Publications by authors named "Janice Lee"

152 Publications

Impact of an orthogeriatric collaborative care model for older adults with hip fracture in a community hospital setting.

Can J Surg 2021 Mar 26;64(2):E211-E217. Epub 2021 Mar 26.

From the University of Toronto, Toronto, Ont. (Lee, E.K.C. Wong, C.L. Wong); the Markham Stouffville Hospital, Markham, Ont. (Koo, Naqvi); Unity Health, Toronto, Ont. (E.K.C. Wong, C.L. Wong); and the Li Ka Shing Knowledge Institute, Toronto, Ont. (E.K.C. Wong, C.L. Wong).

Background: Studies have shown that the incidence of postoperative delirium, the hospital length of stay and time to surgery are reduced when older adults with a hip fracture are cared for by a multidisciplinary team providing comprehensive geriatric assessments. Most of these studies have been conducted in academic centres. We sought to determine if implementation of an orthogeriatric collaborative care model would improve key quality of care metrics in a community hospital setting.

Methods: This retrospective pre- and postintervention single-site study was conducted in a community hospital in Ontario, Canada. We included consecutive patients aged 65 years or older who were admitted for a hip fracture between June 2015 and June 2017. In the intervention period, a new postoperative order set included a referral to a geriatrician for comprehensive geriatric assessment, with direct implementation of recommendations. Primary outcomes were the incidence of postoperative delirium and length of stay. Secondary outcomes included Health Quality Ontario's quality standards for hip fracture.

Results: A total of 212 consecutive patients (95 in the preintervention group and 117 in the postintervention group) were included in the study. The incidence of postoperative delirium (26.3% v. 26.5%, p = 0.98) and length of stay (interquartile range 4-10 v. 5-10 d, p = 0.32) were similar in the preintervention and postintervention groups. There were improvements (p < 0.001) in the rates of asssessment of mental status, falls and bone health; identification of delirium prevention strategies; prescription of vitamin D or calcium or both; and recommendations for antiresorptive therapy. Despite systemic implementation of the orthogeriatric model, only 74.4% of patients in the postintervention group were seen by a geriatric medicine consultant.

Conclusion: Although the implementation of an orthogeriatric collaborative care model for older adults with a hip fracture did not reduce the incidence of postoperative delirium or length of stay, there were improvements in the rates at which several other key quality standards for hip fracture care were met. Earlier proactive, comprehensive geriatric assessment in a community hospital setting will be the target for further quality improvement initiatives.
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http://dx.doi.org/10.1503/cjs.001720DOI Listing
March 2021

SARS-CoV-2 infection of the oral cavity and saliva.

Nat Med 2021 Mar 25. Epub 2021 Mar 25.

Division of Oral & Craniofacial Health Sciences, University of North Carolina Adams School of Dentistry, Chapel Hill, NC, USA.

Despite signs of infection-including taste loss, dry mouth and mucosal lesions such as ulcerations, enanthema and macules-the involvement of the oral cavity in coronavirus disease 2019 (COVID-19) is poorly understood. To address this, we generated and analyzed two single-cell RNA sequencing datasets of the human minor salivary glands and gingiva (9 samples, 13,824 cells), identifying 50 cell clusters. Using integrated cell normalization and annotation, we classified 34 unique cell subpopulations between glands and gingiva. Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) viral entry factors such as ACE2 and TMPRSS members were broadly enriched in epithelial cells of the glands and oral mucosae. Using orthogonal RNA and protein expression assessments, we confirmed SARS-CoV-2 infection in the glands and mucosae. Saliva from SARS-CoV-2-infected individuals harbored epithelial cells exhibiting ACE2 and TMPRSS expression and sustained SARS-CoV-2 infection. Acellular and cellular salivary fractions from asymptomatic individuals were found to transmit SARS-CoV-2 ex vivo. Matched nasopharyngeal and saliva samples displayed distinct viral shedding dynamics, and salivary viral burden correlated with COVID-19 symptoms, including taste loss. Upon recovery, this asymptomatic cohort exhibited sustained salivary IgG antibodies against SARS-CoV-2. Collectively, these data show that the oral cavity is an important site for SARS-CoV-2 infection and implicate saliva as a potential route of SARS-CoV-2 transmission.
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http://dx.doi.org/10.1038/s41591-021-01296-8DOI Listing
March 2021

Evaluating a large-scale online behaviour change intervention aimed at wildlife product consumers in Singapore.

PLoS One 2021 24;16(3):e0248144. Epub 2021 Mar 24.

Department of Zoology, University of Oxford, Oxford, United Kingdom.

Interventions to shift the behaviour of consumers using unsustainable wildlife products are key to threatened species conservation. Whether these interventions are effective is largely unknown due to a dearth of detailed evaluations. We previously conducted a country-level online behaviour change intervention targeting consumers of the Critically Endangered saiga antelope (Saiga tatarica) horn in Singapore. To evaluate intervention impact, we carried out in-person consumer surveys with >2,000 individuals pre- and post-intervention (2017 and 2019), and 93 in-person post-intervention surveys with traditional Chinese medicine (TCM) shopkeepers (2019). The proportion of self-reported high-usage saiga horn consumers in the target audience (Chinese Singaporean women aged 35-59) did not change significantly from pre- to post-intervention (24.4% versus 22.6%). However, post-intervention the target audience was significantly more likely than the non-target audience to accurately recall the intervention message and to report a decrease in saiga horn usage (4% versus 1% reported a behaviour change). Within the target audience, high-usage consumers were significantly more likely than lower-usage consumers to recall the message and report a behaviour change. Across respondents who reported a decrease in saiga horn usage, they cited the intervention message as a specific reason for their behaviour change significantly more than other reasons. Additionally, across all respondents, the belief that saiga is a common species in the wild decreased significantly from pre- to post-intervention. TCM shopkeepers, however, cited factors such as price and availability as the strongest influences on saiga horn sales. In sum, the intervention did significantly influence some consumers but the reduction of high-usage consumer frequency was not significant at the population level. We explore reasons for these findings, including competing consumer influences, characteristics of the intervention, and evaluation timing. This work suggests our intervention approach has potential, and exemplifies a multi-pronged in-person evaluation of an online wildlife trade consumer intervention.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0248144PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7990170PMC
March 2021

Mitigating osteonecrosis of the jaw (ONJ) through preventive dental care and understanding of risk factors.

Bone Res 2020 Mar 11;8(1):14. Epub 2020 Mar 11.

National Institute of Dental and Craniofacial Research, National Institutes of Health, Bethesda, MD, USA.

It is well established that alterations in phosphate metabolism have a profound effect on hard and soft tissues of the oral cavity. The present-day clinical form of osteonecrosis of the jaw (ONJ) was preceded by phosphorus necrosis of the jaw, ca. 1860. The subsequent removal of yellow phosphorus from matches in the early 20th century saw a parallel decline in "phossy jaw" until the early 2000s, when similar reports of unusual jaw bone necrosis began to appear in the literature describing jaw necrosis in patients undergoing chemotherapy and concomitant steroid and bisphosphonate treatment. Today, the potential side effect of ONJ associated with medications that block osteoclast activity (antiresorptive) is well known, though the mechanism remains unclear and the management and outcomes are often unsatisfactory. Much of the existing literature has focused on the continuing concerns of appropriate use of bisphosphonates and other antiresorptive medications, the incomplete or underdeveloped research on ONJ, and the use of drugs with anabolic potential for treatment of osteoporosis. While recognizing that ONJ is a rare occurrence and ONJ-associated medications play an important role in fracture risk reduction in osteoporotic patients, evidence to date suggests that health care providers can lower the risk further by dental evaluations and care prior to initiating antiresorptive therapies and by monitoring dental health during and after treatment. This review describes the current clinical management guidelines for ONJ, the critical role of dental-medical management in mitigating risks, and the current understanding of the effects of predominantly osteoclast-modulating drugs on bone homeostasis.
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http://dx.doi.org/10.1038/s41413-020-0088-1DOI Listing
March 2020

ErbB3 is a critical regulator of cytoskeletal dynamics in brain microvascular endothelial cells: Implications for vascular remodeling and blood-brain-barrier modulation.

J Cereb Blood Flow Metab 2021 Feb 14:271678X20984976. Epub 2021 Feb 14.

Neuroprotection Research Laboratory, Massachusetts General Hospital, Harvard Medical School, Charlestown, USA.

Neuregulin (NRG)1 - ErbB receptor signaling has been shown to play an important role in the biological function of peripheral microvascular endothelial cells. However, little is known about how NRG1/ErbB signaling impacts brain endothelial function and blood-brain barrier (BBB) properties. NRG1/ErbB pathways are affected by brain injury; when brain trauma was induced in mice in a controlled cortical impact model, endothelial ErbB3 gene expression was reduced to a greater extent than that of other NRG1 receptors. This finding suggests that ErbB3-mediated processes may be significantly compromised after injury, and that an understanding of ErbB3 function would be important in the of study of endothelial biology in the healthy and injured brain. Towards this goal, cultured brain microvascular endothelial cells were transfected with siRNA to ErbB3, resulting in alterations in F-actin organization and microtubule assembly, cell morphology, migration and angiogenic processes. Importantly, a significant increase in barrier permeability was observed when ErbB3 was downregulated, suggesting ErbB3 involvement in BBB regulation. Overall, these results indicate that neuregulin-1/ErbB3 signaling is intricately connected with the cytoskeletal processes of the brain endothelium and contributes to morphological and angiogenic changes as well as to BBB integrity.
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http://dx.doi.org/10.1177/0271678X20984976DOI Listing
February 2021

Journal editors: How do their editing incomes compare?

F1000Res 2020 24;9:1027. Epub 2020 Aug 24.

University of Toronto, Toronto, Canada.

The work of journal editors is essential to producing high-quality literature, and editing can be a very rewarding career; however, the profession may not be immune to gender pay gaps found in many professions and industries, including academia and clinical medicine. Our study aimed to quantify remuneration for journal editors from core clinical journals, determine if a gender pay gap exists, and assess if there are remuneration differences across publishing models and journal characteristics. We completed an online survey of journal editors with substantial editing roles including section editors and editors-in-chief, identified from the Abridged Index Medicus "Core Clinical" journals in MEDLINE. We analyzed information on demographics, editing income, and journal characteristics using a multivariable partial proportional odds model for ordinal logistic regression. There were 166 survey respondents (response rate of 9%), which represented editors from 69 of 111 journals (62%). A total of 140 fully completed surveys were analyzed (95 males and 45 females); 50 (36%) editors did not receive remuneration for editorial work. No gender pay gap and no difference in remuneration between editors who worked in subscription-based publishing vs. open access journals were detected. Editors who were not primarily health care providers were more likely to have higher editing incomes (adjusted odds ratio [OR] 2.96, 95% confidence interval [CI] 1.18-7.46). Editors who worked more than 10 hours per week editing earned more than those who worked 10 hours or less per week (adjusted OR 16.7, 95%CI 7.02-39.76). We were unable to detect a gender pay gap and a difference in remuneration between editors who worked in subscription-based publishing and those in open access journals. More than one third of editors surveyed from core clinical journals did not get remunerated for their editing work.
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http://dx.doi.org/10.12688/f1000research.25620.3DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7836083.3PMC
August 2020

The environmental impacts of palm oil in context.

Nat Plants 2020 12 7;6(12):1418-1426. Epub 2020 Dec 7.

Faculty of Environmental Sciences and Natural Resource Management, Norwegian University of Life Sciences, Ås, Norway.

Delivering the Sustainable Development Goals (SDGs) requires balancing demands on land between agriculture (SDG 2) and biodiversity (SDG 15). The production of vegetable oils and, in particular, palm oil, illustrates these competing demands and trade-offs. Palm oil accounts for ~40% of the current global annual demand for vegetable oil as food, animal feed and fuel (210 Mt), but planted oil palm covers less than 5-5.5% of the total global oil crop area (approximately 425 Mha) due to oil palm's relatively high yields. Recent oil palm expansion in forested regions of Borneo, Sumatra and the Malay Peninsula, where >90% of global palm oil is produced, has led to substantial concern around oil palm's role in deforestation. Oil palm expansion's direct contribution to regional tropical deforestation varies widely, ranging from an estimated 3% in West Africa to 50% in Malaysian Borneo. Oil palm is also implicated in peatland draining and burning in Southeast Asia. Documented negative environmental impacts from such expansion include biodiversity declines, greenhouse gas emissions and air pollution. However, oil palm generally produces more oil per area than other oil crops, is often economically viable in sites unsuitable for most other crops and generates considerable wealth for at least some actors. Global demand for vegetable oils is projected to increase by 46% by 2050. Meeting this demand through additional expansion of oil palm versus other vegetable oil crops will lead to substantial differential effects on biodiversity, food security, climate change, land degradation and livelihoods. Our Review highlights that although substantial gaps remain in our understanding of the relationship between the environmental, socio-cultural and economic impacts of oil palm, and the scope, stringency and effectiveness of initiatives to address these, there has been little research into the impacts and trade-offs of other vegetable oil crops. Greater research attention needs to be given to investigating the impacts of palm oil production compared to alternatives for the trade-offs to be assessed at a global scale.
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http://dx.doi.org/10.1038/s41477-020-00813-wDOI Listing
December 2020

Integrated Single-Cell Atlases Reveal an Oral SARS-CoV-2 Infection and Transmission Axis.

medRxiv 2020 Oct 27. Epub 2020 Oct 27.

Despite signs of infection, the involvement of the oral cavity in COVID-19 is poorly understood. To address this, single-cell RNA sequencing data-sets were integrated from human minor salivary glands and gingiva to identify 11 epithelial, 7 mesenchymal, and 15 immune cell clusters. Analysis of SARS-CoV-2 viral entry factor expression showed enrichment in epithelia including the ducts and acini of the salivary glands and the suprabasal cells of the mucosae. COVID-19 autopsy tissues confirmed in vivo SARS-CoV-2 infection in the salivary glands and mucosa. Saliva from SARS-CoV-2-infected individuals harbored epithelial cells exhibiting expression and SARS-CoV-2 RNA. Matched nasopharyngeal and saliva samples found distinct viral shedding dynamics and viral burden in saliva correlated with COVID-19 symptoms including taste loss. Upon recovery, this cohort exhibited salivary antibodies against SARS-CoV-2 proteins. Collectively, the oral cavity represents a robust site for COVID-19 infection and implicates saliva in viral transmission.
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http://dx.doi.org/10.1101/2020.10.26.20219089DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7605572PMC
October 2020

Malocclusion Classification on 3D Cone-Beam CT Craniofacial Images Using Multi-Channel Deep Learning Models

Annu Int Conf IEEE Eng Med Biol Soc 2020 07;2020:1294-1298

Analyzing and interpreting cone-beam computed tomography (CBCT) images is a complicated and often time-consuming process. In this study, we present two different architectures of multi-channel deep learning (DL) models: "Ensemble" and "Synchronized multi-channel", to automatically identify and classify skeletal malocclusions from 3D CBCT craniofacial images. These multi-channel models combine three individual single-channel base models using a voting scheme and a two-step learning process, respectively, to simultaneously extract and learn a visual representation from three different directional views of 2D images generated from a single 3D CBCT image. We also employ a visualization method called "Class-selective Relevance Mapping" (CRM) to explain the learned behavior of our DL models by localizing and highlighting a discriminative area within an input image. Our multi-channel models achieve significantly better performance overall (accuracy exceeding 93%), compared to single-channel DL models that only take one specific directional view of 2D projected image as an input. In addition, CRM visually demonstrates that a DL model based on the sagittal-left view of 2D images outperforms those based on other directional 2D images.Clinical Relevance- the proposed method aims at assisting orthodontist to determine the best treatment path for the patient be it orthodontic or surgical treatment or a combination of both.
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http://dx.doi.org/10.1109/EMBC44109.2020.9176672DOI Listing
July 2020

Bayesian hierarchical dose-response meta-analysis of epidemiological studies: Modeling and target population prediction methods.

Environ Int 2020 12 21;145:106111. Epub 2020 Sep 21.

Center for Public Health and Environmental Assessment, U.S. EPA, Washington, DC, USA. Electronic address:

When assessing the human risks due to exposure to environmental chemicals, traditional dose-response analyses are not straightforward when there are numerous high-quality epidemiological studies of priority cancer and non-cancer health outcomes. Given this wealth of information, selecting a single "best" study on which to base dose-response analyses is difficult and would potentially ignore much of the available data. Therefore, systematic approaches are necessary for the analysis of these rich databases. Examples are meta-analysis (and further, meta-regression), which are well established methods that consider and incorporate information from multiple studies into the estimation of risks due to exposure to environmental contaminants. In this paper, we propose a hierarchical, Bayesian meta-analysis approach for the dose-response analysis of multiple epidemiological studies. This paper is the second of two papers detailing this approach; the first covered "pre-analysis" steps necessary to prepare the data for dose-response modeling. This paper focuses on the hierarchical Bayesian approach to dose-response modeling and extrapolation of risk to populations of interest using the association between bladder cancer and oral inorganic arsenic (iAs) exposure as an illustrative case study. In particular, this paper addresses the modeling of both case-control and cohort studies with a flexible, logistic model in a hierarchical Bayesian framework that estimates study-specific slopes, as well as a pooled slope across all studies. This approach is akin to a random effects model in which no assumption is made a priori that there is a single, common slope for all included studies. Further, this paper also details extrapolation of the estimates of logistic slope to extra risk in a target population using a lifetable analysis and basic assumptions about background iAs exposure levels. In this case, the target population was the general United States population and information on all-cause mortality and incidence and mortality from bladder cancer was used to perform the lifetable analysis. The methods herein were developed for general use in investigating the association between any pollutant and observed health-effects in epidemiological studies. In order to demonstrate these methods, inorganic arsenic was chosen as a case study given the large epidemiological database that exists for this contaminant.
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http://dx.doi.org/10.1016/j.envint.2020.106111DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7780081PMC
December 2020

Use of study-specific MOE-like estimates to prioritize health effects from chemical exposure for analysis in human health assessments.

Environ Int 2020 11 30;144:105986. Epub 2020 Aug 30.

CPHEA, U.S. Environmental Protection Agency, Research Triangle Park, NC, USA. Electronic address:

There are unique challenges in estimating dose-response with chemicals that are associated with multiple health outcomes and numerous studies. Some studies are more suitable than others for quantitative dose-response analyses. For such chemicals, an efficient method of screening studies and endpoints to identify suitable studies and potentially important health effects for dose-response modeling is valuable. Using inorganic arsenic as a test case, we developed a tiered approach that involves estimating study-specific margin of exposure (MOE)-like unitless ratios for two hypothetical scenarios. These study-specific unitless ratios are derived by dividing the exposure estimated to result in a 20% increase in relative risk over the background exposure (RRE) by the background exposure, as estimated in two different ways. In our case study illustration, separate study-specific ratios are derived using estimates of United States population background exposure (RRB-US) and the mean study population reference group background exposure (RRB-SP). Systematic review methods were used to identify and evaluate epidemiologic studies, which were categorized based on study design (case-control, cohort, cross-sectional), various study quality criteria specific to dose-response analysis (number of dose groups, exposure ascertainment, exposure uncertainty), and availability of necessary dose-response data. Both case-control and cohort studies were included in the RRB analysis. The RRE estimates were derived by modeling effective counts of cases and controls estimated from study-reported adjusted odds ratios and relative risks. Using a broad (but not necessarily comprehensive) set of epidemiologic studies of multiple health outcomes selected for the purposes of illustrating the RRB approach, this test case analysis would suggest that diseases of the circulatory system, bladder cancer, and lung cancer may be arsenic health outcomes that warrant further analysis. This is suggested by the number of datasets from adequate dose-response studies demonstrating an effect with RRBs close to 1 (i.e., RRE values close to estimated background arsenic exposure levels).
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http://dx.doi.org/10.1016/j.envint.2020.105986DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7572727PMC
November 2020

A comparison of electronically-delivered and face to face cognitive behavioural therapies in depressive disorders: A systematic review and meta-analysis.

EClinicalMedicine 2020 Jul 27;24:100442. Epub 2020 Jun 27.

Department of Health Research Methods, Evidence and Impact, McMaster University, 1280 Main St. West, Hamilton, ON, Canada.

Background: Cognitive behavioural therapy (CBT) is a widely used treatment for depression. However, limited resource availability poses several barriers to patients seeking access to care, including lengthy wait times and geographical limitations. This has prompted health care services to introduce electronically delivered CBT (eCBT) to facilitate access. Although previous reviews have compared the effects of eCBT to face-to-face CBT, there is an overall lack of adequately powered and up-to-date evidence in the literature to provide a reliable comparison between the two modes of administration. The purpose of this study is to evaluate the effects of eCBT compared to face-to-face CBT through a systematic review of the literature.

Methods: To be eligible for this review, studies needed to be randomized controlled trials evaluating the clinical effectiveness of any form of eCBT compared to face-to-face CBT. These encompassed studies evaluating a wide range of outcomes including severity of symptoms, adverse outcomes, clinically relevant outcomes, global functionality, participant satisfaction, quality of life, and affordability. There were no restrictions on participant age or sex.We searched MEDLINE, EMBASE, Psych Info, Cochrane CENTRAL and CINAHL databases from inception to February 20th, 2020 using a comprehensive search strategy. All stages of literature screening and data extraction were completed independently in duplicate. Data extraction and risk of bias analyses, including GRADE ratings, were conducted on studies meeting inclusion criteria. Qualitative measures are reported in a narrative summary. We pooled quantitative data in meta-analyses to provide an estimated summary effect. This review adheres to PRISMA reporting guidelines.

Findings: In total, we included 17 studies in our analyses. Our results demonstrated that eCBT was more effective than face-to-face CBT at reducing depression symptom severity (Standardized mean difference [SMD]: -1.73; 95% confidence interval [CI]: -2.72, -0.74; GRADE: moderate quality of evidence). There were no significant differences between the two interventions on participant satisfaction (SMD 0.13 95%; CI -0.32, 0.59; GRADE: low quality of evidence). One RCT reported eCBT to be less costly than face-to-face CBT (GRADE: low quality of evidence). Results did not differ when stratified by subgroups such as participant age and study location.

Interpretation: Although we found eCBT to have moderate evidence of effectiveness in reducing symptoms of depression, high heterogeneity among studies precludes definitive conclusions for all outcomes. With the current reliance and accessibility of technology to increasing number of people worldwide, serious consideration in utilizing technology should be given to maximize accessibility for depression treatments. Our results found eCBT is at least as effective as face to face CBT, thus eCBT should be offered if preferred by patients and therapists.

Funding: This research received no specific grant from any funding agency in the public, commercial or not-for-profit sectors.
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http://dx.doi.org/10.1016/j.eclinm.2020.100442DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7393662PMC
July 2020

Utility of Optical Coherence Tomography in the Diagnosis and Management of Optic Neuropathy in Patients with Fibrous Dysplasia.

J Bone Miner Res 2020 11 24;35(11):2199-2210. Epub 2020 Aug 24.

Skeletal Disorders and Mineral Homeostasis Section, National Institute of Dental and Craniofacial Research, National Institutes of Health, Bethesda, MD, USA.

Optic neuropathy (ON) is a highly disabling complication of fibrous dysplasia (FD). The optimal test for identifying and monitoring ON in FD is unknown. Optical coherence tomography (OCT) is an imaging modality that detects retinal nerve fiber layer (RNFL) thinning, a sign of optic nerve atrophy. The purpose of this study was to (i) assess the ability of OCT RNFL thickness measurements to identify ON in FD; (ii) compare the performance of RNFL thickness to computed tomography measurements; and (iii) examine changes in RNFL thickness over time to assess disease progression. A retrospective cohort study was performed to assess subjects (n = 70) who underwent neuro-ophthalmologic examination, including OCT. The diagnostic utility of RNFL thickness was determined using receiver operator characteristic (ROC) curve analysis, and the accuracy was compared with computed tomography measurements. The relationship between RNFL thickness and age was assessed cross-sectionally, using generalized estimating equation methodology, and longitudinally, using a generalized mixed model. Eleven subjects were identified with ON. RNFL thickness identified ON (area under curve = 0.997, p < 0.0001) with sensitivity and specificity of 100% and 95%, respectively, when using the diagnostic criterion of ≤71 μm. RNFL thickness outperformed computed tomography measurements of optic canal narrowing and optic nerve stretch. Subjects with ON exhibited a greater decrease in RNFL thickness with each year of age (-0.70 μm/year, p < 0.001) than subjects with normal vision (-0.16 μm/year, p < 0.05). When assessed longitudinally, subjects with normal vision demonstrated an increase in RNFL thickness until approximately age 20 years that decreased thereafter. In contrast, subjects with ON exhibited an earlier decrease in RNFL thickness during adolescence. In conclusion, RNFL thickness of ≤71 μm accurately identified ON in this population. By establishing the difference in rate of RNFL thinning in patients with and without ON, clinicians may distinguish between patients at risk for ON and intervene before irreversible damage. © 2020 American Society for Bone and Mineral Research.
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http://dx.doi.org/10.1002/jbmr.4129DOI Listing
November 2020

Model averaging methods for the evaluation of dose-response model uncertainty when assessing the suitability of studies for estimating risk.

Environ Int 2020 10 29;143:105857. Epub 2020 Jun 29.

CPHEA U.S. Environmental Protection Agency, Research Triangle Park, NC, USA.

This paper describes the use of multiple models and model averaging for considering dose-response uncertainties when extrapolating low-dose risk from studies of populations with high levels of exposure. The model averaging approach we applied builds upon innovative methods developed by the U.S. Food and Drug Administration (FDA), principally through the relaxing of model constraints. The relaxing of model constraints allowed us to evaluate model uncertainty using a broader set of model forms and, within the context of model averaging, did not result in the extreme supralinearity that is the primary concern associated with the application of individual unconstrained models. A study of the relationship between inorganic arsenic exposure to a Taiwanese population and potential carcinogenic effects is used to illustrate the approach. We adjusted the reported number of cases from two published prospective cohort studies of bladder and lung cancer in a Taiwanese population to account for potential covariates and less-than-lifetime exposure (for estimating effects on lifetime cancer incidence), used bootstrap methods to estimate the uncertainty surrounding the µg/kg-day inorganic arsenic dose from drinking water and dietary intakes, and fit multiple models weighted by Bayesian Information Criterion to the adjusted incidence and dose data to generate dose-specific mean, 2.5th and 97.5th percentile risk estimates. Widely divergent results from adequate model fits for a broad set of constrained and unconstrained models applied individually and in a model averaging framework suggest that substantial model uncertainty exists in risk extrapolation from estimated doses in the Taiwanese studies to lower doses more relevant to countries like the U.S. that have proportionally lower arsenic intake levels.
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http://dx.doi.org/10.1016/j.envint.2020.105857DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7708422PMC
October 2020

Systematic dose-response of environmental epidemiologic studies: Dose and response pre-analysis.

Environ Int 2020 09 17;142:105810. Epub 2020 Jun 17.

Center for Public Health and Environmental Assessment, U.S. EPA, Washington, DC, USA.

Meta-analysis approaches can be used to assess the human risks due to exposure to environmental chemicals when there are numerous high-quality epidemiologic studies of priority outcomes in a database. However, methodological issues related to how different studies report effect measures and incorporate exposure into their analyses arise that complicate the pooled analysis of multiple studies. As such, there are "pre-analysis" steps that are often necessary to prepare summary data reported in epidemiologic studies for dose-response analysis. This paper uses epidemiologic studies of arsenic-induced health effects as a case example and addresses the issues surrounding the estimation of mean doses from censored dose- or exposure-intervals reported in the literature (e.g., estimation of mean doses from high exposures that are only reported as an open-ended interval), calculation of a common dose metric for use in a dose-response meta-analysis (one that takes into consideration inter-individual variability), and calculation of response "effective counts" that inherently account for confounders. The methods herein may be generalizable to 1) the analysis of other environmental contaminants with a suitable database of epidemiologic studies, and 2) any meta-analytic approach used to pool information across studies. A second companion paper detailing the use of "pre-analyzed" data in a hierarchical Bayesian dose-response model and techniques for extrapolating risks to target populations follows.
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http://dx.doi.org/10.1016/j.envint.2020.105810DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7534797PMC
September 2020

Author Correction: Potential circadian effects on translational failure for neuroprotection.

Nature 2020 Jul;583(7814):E14

Neuroprotection Research Laboratories, Departments of Radiology and Neurology, Massachusetts General Hospital, Harvard Medical School, Boston, MA, USA.

An amendment to this paper has been published and can be accessed via a link at the top of the paper.
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http://dx.doi.org/10.1038/s41586-020-2427-1DOI Listing
July 2020

Generation of human induced pluripotent stem cell line (NIDCRi001-A) from a Muenke syndrome patient with an FGFR3 p.Pro250Arg mutation.

Stem Cell Res 2020 07 19;46:101823. Epub 2020 May 19.

Skeletal Biology Section, National Institute of Dental and Craniofacial Research, National Institutes of Health, Department of Health and Human Services, Bethesda, MD 20892, USA. Electronic address:

Muenke syndrome is the leading genetic cause of craniosynostosis and results in a variety of disabling clinical phenotypes. To model the disease and study the pathogenic mechanisms, a human induced pluripotent stem cell (hiPSC) line was generated from a patient diagnosed with Muenke syndrome. Successful reprogramming was validated by morphological features, karyotyping, loss of reprogramming factors, expression of pluripotency markers, mutation analysis and teratoma formation.
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http://dx.doi.org/10.1016/j.scr.2020.101823DOI Listing
July 2020

Potential circadian effects on translational failure for neuroprotection.

Nature 2020 06 3;582(7812):395-398. Epub 2020 Jun 3.

Neuroprotection Research Laboratories, Departments of Radiology and Neurology, Massachusetts General Hospital, Harvard Medical School, Boston, MA, USA.

Neuroprotectant strategies that have worked in rodent models of stroke have failed to provide protection in clinical trials. Here we show that the opposite circadian cycles in nocturnal rodents versus diurnal humans may contribute to this failure in translation. We tested three independent neuroprotective approaches-normobaric hyperoxia, the free radical scavenger α-phenyl-butyl-tert-nitrone (αPBN), and the N-methyl-D-aspartic acid (NMDA) antagonist MK801-in mouse and rat models of focal cerebral ischaemia. All three treatments reduced infarction in day-time (inactive phase) rodent models of stroke, but not in night-time (active phase) rodent models of stroke, which match the phase (active, day-time) during which most strokes occur in clinical trials. Laser-speckle imaging showed that the penumbra of cerebral ischaemia was narrower in the active-phase mouse model than in the inactive-phase model. The smaller penumbra was associated with a lower density of terminal deoxynucleotidyl transferase dUTP nick end labelling (TUNEL)-positive dying cells and reduced infarct growth from 12 to 72 h. When we induced circadian-like cycles in primary mouse neurons, deprivation of oxygen and glucose triggered a smaller release of glutamate and reactive oxygen species, as well as lower activation of apoptotic and necroptotic mediators, in 'active-phase' than in 'inactive-phase' rodent neurons. αPBN and MK801 reduced neuronal death only in 'inactive-phase' neurons. These findings suggest that the influence of circadian rhythm on neuroprotection must be considered for translational studies in stroke and central nervous system diseases.
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http://dx.doi.org/10.1038/s41586-020-2348-zDOI Listing
June 2020

Lineage-specific differentiation of osteogenic progenitors from pluripotent stem cells reveals the FGF1-RUNX2 association in neural crest-derived osteoprogenitors.

Stem Cells 2020 09 9;38(9):1107-1123. Epub 2020 Jun 9.

Department of Health and Human Services, Craniofacial and Skeletal Diseases Branch, National Institute of Dental and Craniofacial Research, National Institutes of Health, Bethesda, Maryland, USA.

Human pluripotent stem cells (hPSCs) can provide a platform to model bone organogenesis and disease. To reflect the developmental process of the human skeleton, hPSC differentiation methods should include osteogenic progenitors (OPs) arising from three distinct embryonic lineages: the paraxial mesoderm, lateral plate mesoderm, and neural crest. Although OP differentiation protocols have been developed, the lineage from which they are derived, as well as characterization of their genetic and molecular differences, has not been well reported. Therefore, to generate lineage-specific OPs from human embryonic stem cells and human induced pluripotent stem cells, we employed stepwise differentiation of paraxial mesoderm-like cells, lateral plate mesoderm-like cells, and neural crest-like cells toward their respective OP subpopulation. Successful differentiation, confirmed through gene expression and in vivo assays, permitted the identification of transcriptomic signatures of all three cell populations. We also report, for the first time, high FGF1 levels in neural crest-derived OPs-a notable finding given the critical role of fibroblast growth factors (FGFs) in osteogenesis and mineral homeostasis. Our results indicate that FGF1 influences RUNX2 levels, with concomitant changes in ERK1/2 signaling. Overall, our study further validates hPSCs' power to model bone development and disease and reveals new, potentially important pathways influencing these processes.
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http://dx.doi.org/10.1002/stem.3206DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7484058PMC
September 2020

Mitigating osteonecrosis of the jaw (ONJ) through preventive dental care and understanding of risk factors.

Bone Res 2020 11;8:14. Epub 2020 Mar 11.

1National Institute of Dental and Craniofacial Research, National Institutes of Health, Bethesda, MD USA.

It is well established that alterations in phosphate metabolism have a profound effect on hard and soft tissues of the oral cavity. The present-day clinical form of osteonecrosis of the jaw (ONJ) was preceded by phosphorus necrosis of the jaw, ca. 1860. The subsequent removal of yellow phosphorus from matches in the early 20th century saw a parallel decline in "phossy jaw" until the early 2000s, when similar reports of unusual jaw bone necrosis began to appear in the literature describing jaw necrosis in patients undergoing chemotherapy and concomitant steroid and bisphosphonate treatment. Today, the potential side effect of ONJ associated with medications that block osteoclast activity (antiresorptive) is well known, though the mechanism remains unclear and the management and outcomes are often unsatisfactory. Much of the existing literature has focused on the continuing concerns of appropriate use of bisphosphonates and other antiresorptive medications, the incomplete or underdeveloped research on ONJ, and the use of drugs with anabolic potential for treatment of osteoporosis. While recognizing that ONJ is a rare occurrence and ONJ-associated medications play an important role in fracture risk reduction in osteoporotic patients, evidence to date suggests that health care providers can lower the risk further by dental evaluations and care prior to initiating antiresorptive therapies and by monitoring dental health during and after treatment. This review describes the current clinical management guidelines for ONJ, the critical role of dental-medical management in mitigating risks, and the current understanding of the effects of predominantly osteoclast-modulating drugs on bone homeostasis.
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http://dx.doi.org/10.1038/s41413-020-0088-1DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7064532PMC
March 2020

Severity of oro-dental anomalies in Loeys-Dietz syndrome segregates by gene mutation.

J Med Genet 2020 10 8;57(10):699-707. Epub 2020 Mar 8.

Craniofacial Anomalies and Regeneration Section, National Institute of Dental and Craniofacial Research, Bethesda, Maryland, USA

Loeys-Dietz syndrome (LDS), an autosomal dominant rare connective tissue disorder, has multisystemic manifestations, characterised by vascular tortuosity, aneurysms and craniofacial manifestations. Based on the associated gene mutations along the transforming growth factor-beta (TGF-β) pathway, LDS is presently classified into six subtypes. We present the oro-dental features of a cohort of 40 patients with LDS from five subtypes. The most common oro-dental manifestations were the presence of a high-arched and narrow palate, and enamel defects. Other common characteristics included bifid uvula, submucous cleft palate, malocclusion, dental crowding and delayed eruption of permanent teeth. Both deciduous and permanent teeth had enamel defects in some individuals. We established a grading system to measure the severity of enamel defects, and we determined that the severity of the enamel anomalies in LDS is subtype-dependent. In specific, patients with TGF-β receptor II mutations (LDS2) presented with the most severe enamel defects, followed by patients with TGF-β receptor I mutations (LDS1). LDS2 patients had higher frequency of oro-dental deformities in general. Across all five subtypes, as well as within each subtype, enamel defects exhibited incomplete penetrance and variable expression, which is not associated with the location of the gene mutations. This study describes, in detail, the oro-dental manifestations in a cohort of LDS, and we conclude that LDS2 has the most severely affected phenotype. This extensive characterisation, as well as some identified distinguishing features can significantly aid dental and medical care providers in the diagnosis and clinical management of patients with this rare connective tissue disorder.
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http://dx.doi.org/10.1136/jmedgenet-2019-106678DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7525783PMC
October 2020

Abacavir Exposure in Children Cotreated for Tuberculosis with Rifampin and Superboosted Lopinavir-Ritonavir.

Antimicrob Agents Chemother 2020 04 21;64(5). Epub 2020 Apr 21.

Division of Clinical Pharmacology, Department of Medicine, University of Cape Town, Cape Town, South Africa

In children requiring lopinavir coformulated with ritonavir in a 4:1 ratio (lopinavir-ritonavir-4:1) and rifampin, adding ritonavir to achieve a 4:4 ratio with lopinavir (LPV/r-4:4) overcomes the drug-drug interaction. Possible drug-drug interactions within this regimen may affect abacavir concentrations, but this has never been studied. Children weighing <15 kg needing rifampin and LPV/r-4:4 were enrolled in a pharmacokinetic study and underwent intensive pharmacokinetic sampling on 3 visits: (i) during the intensive and (ii) continuation phases of antituberculosis treatment with LPV/r-4:4 and (iii) 1 month after antituberculosis treatment completion on LPV/r-4:1. Pharmacometric modeling and simulation were used to compare exposures across weight bands with adult target exposures. Eighty-seven children with a median (interquartile range) age and weight of 19 (4 to 64) months and 8.7 (3.9 to 14.9) kg, respectively, were included in the abacavir analysis. Abacavir pharmacokinetics were best described by a two-compartment model with first-order elimination and transit compartment absorption. After allometric scaling adjusted for the effect of body size, maturation could be identified: clearance was predicted to be fully mature at about 2 years of age and to reach half of this mature value at about 2 months of age. Abacavir bioavailability decreased 36% during treatment with rifampin and LPV/r-4:4 but remained within the median adult recommended exposure, except for children in the 3- to 4.9-kg weight band, in which the exposures were higher. The observed predose morning trough concentrations were higher than the evening values. Though abacavir exposure significantly decreased during concomitant administration of rifampin and LPV/r-4:4, it remained within acceptable ranges. (This study is registered in ClinicalTrials.gov under identifier NCT02348177.).
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http://dx.doi.org/10.1128/AAC.01923-19DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7179606PMC
April 2020

Insight Into the Ontogeny of GnRH Neurons From Patients Born Without a Nose.

J Clin Endocrinol Metab 2020 05;105(5)

Clinical Research Branch, National Institute of Environmental Health Sciences, Durham, North Carolina.

Context: The reproductive axis is controlled by a network of gonadotropin-releasing hormone (GnRH) neurons born in the primitive nose that migrate to the hypothalamus alongside axons of the olfactory system. The observation that congenital anosmia (inability to smell) is often associated with GnRH deficiency in humans led to the prevailing view that GnRH neurons depend on olfactory structures to reach the brain, but this hypothesis has not been confirmed.

Objective: The objective of this work is to determine the potential for normal reproductive function in the setting of completely absent internal and external olfactory structures.

Methods: We conducted comprehensive phenotyping studies in 11 patients with congenital arhinia. These studies were augmented by review of medical records and study questionnaires in another 40 international patients.

Results: All male patients demonstrated clinical and/or biochemical signs of GnRH deficiency, and the 5 men studied in person had no luteinizing hormone (LH) pulses, suggesting absent GnRH activity. The 6 women studied in person also had apulsatile LH profiles, yet 3 had spontaneous breast development and 2 women (studied from afar) had normal breast development and menstrual cycles, suggesting a fully intact reproductive axis. Administration of pulsatile GnRH to 2 GnRH-deficient patients revealed normal pituitary responsiveness but gonadal failure in the male patient.

Conclusions: Patients with arhinia teach us that the GnRH neuron, a key gatekeeper of the reproductive axis, is associated with but may not depend on olfactory structures for normal migration and function, and more broadly, illustrate the power of extreme human phenotypes in answering fundamental questions about human embryology.
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http://dx.doi.org/10.1210/clinem/dgaa065DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7108682PMC
May 2020

Craniofacial Analysis May Indicate Co-Occurrence of Skeletal Malocclusions and Associated Risks in Development of Cleft Lip and Palate.

J Dev Biol 2020 Jan 28;8(1). Epub 2020 Jan 28.

Craniofacial Anomalies and Regeneration Section, NIDCR, NIH, Bethesda, MD 20892-1470, USA.

Non-syndromic orofacial clefts encompass a range of morphological changes affecting the oral cavity and the craniofacial skeleton, of which the genetic and epigenetic etiologic factors remain largely unknown. The objective of this study is to explore the contribution of underlying dentofacial deformities (also known as skeletal malocclusions) in the craniofacial morphology of non-syndromic cleft lip and palate patients (nsCLP). For that purpose, geometric morphometric analysis was performed using full skull cone beam computed tomography (CBCT) images of patients with nsCLP ( = 30), normocephalic controls ( = 60), as well as to sex- and ethnicity- matched patients with an equivalent dentofacial deformity ( = 30). Our outcome measures were shape differences among the groups quantified via principal component analysis and associated principal component loadings, as well as mean shape differences quantified via a Procrustes distance among groups. According to our results, despite the shape differences among all three groups, the nsCLP group shares many morphological similarities in the maxilla and mandible with the dentofacial deformity group. Therefore, the dentoskeletal phenotype in nsCLP could be the result of the cleft and the coexisting dentofacial deformity and not simply the impact of the cleft.
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http://dx.doi.org/10.3390/jdb8010002DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7151201PMC
January 2020

Primary Cilia Signaling Promotes Axonal Tract Development and Is Disrupted in Joubert Syndrome-Related Disorders Models.

Dev Cell 2019 12;51(6):759-774.e5

UNC Neuroscience Center and the Department of Cell and Molecular Physiology, University of North Carolina School of Medicine, Chapel Hill, NC 27599, USA. Electronic address:

Appropriate axonal growth and connectivity are essential for functional wiring of the brain. Joubert syndrome-related disorders (JSRD), a group of ciliopathies in which mutations disrupt primary cilia function, are characterized by axonal tract malformations. However, little is known about how cilia-driven signaling regulates axonal growth and connectivity. We demonstrate that the deletion of related JSRD genes, Arl13b and Inpp5e, in projection neurons leads to de-fasciculated and misoriented axonal tracts. Arl13b deletion disrupts the function of its downstream effector, Inpp5e, and deregulates ciliary-PI3K/AKT signaling. Chemogenetic activation of ciliary GPCR signaling and cilia-specific optogenetic modulation of downstream second messenger cascades (PI3K, AKT, and AC3) commonly regulated by ciliary signaling receptors induce rapid changes in axonal dynamics. Further, Arl13b deletion leads to changes in transcriptional landscape associated with dysregulated PI3K/AKT signaling. These data suggest that ciliary signaling acts to modulate axonal connectivity and that impaired primary cilia signaling underlies axonal tract defects in JSRD.
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http://dx.doi.org/10.1016/j.devcel.2019.11.005DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6953258PMC
December 2019

Oral health-related quality of life in Loeys-Dietz syndrome, a rare connective tissue disorder: an observational cohort study.

Orphanet J Rare Dis 2019 12 16;14(1):291. Epub 2019 Dec 16.

Craniofacial Anomalies and Regeneration Section, National Institute of Dental and Craniofacial Research, National Institutes of Health, Bethesda, MD, USA.

Background: Loeys-Dietz syndrome (LDS) is a rare connective tissue disorder whose oral manifestations and dental phenotypes have not been well-characterized. The aim of this study was to explore the influence of oral manifestations on oral health-related quality of life (OHRQoL) in LDS patients.

Material And Methods: LDS subjects were assessed by the craniofacial team at the National Institutes of Health Clinical Center Dental Clinic between June 2015 and January 2018. Oral Health Impact Profile (OHIP-14) questionnaire, oral health self-care behavior questionnaire and a comprehensive dental examination were completed for each subject. OHRQoL was assessed using the OHIP-14 questionnaire with higher scores corresponding to worse OHRQoL. Regression models were used to determine the relationship between each oral manifestation and the OHIP-14 scores using a level of significance of p ≤ 0.05.

Results: A total of 33 LDS subjects (51.5% female) aged 3-57 years (19.6 ± 15.1 years) were included in the study. The OHIP-14 scores (n = 33) were significantly higher in LDS subjects (6.30 [SD 6.37]) when compared to unaffected family member subjects (1.50 [SD 2.28], p < 0.01), and higher than the previously reported scores of the general U.S. population (2.81 [SD 0.12]). Regarding oral health self-care behavior (n = 32), the majority of LDS subjects reported receiving regular dental care (81%) and maintaining good-to-excellent daily oral hygiene (75%). Using a crude regression model, worse OHRQoL was found to be associated with dental hypersensitivity (β = 5.24; p < 0.05), temporomandibular joints (TMJ) abnormalities (β = 5.92; p < 0.01), self-reported poor-to-fair oral health status (β = 6.77; p < 0.01), and cumulation of four or more oral manifestations (β = 7.23; p < 0.001). Finally, using a parsimonious model, self-reported poor-to-fair oral health status (β = 5.87; p < 0.01) and TMJ abnormalities (β = 4.95; p < 0.01) remained significant.

Conclusions: The dental hypersensitivity, TMJ abnormalities, self-reported poor-to-fair oral health status and cumulation of four-or-more oral manifestations had significant influence on worse OHRQoL. Specific dental treatment guidelines are necessary to ensure optimal quality of life in patients diagnosed with LDS.
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http://dx.doi.org/10.1186/s13023-019-1250-yDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6915860PMC
December 2019

Heterogeneity of microglia and their differential roles in white matter pathology.

CNS Neurosci Ther 2019 12 15;25(12):1290-1298. Epub 2019 Nov 15.

Neuroprotection Research Laboratory, Departments of Radiology and Neurology, Massachusetts General Hospital and Harvard Medical School, Charlestown, MA, USA.

Microglia are resident immune cells that play multiple roles in central nervous system (CNS) development and disease. Although the classical concept of microglia/macrophage activation is based on a biphasic beneficial-versus-deleterious polarization, growing evidence now suggests a much more heterogenous profile of microglial activation that underlie their complex roles in the CNS. To date, the majority of data are focused on microglia in gray matter. However, demyelination is a prominent pathologic finding in a wide range of diseases including multiple sclerosis, Alzheimer's disease, and vascular cognitive impairment and dementia. In this mini-review, we discuss newly discovered functional subsets of microglia that contribute to white matter response in CNS disease onset and progression. Microglia show different molecular patterns and morphologies depending on disease type and brain region, especially in white matter. Moreover, in later stages of disease, microglia demonstrate unconventional immuno-regulatory activities such as increased phagocytosis of myelin debris and secretion of trophic factors that stimulate oligodendrocyte lineage cells to facilitate remyelination and disease resolution. Further investigations of these multiple microglia subsets may lead to novel therapeutic approaches to treat white matter pathology in CNS injury and disease.
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http://dx.doi.org/10.1111/cns.13266DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6887901PMC
December 2019

Data-driven method to enhance craniofacial and oral phenotype vocabularies.

J Am Dent Assoc 2019 11;150(11):933-939.e2

Background: A significant amount of clinical information captured as free-text narratives could be better used for several applications, such as clinical decision support, ontology development, evidence-based practice, and research. The Human Phenotype Ontology (HPO) is specifically used for semantic comparisons for diagnostic purposes. All these functions require quality coverage of the domain of interest. The authors used natural language processing to capture craniofacial and oral phenotype signatures from electronic health records and then used these signatures for evaluation of existing oral phenotype ontology coverage.

Methods: The authors applied a text-processing pipeline based on the clinical Text Analysis and Knowledge Extraction System to annotate the clinical notes with Unified Medical Language System codes. The authors extracted the disease or disorder phenotype terms, which were then compared with HPO terms and their synonyms.

Results: The authors retrieved 2,153 deidentified clinical notes from 558 patients. Finally, 2,416 unique diseases or disorders phenotype terms were extracted, which included 210 craniofacial or oral phenotype terms. Twenty-six of these phenotypes were not found in the HPO.

Conclusions: The authors demonstrated that natural language processing tools could extract relevant phenotype terms from clinical narratives, which could help identify gaps in existing ontologies and enhance craniofacial and dental phenotyping vocabularies.

Practical Implications: The expansion of terms in the dental, oral, and craniofacial domains in the HPO is particularly important as the dental community moves toward electronic health records.
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http://dx.doi.org/10.1016/j.adaj.2019.05.029DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6827714PMC
November 2019

Saiga horn user characteristics, motivations, and purchasing behaviour in Singapore.

PLoS One 2019 10;14(9):e0222038. Epub 2019 Sep 10.

Department of Zoology, University of Oxford, Oxford, United Kingdom.

Unsustainable wildlife trade is a pervasive issue affecting wildlife globally. To address this issue, a plethora of demand reduction efforts have been carried out. These necessitate consumer research which provides crucial knowledge for designing and evaluating targeted interventions. We implemented a rigorous consumer survey on saiga (Saiga tatarica) horn use in Singapore, where usage is legal and widely sold. Saiga are Critically Endangered antelopes from Central Asia with horns (often marketed as ling yang) used in traditional Chinese medicine (TCM). Few past studies have assessed saiga horn consumers. This work is the most extensive consumer research to date specifically characterising saiga horn consumers and usage. We conducted 2294 in-person surveys on saiga horn use with Chinese Singaporeans, employing neutral questioning approaches. We found 19% of individuals reported saiga horn as a product they choose most often for themselves and/or others when treating fever and/or heatiness (a TCM state of illness), indicating a minimum estimate of high-frequency usage, not including possible low-frequency users. Overall saiga users were most characterised as middle-aged Buddhists and Taoists. However, saiga users were found in a range of demographic groups. Women preferred saiga shavings (the more traditional form), while men preferred saiga cooling water (the more modern form). About 53% of individuals who used saiga horn themselves also bought it for someone else. Buyers for others were most likely to be female middle-aged Buddhists or Taoists. Key motivating reasons for usage were "it works" and "someone recommended it to me." The top two reported recommenders were family and TCM shopkeepers. Saiga users were more likely than non-saiga users to perceive saiga as a common species in the wild. This research holds significance for interventions targeting saiga horn consumption within Singapore and throughout Asia, by identifying potential target audiences, product types, non-desirable alternatives, and motivations for use.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0222038PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6736248PMC
March 2020