Publications by authors named "Emily Kim"

41 Publications

Predictors of attrition in a smoking cessation trial conducted in the lung cancer screening setting.

Contemp Clin Trials 2021 May 5:106429. Epub 2021 May 5.

Georgetown University Medical Center, D.C., USA. Electronic address:

Significance: Although it is a requirement that tobacco treatment is offered to cigarette smokers undergoing low-dose computed tomographic lung cancer screening (LCS), not all smokers engage in treatment. To understand the barriers to tobacco treatment in this setting, we evaluated predictors of attrition in a smoking cessation trial among individuals undergoing LCS.

Methods: Prior to LCS, 926 participants, 50-80 years old, completed the baseline (T0) phone assessment, including demographic, clinical, tobacco, and psychological characteristics. Following LCS and receipt of the results, participants completed the pre-randomization (T1) assessment.

Results: At the T1 assessment, 735 (79%) participants were retained and 191 (21%) dropped out. In multivariable analyses, attrition was higher among those who: smoked >1 pack per day (OR = 1.44, CI 1.01, 2.06) or had undergone their first (vs. annual) LCS scan (OR = 1.70, CI 1.20, 2.42). Attrition was lower among those with: more education (associates (OR = 0.67, CI = 0.46, 0.98) or bachelor's degree (OR = 0.56, CI 0.35, 0.91) vs. high school/GED), some (vs. none/a little) worry about lung cancer (OR = 0.60, CI 0.39, 0.92), or a screening result that was benign (OR = 0.57, CI 0.39, 0.82) or probably benign (OR = 0.38, CI 0.16, 0.90) vs. negative.

Conclusions: This study illuminated several LCS-related factors that contributed to trial attrition. Increasing tobacco treatment in this setting will require targeted strategies for those who. report little lung cancer worry, are undergoing their first LCS exam, and/or who have a negative LCS result. Addressing attrition and reducing barriers to tobacco treatment will increase. the likelihood of cessation, thereby reducing the risk of developing lung cancer.
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http://dx.doi.org/10.1016/j.cct.2021.106429DOI Listing
May 2021

A qualitative study exploring older smokers' attitudes and motivation toward quitting during the COVID-19 pandemic.

Prev Med Rep 2021 Jun 11;22:101359. Epub 2021 Mar 11.

Georgetown University Medical Center, Washington, DC, USA.

Older individuals who smoke are at increased risk of having severe outcomes from COVID-19, due to their long-term smoking and underlying health conditions. In this qualitative study, we explored the impact of COVID-19 on attitudes toward smoking and motivation to quit. Participants (N = 30) were enrolled in a larger ongoing randomized controlled smoking cessation trial conducted in the lung cancer screening setting. From March to May 2020, we assessed quantitative and qualitative responses to participants' overall concern about COVID-19, changes in amount smoked, and motivation to reduce/quit smoking. Responses to the quantitative questions indicated that 64.3% of participants were extremely concerned with COVID-19, 20.7% reported reductions in amount smoked, and 37.9% reported increased motivation to quit. The qualitative responses, which were transcribed and coded using Consensual Qualitative Research guidelines, expanded upon these findings by providing the content of participants' concerns, which included perceived risk of contracting COVID-19, the added stressors caused by COVID-19, and a variable impact on the amount smoked and motivation to quit. Although half of participants expressed extreme concern regarding COVID-19, fewer indicated increased motivation or reduced smoking. Qualitative themes suggested that the initial two months of the pandemic prompted some smokers to reduce or quit, but it exacerbated smoking triggers for others. Understanding how the pandemic continues to affect this vulnerable group will aid in adapting methods to support their efforts to stop smoking and remain abstinent.
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http://dx.doi.org/10.1016/j.pmedr.2021.101359DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8044671PMC
June 2021

A functional genomics screen identifying blood cell development genes in Drosophila by undergraduates participating in a course-based research experience.

G3 (Bethesda) 2021 Jan;11(1)

Department of Molecular, Cell, and Developmental Biology, University of California, Los Angeles, Los Angeles, CA 90095, USA.

Undergraduate students participating in the UCLA Undergraduate Research Consortium for Functional Genomics (URCFG) have conducted a two-phased screen using RNA interference (RNAi) in combination with fluorescent reporter proteins to identify genes important for hematopoiesis in Drosophila. This screen disrupted the function of approximately 3500 genes and identified 137 candidate genes for which loss of function leads to observable changes in the hematopoietic development. Targeting RNAi to maturing, progenitor, and regulatory cell types identified key subsets that either limit or promote blood cell maturation. Bioinformatic analysis reveals gene enrichment in several previously uncharacterized areas, including RNA processing and export and vesicular trafficking. Lastly, the participation of students in this course-based undergraduate research experience (CURE) correlated with increased learning gains across several areas, as well as increased STEM retention, indicating that authentic, student-driven research in the form of a CURE represents an impactful and enriching pedagogical approach.
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http://dx.doi.org/10.1093/g3journal/jkaa028DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8022729PMC
January 2021

In ovo feeding of epidermal growth factor: embryonic expression of intestinal epidermal growth factor receptor and posthatch growth performance and intestinal development in broiler chickens.

Poult Sci 2020 Nov 7;99(11):5736-5743. Epub 2020 Aug 7.

Department of Animal Biosciences, University of Guelph, Guelph, ON, Canada. Electronic address:

We investigated efficacy of in ovo application of epidermal growth factor (EGF) on intestinal expression of EGF receptor (EGFR) during embryogenesis (experiment 1) and posthatch growth performance and gastrointestinal development in broiler chickens (experiment 2). In experiment 1, 450 fertile Ross 708 eggs were allocated to 3 groups (150 eggs/group): 1) control, 2) 160 μg EGF/kg of egg, and 3) 640 μg of EGF/kg of egg. Eggs were candled for live embryos on day 16 and injected with the respective treatment solutions on day 17 and sampled for jejunal tissue from day 17 to hatch for EGFR analyses. There was no effect of EGF (P > 0.05) on EGFR expression on day 17 to 20; however, on day 21, EGF increased (P < 0.05) EGFR expression in EGF birds relative to control birds. In experiment 2, 600 fertile Ross 708 eggs were allocated to 5 treatments: 1) intact, no puncture or injection, 2) punched but not injected, 3) control, no EGF, 4) 80 μg of EGF/kg of egg, and 5) 160 μg of EGF/kg of egg. The eggs were incubated and candled for live embryos on D 19, treated, and subsequently transferred to the hatcher. Upon hatching, chicks were weighed, and 90 chicks per treatment placed in cages (15 birds/cage) and allowed free access to a standard antibiotic-free corn-soybean diet for 21 D. Feed intake and body weight were monitored on a weekly basis. Samples of birds were necropsied on D 0, 7, 14, and 21 for measurements of intestinal weight and jejunal histomorphology and excreta samples taken on D 3 to 5 and 17 to 19 for apparent retention of dry matter. There was no EGF effect (P > 0.05) on any posthatch response criteria. In conclusion, in ovo application of EGF increased EGFR expression but had no effect on posthatch growth performance, DM retention, and intestinal development. The lack of EGF effect on posthatch response was surprising but suggested in ovo application of EGF may not be a viable approach.
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http://dx.doi.org/10.1016/j.psj.2020.07.029DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7647735PMC
November 2020

Adaptation of an Evidence-Based Intervention for Disability Prevention, Implemented by Community Health Workers Serving Ethnic Minority Elders.

Am J Geriatr Psychiatry 2021 03 30;29(3):260-269. Epub 2020 Jul 30.

Disparities Research Unit, Department of Medicine, Massachusetts General Hospital, Boston, MA; Department of Medicine, Harvard Medical School, Boston, MA; Department of Psychiatry, Harvard Medical School, Boston, MA.

Introduction: Changing demographics have created substantial unmet needs for mental health and physical disability services for immigrant and racial/ethnic minority elders. Workforce shortages can be reduced by task-shifting to community health workers (CHWs) who speak the same language and share the culture of these elders. Yet, implementation of interventions offered by CHWs requires adaptations of content and delivery, ideally under clinical supervision.

Objective: To culturally adapt two evidence-based interventions, offered in community settings, to address mental health and physical disability prevention for diverse minority elders.

Methods: We followed the Castro-Barrera stepped model for cultural adaptation of two evidence-based interventions into one combined program of disability management and prevention delivered by CHWs. We used feedback from key stakeholders, including four clinical supervisors, 16 CHWs, 17 exercise trainers, and 153 participants, collected at three time points to further adapt the intervention to a diverse population of elders.

Results: Adaptations for administration by CHWs/exercise trainers included: systematization of supervision process, increased flexibility in sessions offered per participants' needs, inclusion of self-care content, modification of materials to better reflect elders' daily life experiences, and greater focus on patient engagement in care. Areas for additional adaptation included enhancing examples with culturally relevant metaphors, incorporating visual aids, and training CHWs in the importance of building trust.

Conclusion: This study identifies key aspects of the cultural adaptation process that facilitates broader cultural sensitivity of service delivery by CHWs to diverse elders in community settings.
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http://dx.doi.org/10.1016/j.jagp.2020.07.014DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7855421PMC
March 2021

The importance of using multiple outcome measures in infant research.

Infancy 2020 07 28;25(4):420-437. Epub 2020 Apr 28.

University of Sussex, Brighton, UK.

Collecting data with infants is notoriously difficult. As a result, many of our studies consist of small samples, with only a single measure, in a single age group, at a single time point. With renewed calls for greater academic rigor in data collection practices, using multiple outcome measures in infant research is one way to increase rigor, and, at the same time, enable us to more accurately interpret our data. Here, we illustrate the importance of using multiple measures in psychological research with examples from our own work on rapid threat detection and from the broader infancy literature. First, we describe our initial studies using a single outcome measure, and how this strategy caused us to nearly miss a rich and complex story about attention biases for threat and their development. We demonstrate how using converging measures can help researchers make inferences about infant behavior, and how using additional measures allows us to more deeply examine the mechanisms that drive developmental change. Finally, we provide practical and statistical recommendations for how researchers can use multiple measures in future work.
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http://dx.doi.org/10.1111/infa.12339DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7405932PMC
July 2020

Using Storybooks to Teach Children About Illness Transmission and Promote Adaptive Health Behavior - A Pilot Study.

Front Psychol 2020 5;11:942. Epub 2020 Jun 5.

Child Study Center, Department of Psychology, Rutgers University, Newark, NJ, United States.

Although there is a large and growing literature on children's developing concepts of illness transmission, little is known about how children develop contagion knowledge before formal schooling begins and how these informal learning experiences can impact children's health behaviors. Here, we asked two important questions: first, do children's informal learning experiences, such as their experiences reading storybooks, regularly contain causal information about illness transmission; and second, what is the impact of this type of experience on children's developing knowledge and behavior? In Study 1, we examined whether children's commercial books about illness regularly contain contagion-relevant causal information. In Study 2, we ran a pilot study examining whether providing children with causal information about illness transmission in a storybook can influence their knowledge and subsequent behavior when presented with a contaminated object. The results from Study 1 suggest that very few (15%) children's books about illness feature biological causal mechanisms for illness transmission. However, results from Study 2 suggest that storybooks containing contagion-relevant explanations about illness transmission may encourage learning and avoidance of contaminated objects. Altogether, these results provide preliminary data suggesting that future research should focus on engaging children in learning about contagion and encouraging adaptive health behaviors.
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http://dx.doi.org/10.3389/fpsyg.2020.00942DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7289927PMC
June 2020

Differences in stability and calcium sensitivity of the Ig domains in titin's N2A region.

Protein Sci 2020 05 7;29(5):1160-1171. Epub 2020 Mar 7.

Chemistry Department, University of Massachusetts Lowell, Lowell, Massachusetts, USA.

Titin is a large filamentous protein that spans half a sarcomere, from Z-disk to M-line. The N2A region within the titin molecule exists between the proximal immunoglobulin (Ig) region and the PEVK region and protein-protein interactions involving this region are required for normal muscle function. The N2A region consists of four Ig domains (I80-I83) with a 105 amino acid linker region between I80 and I81 that has a helical nature. Using chemical stability measurements, we show that predicted differences between the adjacent Ig domains (I81-I83) correlate with experimentally determined differences in chemical stability and refolding kinetics. Our work further shows that I83 has the lowest ΔG , which is increased in the presence of calcium (pCa 4.3), indicating that Ca plays a role in stabilizing this immunoglobulin domain. The characteristics of N2A's three Ig domains provide insight into the stability of the binding sites for proteins that interact with the N2A region. This work also provides insights into how Ca might influence binding events involving N2A.
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http://dx.doi.org/10.1002/pro.3848DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7184778PMC
May 2020

Treatment with an immature dendritic cell-targeting vaccine supplemented with IFN-α and an inhibitor of DNA methylation markedly enhances survival in a murine melanoma model.

Cancer Immunol Immunother 2020 Apr 24;69(4):569-580. Epub 2020 Jan 24.

The W. Harry Feinstone Department of Molecular Microbiology and Immunology, Johns Hopkins Bloomberg School of Public Health, 615 N. Wolfe Street, Baltimore, MD, 21205, USA.

Background: The chemokine MIP-3α (CCL20) binds to CCR6 on immature dendritic cells. DNA vaccines fusing MIP-3α to melanoma-associated antigens have shown improved efficacy and immunogenicity in the B16F10 mouse melanoma model. Here, we report that the combination of type-I interferon therapy (IFNα) with 5-Aza-2'-deoxycitidine (5Aza) profoundly enhanced the therapeutic efficacy of a MIP-3α-Gp100-Trp2 DNA vaccine.

Methods: Beginning on day 5 post-transplantation of B16F10 melanoma, vaccine was administered intramuscularly (i.m.) by electroporation. CpG adjuvant was given 2 days later. 5Aza was given intraperitoneally at 1 mg/kg and IFNα therapy either intratumorally or i.m. as noted. Tumor sizes, tumor growth, and mouse survival were assessed. Tumor lysate gene expression levels and tumor-infiltrating lymphocytes (TILs) were assessed by qRT-PCR and flow cytometry, respectively.

Results: Adding IFNα and 5Aza treatments to mice vaccinated with MIP-3α-Gp100-Trp2 leads to reduced tumor burden and increased median survival (39% over vaccine and 95% over controls). Tumor lysate expression of CCL19 and CCR7 were upregulated ten and fivefold over vaccine, respectively. Vaccine-specific and overall CD8+ TILs were increased over vaccine (sevenfold and fourfold, respectively), as well as the proportion of TILs that were CD8+ (twofold).

Conclusions: Efficient targeting of antigen to immature dendritic cells with a chemokine-fusion vaccine offers an alternative to classic and dendritic cell vaccines. Combining this approach with IFNα and 5Aza treatment significantly improved vaccine efficacy. This improved efficacy correlated with changes in chemokine gene expression and CD8+ TIL infiltration and was dependent on the presence of all therapeutic components.
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http://dx.doi.org/10.1007/s00262-019-02471-0DOI Listing
April 2020

Loss of Oxidation Resistance 1, OXR1, Is Associated with an Autosomal-Recessive Neurological Disease with Cerebellar Atrophy and Lysosomal Dysfunction.

Am J Hum Genet 2019 12 27;105(6):1237-1253. Epub 2019 Nov 27.

Centre Hospitalier Universitaire Saint-Justine Research Center, CHU Sainte-Justine, Montreal, QC H3T 1J4, Canada. Electronic address:

We report an early-onset autosomal-recessive neurological disease with cerebellar atrophy and lysosomal dysfunction. We identified bi-allelic loss-of-function (LoF) variants in Oxidative Resistance 1 (OXR1) in five individuals from three families; these individuals presented with a history of severe global developmental delay, current intellectual disability, language delay, cerebellar atrophy, and seizures. While OXR1 is known to play a role in oxidative stress resistance, its molecular functions are not well established. OXR1 contains three conserved domains: LysM, GRAM, and TLDc. The gene encodes at least six transcripts, including some that only consist of the C-terminal TLDc domain. We utilized Drosophila to assess the phenotypes associated with loss of mustard (mtd), the fly homolog of OXR1. Strong LoF mutants exhibit late pupal lethality or pupal eclosion defects. Interestingly, although mtd encodes 26 transcripts, severe LoF and null mutations can be rescued by a single short human OXR1 cDNA that only contains the TLDc domain. Similar rescue is observed with the TLDc domain of NCOA7, another human homolog of mtd. Loss of mtd in neurons leads to massive cell loss, early death, and an accumulation of aberrant lysosomal structures, similar to what we observe in fibroblasts of affected individuals. Our data indicate that mtd and OXR1 are required for proper lysosomal function; this is consistent with observations that NCOA7 is required for lysosomal acidification.
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http://dx.doi.org/10.1016/j.ajhg.2019.11.002DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6904826PMC
December 2019

Growth characteristics and therapeutic decision markers in von Hippel-Lindau disease patients with renal cell carcinoma.

Orphanet J Rare Dis 2019 10 28;14(1):235. Epub 2019 Oct 28.

Department of Nephrology and Primary Care, Medical Center - University of Freiburg, Faculty of Medicine, University of Freiburg, Hugstetter Str. 55, 79106, Freiburg, Germany.

Background: Von Hippel-Lindau (VHL) disease is a multi-systemic hereditary disease associated with several benign and malignant tumor entities, including clear cell renal cell carcinoma (ccRCC). Since ccRCCs grow slowly, nephron sparing surgery is typically performed at a tumor diameter of 3-4 cm before the tumor metastasizes. However, in the case of recurrent disease, repeated surgical intervention can impair renal function. Therefore, it is crucial to optimize the timing for surgical interventions through a better understanding of the growth kinetics of ccRCCs in VHL. We investigated tumor growth kinetics and modern volumetric assessment to guide future therapeutic decisions.

Results: The prevalence of ccRCC was 28% in a cohort of 510 VHL patients. Of 144 patients with ccRCC, 41 were followed with serial imaging which identified 102 renal tumors, which exhibited heterogeneous growth kinetics. ccRCCs grew at an average absolute growth rate of 0.287 cm/year, an average relative growth rate [(lnV-lnV)/(t-t)] of 0.42% and an average volume doubling time of 27.15 months. Women had a faster relative growth rate than men. Age and specific mutations did not influence tumor growth. Because of the tumor heterogeneity, we developed an additional cut-off volume of 40 cm for surgical intervention.

Conclusions: Tumor heterogeneity and differences in growth kinetics is suggestive of a state of transient tumor dormancy in ccRCCs of VHL patients. The relative growth rate has not been previously described in other studies. Volumetric assessment as an additional parameter for surgical intervention could be a useful clinical tool and needs further investigation.
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http://dx.doi.org/10.1186/s13023-019-1206-2DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6819544PMC
October 2019

Study protocol for a telephone-based smoking cessation randomized controlled trial in the lung cancer screening setting: The lung screening, tobacco, and health trial.

Contemp Clin Trials 2019 07 23;82:25-35. Epub 2019 May 23.

Department of Pulmonary and Sleep Medicine, Georgetown University Medical Center, Washington, DC, United States.

Lung cancer mortality can be reduced by 20% via low dose CT lung cancer screening (LCS) and treatment of early-stage disease. Providing tobacco use treatment to high risk cigarette smokers in the LCS setting may result in health benefits beyond the impact of LCS. As one of the nine trials in the National Cancer Institute's Smoking Cessation at Lung Examination (SCALE) collaboration, the goal of the Lung Screening, Tobacco, and Health (LSTH) trial is to develop a scalable and cost-effective cessation intervention for subsequent implementation by LCS programs. Guided by the RE-AIM Framework, the LSTH trial is a two-arm RCT (N = 1330) enrolling English- and Spanish-speaking smokers registered for LCS at one of seven collaborating sites. Participants are randomly assigned to Usual Care (UC; three proactive telephone counseling sessions/two weeks of nicotine patches) vs. Intensive Telephone Counseling (ITC; eight proactive sessions/eight weeks of nicotine patches, plus discussion of the LCS results to increase motivation to quit). Telephone counseling is provided by tobacco treatment specialists. To increase continuity of care, referring physicians are notified of participant enrollment and smoking status following the intervention. Outcomes include: 1) self-reported 7-day, 30-day, and sustained abstinence, and biochemically-verified at 3-, 6-, and 12-months post-randomization, 2) reach and engagement of the interventions, and 3) cost-effectiveness of the interventions. The Cancer Intervention and Surveillance Modeling Network (CISNET) will model long-term impacts of six SCALE trials on the cost per life year saved, quality-adjusted life years saved, lung cancer mortality reduction, and population mortality. CLINICAL TRIALS REGISTRATION: The trial is registered at clinical trials.gov: NCT03200236.
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http://dx.doi.org/10.1016/j.cct.2019.05.006DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6657688PMC
July 2019

CD24 Cell Depletion Permits Effective Enrichment of Thymic NKT Cells While Preserving Their Subset Composition.

Immune Netw 2019 Apr 5;19(2):e14. Epub 2019 Mar 5.

Experimental Immunology Branch, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892, USA.

Invariant NKT (NKT) cells are a small subset of thymus-generated T cells that produce cytokines to control both innate and adaptive immunity. Because of their very low frequency in the thymus, in-depth characterization of NKT cells can be facilitated by their enrichment from total thymocytes. Magnetic-activated cell sorting (MACS) of glycolipid antigen-loaded CD1d-tetramer-binding cells is a commonly used method to enrich NKT cells. Surprisingly, we found that this procedure also dramatically altered the subset composition of enriched NKT cells. As such, NKT2 lineage cells that express large amounts of the transcription factor promyelocytic leukemia zinc finger were markedly over-represented, while NKT1 lineage cells expressing the transcription factor T-bet were significantly reduced. To overcome this limitation, here, we tested magnetic-activated depletion of CD24 immature thymocytes as an alternative method to enrich NKT cells. We found that the overall recovery in NKT cell numbers did not differ between these 2 methods. However, enrichment by CD24 cell depletion preserved the subset composition of NKT cells in the thymus, and thus permitted accurate and reproducible analysis of thymic NKT cells in further detail.
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http://dx.doi.org/10.4110/in.2019.19.e14DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6494763PMC
April 2019

Effect of cyclical intermittent hypoxia on Ad5CMVCre induced solitary lung cancer progression and spontaneous metastases in the KrasG12D+; p53fl/fl; myristolated p110fl/fl ROSA-gfp mouse.

PLoS One 2019 27;14(2):e0212930. Epub 2019 Feb 27.

Center for Sleep and Circadian Neurobiology, University of Pennsylvania, Philadelphia, Pennsylvania, United States of America.

Background: Epidemiological data suggests that obstructive sleep apnea (OSA) is associated with increased cancer incidence and mortality. We investigate the effects of cyclical intermittent hypoxia (CIH), akin to the underlying pathophysiology of OSA, on lung cancer progression and metastatic profile in a mouse model.

Methods: Intrathoracic injection of Ad5CMVCre virus into a genetically engineered mouse (GEM) KrasG12D+/-; p53fl/fl; myristolated-p110αfl/fl-ROSA-gfp was utilized to induce a solitary lung cancer. Male mice were then exposed to either CIH or Sham for 40-41 days until harvest. To monitor malignant progression, serial micro CT scans with respiratory gating (no contrast) was performed. To detect spontaneous metastases in distant organs, H&E and immunohistochemistry were performed.

Results: Eighty-eight percent of injected Ad5CMVCre virus was recovered from left lung tissue, indicating reliable and accurate injections. Serial micro CT demonstrated that CIH increases primary lung tumor volume progression compared to Sham on days 33 (p = 0.004) and 40 (p<0.001) post-injection. In addition, CIH increases variability in tumor volume on day 19 (p<0.0001), day 26 (p<0.0001), day 33 (p = 0.025) and day 40 (p = 0.004). Finally, metastases are frequently detected in heart, mediastinal lymph nodes, and right lung using H&E and immunohistochemistry.

Conclusions: Using a GEM mouse model of metastatic lung cancer, we report that male mice with solitary lung cancer have accelerated malignant progression and increased variability in tumor growth when exposed to cyclical intermittent hypoxia. Our results indicate that cyclical intermittent hypoxia is a pathogenic factor in non-small cell lung cancer that promotes the more rapid growth of developing tumors.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0212930PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6392281PMC
November 2019

Clinical and molecular spectrum of thymidine kinase 2-related mtDNA maintenance defect.

Mol Genet Metab 2018 06 28;124(2):124-130. Epub 2018 Apr 28.

Department of Human and Molecular Genetics, Baylor College of Medicine, One Baylor Plaza, Houston, TX 77030, United States. Electronic address:

Mitochondrial DNA maintenance (mtDNA) defects have a wide range of causes, each with a set of phenotypes that overlap with many other neurological or muscular diseases. Clinicians face the challenge of narrowing down a long list of differential diagnosis when encountered with non-specific neuromuscular symptoms. Biallelic pathogenic variants in the Thymidine Kinase 2 (TK2) gene cause a myopathic form of mitochondrial DNA maintenance defect. Since the first description in 2001, there have been 71 patients reported with 42 unique pathogenic variants. Here we are reporting 11 new cases with 5 novel pathogenic variants. We describe and analyze a total of 82 cases with 47 unique TK2 pathogenic variants in effort to formulate a comprehensive molecular and clinical spectrum of TK2-related mtDNA maintenance disorders.
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http://dx.doi.org/10.1016/j.ymgme.2018.04.012DOI Listing
June 2018

Renal Cell Carcinoma in von Hippel-Lindau Disease-From Tumor Genetics to Novel Therapeutic Strategies.

Front Pediatr 2018 9;6:16. Epub 2018 Feb 9.

Renal Division, Department of Medicine IV, Faculty of Medicine, Albert Ludwigs University of Freiburg, Freiburg, Germany.

von Hippel-Lindau (VHL) disease is an autosomal dominant syndrome caused by mutations in the VHL tumor-suppressor gene, leading to the dysregulation of many hypoxia-induced genes. Affected individuals are at increased risk of developing recurrent and bilateral kidney cysts and dysplastic lesions which may progress to clear cell renal cell carcinoma (ccRCC). Following the eponymous gene inactivation, ccRCCs evolve through additional genetic alterations, resulting in both intratumor and intertumor heterogeneity. Genomic studies have identified frequent mutations in genes involved in epigenetic regulation and phosphoinositide 3-kinase-AKT-mechanistic target of rapamycin (mTOR) pathway activation. Currently, local therapeutic options include nephron-sparing surgery and alternative ablative procedures. For advanced metastatic disease, systemic treatment, including inhibition of vascular endothelial growth factor pathways and mTOR pathways, as well as immunotherapy are available. Multimodal therapy, targeting multiple signaling pathways and/or enhancing the immune response, is currently being investigated. A deeper understanding of the fundamental biology of ccRCC development and progression, as well as the development of novel and targeted therapies will be accelerated by new preclinical models, which will greatly inform the search for clinical biomarkers for diagnosis, prognosis, and response to treatment.
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http://dx.doi.org/10.3389/fped.2018.00016DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5811471PMC
February 2018

Mortality from an aspiration of dental crown during extraction.

Gerodontology 2017 Dec;34(4):498-500

University of Pennsylvania School of Dental Medicine, Penn Presbyterian Medical Center, Philadelphia Veterans Affairs Medical Center, Philadelphia, PA, USA.

An aspiration of a dental crown during a dental extraction requires appropriate and timely diagnosis and management. While foreign body aspiration in dental procedures is relatively uncommon, it constitutes a true medical emergency and is associated with significant morbidity and mortality. We report a case of mortality from a foreign body aspiration and discuss the epidemiology, risk factors, signs and symptoms, management, and prevention of foreign body ingestion and aspiration events.
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http://dx.doi.org/10.1111/ger.12288DOI Listing
December 2017

Religion, repulsion, and reaction formation: Transforming repellent attractions and repulsions.

J Pers Soc Psychol 2018 Sep 12;115(3):564-584. Epub 2017 Jun 12.

Department of Psychology, Southern Methodist University.

Protestants were more likely than non-Protestants to demonstrate phenomena consistent with the use of reaction formation. Lab experiments showed that when manipulations were designed to produce taboo attractions (to unconventional sexual practices), Protestants instead showed greater repulsion. When implicitly conditioned to produce taboo repulsions (to African Americans), Protestants instead showed greater attraction. Supportive evidence from other studies came from clinicians' judgments, defense mechanism inventories, and a survey of respondent attitudes. Other work showed that Protestants who diminished and displaced threatening affect were more likely to sublimate this affect into creative activities; the present work showed that Protestants who do not or cannot diminish or displace such threatening affect instead reverse it. Traditional individual difference variables showed little ability to predict reaction formation, suggesting that the observed processes go beyond what we normally study when we talk about self-control. (PsycINFO Database Record
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http://dx.doi.org/10.1037/pspp0000151DOI Listing
September 2018

Roads more and less traveled: Different emotional routes to creativity among Protestants and Catholics.

Authors:
Emily Kim Dov Cohen

J Pers Soc Psychol 2017 Jun 2;112(6):901-925. Epub 2017 Mar 2.

Department of Psychology, University of Illinois at Urbana Champaign.

Western culture has 2 contradictory images of creativity: the artist as intensely emotional versus the artist as sublimator, for whom work becomes the outlet for what is repressed and denied. We show that both images are correct, but that the routes to creativity are culturally patterned, such that Catholic creatives are relatively more likely to take the emotionally intense route and Protestant creatives relatively more likely to take the sublimating route. This pattern is consistent for both the Big-C creativity of historical eminents (Studies 1 and 1b) and small-c creativity of student samples (Studies 2 and 3). The student samples also highlighted the moderating role of Protestant asceticism, as Protestants who were high in asceticism and who also repressed or minimized troublesome emotions were particularly creative. Analyses of behavioral data in previous lab experiments (Studies 2b and 3b) provided conceptual validation of the findings reported in Studies 2 and 3. (PsycINFO Database Record
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http://dx.doi.org/10.1037/pspp0000105DOI Listing
June 2017

The impact on women's health and the cervical cancer screening budget of primary HPV screening with dual-stain cytology triage in Belgium.

Eur J Obstet Gynecol Reprod Biol 2017 May 5;212:171-181. Epub 2017 Jan 5.

Roche Diagnostics, Vilvoorde, Belgium.

Dual stain cytology, or "diagnostic cytology", offers a significant increase in sensitivity compared to cytology, with a slight decrease in specificity. This can reduce additional investigations like colposcopies, biopsies, and follow-up visits. Cervical cancer screening for women between 25 and 65 years of age with diagnostic cytology is estimated to reduce the incidence of cervical cancer by 36% and reduce annual cervical cancer mortalities by 40%. The reduced number of screening visits and the decrease in incidence and mortality will improve quality of life. In this article, a model was created to evaluate the cost-effectiveness of diagnostic cytology for Belgium. In this approach, precancerous cells are more likely to be immediately identified during the first screening visit. This reduces both the number and frequency of follow-up visits required. After two cycles (6 years), the prevalence of CIN and cervical cancer is decreased significantly in the screened population. At a population level, these shifts can reduce the screening budget by 21%, resulting in savings of 5.3 million euro a year in Belgium. Diagnostic cytology benefits all stakeholders involved in cervical cancer screening.
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http://dx.doi.org/10.1016/j.ejogrb.2017.01.010DOI Listing
May 2017

Different cyclical intermittent hypoxia severities have different effects on hippocampal microvasculature.

J Appl Physiol (1985) 2016 07 28;121(1):78-88. Epub 2016 Apr 28.

Division of Sleep Medicine, Department of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania; Center for Sleep and Circadian Neurobiology, University of Pennsylvania, Philadelphia, Pennsylvania;

Recent studies have shown an association between obstructive sleep apnea (OSA) and cognitive impairment. This study was done to investigate whether varied levels of cyclical intermittent hypoxia (CIH) differentially affect the microvasculature in the hippocampus, operating as a mechanistic link between OSA and cognitive impairment. We exposed C57BL/6 mice to sham [continuous air, arterial O2 saturation (SaO2 ) 97%], severe CIH to inspired O2 fraction (FiO2 ) = 0.10 (CIH10; SaO2 nadir of 61%), or very severe CIH to FiO2 = 0.05 (CIH5; SaO2 nadir of 37%) for 12 h/day for 2 wk. We quantified capillary length using neurostereology techniques in the dorsal hippocampus and utilized quantitative PCR methods to measure changes in sets of genes related to angiogenesis and to metabolism. Next, we employed immunohistochemistry semiquantification algorithms to quantitate GLUT1 protein on endothelial cells within hippocampal capillaries. Capillary length differed among CIH severity groups (P = 0.013) and demonstrated a linear relationship with CIH severity (P = 0.002). There was a strong association between CIH severity and changes in mRNA for VEGFA (P < 0.0001). Less strong, but nominally significant associations with CIH severity were also observed for ANGPT2 (PANOVA = 0.065, PTREND = 0.040), VEGFR2 (PANOVA = 0.032, PTREND = 0.429), and TIE-2 (PANOVA = 0.006, PTREND = 0.010). We found that the CIH5 group had increased GLUT1 protein relative to sham (P = 0.006) and CIH10 (P = 0.001). There was variation in GLUT1 protein along the microvasculature in different hippocampal subregions. An effect of CIH5 on GLUT1 mRNA was seen (PANOVA = 0.042, PTREND = 0.012). Thus CIH affects the microvasculature in the hippocampus, but consequences depend on CIH severity.
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http://dx.doi.org/10.1152/japplphysiol.01040.2015DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4967251PMC
July 2016

Effect of pharmacy students as primary pharmacy members on inpatient interdisciplinary mental health teams.

Am J Health Syst Pharm 2015 Apr;72(8):663-7

Monica Mathys, Pharm. D., CGP, BCPP, is Associate Professor of Pharmacy Practice, School of Pharmacy, Texas Tech University Health Sciences Center (TTUHSC), Dallas. Elizabeth Neyland-Turner, M.S., Pharm.D., is Staff Pharmacist, CVS Pharmacy, Grand Prairie, TX; when this study was performed she was a Pharm. D. student, School of Pharmacy, Ttuhsc, Dallas. Keenan Hamouie, Pharm. D., is Staff Pharmacist, H-E-B Pharmacy, Houston, TX; when this study was performed he was a Pharm. D. student, School of Pharmacy, TTUHSC, Dallas. Emily Kim, Pharm. D., is Postgraduate Year 1 Pharmacy Practice Resident, Palmetto General Hospital, Hialeah, FL; when this study was performed she was a Pharm.D. student, School of Pharmacy, TTUHSC, Dallas.

Purpose: The effect of pharmacy students as primary pharmacy members on inpatient interdisciplinary mental health teams was investigated.

Methods: This retrospective study used Veterans Affairs data from veterans who were admitted to an inpatient mental health unit from January 1, 2010, through December 31, 2012. Eligible veterans had to have been hospitalized for at least five days and treated with at least five scheduled medications during the hospitalization. Information collected by the investigators included patient age, psychiatric diagnoses, accuracy of medication reconciliation on admission and at discharge, and readmission rates within six months and one year. Additional information collected included monitoring parameters for lithium, divalproex, first-generation antipsychotics, and second-generation antipsychotics. The primary outcome was the percentage of accurate medication reconciliations for treatment teams with a fourth-year pharmacy student and without a pharmacy student. Clinical monitoring and readmission rates were also compared.

Results: A total of 526 patients were eligible for study inclusion. Medication reconciliation was performed on admission for all patients followed by a team involving a pharmacy student (experimental group), but only 51% of patients in the control group had documented medication reconciliations in the medical chart. Of the medication reconciliations completed, 82% were performed correctly in the experimental group, compared with 61% when a pharmacy student was not involved (p = 0.006). There were no significant differences between groups in psychotropic monitoring and readmission rates.

Conclusion: The presence of fourth-year pharmacy students on inpatient mental health interdisciplinary teams was associated with more frequent interventions, patient counseling, and medication reconciliation, compared with rates for teams without a pharmacy student. Medication reconciliation was performed more consistently and accurately when the teams had a pharmacy student than when they did not.
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http://dx.doi.org/10.2146/ajhp140411DOI Listing
April 2015

The Pediatric Emergency Care Applied Research Network: a history of multicenter collaboration in the United States.

Pediatr Emerg Care 2015 Jan;31(1):70-6

From the Departments of *Emergency Medicine and †Pediatrics, University of California, Davis School of Medicine, Sacramento, CA.

In this article, we review the history and progress of a large multicenter research network pertaining to emergency medical services for children. We describe the history, organization, infrastructure, and research agenda of the Pediatric Emergency Care Applied Research Network and highlight some of the important accomplishments since its inception. We also describe the network's strategy to grow its research portfolio, train new investigators, and study how to translate new evidence into practice. This strategy ensures not only the sustainability of the network in the future but the growth of research in emergency medical services for children in general.
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http://dx.doi.org/10.1097/PEC.0000000000000303DOI Listing
January 2015

The Pediatric Emergency Care Applied Research Network: a history of multicenter collaboration in the United States.

Clin Exp Emerg Med 2014 Dec 31;1(2):78-86. Epub 2014 Dec 31.

Department of Emergency Medicine, University of California Davis School of Medicine, Sacramento, CA, USA; Department of Pediatrics, University of California Davis School of Medicine, Sacramento, CA, USA.

In this article, we review the history and progress of a large multicenter research network pertaining to emergency medical services for children. We describe the history, organization, infrastructure, and research agenda of the Pediatric Emergency Care Applied Research Network (PECARN), and highlight some of the important accomplishments since its inception. We also describe the network's strategy to grow its research portfolio, train new investigators, and study how to translate new evidence into practice. This strategy ensures not only the sustainability of the network in the future, but the growth of research in emergency medical services for children in general.
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http://dx.doi.org/10.15441/ceem.14.050DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5052835PMC
December 2014

Simulating obstructive sleep apnea patients' oxygenation characteristics into a mouse model of cyclical intermittent hypoxia.

J Appl Physiol (1985) 2015 Mar 26;118(5):544-57. Epub 2014 Nov 26.

Division of Sleep Medicine, Department of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania; Center for Sleep and Circadian Neurobiology, University of Pennsylvania, Philadelphia, Pennsylvania;

Mouse models of cyclical intermittent hypoxia (CIH) are used to study the consequences of both hypoxia and oxidative stress in obstructive sleep apnea (OSA). Whether or not a mouse model of CIH that simulates OSA patients' oxygenation characteristics would translate into improved patient care remains unanswered. First we identified oxygenation characteristics using the desaturation and resaturation time in 47 OSA subjects from the Molecular Signatures of Obstructive Sleep Apnea Cohort (MSOSA). We observe that a cycle of intermittent hypoxia is not sinusoidal; specifically, desaturation time increases in an almost linear relationship to the degree of hypoxia (nadir), whereas resaturation time is somewhat constant (∼15 s), irrespective of the nadir. Second, we modified the Hycon mouse model of CIH to accommodate a 15-s resaturation time. Using this modified CIH model, we explored whether a short resaturation schedule (15 s), which includes the characteristics of OSA patients, had a different effect on levels of oxidative stress (i.e., urinary 8,12-iso-iPF2α-VI levels) compared with sham and a long resaturation schedule (90 s), a schedule that is not uncommon in rodent models of CIH. Results suggest that shorter resaturation time may result in a higher level of 8,12-iso-iPF2α-VI compared with long resaturation or sham conditions. Therefore, simulating the rodent model of CIH to reflect this and other OSA patients' oxygenation characteristics may be worthy of consideration to better understand the effects of hypoxia, oxidative stress, and their interactions.
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http://dx.doi.org/10.1152/japplphysiol.00629.2014DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4346743PMC
March 2015

Cytolethal distending toxins require components of the ER-associated degradation pathway for host cell entry.

PLoS Pathog 2014 Jul 31;10(7):e1004295. Epub 2014 Jul 31.

Department of Microbiology, Immunology and Molecular Genetics, University of California, Los Angeles, Los Angeles, California, United States of America; California NanoSystems Institute, University of California, Los Angeles, Los Angeles, California, United States of America.

Intracellular acting protein exotoxins produced by bacteria and plants are important molecular determinants that drive numerous human diseases. A subset of these toxins, the cytolethal distending toxins (CDTs), are encoded by several Gram-negative pathogens and have been proposed to enhance virulence by allowing evasion of the immune system. CDTs are trafficked in a retrograde manner from the cell surface through the Golgi apparatus and into the endoplasmic reticulum (ER) before ultimately reaching the host cell nucleus. However, the mechanism by which CDTs exit the ER is not known. Here we show that three central components of the host ER associated degradation (ERAD) machinery, Derlin-2 (Derl2), the E3 ubiquitin-protein ligase Hrd1, and the AAA ATPase p97, are required for intoxication by some CDTs. Complementation of Derl2-deficient cells with Derl2:Derl1 chimeras identified two previously uncharacterized functional domains in Derl2, the N-terminal 88 amino acids and the second ER-luminal loop, as required for intoxication by the CDT encoded by Haemophilus ducreyi (Hd-CDT). In contrast, two motifs required for Derlin-dependent retrotranslocation of ERAD substrates, a conserved WR motif and an SHP box that mediates interaction with the AAA ATPase p97, were found to be dispensable for Hd-CDT intoxication. Interestingly, this previously undescribed mechanism is shared with the plant toxin ricin. These data reveal a requirement for multiple components of the ERAD pathway for CDT intoxication and provide insight into a Derl2-dependent pathway exploited by retrograde trafficking toxins.
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http://dx.doi.org/10.1371/journal.ppat.1004295DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4117610PMC
July 2014

Autosomal recessive phosphoglucomutase 3 (PGM3) mutations link glycosylation defects to atopy, immune deficiency, autoimmunity, and neurocognitive impairment.

J Allergy Clin Immunol 2014 May 28;133(5):1400-9, 1409.e1-5. Epub 2014 Feb 28.

Laboratory of Allergic Diseases, National Institutes of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Md. Electronic address:

Background: Identifying genetic syndromes that lead to significant atopic disease can open new pathways for investigation and intervention in allergy.

Objective: We sought to define a genetic syndrome of severe atopy, increased serum IgE levels, immune deficiency, autoimmunity, and motor and neurocognitive impairment.

Methods: Eight patients from 2 families with similar syndromic features were studied. Thorough clinical evaluations, including brain magnetic resonance imaging and sensory evoked potentials, were performed. Peripheral lymphocyte flow cytometry, antibody responses, and T-cell cytokine production were measured. Whole-exome sequencing was performed to identify disease-causing mutations. Immunoblotting, quantitative RT-PCR, enzymatic assays, nucleotide sugar, and sugar phosphate analyses, along with matrix-assisted laser desorption/ionization-time-of-flight mass spectrometry of glycans, were used to determine the molecular consequences of the mutations.

Results: Marked atopy and autoimmunity were associated with increased T(H)2 and T(H)17 cytokine production by CD4(+) T cells. Bacterial and viral infection susceptibility were noted along with T-cell lymphopenia, particularly of CD8(+) T cells, and reduced memory B-cell numbers. Apparent brain hypomyelination resulted in markedly delayed evoked potentials and likely contributed to neurologic abnormalities. Disease segregated with novel autosomal recessive mutations in a single gene, phosphoglucomutase 3 (PGM3). Although PGM3 protein expression was variably diminished, impaired function was demonstrated by decreased enzyme activity and reduced uridine diphosphate-N-acetyl-D-glucosamine, along with decreased O- and N-linked protein glycosylation in patients' cells. These results define a new congenital disorder of glycosylation.

Conclusions: Autosomal recessive hypomorphic PGM3 mutations underlie a disorder of severe atopy, immune deficiency, autoimmunity, intellectual disability, and hypomyelination.
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http://dx.doi.org/10.1016/j.jaci.2014.02.013DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4016982PMC
May 2014

Sublimation, culture, and creativity.

J Pers Soc Psychol 2013 Oct 8;105(4):639-66. Epub 2013 Jul 8.

Department of Psychology, University of Illinois at Urbana-Champaign.

Combining insights from Freud and Weber, this article explores whether Protestants (vs. Catholics and Jews) are more likely to sublimate their taboo feelings and desires toward productive ends. In the Terman sample (Study 1), Protestant men and women who had sexual problems related to anxieties about taboos and depravity had greater creative accomplishments, as compared to those with sexual problems unrelated to such concerns and to those reporting no sexual problems. Two laboratory experiments (Studies 2 and 3) found that Protestants produced more creative artwork (sculptures, poems, collages, cartoon captions) when they were (a) primed with damnation-related words, (b) induced to feel unacceptable sexual desires, or (c) forced to suppress their anger. Activating anger or sexual attraction was not enough; it was the forbidden or suppressed nature of the emotion that gave the emotion its creative power. The studies provide possibly the first experimental evidence for sublimation and suggest a cultural psychological approach to defense mechanisms.
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http://dx.doi.org/10.1037/a0033487DOI Listing
October 2013

Variability of prehospital spinal immobilization in children at risk for cervical spine injury.

Pediatr Emerg Care 2013 Apr;29(4):413-8

Department of Emergency Medicine, University of California, Davis School of Medicine, Sacramento, CA 95817, USA.

Objective: This study aimed to compare prehospital spinal immobilization techniques applied to age-based cohorts of children with and without cervical spine injury (CSI) after blunt trauma.

Methods: We compared prehospital spinal immobilization in 3 age-based cohorts of children with blunt trauma-related CSI transported to 1 of 17 participating hospitals. We also compared children younger than 2 years with CSI with those at risk for but without CSI after blunt trauma. We identified patients through query of billing and radiology databases. We compared immobilization methods using Fisher's exact test for homogeneity.

Results: We identified 16 children younger than 2 years, 78 children 2 to 7 years old, and 221 children 8 to 15 years old with CSI, and 66 children younger than 2 years without CSI. There were no significant differences in spinal immobilization techniques applied to children younger than 2 years old with and without CSI (P = 0.34). Of the 82 children younger than 2 years, 34 (41%) were fully immobilized in a cervical collar and rigid long board. There was a significant difference between spinal immobilization techniques applied to children with CSI younger than 2 years and 8 to 15 years old (P < 0.01). Six (38%) children with CSI younger than 2 years were fully immobilized versus 49 (63%) children 2 to 7 years old and 175 (79%) children 8 to 15 years old.

Conclusions: In this retrospective, observational study involving several emergency departments and Emergency Medical Services systems, we found that full spinal immobilization is inconsistently applied to children younger than 2 years after blunt trauma regardless of the presence of CSI. Full spinal immobilization is applied more consistently to older children with CSI.
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http://dx.doi.org/10.1097/PEC.0b013e318289d743DOI Listing
April 2013