Combat injury profiles among U.S. military personnel who survived serious wounds in Iraq and Afghanistan: A latent class analysis.

BACKGROUND: The U.S. military conflicts in Iraq and Afghanistan had the most casualties since Vietnam with more than 53,000 wounded in action. Novel injury mechanisms, such as improvised explosive devices, and higher rates of survivability compared with previous wars led to a new pattern of combat injuries. The purpose of the present study was to use latent class analysis (LCA) to identify combat injury profiles among U.S. military personnel who survived serious wounds. METHODS: A total of 5,227 combat casualty events with an Injury Severity Score (ISS) of 9 or greater that occurred in Iraq and Afghanistan from December 2002 to July 2019 were identified from the Expeditionary Medical Encounter Database for analysis. The Barell Injury Diagnosis Matrix was used to classify injuries into binary variables by site and type of injury. LCA was employed to identify injury profiles that accounted for co-occurring injuries. Injury profiles were described and compared by demographic, operational, and injury-specific variables. RESULTS: Seven injury profiles were identified and defined as: (1) open wounds (18.8%), (2) Type 1 traumatic brain injury (TBI)/facial injuries (14.2%), (3) disseminated injuries (6.8%), (4) Type 2 TBI (15.4%), (5) lower extremity injuries (19.8%), (6) burns (7.4%), and (7) chest and/or abdominal injuries (17.7%). Profiles differed by service branch, combat location, year of injury, injury mechanism, combat posture at the time of injury, and ISS. CONCLUSION: LCA identified seven distinct and interpretable injury profiles among U.S. military personnel who survived serious combat injuries in Iraq or Afghanistan. These findings may be of interest to military medical planners as resource needs are evaluated and projected for future conflicts, and medical professionals involved in the rehabilitation of wounded service members.

Reductive Cleavage of Organic Peroxides by Iron Salts and Thiols.

Despite the low bond strength of the oxygen-oxygen bond, organic peroxides are often surprisingly resistant to cleavage by nucleophiles and reductants. As a result, achieving decomposition under mild conditions can be challenging. Herein, we explore the reactivity of a selection of peroxides toward thiolates, phenyl selenide, Fe(II) salts, and iron thiolates. Peroxides activated by conjugation, strain, or stereoelectronics are rapidly cleaved at room temperature by thiolate anions, phenylselenide, or Fe(II) salts. Under the same conditions, unhindered dialkyl peroxides are only marginally reactive; hindered peroxides, including triacetone triperoxide and diacetone diperoxide (DADP), are inert. In contrast, all but the most hindered of peroxides are rapidly (<1 min at concentrations down to ∼40 mM) cleaved by mixtures of thiols and iron salts. Our observations suggest the possible intermediacy of strongly reducing complexes that are readily regenerated in the presence of stoichiometric thiolate or hydride. In the case of DADP, an easily prepared explosive of significant societal concern, catalytic amounts of iron and thiol are capable of promoting rapid and complete disproportionation. The availability of inexpensive and readily available catalysts for the mild reductive degradation of all but the most hindered of peroxides could have significant applications for controlled remediation of explosives or unwanted radical initiators.

Synthesis of a 2,4,6,8,10-dodecapentanoic acid thioester as a substrate for biosynthesis of Heat Stable Antifungal Factor (HSAF).

The N-acetylcystamine (SNAC) thioester of dodecapentaenoic acid, an analog of a putative intermediate in the biosynthesis of Heat Stable Antifungal Factor (HSAF), is synthesized. Key steps include sequential Horner-Emmons homologations with the Weinreb amide of diethylphosponoacetic acid, and thioesterification of an aldol-derived 3-hydroxyalkanoate, which serves as a stable precursor of the sensitive polyenoate. The thioester was investigated as a biosynthetic substrate using a purified nonribosomal peptide synthetase and was not incorporated in the observed products.

Fatty Acyl Incorporation in the Biosynthesis of WAP-8294A, a Group of Potent Anti-MRSA Cyclic Lipodepsipeptides.

WAP-8294A is a family of at least 20 cyclic lipodepsipeptides exhibiting potent anti-MRSA activity. These compounds differ mainly in the hydroxylated fatty acyl chain; WAP-8294A2, the most potent member of the family that reached clinical trials, is based on (R)-3-hydroxy-7-methyloctanoic acid. It is unclear how the acyl group is incorporated because no acyl-CoA ligase (ACL) gene is present in the WAP-8294A gene cluster in Lysobacter enzymogenes OH11. Here, we identified seven putative ACL genes in the OH11 genome and showed that the yield of WAP-8294A2 was impacted by multiple ACL genes with the ACL6 gene having the most significant effect. We then investigated several (R)-3-hydroxy fatty acids and their acyl SNAC (N-acetylcysteamine) thioesters as substrates for the ACLs. Feeding (R)-3-hydroxy-7-methyloctanoate-SNAC to the ACL6 gene deletion mutant restored the production of WAP-8294A2. Finally, we heterologously expressed the seven ACL genes in E. coli and purified six of the proteins. While these enzymes exhibit a varied level of activity in vitro, ACL6 showed the highest catalytic efficiency in converting (R)-3-hydroxy-7-methyloctanoic acid to its CoA thioester when incubated with coenzyme A and ATP. These results provided both in vivo and in vitro evidence to support the fact that ACL6 is the main player for fatty acyl activation and incorporation in WAP-8294A2 biosynthesis. The results also suggest that the molecular basis for the acyl chain diversity in the WAP-8294A family is the presence of functionally overlapping ACLs.

Chemiluminescent identification and quantification of artemisinin and relevant sesquiterpene lactone derivatives.

A simple, sensitive, and rapid chemiluminescence method was developed for the detection and quantification of selected derivatives of artemisinin. It was found that the chemiluminescence (CL) signal resulting from the alkaline luminol reaction of the artemisinin derivatives in the presence of hematin was linear over a wide concentration range. We report results that suggest that a visual test or a test involving digital image capture may be used in addition to a field-ready instrumental approach to combat drug counterfeiting of malarial therapies.