Criteria for Deployment of the United States National Guard to Domestic Sudden-Onset Natural Disasters: A Scoping Review.

INTRODUCTION: This study is a scoping review to identify literature pertinent to the question: "What are the criteria for deployment of the United States National Guard (USNG) to domestic sudden-onset natural disasters (SODs)?" As this question relies on factors across many disciplines-legal, medical, technical, cultural-and as there is no foundational body of academic literature or unified governmental or USNG policy addressing this question, a scoping review was designed to identify the body of literature on which further research and policy decisions surrounding this question may be based. MATERIALS AND METHODS: On January 23, 2023 a modified PRISMA-ScR search was performed using an online search engine of the following databases: Academic Search Premier, Google Scholar, JSTOR, PubMed, Web of Science, and WorldCat. The inclusion criteria included the involvement of the USNG response to U.S. domestic SOD. Non-SOD results were excluded. Results from all years and of any type of literature were considered and were limited to the English language. First, titles and abstracts were screened by 2 independent reviewers. Then, a full-text review was performed by 2 independent reviewers. Finally, data were extracted from included texts by 2 independent reviewers. A third reviewer resolved any discrepancies at each stage. This study did not require approval of an institutional review board. RESULTS: Out of the 886 results identified by the original search, after the complete review process, 34 sources were relevant to the research question. Fifteen criteria for the deployment of the USNG to SODs were identified. Overwhelmed local responders, utility failure, the need for the provision of security, and the need for logistical coordination were the most commonly identified criteria. Hurricanes were the most common SOD addressed in the included literature, and most results were event reports. CONCLUSIONS: This modified PRISMA-ScR identified a foundation on which elected officials, USNG leadership, and the larger disaster response community may develop policies and disaster response plans to optimize available resources through the activation of the USNG when responding to SODs.

Disasters in the Northern Triangle: A Descriptive Analysis Using the EM-DAT Database 1902-2022.

INTRODUCTION: Since 1902, disasters in the Northern Triangle of Central America, which consists of the countries Guatemala, Honduras, and El Salvador, have caused over one-hundred-thousand deaths, affected millions of people, and caused tens of billions of dollars in damages. Understanding the nature and frequency of these events will allow stakeholders to decrease both the acute damages and the long-term deleterious consequences of disasters. STUDY OBJECTIVE: This study provides a descriptive analysis of all disasters recorded in the Emergency Events Database (EM-DAT) affecting Guatemala, Honduras, and El Salvador from 1902-2022. METHODS: Data were collected and analyzed from the EM-DAT, which categorizes disasters by frequency, severity, financial cost, distribution by country, burden of death, number of people affected, financial cost by country, and type of disasters most prevalent in each country. Results are presented as absolute numbers and as a percentage of the overall disaster burden. These trends are then graphed over the time period of the database. RESULTS: The EM-DAT recorded 359 disasters in the Northern Triangle from 1902 through 2022. Meteorologic events (floods and storms) were the most common types of disaster (44%), followed by transport accidents (13%). Meteorologic events and earthquakes were the most severe, as measured by deaths (62%), people affected (60%), and financial cost (86%). Guatemala had the greatest number of disasters (45%), deaths (68%), and affected people (52%). The financial costs of the disasters were evenly distributed between the three countries. CONCLUSION: Meteorologic disasters are the most common and most severe type of disaster in the Northern Triangle. Earthquakes and transport accidents are also common. As climate change causes more severe storms in the region, disasters are likely to increase in severity as well. Governments and aid organizations should develop disaster preparedness and mitigation strategies to lessen the catastrophic effects of future disasters. Missing data limit the conclusions of this study to general trends.

Racial differences in opiate administration for pain relief at an academic emergency department.

INTRODUCTION: The decision to treat pain in the emergency department (ED) is a complex, idiosyncratic process. Prior studies have shown that EDs undertreat pain. Several studies demonstrate an association between analgesia administration and race. This is the first Midwest single institution study to address the question of race and analgesia, in addition to examining the effects of both patient and physician characteristics on race-based disparities in analgesia administration. METHODS: This was a retrospective chart review of patients presenting to an urban academic ED with an isolated diagnosis of back pain, migraine, or long bone fracture (LBF) from January 1, 2007 to December 31, 2011. Demographic and medication administration information was collected from patient charts by trained data collectors blinded to the hypothesis of the study. The primary outcome was the proportion of African-Americans who received analgesia and opiates, as compared to Caucasians, using Pearson's chi-squared test. We developed a multiple logistic regression model to identify which physician and patient characteristics correlated with increased opiate administration. RESULTS: Of the 2,461 patients meeting inclusion criteria, 57% were African-American and 30% Caucasian (n=2136). There was no statistically significant racial difference in the administration of any analgesia (back pain: 86% vs. 86%, p=0.81; migraine: 83% vs. 73%, p=0.09; LBF: 94% vs. 90%, p=0.17), or in opiate administration for migraine or LBF. African-Americans who presented with back pain were less likely to receive an opiate than Caucasians (50% vs. 72%, p<0.001). Secondary outcomes showed that higher acuity, older age, physician training in emergency medicine, and male physicians were positively associated with opiate administration. Neither race nor gender patient-physician congruency correlated with opiate administration. CONCLUSION: No race-based disparity in overall analgesia administration was noted for all three conditions: LBF, migraine, and back pain at this institution. A race-based disparity in the likelihood of receiving opiate analgesia for back pain was observed in this ED. The etiology of this is likely multifactorial, but understanding physician and patient characteristics of institutions may help to decrease the disparity by raising awareness of practice patterns and can provide the basis for quality improvement projects.

Allergen-induced proliferation and interleukin-5 production by bronchoalveolar lavage and blood T cells after segmental allergen challenge.

In order to detect and characterize allergen-specific T cells in the airways of atopic asthmatics, we measured proliferation and cytokine production by bronchoalveolar lavage (BAL) T cells isolated from Dermatophagoides pteronyssinus (Der p)-sensitive asthmatics and nonatopic control subjects, and compared the results with those generated using peripheral blood (PB) T cells. BAL and PB mononuclear cells were collected 24 h after segmental allergen challenge by fibreoptic bronchoscopy and venepuncture, respectively. T cells purified from BAL and PB were stimulated with autologous, irradiated antigen-presenting cells and D. pteronyssinus extract or a control, nonallergen antigen (M. tuberculosis purified protein derivative [PPD]). IL-5 and IFN-gamma concentrations were measured in culture supernatants by ELISA, and T-cell proliferation by 3H-thymidine uptake. D. pteronyssinus-induced proliferation of T cells derived from both BAL and PB was elevated in asthmatics when compared with control subjects (p < 0.05), whereas PPD-induced proliferation was equivalent in both compartments. In the asthmatics, D. pteronyssinus-induced proliferative responses of equivalent numbers of BAL and PB T cells obtained after allergen challenge were statistically equivalent. Nevertheless, BAL T cells stimulated with D. pteronyssinus produced significantly greater amounts of IL-5 than did PB T cells (p < 0.05). Allergen-induced proliferation and IL-5 production by BAL T cells in the asthmatics after segmental allergen challenge correlated with the percentages of eosinophils in the BAL fluid (p < 0.01). Further, BAL T cells from asthmatic patients produced significantly higher amounts of IL-5 than did the same number of cells from nonatopic control subjects (p < 0.05). We conclude that, in D. pteronyssinus-sensitive asthmatics, allergen-specific T cells can be detected in the bronchial lumen after allergen challenge and that allergen-induced proliferation and IL-5 production by these cells correlates with local eosinophil influx. Although bronchial luminal T cells show an equivalent proliferative response to allergen stimulation as compared with PB T cells, they do produce more IL-5, consistent with the hypothesis that local differentiation or priming of these cells within the bronchial mucosal environment results in upregulation of allergen-induced IL-5 secretion.

IL-5 production by allergen-stimulated T cells following grass pollen immunotherapy for seasonal allergic rhinitis.

Grass pollen immunotherapy for the treatment of seasonal allergic rhinitis ('summer hayfever') results in improvement in symptoms, a reduction in the early and late phase responses to allergen provocation and decreased tissue eosinophilia. Immunotherapy may act by altering the pattern of cytokine production by allergen-specific T cells from a 'Th2-type' (IL-4 and IL-5) profile to a 'Th1-type' (interferon-gamma (IFN-gamma)) profile. We set out to determine whether clinical improvement following specific allergen immunotherapy is accompanied by reduced production of the pro-eosinophilic and archetypal 'Th2-type' cytokine, IL-5. Peripheral blood mononuclear cells (PBMC) were isolated from (i) 13 patients who had received 6 or 7 years' continuous conventional immunotherapy with timothy grass pollen (Phleum pratense); (ii) 14 patients who had received 3 or 4 years of conventional immunotherapy followed by 3 years of placebo treatment; (iii) 12 matched seasonal rhinitic patients who had never received immunotherapy; and (iv) 17 non-atopic normal controls. PBMC were stimulated with 20 microg/ml and 200 microg/ml P. pratense extract, or 10 microg/ml of Mycobacterium tuberculosis purified protein derivative (PPD), at 2 x 10(6) cells/ml and 5 x 10(6) cells/ml. IL-5 concentrations in culture supernatants collected after 6 days' culture were measured by ELISA. IL-5 production in response to stimulation with P. pratense extract was highly reproducible and was elevated in both of the immunotherapy treated groups and the untreated rhinitics relative to non-atopic controls (P<0.005 for each group relative to non-atopic controls, under each of the four conditions tested). However, no significant reduction was observed in IL-5 production when immunotherapy treated patients were compared with untreated rhinitic controls. Moreover, abrogation of the cutaneous late-phase responses to allergen following treatment was not associated with reduced IL-5 production by allergen-stimulated peripheral blood T cells. Reduced IL-5 production by peripheral blood T cells may not be necessary for immunotherapy to be effective. Local immunodulation of T cell responses may play a role in this form of treatment.

IL-13 production by allergen-stimulated T cells is increased in allergic disease and associated with IL-5 but not IFN-gamma expression.

Interleukin-13 (IL-13) shares many, but not all, of the properties of the prototypic T-helper type 2 (Th2) cytokine IL-4, but its role in allergen-driven T-cell responses remains poorly defined. We hypothesized that allergen stimulation of peripheral blood T cells from patients with atopic disease compared with non-atopic controls results in elevated IL-13 synthesis in the context of a 'Th2-type' pattern. Freshly isolated peripheral blood mononuclear cells (PBMC) obtained from sensitized atopic patients with allergic disease, and non-atopic control subjects, were cultured with the allergens Phleum pratense (Timothy grass pollen) or Dermatophagoides pteronyssinus (house dust mite) and the non-allergenic recall antigen Mycobacterium tuberculosis purified protein derivative (PPD). Supernatant concentrations of IL-13, along with IL-5 and interferon-gamma (IFN-gamma) (Th2- and Th1-type cytokines, respectively) were determined by enzyme-linked immunosorbent assay (ELISA). Allergen-induced IL-13 and IL-5 production by T cells from patients with allergic disease was markedly elevated (P = 0.0075 and P = 0.0004, respectively) compared with non-atopic controls, whereas IFN-gamma production was not significantly different. In contrast to allergen, the prototypic Th1-type antigen M. tuberculosis PPD induced an excess of IFN-gamma over IL-13 and IL-5 production, and absolute concentrations of cytokines were not affected by the presence or absence of atopic disease. Addition of exogenous recombinant IFN-gamma or IL-12, cytokines known to inhibit Th2-type responses, significantly inhibited allergen-driven production of both IL-13 and IL-5, but not T-cell proliferation, whereas exogenous IL-4 did not significantly affect production of IL-13 or IL-5. We conclude that allergen-specific T cells from atopic subjects secrete elevated quantities of IL-13 compared with non-atopic controls, in the context of a Th2-type pattern of cytokine production.

Production of IL-5 and granulocyte-macrophage colony-stimulating factor by naive human mast cells activated by high-affinity IgE receptor ligation.

BACKGROUND: The late-phase allergic reaction is an eosinophilic inflammatory response that begins several hours after allergen exposure, may persist for 24 hours, and is an important pathogenic mechanism in allergic disease. OBJECTIVE: Cultured naive human mast cells were used to investigate whether mast cells are a direct source of the eosinophil-promoting cytokines IL-5, IL-3, and granulocyte-macrophage colony-stimulating factor (GM-CSF). METHODS: Naive human mast cells were derived from bone marrow mononuclear cells cultured in the presence of stem-cell factor. Cytokine message and protein production in response to high-affinity IgE receptor ligation of cultured mast cells were measured by semiquantitative polymerase chain reaction and ELISA, respectively. RESULTS: IL-5, IL-3, and GM-CSF messenger RNA increased within 2 hours of mast cell activation, with IL-5 and GM-CSF message remaining elevated for 24 hours, whereas IL-3 mRNA rapidly declined. IL-5 and GM-CSF protein were measurable 4 to 6 hours after stimulation and peaked by 24 and 12 hours, respectively. IL-3 protein was not detectable. CONCLUSION: These findings demonstrate that naive mast cells do not constitutively produce IL-5 or GM-CSF protein but are a major source of these eosinophilotropic cytokines on high-affinity IgE receptor ligation.

IL-5 secretion by allergen-stimulated CD4+ T cells in primary culture: relationship to expression of allergic disease.

BACKGROUND: IL-5-producing allergen-specific T cells are thought to play a prominent role in the pathogenesis of allergic inflammation. We hypothesized that T cell allergen-driven IL-5 synthesis is elevated in patients with atopic disease as compared with that in atopic patients free of disease and nonatopic control subjects. OBJECTIVES: The purpose of this study was to compare IL-5 and interferon-gamma (IFN-gamma) secretion and proliferation by peripheral blood T cells from sensitized atopic patients with asthma, rhinitis, and no symptoms and from nonatopic control subjects in response to the allergen Dermatophagoides pteronyssinus (Der p) and the control recall antigen Mycobacterium tuberculosis purified protein derivative (PPD). METHODS: To measure allergen-induced IL-5 production and proliferation, we developed a short-term culture technique that required a single antigenic stimulation of freshly isolated peripheral blood mononuclear cells (PBMC). With this technique, we measured Der p- and PPD-induced IL-5 production and proliferation in PBMC from atopic patients with asthma who were allergic to Der p, atopic patients with rhinitis, atopic patients with no symptoms, and a group of nonatopic normal control subjects. In four experiments, CD4+ or CD8+ T cells were depleted from PBMC to confirm that IL-5 synthesis was T cell dependent. RESULTS: T cell IL-5 production, but not IFN-gamma production, in response to Der p was elevated in atopic patients with asthma and atopic patients with rhinitis compared with findings in atopic patients with no symptoms or nonatopic control subjects. IL-5 production was abrogated by depletion of CD4+, but not CD8+, T cells. In subjects with asthma, allergen-driven IL-5 production correlated with bronchial hyperreactivity. Allergen-induced proliferation was also higher in patients with asthma than in atopic subjects with no symptoms or nonatopic controls. T cell IL-5 and IFN-gamma production and proliferation in response to PPD were similar regardless of atopic status or disease. CONCLUSIONS: Elevated IL-5 production is a characteristic of allergen-specific peripheral blood CD4+ T cells from sensitized patients with atopic disease but not atopy per se.

Engineering of a functional interleukin-5 monomer: a paradigm for redesigning helical bundle cytokines with therapeutic potential in allergy and asthma.

Interleukin (IL) 5 specifically induces the differentiation of eosinophils which are central to the pathogenesis of allergies and asthma. Structurally, IL-5 is a unique member of the short-chain helical bundle subfamily of cytokines. In contrast to other subfamily members which fold unimolecularly into a single helical bundle, IL-5 forms a pair of helical bundles by the interdigitation of two identical monomers covalently linked by a pair of intermolecular disulfide bonds. Although a native IL-5 monomer lacks bioactivity, we recently reported the engineering of an insertional mutant of IL-5 (designated mono5) which folds unimolecularly into a single helical bundle and has biological activity similar to that of native IL-5. Here we demonstrate no differences in signal transduction pathways utilized by mono5 and IL-5, as determined by western blot analysis of early tyrosine phosphorylation events, Jak2 activation, and mitogen-activated protein kinase activation. However, binding studies utilizing conformationally dependent neutralizing anti-IL-5 monoclonal antibodies localized a tertiary structural perturbation near the insert of mono5. This perturbation enabled localization of a limited region of the tertiary structure of IL-5 that engages the IL-5 receptor alpha-chain. Fluorescent labeling studies further revealed that the cysteines of mono5 contained free sulfhydryl groups, thereby demonstrating that the role of the disulfide bonds of IL-5 is the structural maintenance of other functional domains. The retention of conformation epitopes by mono5, but not IL-5, under reducing conditions and the equivalent thermostability of mono5 and IL-5 despite the absence of a disulfide bond in mono5 indicated that the conformation assumed by mono5 is very stable. In addition to providing the structural framework for designing novel IL-5 agonists and antagonists, the knowledge gained from the development of mono5 will enable other helical bundle proteins to be redesigned with therapeutic potential.

Delineation of IL-5 domains predicted to engage the IL-5 receptor complex.

IL-5 is an interdigitating homodimeric glycoprotein and a member of the helical bundle family of cytokines. IL-5 is a potent activator of eosinophils and a specific promoter of their differentiation. This activity has implicated IL-5 in the pathogenesis of asthma and allergic disease. A detailed understanding of IL-5 structure and function is required to develop immunomodulators of IL-5-mediated inflammatory responses. We generated a panel of neutralizing anti-IL-5 mAbs which were used to map functional domains on IL-5. In addition, the nucleotide sequences for human IL-5, murine IL-5, rat IL-5, and eight human/murine IL-5 chimeras were engineered and expressed in COS-7 cells. These recombinant cytokines and mAbs were used in TF-1 bioassays to identify five functional epitopes on the tertiary structure of IL-5. Residues responsible for the species-specific activity of human IL-5 were identified with the murine BCL1 bioassay. One set of epitopes cluster around the helix A-loop 2 region, which is predicted to engage the IL-5 receptor beta-chain. The second set of epitopes as well as the species specificity domain cluster around the loop 3-helix D region, which is predicted to engage the IL-5 receptor alpha-chain. Together, these analyses target the A/D helical face of IL-5 as the region involved in receptor engagement.

Creation of a biologically active interleukin-5 monomer.

Interleukin-5 (IL-5) specifically induces the differentiation of eosinophils, which are important in host defence and the pathogenesis of allergies and asthma. Structurally, IL-5 is a unique member of the short-chain helical-bundle subfamily of cytokines whose canonical motif contains four helices (A-D) arranged in an up-up-down-down topology. In contrast to other subfamily members, which fold unimolecularly into a single helical bundle, IL-5 forms a pair of helical bundles by the interdigitation of two identical monomers that contribute a D helix to the other's A-C helices. We predicted that the lack of bioactivity by an IL-5 monomer was due to a short loop between helices C and D which physically prevents unimolecular folding of helix D into a functionally obligate structural motif. Here we report that, by lengthening this loop, we have engineered an insertional mutant of IL-5 that was expressed as a monomer with biological activity similar to that of native IL-5. These studies demonstrate that all of the structural features necessary for IL-5 to function are contained within a single helical bundle.

Secretion of the eosinophil-active cytokines interleukin-5, granulocyte/macrophage colony-stimulating factor and interleukin-3 by bronchoalveolar lavage CD4+ and CD8+ T cell lines in atopic asthmatics, and atopic and non-atopic controls.

Specific eosinophil accumulation and activation within the asthmatic bronchial mucosa are thought to occur at least partly through the actions of cytokines, including interleukin (IL)-5, IL-3 and granulocyte/macrophage colony-stimulating factor (GM-CSF). Although mRNA encoding some of these cytokines has been demonstrated in bronchoalveolar lavage (BAL) fluid cells and bronchial biopsies from asthmatics, it has yet to be established whether these cells produce the translated products and whether expression is associated with CD4+ T helper or CD8+ cytotoxic T cells. We addressed this problem by raising polyclonal CD4+ and CD8+ T cell lines from the BAL fluid of six atopic asthmatics, five atopic non-asthmatics and seven non-atopic non-asthmatic controls. BAL fluid cells obtained at fiberoptic bronchoscopy were depleted of adherent cells, and then T lymphocytes expanded by stimulation with monoclonal anti-CD3 antibody and recombinant human IL-2. When lymphocytes had expanded to sufficient numbers, CD4+ and CD8+ cells were separated by positive selection with magnetic beads coated with anti-CD4 or anti-CD8 monoclonal antibodies and further expanded. Cytokine secretion by standardized cell numbers was measured by enzyme-linked immunosorbent assays. BAL CD4+ T cell lines from the asthmatics secreted significantly elevated quantities of both IL-5 and GM-CSF as compared with lines from the atopic and non-atopic controls (p = 0.023-0.003). In contrast, IL-3 secretion did not significantly differ between the groups. In some subjects, CD8+ T cell lines also secreted significant quantities of these cytokines and there was a trend for IL-5 secretion by these cells to be higher in asthmatics than non-atopic controls (p = 0.035). These data are consistent with the hypothesis that activated T lymphocytes from asthmatics, particularly of the CD4+ subset, are predisposed to release elevated quantities of cytokines relevant to the accumulation and activation of eosinophils.

Versatile E. coli thioredoxin specific monoclonal antibodies afford convenient analysis and purification of prokaryote expressed soluble fusion protein.

A recently developed E. coli thioredoxin (Trx) gene fusion expression system has circumvented the difficulties associated with inclusion body formation. Although ample quantities of soluble recombinant protein can be expressed using this system, no universal means of quantifying or purifying the fusion product exists. To facilitate the study of Trx fusion proteins, anti-E. coli Trx monoclonal antibodies (mAb) were generated. Two distinct Trx epitopes were defined by competitive ELISA. Both mAb were capable of detecting Trx fusion proteins by sandwich ELISA, and by immunoblot analysis under reducing and non-reducing conditions. In addition, these mAb enabled purification of Trx fusion proteins by immunoprecipitation, as well as affinity chromatography. This report provides the first description of anti-Trx antibodies. These reagents represent a major advance in the isolation and analysis of prokaryote expressed recombinant Trx fusion proteins.

Enhanced detection of human IL-5 in biological fluids utilizing murine monoclonal antibodies which delineate distinct neutralizing epitopes.

Interleukin 5 (IL-5) is a homodimeric cytokine arranged in a head-to-tail configuration covalently linked by two disulfide bonds. IL-5 has pleiotropic effects on murine and human leukocytes and has been implicated in the pathogenesis of many inflammatory disorders. To facilitate the study of functionally relevant IL-5 domains involved in receptor binding and to develop a highly sensitive and specific ELISA capable of detecting IL-5 in biological fluids, a library of murine anti-human IL-5 (hIL-5) mAb was generated to baculovirus expressed recombinant hIL-5 (rhIL-5). Fifteen subclones of seven hybridomas were characterized. All mAb bound hIL-5, but not murine IL-5 (mIL-5), and neutralized hIL-5 biological activity in the BCl1 proliferation assay. By competitive ELISA, the mAb were divided into two binding groups. Utilizing comparative analysis with TRFK-5, a rat anti-mIL-5 mAb crossreactive with hIL-5, at least three hIL-5 neutralizing epitopes were defined. By ELISA and Western analysis, each epitope was shown to be present as a conformationally identical pair on the hIL-5 dimer. Various combinations of mAb in sandwich ELISA were used to predict the relative proximity of each epitope pair. Utilizing mAb binding characteristics, highly sensitive and specific sandwich ELISA were developed with a minimum detection limit of 6.25 pg hIL-5/ml (P < 0.05). Quantitation of hIL-5 in both serum and bronchoalveolar lavage (BAL) fluid demonstrated the utility of these anti-hIL-5 mAb for investigating the role of hIL-5 in inflammation. These mAb should also serve as useful reagents for epitope mapping of functional hIL-5 domains.