and knee arthroplasty in the United States and to determine if the age or gender-based procedural rates and overall revision burden are changing over time.

Methods: The National Hospital Discharge Survey (NHDS) for 1990 through 2002 was used in conjunction with United States Census data to quantify the rates of primary and revision arthroplasty as a function of age and gender within the United States with use of methodology published by the American Academy of Orthopaedic Surgeons. Poisson regression analysis was used to evaluate the procedural rate and to determine year-to-year trends in primary and revision arthroplasty rates as a function of both age and gender.

Results: Both the number and the rate of total hip and knee arthroplasties (particularly knee arthroplasties) increased steadily between 1990 and 2002. Over the thirteen years, the rate of primary total hip arthroplasties per 100,000 persons increased by approximately 50%, whereas the corresponding rate of primary total knee arthroplasties almost tripled. The rate of revision total hip arthroplasties increased by 3.7 procedures per 100,000 persons per decade, and that of revision total knee arthroplasties, by 5.4 procedures per 100,000 persons per decade. However, the mean revision burden of 17.5% for total hip arthroplasty was more than twice that for total knee arthroplasty (8.2%), and this did not change substantially over time.

Conclusions: The number and prevalence of primary hip and knee replacements increased substantially in the United States between 1990 and 2002, but the trend was considerably more pronounced for primary total knee arthroplasty.

Clinical Relevance: The reported prevalence trends have important ramifications with regard to the number of joint replacements expected to be performed by orthopaedic surgeons in the future. Because the revision burden has been relatively constant over time, we can expect that a greater number of primary replacements will result in a greater number of revisions unless some limiting mechanism can be successfully implemented to reduce the future revision burden.
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http://dx.doi.org/10.2106/JBJS.D.02441DOI Listing
July 2005

Palmitoyl lysophosphatidylcholine mediated mobilization of LPL to the coronary luminal surface requires PKC activation.

J Mol Cell Cardiol 2004 Nov;37(5):931-8

Division of Pharmacology and Toxicology, Faculty of Pharmaceutical Sciences, The University of British Columbia, 2146 East Mall, Vancouver, BC, Canada V6T 1Z3.

Following diazoxide (DZ) induced hypoinsulinemia, cardiac luminal lipoprotein lipase (LPL) increases [Cardiovasc. Res. 3 (2003) 788]. To identify circulating mediators that maintain high LPL in vivo, DZ hearts were perfused for 1 h in the presence or absence of glucose, triglyceride (TG), palmitic acid or palmitoyl lysophosphatidylcholine (PLPC). Only PLPC maintained high luminal LPL in DZ hearts, likely through enzyme recruitment from the cardiomyocyte. PLPC perfusion activated whole heart protein kinase C (PKC) epsilon. As calphostin pretreatment blocked PLPC induced PKC activation, and increases in luminal LPL activity, PKC activation is essential for the effects of PLPC. Incubation of myocytes with PLPC had no effects on either surface or intracellular LPL or PKC suggesting that PKC activation occurs in cells other than the myocyte or that metabolism of PLPC is required for its downstream effects. Since exposure of endothelial cells to PLPC activated PKC, whole heart PKC activation likely occurred in these cells. Incubation of myocytes with LPA, a phospholipase D (PLD) mediated breakdown metabolite of PLPC, significantly enhanced basal and heparin-releasable myocyte LPL activity, an effect that was duplicated by co-incubation of control myocytes with exogenous PLD and PLPC. Our data suggest that at least in the whole heart, the LPL augmenting property of PLPC likely requires endothelial PKC activation, formation of LPA, and mobilization of enzyme from the myocyte to the coronary lumen.
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http://dx.doi.org/10.1016/j.yjmcc.2004.07.003DOI Listing
November 2004

Evidence for rapid "metabolic switching" through lipoprotein lipase occupation of endothelial-binding sites.

J Mol Cell Cardiol 2003 Sep;35(9):1093-103

Division of Pharmacology and Toxicology, Faculty of Pharmaceutical Sciences, University of British Columbia, 2146 East Mall, Vancouver, British Columbia, Canada V6T 1Z3.

During diabetes, impaired glucose transport and utilization by the heart switches energy production to exclusive beta-oxidation of fatty acid (FA). In the current study, we examined the contribution of cardiac lipoprotein lipase (LPL) towards providing FA to the diabetic heart. Streptozotocin (STZ) caused an augmentation of LPL activity at the coronary lumen, an effect duplicated by diazoxide (DZ). With DZ, the amplification of LPL at the coronary luminal surface was determined to be exceptionally rapid. Interestingly, unlike DZ, the capability of hearts from STZ animals to maintain this amplified LPL activity was sustained in vitro. This increased enzyme in the hyperglycemic heart is likely unrelated to an increase in the number of capillary endothelial LPL-binding sites. Our data imply that binding sites for LPL in the control rat heart are only partly occupied by the enzyme and diabetes rapidly initiates filling of all of these sites. Phloridzin treatment of STZ animals normalized plasma glucose with no effect on luminal LPL suggesting that the effects of diabetes on LPL are also largely independent of changes in blood glucose. Both 2 and 8 U of insulin normalized plasma glucose in DZ-treated animals but only 8 U reversed DZ-induced augmentation of cardiac luminal LPL. Our data suggest that impaired intracellular glucose utilization allows rapid vectorial transfer of LPL to unoccupied binding sites to supply the diabetic heart with excess FA. The persistence of increased coronary luminal LPL even in a setting of normoglycemia may provide excessive FA to the diabetic heart with deleterious consequences over the long term.
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http://dx.doi.org/10.1016/s0022-2828(03)00205-0DOI Listing
September 2003
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