The Antietam Staff Walk at the Uniformed Services University: A Program Evaluation.

INTRODUCTION: The battle along Antietam Creek in September 1862 was pivotal in shaping future combat medical readiness practices. With the full confidence of his commander, Major (Dr) Jonathan Letterman implemented an innovative ambulance corps system, which contributed immensely to modern-day battlefield medicine. Each year, the Uniformed Services University (USU) holds the Antietam Staff Walk, during which military medical students are engaged by faculty at various "stops" along the 6-mile walk. The four learning objectives for the Antietam Staff Walk are to (1) introduce the role of the "staff ride," (2) orient learners to reading terrain, (3) reinforce the six principles of health service support, and (4) recall the heritage of the military medical officer. The Department of Military and Emergency Medicine at USU commissioned a program evaluation to determine if these course objectives were being met, evaluate the effectiveness of the Antietam Staff Walk as a teaching tool, and make recommendations for improving its educational impact. MATERIALS AND METHODS: We engaged in qualitative program evaluation to evaluate the Antietam Staff Walk course objectives. Our research team analyzed 156 reflection papers written by second-year military medical students attending Antietam in August 2021. We coded each of the papers, noting important words and phrases that were salient to the students' learning experiences at Antietam. Our research team then compiled each of these codes into a master list and then determined how to divide this list into major categories. We collectively defined each of these categories, which served as the resulting themes of this program evaluation. RESULTS: Three themes emerged: (1) creation of an ambulance corps allows for proximal battlefield medicine, (2) a lack of buddy aid inspires Tactical Casualty Combat Care, and (3) disease/nonbattle injury necessitates preventative medicine. The students foremost gained an appreciation for the impact of the ambulance corps and recognized that the ambulance corps not only impacted medical care, but also the mission as a whole. However, may not have completely understood the long, slow evolution of battlefield care and may have overestimated the knowledge of physicians practicing mid-19th century medicine. We provided recommendations for addressing these learning opportunities during future Antietam Staff Walks at USU. CONCLUSIONS: Our review of the Antietam Staff Ride resulted in several curricular recommendations for enhancing its learning impact. Our program evaluation serves as a model for line units and other military organizations to optimize the impact of the historical staff ride as a teaching tool.

'Through and Through' History: The Management of Gunshot Wounds From the 14th Century to the Present.

Gun violence killed over 46,000 Americans in 2021; almost 120,000 suffered gunshot wounds. This epidemic has attracted national attention and increasing concern from medical and surgical organizations, as evident in this special issue. 'Through and Through History' explores the surgical management of gunshot wounds from their earliest appearance in 14th-century Europe to the present. Interweaving the civilian and military experience, it details not only the evolution of care directly applied to patients but also the social, political, and scientific milieu that shaped decisions made and actions performed both in and out of the operating room. The article describes how surgeons have pushed the boundaries of medicine and science in each era, developing new therapies for their patients, a historical trend that persists today when such care has the potential to save tens of thousands of lives each year.

Historical review of emergency tourniquet use to stop bleeding.

BACKGROUND: Although a common first aid topic, emergency tourniquets to stop bleeding are controversial because there is little experience on which to guide use. Absent an adequate historical analysis, we have researched development of emergency tourniquets from antiquity to the present. METHODS: We selected sources emphasizing historical development of tourniquets from books and databases such as PubMed. RESULTS: The history of the emergency tourniquet is long and disjointed, mainly written by hospital surgeons with little accounting, until recently, of the needs of forward medics near the point injury. Many investigators often are unaware of the breadth of the tourniquet's history and voice opinions based on anecdotal observations. CONCLUSIONS: Reporting the historical development of tourniquet use allowed us to recognize disparate problems investigators discuss but do not recognize, such as venous tourniquet use. We relate past observations with recent observations for use by subsequent investigators.

Identification of N-acylphosphatidylserine molecules in eukaryotic cells.

While profiling the lipidome of the mouse brain by mass spectrometry, we discovered a novel family of N-acylphosphatidylserine (N-acyl-PS) molecules. These N-acyl-PS species were enriched by DEAE-cellulose column chromatography, and they were then characterized by accurate mass measurements, tandem mass spectrometry, liquid chromatography/mass spectrometry, and comparison to an authentic standard. Mouse brain N-acyl-PS molecules are heterogeneous and constitute about 0.1% of the total lipid. In addition to various ester-linked fatty acyl chains on their glycerol backbones, the complexity of the N-acyl-PS series is further increased by the presence of diverse amide-linked N-acyl chains, which include saturated, monounsaturated, and polyunsaturated species. N-Acyl-PS molecular species were also detected in the lipids of pig brain, mouse RAW264.7 macrophage tumor cells, and yeast, but not Escherichia coli. N-Acyl-PSs may be biosynthetic precursors of N-acylserine molecules, such as the recently reported signaling lipid N-arachidonoylserine from bovine brain. We suggest that a phospholipase D might cleave N-acyl-PS to generate N-acylserine, in analogy to the biosynthesis of the endocannabinoid N-arachidonoylethanolamine (anadamide) from N-arachidonoylphosphatidylethanolamine.

Kdo2-Lipid A of Escherichia coli, a defined endotoxin that activates macrophages via TLR-4.

The LIPID MAPS Consortium (www.lipidmaps.org) is developing comprehensive procedures for identifying all lipids of the macrophage, following activation by endotoxin. The goal is to quantify temporal and spatial changes in lipids that occur with cellular metabolism and to develop bioinformatic approaches that establish dynamic lipid networks. To achieve these aims, an endotoxin of the highest possible analytical specification is crucial. We now report a large-scale preparation of 3-deoxy-D-manno-octulosonic acid (Kdo)(2)-Lipid A, a nearly homogeneous Re lipopolysaccharide (LPS) sub-structure with endotoxin activity equal to LPS. Kdo(2)-Lipid A was extracted from 2 kg cell paste of a heptose-deficient Escherichia coli mutant. It was purified by chromatography on silica, DEAE-cellulose, and C18 reverse-phase resin. Structure and purity were evaluated by electrospray ionization/mass spectrometry, liquid chromatography/mass spectrometry and (1)H-NMR. Its bioactivity was compared with LPS in RAW 264.7 cells and bone marrow macrophages from wild-type and toll-like receptor 4 (TLR-4)-deficient mice. Cytokine and eicosanoid production, in conjunction with gene expression profiling, were employed as readouts. Kdo(2)-Lipid A is comparable to LPS by these criteria. Its activity is reduced by >10(3) in cells from TLR-4-deficient mice. The purity of Kdo(2)-Lipid A should facilitate structural analysis of complexes with receptors like TLR-4/MD2.

De novo synthesis of a new diethylenetriaminepentaacetic acid (DTPA) bifunctional chelating agent.

Diethylene triamine pentaacetic acid (DTPA) has been in extensive use as a metal chelator in the development of radiopharmaceuticals and contrast agents. The former application uses DTPA mostly as a bifunctional chelating agent (BCA) conjugated to tumor-targeting vehicles (TTVs) such as monoclonal antibodies (MAbs) and receptor-directed peptides. A new bifunctional DTPA derivative was synthesized by a fully organic scheme. This compound, N(4),N(alpha),N(alpha),N(epsilon),N(epsilon)-[pentakis(carboxymethyl)]-N(4)-(carboxymethyl)-2,6-diamino-4-azahexanoic hydrazide (20) was prepared by a convergent synthesis strategy using N(alpha)-benzyloxycarbonyl-2,3-diaminopropionic acid as the starting compound. This commercially available material was used to build a functionalized triamine which served as the molecular core template for assembling the target molecule. To evaluate the conjugation and radiolabeling capabilities of this new molecule, it was covalently attached to the anti-TAG-72 MAb, Delta CH2HuCC49, and the conjugate was radiolabeled in near-quantitative yields with yttrium-90 ((90)Y) and lutetium-177 ((177)Lu). Biodistribution of the (177)Lu-labeled DTPA-Delta CH2HuCC49 in tumor-bearing nude mice demonstrated preservation of the immunoreactivity of the MAb as indicated by high tumor uptake. In addition to the introduction of a new bifunctional DTPA, this work reports on a novel synthetic approach for preparation of this useful metal chelator and introduces a new conjugation protocol.

Synthesis of the first diethylenetriaminepentahydroxamic acid (DTPH) bifunctional chelating agent.

Synthesis of a new pentahydroxamic acid bifunctional chelating agent (BCA), constructed on the aminoazaalkyl core of diethylenetriaminepentaacetic acid (DTPA), is reported. Rational modifications in the structure of DTPA, which could result in an enhancement of its chelation properties, add to the collection of diagnostic and therapeutic metals bound by this chelator, and might implement significant improvements in the in vivo behavior of this compound, are described. Further improvements in the stability of the ligand-metal complexes of DTPA may improve both diagnostic and therapeutic outcomes such as tumor-to-normal tissue ratios and target-delivered radioactivity. A combination of hydroxamate functions with the azaalkyl backbone of DTPA might be a suitable approach to generate such higher stabilities. This rationale may be justified by the well-known affinity of hydroxamates against different transition metals and favorable properties of DTPA as a versatile chelator. Thus, the N(4),N(alpha),N(alpha),N(epsilon),N(epsilon)-pentakis[[((N-hydroxy-N-methyl]carbonyl)methyl]-2, 6-diamino-4-azahexanoic hydrazide (5, DTPH) was designed and synthesized through a convergent synthesis and in 40.7% overall yield. Conjugation of this compound to the monoclonal antibody (MAb) Delta Ch2HuCC49, used as a model protein, was carried out to evaluate the efficiency of this molecule as a BCA. Radiolabeling of the DTPH-Delta CH2HuCC49 conjugate with lutetium-177 ((177)Lu) and biodistribution of the labeled conjugate in athymic nude mice, bearing LS174T human colon carcinoma xenografts, are reported.