Publications by authors named "Brian Kim"

332 Publications

Moderately Inducing Autophagy Reduces Tertiary Brain Injury after Perinatal Hypoxia-Ischemia.

Cells 2021 Apr 14;10(4). Epub 2021 Apr 14.

Department of Pharmacology, Physiology and Neuroscience, Rutgers-New Jersey Medical School, Newark, NJ 07103, USA.

Recent studies of cerebral hypoxia-ischemia (HI) have highlighted slowly progressive neurodegeneration whose mechanisms remain elusive, but if blocked, could considerably improve long-term neurological function. We previously established that the cytokine transforming growth factor (TGF)β1 is highly elevated following HI and that delivering an antagonist for TGFβ receptor activin-like kinase 5 (ALK5)-SB505124-three days after injury in a rat model of moderate pre-term HI significantly preserved the structural integrity of the thalamus and hippocampus as well as neurological functions associated with those brain structures. To elucidate the mechanism whereby ALK5 inhibition reduces cell death, we assessed levels of autophagy markers in neurons and found that SB505124 increased numbers of autophagosomes and levels of lipidated light chain 3 (LC3), a key protein known to mediate autophagy. However, those studies did not determine whether (1) SB was acting directly on the CNS and (2) whether directly inducing autophagy could decrease cell death and improve outcome. Here we show that administering an ALK5 antagonist three days after HI reduced actively apoptotic cells by ~90% when assessed one week after injury. Ex vivo studies using the lysosomal inhibitor chloroquine confirmed that SB505124 enhanced autophagy flux in the injured hemisphere, with a significant accumulation of the autophagic proteins LC3 and p62 in SB505124 + chloroquine treated brain slices. We independently activated autophagy using the stimulatory peptide Tat-Beclin1 to determine if enhanced autophagy is directly responsible for improved outcomes. Administering Tat-Beclin1 starting three days after injury preserved the structural integrity of the hippocampus and thalamus with improved sensorimotor function. These data support the conclusion that intervening at this phase of injury represents a window of opportunity where stimulating autophagy is beneficial.
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http://dx.doi.org/10.3390/cells10040898DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8070811PMC
April 2021

Bidirectional sensory neuron-immune interactions: a new vision in the understanding of allergic inflammation.

Curr Opin Immunol 2021 Apr 16;72:79-86. Epub 2021 Apr 16.

Toulouse Institute for Infectious and Inflammatory Diseases (Infinity), Inserm UMR1291 CNRS UMR5051, University of Toulouse III, Toulouse, France. Electronic address:

Peripheral neurons (including sensory neurons) are ubiquitously distributed in all tissues, particularly at the interface with the environment. The primary function of sensory neurons is the transmission of sensations of temperature, pain and itch to elicit appropriate behavioral responses. More recently, sensory neurons have emerged as potent regulators of type 2 immune responses and allergic inflammation. There is increasing evidence showing that neurons can express receptors previously thought to be restricted to the immune compartment. In addition, certain subtypes of immune cells (e.g. mast cells, ILC2s or macrophages) also express specific neuroreceptors that provide them with the capacity to integrate neuron-derived signals and modulate their activation status during the development of allergic inflammation.
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http://dx.doi.org/10.1016/j.coi.2021.03.012DOI Listing
April 2021

HLA Class I Polymorphisms Influencing Both Peptide Binding and KIR Interactions Are Associated with Remission among Children with Atopic Dermatitis: A Longitudinal Study.

J Immunol 2021 May 16;206(9):2038-2044. Epub 2021 Apr 16.

Department of Pathology and Laboratory Medicine, Children's Hospital of Philadelphia, Philadelphia, PA;

Atopic dermatitis (AD) is a disease of immune dysregulation and skin barrier dysfunction with a relapsing, remitting course and has been associated with several different genetic risk variants. HLA represent a highly variable set of genes that code for cell surface protein molecules involved in the Ag-specific immune response, including the regulation or functioning of T cells, NK cells, and APCs. The purpose of this study was to evaluate associations between HLA class I polymorphisms and the progression of AD over time. We evaluated the associations of AD symptoms and HLA class I polymorphisms based on high-resolution two-field typing in a longitudinal cohort of children with AD (up to 10 y of follow-up). Seven hundred and ninety-two children were evaluated every 6 mo, resulting in 12,752 AD evaluations. Using generalized estimating equations and corrected values, B*44:02 was found to be associated with AD remission (1.83 [1.35, 2.47]; = 0.0015). The HLA-B residues at position 116 (d-aspartate) and 80 (T-threonine) were associated with remission (1.42 [1.13, 1.76], = 0.003; corrected = 0.028) and (1.45 [1.17, 1.80], = 0.0008; corrected = 0.0024), respectively. B80T is a killer-cell Ig-like receptor (KIR) site. Our findings reveal that two axes of immune response (T cell and NK cell) may influence disease progression. Identifying binding pocket changes in addition to other factors (e.g., allergens) that increase the risk or severity of AD can improve our understanding of the immunologic mechanisms associated with AD and may lead to personalized therapies for improving patient care.
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http://dx.doi.org/10.4049/jimmunol.2001252DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8062288PMC
May 2021

Prophylactic placement of inferior vena cava filters and the risk of death or venous thromboembolism in severe trauma patients: a retrospective study comparing two hospitals with different approaches.

Acta Radiol Open 2021 Mar 9;10(3):2058460121999345. Epub 2021 Mar 9.

Institute of Clinical Medicine, Faculty of Medicine, University of Oslo, Oslo, Norway.

Background: Prophylactic use of inferior vena cava filters to prevent pulmonary embolism in trauma is controversial. The practice varies between hospitals and countries, in part due to conflicting evidence and guidelines.

Purpose: To compare the effects of pulmonary embolism, deep venous thrombosis and mortality in two hospitals using prophylactic inferior vena cava filter placement or prophylactic anticoagulation alone.

Material And Methods: Patients presenting with severe trauma were recruited from two level-1 trauma centres between January 2008 and December 2013. Recruited patients from an US hospital having prophylactic inferior vena cava filter inserted were compared to a Scandinavian hospital using prophylactic anticoagulation alone. Inclusion criteria were age >15 years, Injury Severity Score >15 and survival >24 h after hospital admission. Patients with venous thromboembolism diagnosed prior to inferior vena cava filter placement were excluded. A Cox proportional hazard regression model was used with adjustment for immortal time bias and predictor variables.

Results: In total, 951 patients were reviewed, 282 from an US hospital having inferior vena cava filters placed and 669 from a Scandinavian hospital without inferior vena cava filters. The mean age was 45.9 vs. 47.4 years and the mean Injury Severity Score was 29.8 vs. 25.9, respectively. Inferior vena cava filter placement was not associated with the hazard of pulmonary embolism (Hazard ratio=0.43; 95% confidence interval (CI) 0.12, 1.45; P=0.17) or mortality (Hazard ratio=1.16; 95% CI 0.70, 1.95; P=0.56). However, an increased rate of deep venous thrombosis was observed with inferior vena cava filters in place (Hazard ratio=3.75; 95% CI 1.68, 8.36; P=0.001).

Conclusion: In severely injured trauma patients, prophylactic inferior vena cava filter placement was not associated with pulmonary embolism or mortality. However, inferior vena cava filters were associated with increased rate of deep venous thrombosis.
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http://dx.doi.org/10.1177/2058460121999345DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7952846PMC
March 2021

Choosing the Optimal Power Coils Using Open-Source k-Oriented Design Automation.

IEEE Trans Biomed Circuits Syst 2021 Feb 30;15(1):159-170. Epub 2021 Mar 30.

Wireless power coils have found important use in implantable medical devices for safe and reliable wireless power transfer. Designing coils for each specific application is a complex process with many interdependent design variables; determining the most optimal design parameters for each pair is challenging and time-consuming. In this paper, we develop an automated design method for planar square-spiral coils that generates the idealized design parameters for maximum power transfer efficiency according to the input design requirements. Computational complexity is first reduced by isolating the inductive coupling coefficient, k, from other design parameters. A simplified but accurate equivalent circuit model is then developed, where skin effect, proximity effect, and parasitic capacitive coupling are iteratively considered. The proposed method is implemented in an open-source software which accounts for the input fabrication limitations and application specific requirements. The accuracy of the estimated power transfer efficiency is validated via finite element method simulation. Using the presented approach, the coil design process is fully automated and can be done in few minutes.
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http://dx.doi.org/10.1109/TBCAS.2021.3059934DOI Listing
February 2021

Local insulin application has a dose-dependent effect on lumbar fusion in a rabbit model.

J Tissue Eng Regen Med 2021 May 12;15(5):442-452. Epub 2021 Mar 12.

Department of Orthopaedics, Rutgers-New Jersey Medical School, Newark, NJ, USA.

The purpose of this study was to determine if locally applied insulin has a dose-responsive effect on posterolateral lumbar fusion. Adult male New Zealand White rabbits underwent posterolateral intertransverse spinal fusions (PLFs) at L5-L6 using suboptimal amounts of autograft. Fusion sites were treated with collagen sponge soaked in saline (control, n = 11), or with insulin at low (5 or 10 units, n = 13), mid (20 units, n = 11), and high (40 units, n = 11) doses. Rabbits were euthanized at 6 weeks. The L5-L6 spine segment underwent manual palpation and radiographic evaluation performed by two fellowship trained spine surgeons blinded to treatment. Differences between groups were evaluated by analysis of variance on ranks followed by post-hoc Dunn's tests. Forty-three rabbits were euthanized at the planned 6 weeks endpoint, while three died or were euthanized prior to the endpoint. Radiographic evaluation found bilateral solid fusion in 10%, 31%, 60%, and 60% of the rabbits from the control and low, mid, and high-dose insulin-treated groups, respectively (p < 0.05). As per manual palpation, 7 of 10 rabbits in the mid-dose insulin group were fused as compared to 1 of 10 rabbits in the control group (p < 0.05). This study demonstrates that insulin enhanced the effectiveness of autograft to increase fusion success in the rabbit PLF model. The study indicates that insulin or insulin-mimetic compounds can be used to promote bone regeneration.
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http://dx.doi.org/10.1002/term.3182DOI Listing
May 2021

Using Public Datasets to Identify Priority Areas for Ocular Telehealth.

Telemed J E Health 2021 Feb 18. Epub 2021 Feb 18.

Division of Ophthalmology, Department of Surgery, University of Vermont Larner College of Medicine, Burlington, Vermont, USA.

Telemedicine can expand access to ocular services, but barriers include restrictive policies and poor reimbursement. A tool to identify priority regions for interventions is needed. Eye care provider (ECP) density, self-reported visual disability, and demographics were calculated using census data and professional registries. The relationship between visual disability and ECP density was explored in fractional regression models. These data were compared with state telemedicine policy favorability. For each additional ECP per 100,000 population, there was 0.0111% less disability in the county (95% confidence interval -0.0150% to -0.00719%) in an adjusted model. Of 3,142 counties, 1,078 (34%) were in the worst population-weighted quartile for ECP density and visual disability. Low ECP density is associated with higher visual disability, suggesting an opportunity for ocular telehealth. Counties with favorable policy climates should be prioritized for telemedicine implementation. Public datasets can be used to survey wide geographic areas to identify areas worthy of detailed needs assessments.
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http://dx.doi.org/10.1089/tmj.2020.0433DOI Listing
February 2021

Low-Level Red Plus Near Infrared Lights Combination Induces Expressions of Collagen and Elastin in Human Skin In Vitro.

Int J Cosmet Sci 2021 Feb 16. Epub 2021 Feb 16.

The Johnson & Johnson Skin Research Center, Johnson & Johnson Consumer Health, Skillman, NJ, USA.

Objective: Light therapy has attracted medical interests as a safe, alternative treatment for photo-aging and photo-damaged skin. Recent research suggested the therapeutic activity of red and infrared (IR) lights may be effective at much lower energy levels than those used clinically. This study was to evaluate the efficacy of low-level red plus near IR light emitting diode (LED) combination on collagen and elastin and ATP production.

Methods: Human dermal fibroblasts or skin tissues were irradiated daily by red (640 nm) plus near IR (830 nm) LED lights combination at 0.5 mW/cm for 10 minutes (0.3 J/cm ). qPCR, ELISAs or histology were used to determine the gene and protein expressions. Fluorescent measurement was used to assess cross-links of collagen and elastic fibers. ATP production was evaluated by ATP assay.

Results: Treatment of human fibroblast cell cultures with low level red plus near IR lights combination was found to significantly increase LOXL1, ELN and COL1A1 and COL3A1 gene expressions as well as the synthesis of the procollagen type I and elastin proteins. Treating human skin explants with low level red plus near IR lights combination similarly induced significant increases of the same genes expressions, type III collagen and elastic fiber formation and cross-links. ATP production was increased in human dermal fibroblasts after red plus near IR lights combination treatment.

Conclusion: Low level red plus near IR lights combination stimulated the production of collagen and elastin production associated with anti-aging benefits. These findings suggest that low level red plus near IR LED light combination may provide an effective treatment opportunity for people with photo-aged skin.
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http://dx.doi.org/10.1111/ics.12698DOI Listing
February 2021

CT-derived sarcopenia should not preclude surgical stabilization of traumatic rib fractures.

Eur Radiol Exp 2021 Feb 16;5(1). Epub 2021 Feb 16.

Department of Surgery, Mayo Clinic, 200 First Street SW, Rochester, MN, 55905, USA.

Background: Rib fractures are associated with considerable morbidity and mortality. Surgical stabilization of rib fractures (SSRF) can be performed to mitigate complications. Sarcopenia is in general known to be associated with poor clinical outcomes. We investigated if sarcopenia impacted number of days of mechanical ventilation, intensive care unit (ICU) stay, and total hospital stay in patients who underwent SSRF.

Methods: A retrospective single institutional review was performed including patients who underwent SSRF (2009-2017). Skeletal muscle index (SMI) was semiautomatically calculated at the L3 spinal level on computed tomography (CT) images and normalized by patient height. Sarcopenia was defined as SMI < 55 cm/m in males and < 39 cm/m in females. Demographics, operative details, and postoperative outcomes were reviewed. Univariate and multivariate analyses were performed.

Results: Of 238 patients, 88 (36.9%) had sarcopenia. There was no significant difference in number of days of mechanical ventilation (2.8 ± 4.9 versus 3.1 ± 4.3, p = 0.304), ICU stay (5.9 ± 6.5 versus 4.9 ± 5.7 days, p = 0.146), or total hospital stay (13.3 ± 7.2 versus 12.9 ± 8.2 days, p = 0.183) between sarcopenic and nonsarcopenic patients. Sarcopenic patients demonstrated increased modified frailty index scores (1.5 ± 1.1 versus 0.9 ± 0.9, p < 0.001) compared to nonsarcopenic patients.

Conclusions: For patients who underwent SSRF for rib fractures, sarcopenia did not increase the number of days of mechanical ventilation, ICU stay, or total hospital stay. Sarcopenia should not preclude the utilization of SSRF in these patients.
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http://dx.doi.org/10.1186/s41747-021-00206-4DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7884563PMC
February 2021

Beyond somatosensation: Mrgprs in mucosal tissues.

Neurosci Lett 2021 03 11;748:135689. Epub 2021 Feb 11.

Department of Biology, School of Arts and Sciences, University of Pennsylvania, Philadelphia, PA, USA. Electronic address:

Mas-related G coupled receptors (Mrgprs) are a superfamily of receptors expressed in sensory neurons that are known to transmit somatic sensations from the skin to the central nervous system. Interestingly, Mrgprs have recently been implicated in sensory and motor functions of mucosal-associated neuronal circuits. The gastrointestinal and pulmonary tracts are constantly exposed to noxious stimuli. Therefore, it is likely that neuronal Mrgpr signaling pathways in mucosal tissues, akin to their family members expressed in the skin, might relay messages that alert the host when mucosal tissues are affected by damaging signals. Further, Mrgprs have been proposed to mediate the cross-talk between sensory neurons and immune cells that promotes host-protective functions at barrier sites. Although the mechanisms by which Mrgprs are activated in mucosal tissues are not completely understood, these exciting studies implicate Mrgprs as potential therapeutic targets for conditions affecting the intestinal and airway mucosa. This review will highlight the central role of Mrgpr signaling pathways in the regulation of homeostasis at mucosal tissues.
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http://dx.doi.org/10.1016/j.neulet.2021.135689DOI Listing
March 2021

Chronic Itch of Unknown Origin Is Associated With an Enhanced Th2 Skin Immune Profile.

Am J Dermatopathol 2021 Feb 8. Epub 2021 Feb 8.

Department of Pathology and Immunology, Washington University School of Medicine, St. Louis, MO; The Institute for Dermatopathology, Newtown Square, PA; Division of Dermatology, Department of Medicine, Washington University School of Medicine, St. Louis, MO; and Department of Anesthesiology, Washington University School of Medicine, St. Louis, MO.

Abstract: Chronic pruritus of unknown origin (CPUO) is described as chronic itch lasting longer than 6 weeks in the absence of a defined skin rash and any known causative disease process. A retrospective study was performed on biopsy samples from patients with CPUO and normal controls to compare the immune profiles of these patients with healthy individuals. We used dual CD3/T-bet and CD3/GATA3 immunohistochemical staining to assess for T-cells expressing Th1 versus Th2 transcription factors, respectively. Our data showed that CD3+ cells of patients with CPUO co-express significantly more GATA3 compared with normal controls. Meanwhile, the normal control skin showed a much more balanced T-bet/GATA3 ratio of co-expression. Our data suggest an enrichment of Th2 cells in CPUO skin by T cell/GATA3 co-staining, supporting that CPUO is increasingly considered a type 2/Th2 cell-associated disease. We thus speculate that type 2 cytokine blockade-based therapies may represent effective treatments for CPUO.
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http://dx.doi.org/10.1097/DAD.0000000000001902DOI Listing
February 2021

Immunosensation: Neuroimmune Cross Talk in the Skin.

Annu Rev Immunol 2021 Apr 9;39:369-393. Epub 2021 Feb 9.

Division of Dermatology, Department of Medicine, Washington University School of Medicine, St. Louis, Missouri 63110, USA; email:

Classically, skin was considered a mere structural barrier protecting organisms from a diversity of environmental insults. In recent decades, the cutaneous immune system has become recognized as a complex immunologic barrier involved in both antimicrobial immunity and homeostatic processes like wound healing. To sense a variety of chemical, mechanical, and thermal stimuli, the skin harbors one of the most sophisticated sensory networks in the body. However, recent studies suggest that the cutaneous nervous system is highly integrated with the immune system to encode specific sensations into evolutionarily conserved protective behaviors. In addition to directly sensing pathogens, neurons employ novel neuroimmune mechanisms to provide host immunity. Therefore, given that sensation underlies various physiologies through increasingly complex reflex arcs, a much more dynamic picture is emerging of the skin as a truly systemic organ with highly coordinated physical, immunologic, and neural functions in barrier immunology.
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http://dx.doi.org/10.1146/annurev-immunol-101719-113805DOI Listing
April 2021

Treatment of patients with chronic pruritus of unknown origin with dupilumab.

J Dermatolog Treat 2021 Feb 8:1-4. Epub 2021 Feb 8.

Division of Dermatology, Department of Medicine, Washington University School of Medicine, St. Louis, MO, USA.

Background: Chronic pruritus of unknown origin (CPUO) is a highly debilitating disease that lacks effective treatments. This study explores a new therapeutic strategy with dupilumab.

Objectives: To examine whether patients with CPUO demonstrate clinical response to dupilumab.

Patients And Methods: This is a retrospective case series examining all patients with CPUO who were treated with dupilumab from March 2017 to December 2019 at a tertiary referral clinic at Washington University School of Medicine in St. Louis, MO. Numerical rating scale (NRS) itch score changes over time were recorded and analyzed.

Results: Fifteen patients (67% women; mean [SD] age, 68.7 [12.6] years [range, 42-88 years]) were included in the analysis. All patients had a diagnosis of CPUO for a mean [SD] 2.6 [2.8] years. The median [IQR] pruritus NRS itch score before dupilumab injection was 8 [8-10] and the final median [IQR] NRS itch score was 1 [0-2.5]. The mean [SD] reduction in the NRS itch score was 7.0 [1.9]. Dupilumab was well tolerated with one report of mild injection site reaction that was self-resolving.

Conclusion: This study suggests that dupilumab may be an effective treatment for patients with CPUO and supports the design of future randomized placebo-controlled trials to prove its efficacy.
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http://dx.doi.org/10.1080/09546634.2021.1880542DOI Listing
February 2021

PEG-BHD1028 Peptide Regulates Insulin Resistance and Fatty Acid β-Oxidation, and Mitochondrial Biogenesis by Binding to Two Heterogeneous Binding Sites of Adiponectin Receptors, AdipoR1 and AdipoR2.

Int J Mol Sci 2021 Jan 17;22(2). Epub 2021 Jan 17.

EncuraGen, Inc., Anyang, Gyeonggi-do 14057, Korea.

Adiponectin plays multiple critical roles in modulating various physiological processes by binding to its receptors. The functions of PEG-BHD1028, a potent novel peptide agonist to AdipoRs, was evaluated using in vitro and in vivo models based on the reported action spectrum of adiponectin. To confirm the design concept of PEG-BHD1028, the binding sites and their affinities were analyzed using the SPR (Surface Plasmon Resonance) assay. The results revealed that PEG-BHD1028 was bound to two heterogeneous binding sites of AdipoR1 and AdipoR2 with a relatively high affinity. In C2C12 cells, PEG-BHD1028 significantly activated AMPK and subsequent pathways and enhanced fatty acid β-oxidation and mitochondrial biogenesis. Furthermore, it also facilitated glucose uptake by lowering insulin resistance in insulin-resistant C2C12 cells. PEG-BHD1028 significantly reduced the fasting plasma glucose level in db/db mice following a single s.c. injection of 50, 100, and 200 μg/Kg and glucose tolerance at a dose of 50 μg/Kg with significantly decreased insulin production. The animals received 5, 25, and 50 μg/Kg of PEG-BHD1028 for 21 days significantly lost their weight after 18 days in a range of 5-7%. These results imply the development of PEG-BHD1028 as a potential adiponectin replacement therapeutic agent.
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http://dx.doi.org/10.3390/ijms22020884DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7830917PMC
January 2021

Quantifying neurotransmitter secretion at single-vesicle resolution using high-density complementary metal-oxide-semiconductor electrode array.

Nat Commun 2021 01 18;12(1):431. Epub 2021 Jan 18.

Department of Electrical and Computer Engineering, University of Central Florida, Orlando, FL, 32827, USA.

Neuronal exocytosis facilitates the propagation of information through the nervous system pertaining to bodily function, memory, and emotions. Using amperometry, the sub-millisecond dynamics of exocytosis can be monitored and the modulation of exocytosis due to drug treatment or neurodegenerative diseases can be studied. Traditional single-cell amperometry is a powerful technique for studying the molecular mechanisms of exocytosis, but it is both costly and labor-intensive to accumulate statistically significant data. To surmount these limitations, we have developed a silicon-based electrode array with 1024 on-chip electrodes that measures oxidative signal in 0.1 millisecond intervals. Using the developed device, we are able to capture the modulation of exocytosis due to Parkinson's disease treatment (L-Dopa), with statistical significance, within 30 total minutes of recording. The validation study proves our device's capability to accelerate the study of many pharmaceutical treatments for various neurodegenerative disorders that affect neurotransmitter secretion to a matter of minutes.
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http://dx.doi.org/10.1038/s41467-020-20267-0DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7813837PMC
January 2021

A basophil-neuronal axis promotes itch.

Cell 2021 Jan 14;184(2):422-440.e17. Epub 2021 Jan 14.

Division of Dermatology, Department of Medicine, Washington University School of Medicine, St. Louis, MO 63110, USA; Center for the Study of Itch and Sensory Disorders, Washington University School of Medicine, St. Louis, MO 63110, USA; Department of Pathology and Immunology, Washington University School of Medicine, St. Louis, MO 63110, USA; Department of Anesthesiology, Washington University School of Medicine, St. Louis, MO 63110, USA. Electronic address:

Itch is an evolutionarily conserved sensation that facilitates expulsion of pathogens and noxious stimuli from the skin. However, in organ failure, cancer, and chronic inflammatory disorders such as atopic dermatitis (AD), itch becomes chronic, intractable, and debilitating. In addition to chronic itch, patients often experience intense acute itch exacerbations. Recent discoveries have unearthed the neuroimmune circuitry of itch, leading to the development of anti-itch treatments. However, mechanisms underlying acute itch exacerbations remain overlooked. Herein, we identify that a large proportion of patients with AD harbor allergen-specific immunoglobulin E (IgE) and exhibit a propensity for acute itch flares. In mice, while allergen-provoked acute itch is mediated by the mast cell-histamine axis in steady state, AD-associated inflammation renders this pathway dispensable. Instead, a previously unrecognized basophil-leukotriene (LT) axis emerges as critical for acute itch flares. By probing fundamental itch mechanisms, our study highlights a basophil-neuronal circuit that may underlie a variety of neuroimmune processes.
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http://dx.doi.org/10.1016/j.cell.2020.12.033DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7878015PMC
January 2021

Real-life utilization of BioFire Filmarray pneumonia panel as an antibiotic stewardship tool.

Infect Dis (Lond) 2021 Apr 30;53(4):308-313. Epub 2020 Dec 30.

David Geffen School of Medicine, University of California, Los Angeles, CA, USA.

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http://dx.doi.org/10.1080/23744235.2020.1866774DOI Listing
April 2021

Does prophylactic inferior vena cava filter reduce the hazard of pulmonary embolism and mortality in severe trauma? A single center retrospective comparative study.

Eur J Radiol Open 2021 10;8:100299. Epub 2020 Dec 10.

Institute of Clinical Medicine, Faculty of Medicine, University of Oslo, Norway.

Objectives: Use of inferior vena cava (IVC) filters in patients following severe trauma without recent history of venous thromboembolism (VTE) is controversial. Our objective was to determine if IVC filter placement in the setting of severe trauma effects the hazard of in-hospital pulmonary embolism (PE), deep venous thrombosis (DVT) and mortality.

Methods: This retrospective study recruited patients from a single Level I Trauma Center between 1/2008 and 12/2013. Inclusion criteria were age>15 years, Injury Severity Score (ISS)>15 and survival>24 h after hospital admission. Patients with VTE diagnosed prior to IVC filter placement were excluded. A Cox proportional hazards regression model was used, adjusting for immortal time bias with landmark analysis at predefined time after injury. Differences between IVC filter and non-IVC filter groups were adjusted using propensity score.

Results: In total 1451 patients were reviewed; 282 patients received an IVC filter and 1169 patients had no IVC filter placed. The mean age was 45.9 vs. 56.9 years and the mean ISS was 29.8 vs. 22.6 in the IVC filter and the non-IVC filter group, respectively. IVC filter placement was not associated with the hazard of PE (HR = 0.46; 95 % CI, 0.12,1.70; P = 0.24) or mortality (HR = 1.02; 95 % CI 0.60,1.75; P = 0.93). However, IVC filter placement was associated with the hazard of DVT (HR = 2.73; 95 % CI, 1.28,5.85; P = 0.01).

Conclusions: In patients with severe trauma, those with prophylactic IVC filter placement did not have a reduced hazard of PE or mortality, but an increased hazard of DVT was observed.
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http://dx.doi.org/10.1016/j.ejro.2020.100299DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7734225PMC
December 2020

Hyperbolic Cooper-Pair Polaritons in Planar Graphene/Cuprate Plasmonic Cavities.

Nano Lett 2021 Jan 15;21(1):308-316. Epub 2020 Dec 15.

Department of Physics, Columbia University, New York, New York 10027, United States.

Hyperbolic Cooper-pair polaritons (HCP) in cuprate superconductors are of fundamental interest due to their potential for providing insights into the nature of unconventional superconductivity. Here, we critically assess an experimental approach using near-field imaging to probe HCP in BiSrCaCuO (Bi-2212) in the presence of graphene surface plasmon polaritons (SPP). Our simulations show that inherently weak HCP features in the near-field can be strongly enhanced when coupled to graphene SPP in layered graphene/hexagonal boron nitride (hBN)/Bi-2212 heterostructures. This enhancement arises from our multilayered structures effectively acting as plasmonic cavities capable of altering collective modes of a layered superconductor by modifying its electromagnetic environment. The degree of enhancement can be selectively controlled by tuning the insulating spacer thickness with atomic precision. Finally, we verify the expected renormalization of room-temperature graphene SPP using near-field infrared imaging. Our modeling, augmented with data, attests to the validity of our approach for probing HCP modes in cuprate superconductors.
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http://dx.doi.org/10.1021/acs.nanolett.0c03684DOI Listing
January 2021

An evolving role for GRADE-trained methodologists in the American Thyroid Association Clinical Practice Guidelines Development Process.

J Clin Epidemiol 2021 Apr 7;132:147-148. Epub 2020 Dec 7.

Co-Chair, American Thyroid Association Guidelines and Statements Committee, Associate Professor of Medicine, Rush University School of Medicine, Chief, Division of Endocrinology, 1725 W Harrison Street, Chicago, IL 60612, USA.

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http://dx.doi.org/10.1016/j.jclinepi.2020.11.025DOI Listing
April 2021

Intercellular Mitochondria Transfer to Macrophages Regulates White Adipose Tissue Homeostasis and Is Impaired in Obesity.

Cell Metab 2021 Feb 4;33(2):270-282.e8. Epub 2020 Dec 4.

Department of Pathology and Immunology, Washington University School of Medicine, St. Louis, MO 63110, USA; Department of Medicine, Washington University School of Medicine, St. Louis, MO 63110, USA. Electronic address:

Recent studies suggest that mitochondria can be transferred between cells to support the survival of metabolically compromised cells. However, whether intercellular mitochondria transfer occurs in white adipose tissue (WAT) or regulates metabolic homeostasis in vivo remains unknown. We found that macrophages acquire mitochondria from neighboring adipocytes in vivo and that this process defines a transcriptionally distinct macrophage subpopulation. A genome-wide CRISPR-Cas9 knockout screen revealed that mitochondria uptake depends on heparan sulfates (HS). High-fat diet (HFD)-induced obese mice exhibit lower HS levels on WAT macrophages and decreased intercellular mitochondria transfer from adipocytes to macrophages. Deletion of the HS biosynthetic gene Ext1 in myeloid cells decreases mitochondria uptake by WAT macrophages, increases WAT mass, lowers energy expenditure, and exacerbates HFD-induced obesity in vivo. Collectively, this study suggests that adipocytes and macrophages employ intercellular mitochondria transfer as a mechanism of immunometabolic crosstalk that regulates metabolic homeostasis and is impaired in obesity.
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http://dx.doi.org/10.1016/j.cmet.2020.11.008DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7858234PMC
February 2021

Dietary Supplement Use According to Sex and Triad Risk Factors in Collegiate Endurance Runners.

J Strength Cond Res 2021 Feb;35(2):404-410

Departments of Family Medicine and Orthopedic Surgery, University of California, Los Angeles, Santa Monica, California.

Abstract: Barrack, MT, Fredericson, M, Dizon, F, Tenforde, AS, Kim, BY, Kraus, E, Kussman, A, Singh, S, and Nattiv, A. Dietary supplement use according to sex and Triad risk factors in collegiate endurance runners. J Strength Cond Res 35(2): 404-410, 2021-This cross-sectional study evaluated the prevalence in the use of dietary supplements among elite collegiate runners among 2 NCAA Division I cross-country teams. At the start of each season from 2015 to 2017, male and female endurance runners were recruited to complete baseline study measures; the final sample included 135 (male n = 65, female n = 70) runners. Runners completed a health survey, web-based nutrition survey, and Triad risk assessment. The prevalence of dietary supplement use and Triad risk factors, including disordered eating, low bone mass, amenorrhea (in women), low body mass index, and stress fracture history, was assessed. A total of 78.5% (n = 106) runners reported taking 1 or more supplements on ≥4 days per week over the past month, 48% (n = 65) reported use of ≥3 supplements. Products used with highest frequency included multivitamin/minerals 46.7% (n = 63), iron 46.7% (n = 63), vitamin D 34.1% (n = 46), and calcium 33.3% (n = 45). More women, compared with men, used iron (61.4 vs. 30.8%, p < 0.001) and calcium (41.4 vs. 24.6%, p = 0.04); men exhibited higher use of amino acids and beta-alanine (6.2 vs. 0%, p = 0.04). Runners with bone stress injury (BSI) history, vs. no previous BSI, reported more frequent use of ≥3 supplements (61.5 vs. 32.8%, p = 0.001), vitamin D (49.2 vs. 19.4%, p < 0.001), and calcium (47.7 vs. 19.4%, p = 0.001). Low bone mineral density was also associated with higher use of vitamin D and calcium. Most runners reported regular use of 1 or more supplements, with patterns of use varying based on sex, history of BSI, and bone mass.
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http://dx.doi.org/10.1519/JSC.0000000000003848DOI Listing
February 2021

Retrospective Assessment of Salvage to 10 kHz Spinal Cord Stimulation (SCS) in Patients Who Failed Traditional SCS Therapy: RESCUE Study.

J Pain Res 2020 10;13:2861-2867. Epub 2020 Nov 10.

Carolinas Pain Institute, Winston-Salem, NC 27103, USA.

Background And Objectives: A randomized clinical trial demonstrated that 10 kHz SCS (10kHz-SCS) therapy is superior to traditional low-frequency SCS (LF-SCS) at 12- and 24-month clinical follow-ups and led to Food and Drug Administration (FDA) approval of the therapy. The results of the study led our practices to trial 10kHz-SCS in patients who had not maintained pain relief with LF-SCS therapy. Here, we report a large set of data from two clinical sites to assess if 10kHz-SCS is an effective salvage modality when LF-SCS fails.

Methods: We conducted a retrospective chart review of 120 patients across two clinical sites who had LF-SCS implants and were salvaged with 10kHz-SCS.

Results: Data were analyzed from 105 patients between 28 and 90 years old (median 60) with chronic pain for 13.6 years. The mean duration of LF-SCS therapy was 4.66±3.9 years. The average Visual Analog Scale (VAS) decreased from 8.30±1.4 (median of 8) cm to 3.32±2.0 (median of 3) cm at 12 months and 3.36±2.0 (median of 3) cm at the most recent clinic visit (p<0.001) following salvage therapy. Pain relief of 50% or more was obtained in 85 out of 105 (81%) patients. Opioid usage decreased from 60.3±77.1 mg to 32.1±44.0 mg MSO4 equivalents (p = 0.001) at 12 months after salvage therapy.

Conclusion: Eighty-one percent of patient cases reviewed, where LF-SCS had failed, achieved >50% pain relief with 10kHz-SCS, and almost all exhibited some clinical improvement. Therefore, 10kHz-SCS should be considered an appropriate option to rescue failed LF-SCS.
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http://dx.doi.org/10.2147/JPR.S281749DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7667504PMC
November 2020

Feasibility and Value of Establishing a Community-Based Virtual Multidisciplinary Sarcoma Case Conference.

JCO Oncol Pract 2020 10;16(10):e1143-e1150

Department of Pathology, Kaiser Permanente Northern California, Santa Clara, CA.

Purpose: Management of soft tissue and bone sarcoma presents many challenges, both diagnostically and therapeutically, and requires multidisciplinary collaboration; however, such collaboration is often challenging to establish, especially in the community setting. We share our experiences of a virtual multidisciplinary sarcoma case conference (VMSCC).

Methods: We conducted retrospective review of the VMSCC data-initially via Webex, now Microsoft Teams-and the surveys of referring physicians to understand the feasibility and value of the VMSCC.

Results: The VMSCC was established in March 2013 in Kaiser Permanente Northern California with consistent participation of the Departments of Musculoskeletal Oncology (orthopedic oncology), Musculoskeletal Radiology, Pathology, Medical Oncology, Radiation Oncology, Nuclear Medicine, Surgical Oncology, and Genetics. Pediatric Oncology participated ad hoc when pediatric sarcoma cases were presented. Referrals were from multiple specialties and regions, including the Kaiser Permanente Mid-Atlantic and Hawaii regions. From March 2013 to December 2019, 1,585 cases were reviewed encompassing 36 histologic types. More than 300 cases were reviewed per year from 2017 to 2019. Survey results of referring physicians demonstrate that the VMSCC enhanced the confidence of treating physicians, and its recommendations frequently led to treatment changes.

Conclusion: Establishing a valuable community-based VMSCC is feasible. VMSCC recommendations frequently led to treatment changes and improved the confidence of treating physicians.
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http://dx.doi.org/10.1200/JOP.20.00110DOI Listing
October 2020

Trauma Activation Responsiveness: An RFID-enabled trauma flowsheet.

Annu Int Conf IEEE Eng Med Biol Soc 2020 07;2020:5718-5721

Manually documented trauma flow sheets contain critical information regarding trauma resuscitations in the emergency department (ED). The American College of Surgeons (ACS) has enforced certain thresholds on trauma surgeons' arrival time to the trauma bay. Due to the complex and fast-paced ED environment, this information can be easily overlooked or erroneously recorded, affecting compliance with ACS standards. This paper is a retrospective study conducted at a Level I trauma center equipped with an RFID system to investigate an automated solution to evaluate and improve the accuracy of measuring trauma surgeons' response time to the highest level (red) trauma activations.Clinical Relevance- Demonstration of timely response to trauma activations is required for ACS verification. As real-time location systems become more prevalent, they may improve a hospital's ability to report accurate response times for trauma team activations.
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http://dx.doi.org/10.1109/EMBC44109.2020.9175880DOI Listing
July 2020

Tunable Dielectric and Thermal Properties of Oxide Dielectrics via Substrate Biasing in Plasma-Enhanced Atomic Layer Deposition.

ACS Appl Mater Interfaces 2020 Oct 24;12(40):44912-44918. Epub 2020 Sep 24.

Division of Mechanical Systems Engineering, Sookmyung Women's University, Seoul 04310, South Korea.

The ability to control the properties of dielectric thin films on demand is of fundamental interest in nanoscale devices. Here, we modulate plasma characteristics at the surface of a substrate to tune both dielectric constant and thermal conductivity of amorphous thin films grown using plasma-enhanced atomic layer deposition. Specifically, we apply a substrate bias ranging from 0 to ∼117 V and demonstrate the systematic tunability of various material parameters of AlO. As a function of the substrate bias, we find a nonmonotonical evolution of intrinsic properties, including density, dielectric constant, and thermal conductivity. A key observation is that the maximum values in dielectric constant and effective thermal conductivity emerge at different substrate biases. The impact of density on both thermal conductivity and dielectric constant is further examined using a differential effective medium theory and the Clausius-Mossotti model, respectively. We find that the peak value in the dielectric constant deviates from the Clausius-Mossotti model, indicating the change of oxygen fraction in our thin films as a function of substrate bias. This finding suggests that the increased local strength of plasma sheath not only enhances material density but also controls the dynamics of microstructural defect formation beyond what is possible with conventional approaches. Based on our experimental observations and modeling, we further build a phenomenological relation between dielectric constant and thermal conductivity. Our results pave invaluable avenues for optimizing dielectric thin films at the atomic scale for a wide range of applications in nanoelectronics and energy devices.
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http://dx.doi.org/10.1021/acsami.0c11086DOI Listing
October 2020

Impact of Socioeconomic Disadvantage and Diabetic Retinopathy Severity on Poor Ophthalmic Follow-Up in a Rural Vermont and New York Population.

Clin Ophthalmol 2020 21;14:2397-2403. Epub 2020 Aug 21.

Department of Surgery, Division of Ophthalmology, University of Vermont Medical Center and Larner College of Medicine, Burlington, VT, USA.

Objective: To investigate the impact of socioeconomic disadvantage and diabetic retinopathy severity on follow-up for vision care among people with diabetes mellitus (DM) residing in rural Vermont and northern New York State.

Methods: A retrospective chart review of people with DM who visited our academic eye clinic at least once between October 1, 2015, and March 31, 2016, was done. Of 1,466 unique patient visits, 500 were chosen for full chart review by simple random sampling. DM follow-up within 1 year was recommended for 331 adults. Data about prescribed and actual follow-up intervals were extracted. Regression models were used to identify factors associated with poor attendance at follow-up appointments.

Results: Sixty-eight [20.5%] patients had poor follow-up, defined as no ophthalmology visit within double the prescribed interval. Of these, 57 were not seen in follow-up by the end of study observation. Poor follow-up was greatest among socioeconomically disadvantaged patients, as defined by Medicaid enrollment (odds ratio [OR], 1.95; 95% CI, 1.07-3.56) in comparison to non-disadvantaged patients. Follow-up was better among those with moderate or worse diabetic retinopathy (OR, 0.38 95% CI, 0.20-0.70), and those with macular edema (OR, 0.19; 95% CI, 0.057-0.62).

Conclusion: Medicaid insurance and better diabetic retinopathy status were associated with worse follow-up among our predominantly rural population of patients. Patients who did not follow-up within double the recommended interval were unlikely to follow-up at all. Interventions are needed to target those at highest risk for poor follow-up.
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http://dx.doi.org/10.2147/OPTH.S258270DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7457718PMC
August 2020

Index Admission Characteristics and All-Cause Readmissions Analysis in Younger and Older Adults with Intracerebral Hemorrhage.

Cerebrovasc Dis 2020 23;49(4):375-381. Epub 2020 Aug 23.

Department of Neurology, Icahn School of Medicine at Mount Sinai, New York, New York, USA,

Introduction: Intracerebral hemorrhage (ICH) comprises 15-20% of all strokes with debilitating consequences. Data regarding characteristics and outcomes of primary ICH in the young are lacking, given its rarity, making comparisons between younger and older cohorts difficult to perform. Nationally representative administrative databases enable analysis of such rare events.

Objective: To determine the baseline characteristics, all-cause readmission rates, and reasons for primary ICH in younger and older adults using a nationally representative database.

Methods: A retrospective cohort analysis was performed using the Nationwide Readmissions Database 2013. Validated ICD-9-CM codes identified index ICH admissions, comorbidities, demographics, behavioral risk factors, procedures, and Elixhauser and Charlson Comorbidity indices. We compared "younger" (age ≤ 45 years) and "older" (age > 45) index ICH admissions by weighted 30-day all-cause readmission rates, primary diagnosis code for 30-day readmissions, most common comorbidities during the index hospitalization, and Kaplan-Meier cumulative risk of readmission up to 1 year.

Results: Older admissions had higher comorbidity scores and mortality, but both groups had similar total comorbidities. Younger admissions exhibited longer length of stay with more procedures performed. Vascular anomalies (aneurysm 7.2 vs. 4.6% and arteriovenous malformation 5.9 vs. 0.8%) and behavioral risk factors (smoking 26.5 vs. 23.0%, alcohol abuse 6.7 vs. 4.6%, and substance use 13.5 vs. 2.9%) were more prevalent in younger admissions, while older patients had more cardiovascular comorbidities. All-cause 30-day readmission rates (13.1 vs. 13.0%) and 1-year cumulative risk of readmission (log-rank p value 0.7209) were similar. Readmissions in the younger cohort were primarily for neurological conditions, and those in the older cohort were for systemic conditions.

Conclusions: Adults <45 years with ICH had similar total comorbidities as older adults but more procedures, longer hospital stay, and more behavioral risk factors. Readmission rates were similar though reasons differed; younger patients were more for neurological reasons than for other systemic causes.
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http://dx.doi.org/10.1159/000509839DOI Listing
November 2020

Scratching Beyond the Surface of Itchy Wounds.

Immunity 2020 08;53(2):235-237

Center for the Study of Itch, Washington University School of Medicine, St. Louis, MO 63110, USA; Division of Dermatology, Department of Medicine, Washington University School of Medicine, St. Louis, MO 63110, USA; Department of Anesthesiology, Washington University School of Medicine, St. Louis, MO 63110, USA; Department of Pathology and Immunology, Washington University School of Medicine, St. Louis, MO 63110, USA. Electronic address:

In this issue of Immunity, Xu et al. reveal that dermal dendritic cells produce interleukin-31, which acts on neurons to promote wound itch. Their findings link itch associated with deeper wounds-wounds that extend beyond the epithelium-to the cells and cytokines that mediate wound healing.
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http://dx.doi.org/10.1016/j.immuni.2020.07.016DOI Listing
August 2020

Severe rapidly progressive Guillain-Barré syndrome in the setting of acute COVID-19 disease.

J Neurovirol 2020 10 27;26(5):797-799. Epub 2020 Jul 27.

Division of Neuromuscular Diseases and Clinical Neurophysiology Laboratories, Department of Neurology, Icahn School of Medicine, Mount Sinai Hospital, 1468 Madison Avenue, New York, NY, 10029, USA.

There is concern that the global burden of coronavirus disease of 2019 (COVID-19) due to severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) infection might yield an increased occurrence of Guillain-Barré syndrome (GBS). It is currently unknown whether concomitant SARS-CoV-2 infection and GBS are pathophysiologically related, what biomarkers are useful for diagnosis, and what is the optimal treatment given the medical comorbidities, complications, and simultaneous infection. We report a patient who developed severe GBS following SARS-CoV-2 infection at the peak of the initial COVID-19 surge (April 2020) in New York City and discuss diagnostic and management issues and complications that may warrant special consideration in similar patients.
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http://dx.doi.org/10.1007/s13365-020-00884-7DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7384559PMC
October 2020