Obesity and Anterior Abdominal Gunshot Wounds: A Cushion Effect.

Background Although the standard of care for anterior abdominal gunshot wounds (AAGSWs) is immediate laparotomy, these operations are associated with a high rate of negativity and potentially serious complications. Recent data suggest the possibility of selective non-operative management (SNOM) of AAGSWs, but none implicate body mass index (BMI) as a factor in patient selection. Anecdotal experience at our trauma center suggested a protective effect of obesity among patients with AAGSWs, and given the exceptionally high rate of obesity in the Bronx, we sought to analyze the associations of AAGSWs and BMI to inform future trauma research and management. In this study, we aimed to evaluate whether BMI is associated with injury severity, resource utilization, and clinical outcomes of AAGSWs. Methodology From our prospectively accrued trauma registry, we retrospectively abstracted all patients greater than 16 years old with Current Procedural Terminology codes associated with gunshot wounds from 2008 to 2016. The electronic medical record was reviewed to define a cohort of patients with at least one AAGSW. Patients were divided into the following cohorts based on BMI: underweight (UW, BMI: <18.5), normal weight (NW, BMI: 18.5-24.9), overweight (OW, BMI: 25-29.9), and obese (OB, BMI: ≥30). Among these cohorts, we analyzed data regarding injury severity, resource utilization, and clinical outcomes. Results In this study, none of the patients were UW, 17 (42.5%) patients were NW, 15 (37.5%) patients were OW, and eight (20%) patients were OB. One patient each in the NW and OB cohorts was successfully managed non-operatively, while all others underwent immediate exploratory laparotomy. The mean new injury severity score was significantly lower as BMI increased (NW = 30.9 ± 17.0, OW = 22.9 ± 16.1, and OB = 12.8 ± 13.7; p = 0.039). Patients in the OB cohort were less likely to have abdominal fascial penetration compared to the OW and NW cohorts (p = 0.027 and 0.004, respectively) and sustained fewer mean visceral injuries compared to the OW and NW cohorts (p = 0.027 and 0.045, respectively). OB patients were significantly more likely to have sustained two or more AAGSWs (OB = 27.5%, OW = 6.7%, and NW = 5.9%; p = 0.033), suggesting higher rates of tangential soft tissue injuries. The mean hospital length of stay down-trended as BMI increased but did not achieve statistical significance (NW = 7.4 ± 5.3, OW = 6.6 ± 6.7, and OB = 3.1 ± 2.3; p = 0.19). The OB cohort had the lowest mean hospital charges. Conclusions Obesity may yield a protective effect among AAGSW victims, and BMI may provide trauma surgeons another tool to triage patients for SNOM of AAGSWs, potentially diminishing the risks associated with negative laparotomy. Our data serve as the basis for the analysis of a larger patient cohort.

Comprehensive lipidomic profiling in serum and multiple tissues from a mouse model of diabetes.

INTRODUCTION: Diabetes mellitus is a serious metabolic disorder causing multiple organ damage in human. However, the lipidomic profiles in different organs and their associations are rarely studied in either diabetic patients or animals. OBJECTIVES: To evaluate and compare the characteristics of lipid species in serum and multiple tissues in a diabetic mouse model. METHODS: Semi-quantitative profiling analyses of intact and oxidized lipids were performed in serum and multiple tissues from a diabetic mouse model fed a high fat diet and treated with streptozotocin by using LC/HRMS and MS/MS. The total content of each lipid class, and the tissue-specific lipid species in all tissue samples were determined and compared by multivariate analyses. RESULTS: The diabetic mouse model displayed characteristic differences in serum and multiple organs: the brain and heart showed the largest reduction in cardiolipin, while the kidney had more alterations in triacylglycerol. Interestingly, the lipidomic differences also existed between different regions of the same organ: cardiolipin species with highly polyunsaturated fatty acyls decreased only in atrium but not in ventricle, while renal cortex showed longer fatty acyl chains for both increased and decreased triacylglycerol species than renal medulla. Importantly, diabetes caused an accumulation of lipid hydroperoxides, suggesting that oxidative stress was induced in all organs except for the brain during the development of diabetes. CONCLUSIONS: These findings provided novel insight into the organ-specific relationship between diabetes and lipid metabolism, which might be useful for evaluating not only diabetic tissue injury but also the effectiveness of diabetic treatments.

Novel Dual-Fluorescent Mitophagy Reporter Reveals a Reduced Mitophagy Flux in Type 1 Diabetic Mouse Heart.

CONTEXT: Patients with diabetes are susceptible to heart failure. Defective mitochondria can cause cardiac damage. Mitochondrial autophagy or mitophagy is a quality control mechanism that eliminates dysfunctional mitochondria through lysosome degradation. Mitophagy is essential for maintaining a pool of healthy mitochondria for normal cardiac function. However, the effect of diabetes on the functional status of cardiac mitophagy remains unclear. OBJECTIVE: To determine and compare cardiac mitophagy flux between diabetic and nondiabetic mice. METHODS: Using a novel dual fluorescent mitophagy reporter termed mt-Rosella, we labeled and traced mitochondrial fragments that are sequestered by the autophagosome and delivered to and degraded in the lysosome. RESULTS: Mitophagic activity was reduced in high-glucose-treated cardiomyocytes and in the heart tissue of type 1 diabetic mice. CONCLUSIONS: Mitophagy was impaired in the heart of diabetic mice, suggesting that restoring or accelerating mitophagy flux may be a useful strategy to reduce cardiac injury caused by diabetes.

RNA polymerase III initiation on coligo DNA templates containing loops of variable sequence, size and nucleotide chemistry.

Circularized oligonucleotides, or coligos, were previously found to serve as RNA polymerase III (Pol III) templates in vitro and in human tissue culture cells. Here we randomized the 12-nucleotide larger loop (L-loop) of a well characterized coligo and found unexpectedly that in vitro transcription by FLAG-Pol III was not significantly affected. This observation allowed us to test the variable of coligo L-loop size separately from the variable of its sequence. Transcription efficiency increased with L-loop size from 3 to 12 nucleotides of randomized sequence, and the smallest loop forced initiation to move into the stem region. To test further the need for any specific sequence we compared seven nucleotide L-loops composed of random, abasic and abasic-acyclic nucleotides, and all supported transcription by Pol III. Transcription of a series of coligos containing twelve contiguous randomized nucleotides placed at different locations within the coligo structure provided further evidence that the stem-loop junction structure is important for precise initiation. Nearly the same transcript pattern was formed in vitro by Pol III from yeast and human cells. Overall, these experiments support structure, rather than L-loop sequence, as the major determinant of coligo transcription initiation by Pol III.