Structure-activity relationship of pyrrolidine pentamine derivatives as inhibitors of the aminoglycoside 6'- N -acetyltransferase type Ib.

Resistance to amikacin and other major aminoglycosides is commonly due to enzymatic acetylation by aminoglycoside 6'- N -acetyltransferase type I enzyme, of which type Ib [AAC(6')-Ib] is the most widespread among Gram-negative pathogens. Finding enzymatic inhibitors could be an effective way to overcome resistance and extend the useful life of amikacin. Small molecules possess multiple properties that make them attractive compounds to be developed as drugs. Mixture-based combinatorial libraries and positional scanning strategy led to the identification of a chemical scaffold, pyrrolidine pentamine, that, when substituted with the appropriate functionalities at five locations (R1 - R5), inhibits AAC(6')-Ib-mediated inactivation of amikacin. Structure-activity relationship (SAR) studies showed that while truncations to the molecule result in loss of inhibitory activity, modifications of functionalities and stereochemistry have different effects on the inhibitory properties. In this study, we show that alterations at position R1 of the two most active compounds, 2700.001 and 2700.003 , reduced inhibition levels, demonstrating the essential nature not only of the presence of an S -phenyl moiety at this location but also the distance to the scaffold. On the other hand, modifications on the R3, R4, and R5 positions have varied effects, demonstrating the potential for optimization. A correlation analysis between molecular docking values (ΔG) and the dose required for two-fold potentiation of compounds described in this and the previous studies showed a significant correlation between ΔG values and inhibitory activity. Highlights: Amikacin resistance in Gram-negatives is mostly caused by the AAC(6')-Ib enzymeAAC(6')-Ib has been identified in most Gram-negative pathogensInhibitors of AAC(6')-Ib could be used to treat resistant infectionsCombinatorial libraries and positional scanning identified an inhibitorThe lead compound can be optimized by structure activity relationship studies.

Antigen-driven CD8 + T cell clonal expansion is a prominent feature of MASH in humans and mice.

Background and Aims: Chronic liver disease due to metabolic dysfunction-associated steatohepatitis (MASH) is a rapidly increasing global epidemic. MASH progression is a consequence of the complex interplay between inflammatory insults and dysregulated hepatic immune responses. T lymphocytes have been shown to accumulate in the liver during MASH, but the cause and consequence of T cell accumulation in the liver remain unclear. Our study aimed to define the phenotype and T cell receptor diversity of T cells from human cirrhotic livers and an animal model of MASH to begin resolving their function in disease. Approach and Results: In these studies, we evaluated differences in T cell phenotype in the context of liver disease we isolated liver resident T cell populations from individuals with cirrhosis and a murine model of MASH. Using both 5' single cell sequencing and flow cytometry we defined the phenotype and T cell receptor repertoire of liver resident T cells during health and disease. Conclusions: MASH-induced cirrhosis and diet-induced MASH in mice resulted in the accumulation of activated and clonally expanded T cells in the liver. The clonally expanded T cells in the liver expressed markers of chronic antigenic stimulation, including PD1 , TIGIT and TOX . Overall, this study establishes for the first time that T cells undergo antigen-dependent clonal expansion and functional differentiation during the progression of MASH. These studies could lead to the identification of potential antigenic targets that drive T cell activation, clonal expansion, and recruitment to the liver during MASH.

Evaluating Clinical Outcomes of Laparoscopic Subtotal and Total Cholecystectomy for Complicated Acute Cholecystitis: A Systematic Review and Meta-Analysis.

INTRODUCTION: This systematic review and meta-analysis aimed to compare clinical outcomes in patients with complicated acute cholecystitis undergoing laparoscopic total vs subtotal cholecystectomy. METHODS: This systematic review and meta-analysis was conducted according to PRISMA guidelines and queried PubMed, Embase, ProQuest, Google Scholar, and Cochrane databases from inception to May 2023. The primary outcome was complication rates including common bile duct injury, wound infection, reoperation, bile leak, retained stones, and subhepatic collection, whereas secondary outcomes were in-hospital mortality and hospital length of stay. RESULTS: A total of 7 studies with 135,233 cases were included for meta-analysis. Patients who underwent laparoscopic total cholecystectomy had a significantly lower risk of postoperative bile leaks (RR: .15; 95% CI: .03, .80) and subhepatic fluid collection (RR: 0.19; 95% CI: .06, .63) and were 2.94 times less likely to die compared to those who underwent subtotal cholecystectomy (RR .34; 95% CI: .15, .77). Patients who underwent subtotal cholecystectomy had significantly longer hospital length of stay (mean difference 1.0 days; 95% CI: .5 days, 1.4 days). CONCLUSIONS: In adult patients presenting with complicated cholecystitis, management with laparoscopic subtotal cholecystectomy presents a unique complication profile with increased risk of postoperative bile leak and subhepatic fluid collection, in-hospital mortality, and longer hospital length-of-stay when used as an alternative approach to laparoscopic total cholecystectomy. Further research into the most appropriate clinical scenarios and patient populations for the use of the subtotal cholecystectomy approach may prove useful in improving its associated outcomes.

Outcomes of Preperitoneal Packing and Angioembolization for Hemorrhage Control in Hemodynamically Unstable Pelvic Fractures: A Systematic Review and Meta-Analysis.

BACKGROUND: Hemodynamically unstable pelvic fractures are often life-threatening injuries; however, the optimal management remains uncertain. This systematic review and meta-analysis aim to evaluate the most appropriate primary management of hemorrhage in adult patients with hemodynamically unstable pelvic fractures by comparing outcomes following the initial use of preperitoneal packing (PPP) vs angioembolization (AE). METHODS: A systematic search of PubMed, Embase, Google Scholar, and ProQuest databases was conducted following PRISMA guidelines. Studies assessing hemorrhage management in trauma patients with hemodynamically unstable pelvic fractures were included. The data extracted from selected articles included patient demographics, study design, and outcomes such as 24-hour PRBC transfusions, in-hospital mortality, and DVT rate. RESULTS: Eight articles were included in the systematic review. Among the included studies, 2040 patients with hemodynamically unstable pelvic fractures were analyzed. Meta-analyses revealed that treatment with PPP was associated with fewer 24-hour PRBC transfusions (mean difference = -1.0, 95% CI: -1.8 to -.2) than AE. However, no significant differences were noted in in-hospital mortality (RR: .91, 95% CI: .80-1.05) and the rate of deep vein thrombosis (RR: .89, 95% CI: .62-1.28) between groups. CONCLUSION: The findings of this study suggest that primary management with PPP was associated with fewer 24-hour PRBC transfusions compared to AE. The choice of primary management with PPP or AE did not significantly impact in-hospital mortality. Future studies should address clinical outcomes and the factors that affect them to better understand the impact of different management strategies and direct the creation of practice management guidelines.

The Association Between Gender and Clinical Outcomes in Patients With Moderate to Severe Traumatic Brain Injury: A Systematic Review and Meta-Analysis.

INTRODUCTION: Traumatic brain injuries (TBIs) are a significant cause of morbidity and mortality in the United States. but have a disproportionate impact on patients based on gender. This systematic review and meta-analysis aim to compare gender differences in clinical outcomes between male and female adult trauma patients with moderate and severe TBI. METHODS: Studies assessing gender differences in outcomes following TBIs on PubMed, Google Scholar, EMBASE, and ProQuest were searched. Meta-analysis was performed for outcomes including in-hospital mortality, hospital length of stay, intensive care unit length of stay, and Glasgow outcome scale (GOS) at 6 mo. RESULTS: Eight studies were included for analysis with 26,408 female and 63,393 male patients. Meta-analysis demonstrated that males had a significantly lower risk of mortality than females (RR: 0.88; 95% CI 0.78, 0.99; P = 0.0001). Females had a shorter hospital length of stay (mean difference -1.4 d; 95% CI - 1.6 d, -1.2 d). No significant differences were identified in intensive care unit length of stay (mean difference -3.0 d; 95% CI -7.0 d, 1.1 d; P = 0.94) or GOS at 6 mo (mean difference 0.2 d; 95% CI -0.9 d, 1.4 d; P = 1). CONCLUSIONS: Compared to male patients, female patients with moderate and severe TBI had a significantly higher in-hospital mortality risk. There were no significant differences in long-term outcomes between genders based on GOS at 6 mo. These findings warrant further investigation into the etiology of these gender disparities and their impact on additional clinical outcome measures.

Assessing the ecological risk of heavy metal sediment contamination from Port Everglades Florida USA.

Port sediments are often contaminated with metals and organic compounds from anthropogenic sources. Remobilization of sediment during a planned expansion of Port Everglades near Fort Lauderdale, Florida (USA) has the potential to harm adjacent benthic communities, including coral reefs. Twelve sediment cores were collected from four Port Everglades sites and a control site; surface sediment was collected at two nearby coral reef sites. Sediment cores, sampled every 5 cm, were analyzed for 14 heavy metals using inductively coupled plasma-mass spectrometry. Results for all three locations yielded concentration ranges (µg/g): As (0.607-223), Cd (n/d-0.916), Cr (0.155-56.8), Co (0.0238-7.40), Cu (0.004-215), Pb (0.0169-73.8), Mn (1.61-204), Hg (n/d-0.736), Mn (1.61-204), Ni (0.232-29.3), Se (n/d-4.79), Sn (n/d-140), V (0.160-176), and Zn (0.112-603), where n/d = non-detected. The geo-accumulation index shows moderate-to-strong contamination of As and Mo in port sediments, and potential ecological risk indicates moderate-to-significantly high overall metal contamination. All four port sites have sediment core subsamples with As concentrations above both threshold effect level (TEL, 7.24 µg/g) and probable effect level (PEL, 41.6 µg/g), while Mo geometric mean concentrations exceed the background continental crust level (1.5 µg/g) threshold. Control site sediments exceed TEL for As, while the reef sites has low to no overall heavy metal contamination. Results of this study indicate there is a moderate to high overall ecological risk from remobilized sediment due to metal contamination. Due to an imminent dredging at Port Everglades, this could have the potential to harm the threatened adjacent coral communities and surrounding protected habitats.

Restoring susceptibility to aminoglycosides: identifying small molecule inhibitors of enzymatic inactivation.

Growing resistance to antimicrobial medicines is a critical health problem that must be urgently addressed. Adding to the increasing number of patients that succumb to infections, there are other consequences to the rise in resistance like the compromise of several medical procedures and dental work that are heavily dependent on infection prevention. Since their introduction in the clinics, aminoglycoside antibiotics have been a critical component of the armamentarium to treat infections. Still, the increase in resistance and their side effects led to a decline in their utilization. However, numerous current factors, like the urgent need for antimicrobials and their favorable properties, led to renewed interest in these drugs. While efforts to design new classes of aminoglycosides refractory to resistance mechanisms and with fewer toxic effects are starting to yield new promising molecules, extending the useful life of those already in use is essential. For this, numerous research projects are underway to counter resistance from different angles, like inhibition of expression or activity of resistance components. This review focuses on selected examples of one aspect of this quest, the design or identification of small molecule inhibitors of resistance caused by enzymatic modification of the aminoglycoside. These compounds could be developed as aminoglycoside adjuvants to overcome resistant infections.

The Parallel Structure-Activity Relationship Screening of Three Compounds Identifies the Common Agonist Pharmacophore of Pyrrolidine Bis-Cyclic Guanidine Melanocortin-3 Receptor (MC3R) Small-Molecule Ligands.

The melanocortin receptors are involved in numerous physiological pathways, including appetite, skin and hair pigmentation, and steroidogenesis. In particular, the melanocortin-3 receptor (MC3R) is involved in fat storage, food intake, and energy homeostasis. Small-molecule ligands developed for the MC3R may serve as therapeutic lead compounds for treating disease states of energy disequilibrium. Herein, three previously reported pyrrolidine bis-cyclic guanidine compounds with five sites for molecular diversity (R1-R5) were subjected to parallel structure-activity relationship studies to identify the common pharmacophore of this scaffold series required for full agonism at the MC3R. The R2, R3, and R5 positions were required for full MC3R efficacy, while truncation of either the R1 or R4 positions in all three compounds resulted in full MC3R agonists. Two additional fragments, featuring molecular weights below 300 Da, were also identified that possessed full agonist efficacy and micromolar potencies at the mMC5R. These SAR experiments may be useful in generating new small-molecule ligands and chemical probes for the melanocortin receptors to help elucidate their roles in vivo and as therapeutic lead compounds.

Outcomes of Transfusion With Whole Blood, Component Therapy, or Both in Adult Civilian Trauma Patients: A Systematic Review and Meta-Analysis.

INTRODUCTION: This systematic review and meta-analysis was conducted to compare outcomes, including transfusion volume, complications, intensive care unit length of stay, and mortality for adult civilian trauma patients transfused with whole blood (WB), components (COMP), or both (WB + COMP). METHODS: A systematic review and meta-analysis were conducted using studies that evaluated outcomes of transfusion of WB, COMP, or WB + COMP for adult civilian trauma patients. A search of PubMed, Embase, and Cochrane from database inception to March 3, 2022 was conducted. The search resulted in 18,400 initial articles with 16 studies remaining after the removal of duplicates and screening for inclusion and exclusion criteria. RESULTS: This study identified an increased risk of 24-h mortality with COMP versus WB + COMP (relative risk: 1.40 [1.10, 1.78]) and increased transfusion volumes of red blood cells with COMP versus WB at 6 and 24 h, respectively (-2.26 [-3.82, -0.70]; -1.94 [-3.22, -0.65] units). There were no differences in the calculated rates of infections or intensive care unit length of stay between WB and COMP, respectively (relative risks: 1.35 [0.53, 3.46]; -0.91 [-2.64, 0.83]). CONCLUSIONS: Transfusion with WB + COMP is associated with lower 24-h mortality versus COMP and transfusion with WB is associated with a lower volume of red blood cells transfused at both 6 and 24 h. Based on these findings, greater utilization of whole blood in civilian adult trauma resuscitation may lead to improved mortality and reduced transfusion requirements.

United Network for Organ Sharing (UNOS) Database Analysis of Factors Associated With Kidney Transplant Time on Waiting List.

INTRODUCTION:  In the United States (U.S.), African Americans and other minority groups have longer wait times for kidney transplantation than Caucasians. To date, many studies analyzing time spent on the waitlist for each race/ethnicity have been done. However, there are few to no studies examining waitlist time after the 2019 policy changes to the geographic distribution of donated kidneys. METHODS: Data collected from the National Organ Procurement and Transplantation Network database were used to analyze associations between race and time spent on the waitlist for a kidney transplant in the U.S. Additional sub-categorical data were analyzed to determine further associations and potential covariates, such as gender, age, citizenship, primary source of payment, region of transplant center, BMI, Kidney Donor Profile Index (KDPI), renal diagnosis, and presence/type of diabetes. Data were analyzed using odds ratios and validated by Bonferroni-Holm's corrected chi-square tests at confidence intervals of 95% to determine if there are statistically significant differences between transplant time spent on the waitlist and ethnicity, as well as age, diagnosis category, region of transplant center, and KDPI. RESULTS: Statistically significant increased odds of remaining on the transplant list at two years existed for all non-white races/ethnicities, except those identifying as multiracial. Asian American candidates had the greatest odds of remaining on the waitlist greater than two years in comparison to white candidates: 1.51 times that of a patient categorized as white (odds ratio [OR] 1.51, confidence interval [CI] 1.44-1.57). African American/Black, (OR 1.38, CI 1.34-1.43) Pacific Islander (OR 1.38, CI 1.17-1.63), Hispanic candidates (OR 1.37, CI 1.32-1.41), and American Indian or Native Alaskan candidates (OR 1.23, CI 1.12-1.46) also had increased odds of remaining on the transplant waitlist greater than two years compared to white candidates. DISCUSSION: In this study, ethnic disparities persisted as a barrier for non-white individuals receiving treatment for end-stage kidney disease, specifically in the context of time spent on the waitlist for a kidney transplant. Further research is needed regarding the causes of these disparities in time spent on the waitlist, such as cultural restrictions in organ donation, racial differences in parameters for organ match, and institutionalized racism in health care practitioners.

Outcomes of Pigtail Catheter Placement versus Chest Tube Placement in Adult Thoracic Trauma Patients: A Systematic Review and Meta-Analysis.

INTRODUCTION: A debate currently exists regarding the efficacy of pigtail catheters vs chest tubes in the management of thoracic trauma. This meta-analysis aims to compare the outcomes of pigtail catheters vs chest tubes in adult trauma patients with thoracic injuries. METHODS: This systematic review and meta-analysis were conducted using PRISMA guidelines and registered with PROSPERO. PubMed, Google Scholar, Embase, Ebsco, and ProQuest electronic databases were queried for studies comparing the use of pigtail catheters vs chest tubes in adult trauma patients from database inception to August 15th, 2022. The primary outcome was the failure rate of drainage tubes, defined as requiring a second tube placement or VATS, unresolved pneumothorax, hemothorax, or hemopneumothorax requiring additional intervention. Secondary outcomes were initial drainage output, ICU-LOS, and ventilator days. RESULTS: A total of 7 studies satisfied eligibility criteria and were assessed in the meta-analysis. The pigtail group had higher initial output volumes vs the chest tube group, with a mean difference of 114.7 mL [95% CI (70.6 mL, 158.8 mL)]. Patients in the chest tube group also had a higher risk of requiring VATS vs the pigtail group, with a relative risk of 2.77 [95% CI (1.50, 5.11)]. CONCLUSIONS: In trauma patients, pigtail catheters rather than chest tubes are associated with higher initial output volume, reduced risk of VATS, and shorter tube duration. Considering the similar rates of failure, ventilator days, and ICU length-of-stay, pigtail catheters should be considered in the management of traumatic thoracic injuries. STUDY TYPE: Systematic Review and meta-analysis.

Comparing Outcomes of Appendectomy Versus Non-operative Antibiotic Therapy for Acute Appendicitis: A Systematic Review and Meta-Analysis of Randomized Clinical Trials.

BACKGROUND: Acute appendicitis is one of the most common etiologies of an acute abdomen in the emergency department and first-line standard surgical care for the condition has recently been reconsidered. We aim to evaluate the effectiveness and outcomes of surgical intervention versus non-operative antibiotic therapy in the treatment of acute appendicitis in adult and pediatric patients. METHODS: A literature search was conducted using PubMed, Google Scholar, and EMBASE. The search included all studies until January 15th, 2022. Preferred Reporting Items for Systematic reviews and Meta-Analysis guidelines were followed for abstracting data and assessing data quality and validity. Data were independently extracted by the authors of the study. Meta-analysis was performed and Cohen's Q test for heterogeneous effects was performed to determine if fixed or random-effects models were appropriate for use. RESULTS: Twelve randomized controlled trials investigating a total of 3703 acute appendicitis patients met inclusion criteria and were included in the meta-analysis. In the systematic review, eleven RCTs demonstrated that appendectomy had improved effectiveness compared to non-operative antibiotic management. The meta-analysis demonstrated that patients undergoing appendectomy had significantly higher treatment effectiveness compared with antibiotics-only treatment (98.4% vs. 73.3%, P < .0001). The meta-analysis did demonstrate a significant .54-day reduction in hospital length of stay for the appendectomy group compared to the non-operative antibiotic therapy group. CONCLUSIONS: Surgical intervention is associated with increased effectiveness of treatment and reduced in-hospital length of stay among patients with acute appendicitis. Guidelines established by institutions and surgical organizations should indicate appendectomy as the standard and superior treatment option for patients presenting with acute appendicitis.

Beta-Blocker Therapy in Patients With Severe Traumatic Brain Injury: A Systematic Review and Meta-Analysis.

INTRODUCTION: Traumatic brain injury (TBI), a leading cause of morbidity and mortality among trauma patients worldwide, poses the risk of secondary neurological insult due to significant catecholamine surge. We aim to investigate the effectiveness and outcomes of beta-blocker administration in patients with severe TBI. METHODS: A search through PubMed, EMBASE, JAMA network, and Google Scholar databases was conducted for relevant peer-reviewed original studies published before February 15, 2022. A standard random-effects model was used, as justified by a high Cohen's Q test. RESULTS: Twelve studies met inclusion criteria and were included in the meta-analysis. Severe TBI patients who were administered beta-blockers had a significantly reduced incidence of in-hospital mortality compared to the non-beta-blocker group (14.5% vs 19.2%). However, the beta-blocker group was reported to have a significantly greater number of ventilator days (5.58 vs 2.60 days). Similarly, intensive care unit (9.00 vs 6.84 days) and hospital (17.30 vs 11.02 days) lengths of stay (LOS) were increased in the beta-blocker group compared to those who were not administered beta-blocker therapy, but only the difference in hospital-LOS was significant. CONCLUSIONS: Beta-blockers have significantly decreased in-hospital mortality in patients with severe TBI despite being associated with an increase in ventilator days and hospital-LOS. The administration of beta-blocker therapy in the management of severe TBI may be warranted and should be discussed in future guidelines.

Gender Distribution & Rank of Authorship in Surgical Literature.

BACKGROUND: Authorship of surgical literature is important for the career advancement of surgeons, and gender disparities in authorship may hinder the representation and leadership of women within academic surgery. The aim of this systematic review and meta-analysis was to evaluate the gender distribution of first, senior, and overall authorship in peer-reviewed surgical journal studies across all surgical specialties to determine if disparities exist. METHODS: PubMed, EMBASE, and Google Scholar databases were searched for studies investigating the gender distribution of authorship of surgical literature published before December 10th, 2021. Meta-analysis was performed and Cohen's Q test for heterogenous effects was used to determine whether random or fixed-effects models were appropriate. RESULTS: Fifteen studies investigating gender distribution of authorship met inclusion, which included a total of 136,627 pooled studies. The meta-analysis demonstrated the meta-proportion of first authorship for women to be 20.6% (95% CI: 13.9, 28.2), the meta-proportion of senior authorship for women to be 11.9% (95% CI: 6.6, 18.5), and the meta-proportion of overall authorship for women to be 23% (95% CI: 16.2, 30.7). In addition, the proportion of senior authorship for women was found to be significantly lower than the proportion of overall authorship for women (11.9% versus 23.0%, P = .0106). CONCLUSION: There is a significantly smaller proportion of women who are first, senior, and overall authors in surgical literature compared to their colleagues who are men. Sustainable and effective solutions aimed at improving the representation of women surgeons in surgical research and research leadership are necessary.

Identification of B Cell and T Cell Epitopes Using Synthetic Peptide Combinatorial Libraries.

This article presents a combinatorial library method that consists of the synthesis and screening of mixture-based synthetic combinatorial libraries of peptide molecules to identify B and T cell epitopes. The protocols employ peptide libraries to identify peptides recognized by MAbs and T cells. The first protocol uses a positional scanning peptide library made up of hexapeptides to identify antigenic determinants recognized by MAbs. The 120 mixtures in the hexapeptide library are tested for their inhibitory activity in a competitive ELISA. The second protocol uses a decapeptide library to identify T cell peptide ligands. The 200 mixtures of the decapeptide library are tested for their ability to induce T cell activation. Support protocols cover optimization of the assay conditions for each MAb or T cell, to achieve the best level of sensitivity and reproducibility, and preparation of a hexapeptide library, along with deconvolution approaches. © 2022 Wiley Periodicals LLC. Basic Protocol 1: Screening peptide library for antibody inhibition Basic Protocol 2: Screening a peptide library to identify CD4+ Or CD8+ T cell ligands Support Protocol 1: Optimizing antigen and antibody concentrations for screening assay Support Protocol 2: Preparing a positional scanning peptide library.

Emergency Resuscitative Thoracotomy for Civilian Thoracic Trauma in the Field and Emergency Department Settings: A Systematic Review and Meta-Analysis.

BACKGROUND: Emergency department resuscitative thoracotomy (ED-RT) or prehospital resuscitative thoracotomy (PH-RT) is performed for trauma patients with impending or full cardiovascular collapse. This systematic review and meta-analysis analyze outcomes in patients with thoracic trauma receiving PH-RT and ED-RT. METHODS: PubMed, JAMA Network, and CINAHL electronic databases were searched to identify studies published on ED-RT or PH-RT between 2000-2020. Patients were grouped by location of procedure and type of thoracic injury (blunt versus penetrating). RESULTS: A total of 49 studies met the criteria for qualitative analysis, and 43 for quantitative analysis. 43 studies evaluated ED-RT and 5 evaluated PH-RT. Time from arrival on scene to PH-RT >5 min was associated with increased neurological complications and time from the initial encounter to PH-RT or ED-RT >10 min was associated with increased mortality. ISS ≥ 25 and absent signs of life were also associated with increased mortality. There was higher mortality in all PH-RT (93.5%) versus all ED-RT (81.8%) (P = 0.02). Among ED-RTs, a significant difference was found in mortality rate between patients with blunt (92.8%) versus penetrating (78.7%) injuries (P < 0.001). When considering only blunt or penetrating injury types, no significant difference in RT mortality rate was found between ED-RT and PH-RT (P = 0.65 and P = 0.95, respectively). CONCLUSIONS: ED-RT and PH-RT are potentially life-saving procedures for patients with penetrating thoracic injuries in extremis and with signs of life. The efficacy of this procedure is time sensitive. Moreover, there appears to be a greater mortality risk for patients with thoracic trauma receiving RT in the PH setting compared to the ED setting. More studies are needed to determine the significance of PH-RT mortality.

Healthcare understanding of COVID-19 antibody.

OBJECTIVE: : The SARS-CoV-2 pandemic has shed light on the difficulties in spreading uniform information. We rely on national and international organizations to provide scientifically accurate information to the public at large. With so many different sources of information, often not scientific, there appears to be an incomplete understanding of many aspects of SARS-CoV-2 infection. We sought to gain information about healthcare worker understanding of the implications of a positive serum COVID-19 antibody test result. We identified a broad range of responses among all categories of healthcare workers in our facility. Most notably we found that there was not complete understanding that there can be asymptomatic spread of COVID-19 infection. METHODS: : We provided health literacy and opinion questions to the healthcare workers of our facility. RESULTS: : Upon analysis of the data, we identified many differences in level of understanding among our healthcare workers. CONCLUSION: : We identified a lack of consensus on important details leading to potentially growing uncertainty with respect to SARS-COV-2 antibody. A diminished health literacy with respect to antibody testing could potentially suggest future issues with understanding the importance of vaccination benefits.

The Relationship Between COVID-19 Infection Rates and Social Determinants of Health in Broward and Miami-Dade Counties, Florida.

Objective To determine the relationship between per capita income and COVID-19 cases in Broward and Miami-Dade Counties of Florida, USA.  Background Low socioeconomic status predisposes individuals to worse health outcomes. For example, during the 2003 SARS-CoV pandemic and the 2009 H1N1 influenza pandemic disadvantaged individuals were more likely to become infected. More recently, a study found that deaths due to COVID-19 were associated with disadvantaged areas across the United States. South Florida, in particular Broward and Miami-Dade Counties, has experienced a significant burden of coronavirus cases. Investigating the association of income on coronavirus cases in Broward and Miami-Dade Counties may aid in identifying and treating those individuals at increased risk.  Methods This retrospective cross-sectional study used data gathered by the Florida Department of Health and 2018 U.S. Census. COVID-19 cases from March 2 - November 1, 2020 were tallied by ZIP code in Florida's Broward and Miami-Dade Counties and scaled per housing unit. An exhaustive regression analysis using County "Miami-Dade" or "Broward," sex, race, ethnicity, median age, and estimated per capita income was performed for each combination of independent variables in MATLAB (MathWorks, Natick, USA). Regression models were evaluated using both adjusted R-squared and the Akaike Information Criterion, along with the number of significant predictors. The most optimal model with the highest number of significant predictors was selected. Results Among all other variables, sex, race, and ethnicity as the variables that best predicted COVID-19 cases per housing unit within a certain ZIP code. The adjusted R-squared of this optimal model was 0.5062, indicating that within each ZIP code in Broward and Miami-Dade Counties 50.62% of the variance in COVID-19 cases per housing unit can be explained by these variables. A significant relationship was found between the number of COVID-19 cases and individuals who were Black or African American (p < 0.001), individuals who were Hispanic or Latino (p < 0.001), and male to female ratio (p = 0.016). Per capita income, age, and county were not statistically significant predictors in any model tested. Conclusions Racial and gender disparities may be more significant contributors to COVID-19 cases than per capita income in housing units. Based on the results of this study, investigators may consider applying this model to similar variables in order to inform the management and prevention of cases in the present and future pandemics.

Functional Mixture-Based Positional Scan Identifies a Library of Antagonist Tetrapeptide Sequences (LAtTeS) with Nanomolar Potency for the Melanocortin-4 Receptor and Equipotent with the Endogenous AGRP(86-132) Antagonist.

The melanocortin-4 receptor (MC4R) plays an important role in appetite. Agonist ligands that stimulate the MC4R decrease appetite, while antagonist compounds increase food consumption. Herein, a functional mixture-based positional scan identified novel MC4R antagonist sequences. Mixtures comprising a library of 12,960,000 tetrapeptides were screened in the presence and absence of the NDP-MSH agonist. These results led to the synthesis of 48 individual tetrapeptides, of which 40 were screened for functional activity at the melanocortin receptors. Thirteen compounds were found to possess nanomolar antagonist potency at the MC4R, with the general tetrapeptide sequence Ac-Aromatic-Basic-Aromatic-Basic-NH2. The most notable results include the identification of tetrapeptide 48 [COR1-25, Ac-DPhe(pI)-Arg-Nal(2')-Arg-NH2], an equipotent MC4R antagonist to agouti-related protein [AGRP(86-132)], more potent than miniAGRP(87-120), and possessing 15-fold selectivity for the MC4R versus the MC3R. These tetrapeptides may serve as leads for novel appetite-inducing therapies to treat states of negative energy balance, such as cachexia and anorexia.