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Recommendations for Patients with Complex Nerve Injuries during the COVID-19 Pandemic
- Kristine M. Chapman, Michael J. Berger, Christopher Doherty, Dimitri J. Anastakis, Heather L. Baltzer, Kirsty Usher Boyd, Sean G. Bristol, Brett Byers, K. Ming Chan, Cameron J.B. Cunningham, Kristen M. Davidge, Jana Dengler, Kate Elzinga, Jennifer L. Giuffre, Lisa Hadley, A Robertson Harrop, Mahdis Hashemi, J. Michael Hendry, Kristin L. Jack, Emily M. Krauss, Timothy J. Lapp, Juliana Larocerie, Jenny C. Lin, Thomas A. Miller, Michael Morhart, Christine B. Novak, Russell O’Connor, Jaret L. Olsen, Benjamin R. Ritsma, Lawrence R. Robinson, Douglas C. Ross, Christiaan Schrag, Alexander Seal, David T. Tang, Jessica Trier, Gerald Wolff, Justin Yeung
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- Journal:
- Canadian Journal of Neurological Sciences / Volume 48 / Issue 1 / January 2021
- Published online by Cambridge University Press:
- 27 August 2020, pp. 50-55
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4468 Evaluating the Emerging Investigators Website as an Educational Resource for Early Career Researchers
- Layla Fattah, Inga Peter, Jenny Lin, Janice Lynn Gabrilove
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- Journal:
- Journal of Clinical and Translational Science / Volume 4 / Issue s1 / June 2020
- Published online by Cambridge University Press:
- 29 July 2020, pp. 61-62
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OBJECTIVES/GOALS: The aim of this project is to assess the usability and acceptance of a web-based educational resource for early career researchers. The Emerging Investigators website is designed to bring together resources, provide educational support and foster a community of early career researchers throughout the Mount Sinai Health System (MSHS). Locally designed and built, this web-based platform is developed using the principles of Community of Inquiry (COI), which considers how the design of online learning environments might best create and sustain a sense of community among learners. Developing a resource that meets the needs of this cohort of researchers requires an iterative implementation strategy guided by user feedback. A formal website roll-out strategy and accompanied evaluation aims to determine the design, navigability, content, relevance and educational value of this online resource from a user perspective. METHODS/STUDY POPULATION: In order to ensure this resource effectively meets the needs of this cohort of researchers, a mixed process of evaluation and design was utilized. An initial phase 1 survey was conducted with TL1 and KL2 scholars. Surveys consisted of standardized questions with answers arranged as Likert-type scales and additional written responses to collect valuable qualitative data. A convenience sample of early career researchers at Mount Sinai were contacted for initial survey participation (N = 10). A total of 3 junior faculty KL2 scholars, 3 TL1 post-doc and 4 TL1 pre-doc scholars responded to the survey. Participants were initially asked to comment on design, functionality and usefulness of content on a Likert scale with qualitative comments to support the given scores. They were subsequently asked to consider what key topics or resources were missing from the website. Based on the initial survey, changes were made to the format and content of the Emerging Investigators website to improve content relevance and usability. For phase 2, an evaluation rubric was developed to assess design, navigability, content, relevance, along with three key COI criteria to determine the educational value of this online resource. The rubric will be utilized to collect feedback in the wider phase 2 roll out of the website. RESULTS/ANTICIPATED RESULTS: The first phase of survey feedback shaped overall design of the resource. The second phase will comprehensively evaluate the value of the website in the context of teaching and learning for emerging investigators. Ten surveys were captured in the first phase. Data collection is ongoing for the second phase. Phase 1 feedback was primarily qualitative, and valuable in informing overall design choices and content. Overall the website was well received, with participants commenting on the value of the resource in terms of content and educational value. Participants particularly appreciated the regularly updated calendar function and the links provided to a wide range of resources. Functionality issues, such as broken links, were reported by participants and repaired for phase 2. Further topics of content were identified, and additional links and multimedia resources were added to address this feedback. The second phase evaluation is ongoing with data collection being conducted via an evaluation rubric. DISCUSSION/SIGNIFICANCE OF IMPACT: The Emerging Investigators website, developed using the principles of COI provides key learning, reading and resources for early career investigators in a format that is well received by a sample group of early career researchers at Mount Sinai. The website has aimed to address the reported need for communication, collaboration and social interaction with peers and other researchers across the MSHS through the addition of further web-based resources such as a LinkedIn page, a blog to feature research and provide a sounding board for research efforts, and a calendar of events targeted specifically at early career researchers. These were highlighted as areas of particular value by the participants. We anticipate the results of phase 2 rubric-based evaluations will provide actionable data that will lead to further refinement of the website, an optimized interface, and improved usability.
2229: Development of an angiogenic proteoglycan mimic to accelerate ischemic diabetic foot ulcer repair
- Jenny Lin, Alyssa Panitch
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- Journal:
- Journal of Clinical and Translational Science / Volume 1 / Issue S1 / September 2017
- Published online by Cambridge University Press:
- 10 May 2018, p. 4
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OBJECTIVES/SPECIFIC AIMS: This project aims to synthesize an angiogenic decorin mimic (VEGFp-DS-SILY) with varying densities of QK and characterize its angiogenic potential and synergism with VEGF by evaluating (1) endothelial cell (EC) migration and proliferation, (2) EC VEGF receptor activation, (3) EC tubule formation in collagen scaffolds, and (4) angiogenesis from a chick chorioallantoic membrane (CAM assay) growing into the scaffold, reflecting the ability of the collagen scaffold to integrate into existing vasculature. The next main goal is to develop and characterize an MMP-degradable nanoparticle system for controlled release of VEGF. Future work will evaluate in vivo effects of VEGFp-DS-SILY bound to a 3D collagen scaffold on ischemic wound repair in a combined excisional wound/bipedical dorsal skin flap rat model. METHODS/STUDY POPULATION: Peptide hydrazides are conjugated to the free carboxylic acid functional groups on dermatan sulfate using EDC chemistry. We added a 3 amino acid spacer (-Gly-Ser-Gly) to the C-terminus of the established QK sequence before the hydrazide functional group and refer to this modified QK as “VEGFp.” VEGFp, SILY, and N-terminal biotinylated versions were synthesized using standard Fmoc solid-phase peptide synthesis protocols and purified using reverse phase HPLC. Coupling efficiencies of peptides to dermatan sulfate were determined spectroscopically at 280 nm measuring the aromatic residues (Trp or Tyr) using a NanoDrop system. Dermatan sulfate with 1 or 4 VEGFp peptides coupled were termed DSV1 and DSV4, respectively. After further conjugation with SILY, we will blend this VEGFp-DS-SILY with unmodified DS-SILY to a total 10 μM to test increasing densities of VEGFp. To verify that the collagen-binding properties of VEGFp-DS-SILY are not compromised by the addition of VEGFp, we will use a streptavidin-HRP system to detect bound biotinylated VEGFp-DS-SILY on collagen-coated plates by established protocols. DSV1 and DSV4 were tested for their effects on endothelial VEGFR2 phosphorylation using an MSD ELISA-type assay and endothelial proliferation using an MTS assay. Cell migration was monitored using an ORIS assay where cells are grown to confluence around a silicone stopper that is then removed to allow cells to migrate inward. Tubulogenesis was evaluated by examining tubule formation on matrigel. Finally, in vivo angiogenesis will be evaluated using a chorioallantoic membrane assay. For extracellular VEGF release, hollow MMP-degradable thermoresponsive nanoparticles [NIPAM, 5 mol% 2-acrylamido-2-methyl-1-propanesulfonic acid (AMPS), 1% Acrylic Acid (AAc), 2 mol% MMP-degradable peptide diacrylate, and potassium persulfate initiator] will be synthesized around noncross-linked polymer cores. The cores will then be diffused out through the shell by dialysis prior to drug loading. SILY (and some biotinylated SILY for visualization) will be conjugated with EDC chemistry for targeting nanoparticles to collagen. NPs size and zeta-potential will be measured on a Malvern Zetasizer. VEGF will be loaded into NPs by co-incubating a loading solution of 1 µg/mL VEGF with 1 mg of NPs, incubating overnight at 4°C. VEGF loading and release will be measured by ELISA. Biological activity of the released VEGF from particles will be determined on ECs using assays similar to those outlined previously. RESULTS/ANTICIPATED RESULTS: Preliminary data have verified the synthesis and purification of SILY and VEGFp (QK-Gly-Ser-Gly-hydrazide), as well as an N-terminal biotinylated version, through mass spectrometry and reverse-phase HPLC, respectively. For proof-of-concept, we have verified binding of VEGFp to the VEGF receptor 2 using a ForteBio Blitz interferometry instrument. In addition to support based on published reports showing retained bioactivity of QK after conjugation using other spacers, our preliminary data suggests that VEGFp still binds to VEGF receptor 2, albeit with decreased affinity like QK as compared with VEGF. Circular dichroism also shows that VEGFp has retained its α-helical structure necessary for bioactivity; however it appears that it has some uncoiling when conjugated to dermatan sulfate. We hypothesize that varying densities of VEGFp conjugated to the decorin mimetic (DS-SILY) will modulate the degree of angiogenic activity and synergy with VEGF. We determined that we can achieve ~70% VEGFp conjugation completion to dermatan sulfate after 3.5 hours. We have quantified VEGFR2 phosphorylation after 5 minute treatments by using phospho-specific antibodies and an ELISA-type protocol in a mesoscale discovery system. Preliminary data with human umbilical vein endothelial cells shows that VEGFp exhibits synergism with VEGF at levels similar to QK. DSV1 and DSV4 data suggests synergy with VEGF, although free-peptides and engineered compounds alone did not show effects similar to VEGF in the conditions tested. Prelminary data with 30 minute treatments suggests that the peptides and compounds may require longer exposures to induce activation, as they may have slower binding rates. In contrast, prolonged stimulation with VEGF causes a sharp increase in receptor activation, peaking around 10 minutes and decreasing significantly by 30 minutes. Peptides QK and VEGFp both slightly increased proliferation of dermal microvascular endothelial cells (HMVECs) after 60 hours incubation. However, incubation with dermatan sulfate and DSV caused significant cell death after 24 hours in reduced growth factor media, likely due to sequestering of growth factors. It is possible that VEGFp-DS-SILY may better stimulate proliferation since it would be presented as a surface bound proteoglycan mimic, rather than as a soluble factor. HMVECs migrated farther for all treatment groups (10 µM QK, 10 µM VEGFp, 1 µM DSV4, and 10 µM DSV4) than the 10 ng/mL VEGF positive control, although more cells migrated in response to VEGF. This may be accounted at least in part by the more pronounced proliferation induced by VEGF. Migration will also be tested in 3D culture within a collagen gel. We are currently testing a 2D matrigel system for tubulogenesis. We have found that 10 µM DSV4 forms qualitatively more well-defined tubules than the untreated control on reduced growth factor matrigel. However, we were not able to quantify the improved tubule formation and are still troubleshooting the tubule analysis. After seeding ECs and culturing for 4, 8, and 12 hours, cells will be fluorescently stained with anti-CD31 and imaged for 3D tubule formation. CAM assay angiogenesis growing into a collagen scaffold. In brief, fertilized chicken embryos are incubated for 2 days before exposing the CAM. VEGFp-DS-SILY bound to a collagen gel will be placed onto the CAM. Some treatment groups will receive additional VEGF to investigate synergistic effects. Light microscope images of angiogenesis into the collagen gel coated with VEGFp-DS-SILY, taken every day from days 10 to 13, will reflect the ability of the collagen scaffold to integrate into existing vasculature and 3D angiogenic potential of VEGFp-DS-SILY with or without VEGF. We expect that VEGFp-DS-SILY treatment will increase the number of vessels formed on the CAM. Preliminary data using a Fluoraldehyde assay indicates that loading of ~300 ng VEGF per mg of nanoparticles can be achieved. We expect that using an MMP-degradable peptide diacrylate crosslinker will allow nanoparticles to degrade in protease-rich environments like the chronic wound bed and release VEGF. Adjustments to the formulation, such as crosslinker density, may need to be modified to control the rate of VEGF release. DISCUSSION/SIGNIFICANCE OF IMPACT: We expect that our angiogenic decorin mimetic will lead to a novel treatment to accelerate healing of ischemic diabetic foot ulcers, thereby reducing the need for limb amputation and mortality rate of diabetic patients. We anticipate that the diabetes research and regenerative medicine communities will (1) gain a platform for targeted delivery of growth factors, (2) understand the dependence of vascularization within 3D collagen constructs on VEGFp densities and VEGF receptor activation in controlling the degree of angiogenesis, and (3) gain the benefits of controlled angiogenesis in ischemic diabetic wound healing.
Association of Weight Perception, Race and Readiness to Quit Smoking amongst a Cohort of Workers
- Jenny J. Lin, Tracey A. Revenson, Alfred I. Neugut, Andrew Rundle, Sumit Mohan, Juan P. Wisnivesky
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- Journal:
- Journal of Smoking Cessation / Volume 13 / Issue 1 / March 2018
- Published online by Cambridge University Press:
- 12 December 2016, pp. 11-17
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- March 2018
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Introduction: Weight concerns may inhibit smoking quit attempts and may be more influential amongst African-Americans who are more likely to be overweight.
Aims: To assess if weight perception is associated with readiness to quit and whether this relationship is modified by race.
Methods: We used data from a cohort of current smokers undergoing routine health examinations. Based on differences between ideal and measured BMI, participants’ weight perceptions were classified as within, somewhat above, or far above ideal weight. Logistic regression analysis was used to evaluate adjusted associations of weight perception and race with readiness to quit.
Results: Of 2,831 current smokers, 23% were obese and 38% overweight. Amongst white smokers, those who perceived being far above ideal weight were more likely to be ready to quit (OR: 1.45, 95% CI: 1.03–2.03), but this association was not observed for African-American smokers who perceived themselves to be somewhat or far above their ideal weight (OR: 0.35, 95% CI: 0.10–1.24 and OR: 0.36, 95% CI: 0.11–1.19, respectively).
Conclusions: Perception of being overweight is associated with increased readiness to quit amongst white but not African-American smokers. Smoking cessation programmes may need to culturally tailor interventions based on smokers’ weight perceptions.
Epigenome-Wide Association Study of Wellbeing
- Bart M. L. Baselmans, Jenny van Dongen, Michel G. Nivard, Bochao D. Lin, BIOS Consortium, Nuno R. Zilhão, Dorret I. Boomsma, Meike Bartels
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- Journal:
- Twin Research and Human Genetics / Volume 18 / Issue 6 / December 2015
- Published online by Cambridge University Press:
- 01 December 2015, pp. 710-719
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Wellbeing (WB) is a major topic of research across several scientific disciplines, partly driven by its strong association with psychological and mental health. Twin-family studies have found that both genotype and environment play an important role in explaining the variance in WB. Epigenetic mechanisms, such as DNA methylation, regulate gene expression, and may mediate genetic and environmental effects on WB. Here, for the first time, we apply an epigenome-wide association study (EWAS) approach to identify differentially methylated sites associated with individual differences in WB. Subjects were part of the longitudinal survey studies of the Netherlands Twin Register (NTR) and participated in the NTR biobank project between 2002 and 2011. WB was assessed by a short inventory that measures satisfaction with life (SAT). DNA methylation was measured in whole blood by the Illumina Infinium HumanMethylation450 BeadChip (HM450k array) and the association between WB and DNA methylation level was tested at 411,169 autosomal sites. Two sites (cg10845147, p = 1.51 * 10−8 and cg01940273, p = 2.34 * 10−8) reached genome-wide significance following Bonferonni correction. Four more sites (cg03329539, p = 2.76* 10−7; cg09716613, p = 3.23 * 10−7; cg04387347, p = 3.95 * 10−7; and cg02290168, p = 5.23 * 10−7) were considered to be genome-wide significant when applying the widely used criterion of a FDR q value < 0.05. Gene ontology (GO) analysis highlighted enrichment of several central nervous system categories among higher-ranking methylation sites. Overall, these results provide a first insight into the epigenetic mechanisms associated with WB and lay the foundations for future work aiming to unravel the biological mechanisms underlying a complex trait like WB.
Discovery of a low-glycaemic index potato and relationship with starch digestion in vitro
- Kai Lin Ek, Shujun Wang, Les Copeland, Jennie C. Brand-Miller
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- Journal:
- British Journal of Nutrition / Volume 111 / Issue 4 / 28 February 2014
- Published online by Cambridge University Press:
- 08 October 2013, pp. 699-705
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- 28 February 2014
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Potatoes are usually a high-glycaemic index (GI) food. Finding a low-GI potato and developing a screening method for finding low-GI cultivars are both health and agricultural priorities. The aims of the present study were to screen the commonly used and newly introduced cultivars of potatoes, in a bid to discover a low-GI potato, and to describe the relationship between in vitro starch digestibility of cooked potatoes and their in vivo glycaemic response. According to International Standard Organisation (ISO) guidelines, seven different potato cultivars were tested for their GI. In vitro enzymatic starch hydrolysis and chemical analyses, including amylose content analysis, were carried out for each potato cultivar, and correlations with the respective GI values were sought. The potato cultivars had a wide range of GI values (53–103). The Carisma cultivar was classified as low GI and the Nicola cultivar (GI = 69) as medium GI and the other five cultivars were classified as high GI according to ISO guidelines. The GI values were strongly and positively correlated with the percentage of in vitro enzymatic hydrolysis of starch in the cooked potatoes, particularly with the hydrolysis percentage at 120 min (r 0·91 and P <0·01). Amylose, dietary fibre and total starch content was not correlated with either in vitro starch digestibility or GI. The findings suggest that low-GI potato cultivars can be identified by screening using a high-throughput in vitro digestion procedure, while chemical composition, including amylose and fibre content, is not indicative.
How do Chinese patients with dementia rate their own quality of life?
- Philip Lin Kiat Yap, Jenny Yen Ni Goh, Linda Mary Henderson, Pei Min Han, Kui Shin Ong, Serene Si Ling Kwek, Elizabeth Yi Hui Ong, Donus Pui Kwan Loh
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- International Psychogeriatrics / Volume 20 / Issue 3 / June 2008
- Published online by Cambridge University Press:
- 17 September 2007, pp. 482-493
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Objective: This study examines the psychometric properties and clinical experience in using the Mandarin translation of the Quality of Life–Alzheimer's Disease (QoL-AD) instrument in Chinese patients with dementia in Singapore.
Methods: A Mandarin version of QoL-AD was established following standard guidelines for transcultural adaptation of QoL measures. The instrument was administered to 70 patient-carer dyads; patients with severe dementia (MMSE < 10) were excluded. Reliability by internal consistency and test-retest, and construct validity by correlating the known domains of QoL-AD with validity measures for the respective domains, was performed. Guidelines for Rating Awareness Deficits (GRAD) measured patients' insight into their deficits.
Results: Three patients were not able to complete the QoL-AD. Internal consistency (Cronbach's α) was high for both patient (0.9) and carer (0.8) QoL-AD ratings, as was test-retest reliability, intraclass correlation coefficient (ICC) 0.7 and 0.8 respectively. Correlation of QoL-AD with domain measures was moderate for carer ratings (0.21 < r < 0.51) and poor for patient (−0.17 < r < 0.13). Patient self-rated QoL correlated poorly with, and was significantly higher than, carer-rated QoL. Correlation between patient and carer QoL-AD was stronger in patients with better insight (GRAD 3–4).
Conclusions: The results suggest that while the Mandarin version of QoL-AD can be used reliably in our population, patients' self perceived QoL can be different from carer ratings and from objective QoL measures. The disparity can be attributed to patients' poor insight, denial, fear of “losing face,” normalization and accommodation of standards with aging. The patients' lack of education and seclusion from Western cultural exposure are also contributory.
First Outbreak of Colonization and Infection With Vancomycin-Resistant Enterococcus faecium in a Tertiary Care Hospital in Singapore
- Maciej Piotr Chlebicki, Moi Lin Ling, Tse Hsien Koh, Li Yang Hsu, Ban Hock Tan, Kue Bien How, Li-Hwei Sng, Grace Chee Yeng Wang, Asok Kurup, Mei Ling Kang, Jenny Guek Hong Low
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- Journal:
- Infection Control & Hospital Epidemiology / Volume 27 / Issue 9 / September 2006
- Published online by Cambridge University Press:
- 21 June 2016, pp. 991-993
- Print publication:
- September 2006
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We report the first outbreak of vancomycin-resistant Enterococcus faecium colonization and infection among inpatients in the hematology ward of an acute tertiary care public hospital in Singapore. Two cases of bacteremia and 4 cases of gastrointestinal carriage were uncovered before implementation of strict infection control measures resulted in control of the outbreak.