Role of platelet-to-lymphocyte ratio at the time of arrival to the emergency room as a predictor of short-term mortality in trauma patients with severe trauma team activation.

BACKGROUND: Platelet-to-Lymphocyte ratio (PLR) has been studied as a prognostic factor for various diseases and traumas. This study examined the utility of PLR as a tool for predicting 30-day mortality in patients experiencing severe trauma. METHODS: This study included 139 patients who experienced trauma and fulfilled ≥1 criteria for activation of the hospital's severe trauma team. Patients were divided into non-survivor and survivor groups. Mean PLR values were compared between the groups, the optimal PLR cut-off value was determined, and mortality and survival analyses were performed. Statistical analyses were performed using SPSS ver. 26.0. The threshold of statistical significance was P<0.05. RESULTS: There was a significant difference in mean (±standard deviation) PLR between the non-survivor (n=36) and survivor (n=103) groups (53.4±30.1 vs. 89.9±53.3, respectively; P<0.001). Receiver operating characteristic (ROC) curve analysis revealed an optimal PLR cut-off of 65.35 (sensitivity, 0.621; specificity, 0.694, respectively; area under the ROC curve, 0.742), and Kaplan-Meier survival analysis revealed a significant difference in mortality rate between the two groups. CONCLUSIONS: PLR can be calculated quickly and easily from a routine complete blood count, which is often performed in the emergency department for individuals who experience trauma. The PLR is useful for predicting 30-day mortality in trauma patients with severe trauma team activation.

Inhibition of Phagocytosis by Silibinin in Mouse Macrophages.

This study investigated the effects of silibinin, derived from milk thistle (Silybum marianum), on lipopolysaccharide (LPS)-induced morphological changes in mouse macrophages. Silibinin was treated at various doses and time points to assess its effects on macrophage activation, including morphological changes and phagocytosis. Silibinin effectively inhibited LPS-induced pseudopodia formation and size increase, while unstimulated cells remained round. Silibinin's impact on phagocytosis was dose- and time-dependent, showing a decrease. We explored its mechanism of action on kinases using a MAPK array. Among the three MAPK family members tested, silibinin had a limited effect on JNK and p38 but significantly inhibited ERK1/2 and related RSK1/2. Silibinin also inhibited MKK6, AKT3, MSK2, p70S6K, and GSK-3ß. These findings highlight silibinin's potent inhibitory effects on phagocytosis and morphological changes in macrophages. We suggest its potential as an anti-inflammatory agent due to its ability to target key inflammatory pathways involving ERK1/2 and related kinases. Overall, this study demonstrates the promising therapeutic properties of silibinin in modulating macrophage function and inflammation.

Effect of Metformin on the Functional and Electrophysiological Recovery of Crush Injury-Induced Facial Nerve Paralysis in Diabetic Rats.

The impact of metformin on the rat facial nerve following crush injury has only occasionally been documented to date. The purpose of the current investigation was to use functional and electrophysiological evaluations to investigate the effects of metformin administration on recovery following crush injury to the rat facial nerve. The rats were randomly divided into four groups: the nonDM/PBS group (n = 4), the nonDM/metformin group (n = 4), the DM/PBS group (n = 4), and the DM/metformin group (n = 4). Diabetes was generated by an intraperitoneal injection of streptozotocin. Facial nerve paralysis was induced by a crush injury 7 days after diabetes induction. The blood glucose levels of the DM/PBS and DM/metformin groups were maintained at over 300 mg/dL, whereas the blood glucose levels of the nonDM/PBS and nonDM/metformin groups were maintained at less than 150 mg/dL. There was no significant difference between the two nonDM groups. In comparison to the PBS group, the metformin group's recurrence of vibrissa fibrillation occurred noticeably sooner over time. The nonDM/metformin group showed the highest recovery rate in the second, third, and fourth weeks post-crush, respectively. The threshold of action potential 4 weeks after crush injury showed that the nonDM/metformin group had a significantly lower mean threshold of MAP compared to other groups. The short-term effect of metformin on the recovery of facial nerve blood flow (FNBF) was significantly increased compared to the DM/PBS group. However, there was no significant difference in FNBF between the nonDM/metformin and nonDM/PBS groups. A diabetic condition promoted a delay in FN regeneration. Metformin is able to accelerate functional recovery in diabetic or nondiabetic FN-injured rats. Further studies using a morphometric or molecular approach are planned to understand the pharmacologic mechanism of metformin.

Evaluation of Melia azedarach extract-loaded poly (vinyl alcohol)/pectin hydrogel for burn wound healing.

BACKGROUND: In this study, a hydrogel comprising poly (vinyl alcohol)/pectin (PVA/PET) was prepared by the addition of Melia azedarach extract for epithelial restoration. M. azedarach extract (MAE) contains volatile organic plant-derived compounds with antimicrobial properties. MAE has a variety of physiological properties, including antimicrobial, insecticidal, and anti-inflammatory activity. This study aimed to investigate whether MAE-loaded PVA/PET hydrogels have protective effects against burn wound healing. METHODS AND FINDINGS: To mix M. azedarach with the gel, nanoparticles containing M. azedarach were prepared using chitosan/maltodextrin as the wall material. A PVA/PET hydrogel containing M. azedarach was developed and its applicability as a wound dressing was evaluated. In the in vitro scratch assay, MAE treatment showed a scratch recovery-promoting effect comparable to that of the positive control TGF-ß1. The MAE-PVA/PET hydrogel was found to be non-toxic, and the antibacterial activity of the hydrogel was excellent against both gram-positive and gram-negative bacteria. Furthermore, as the formulated hydrogel demonstrated strong antimicrobial activity, its wound-healing efficacy was investigated in vivo using a rat model. CONCLUSION: MAE was found to be effective against burn wounds and to have antimicrobial activity in vitro and in vivo.

Agreement between medical students' peer assessments and faculty assessments in advanced resuscitation skills examinations in South Korea.

PURPOSE: In medical education, peer assessment is considered to be an effective learning strategy. Although several studies have examined agreement between peer and faculty assessments regarding basic life support (BLS), few studies have done so for advanced resuscitation skills (ARS) such as intubation and defibrillation. Therefore, this study aimed to determine the degree of agreement between medical students' and faculty assessments of ARS examinations. METHODS: This retrospective explorative study was conducted during the emergency medicine (EM) clinical clerkship of fourth-year medical students from April to July 2020. A faculty assessor (FA) and a peer assessor (PA) assessed each examinee's resuscitation skills (including BLS, intubation, and defibrillation) using a checklist that consisted of 20 binary items (performed or not performed) and 1 global proficiency rating using a 5-point Likert scale. The prior examinee assessed the next examinee after feedback and training as a PA. All 54 students participated in peer assessment. The assessments of 44 FA/PA pairs were analyzed using the intraclass correlation coefficient (ICC) and Gwet's first-order agreement coefficient. RESULTS: The PA scores were higher than the FA scores (mean±standard deviation, 20.2±2.5 [FA] vs. 22.3±2.4 [PA]; P<0.001). The agreement was poor to moderate for the overall checklist (ICC, 0.55; 95% confidence interval [CI], 0.31 to 0.73; P<0.01), BLS (ICC, 0.19; 95% CI, -0.11 to 0.46; P<0.10), intubation (ICC, 0.51; 95% CI, 0.26 to 0.70; P<0.01), and defibrillation (ICC, 0.49; 95% CI, 0.23 to 0.68; P<0.01). CONCLUSION: Senior medical students showed unreliable agreement in ARS assessments compared to faculty assessments. If a peer assessment is planned in skills education, comprehensive preparation and sufficient assessor training should be provided in advance.

The wound-healing effect of 7,3',4'-trimethoxyflavone through increased levels of prostaglandin E2 by 15-hydroxyprostaglandin dehydrogenase inhibition.

OBJECTIVE: To find an inhibitor of 15-hydroxyprostaglandin dehydrogenase (15-PGDH) that rapidly metabolises Prostaglandin E2 (PGE2) as a mediator of wound healing, we examined seven flavonoids for this role. RESULTS: 7,3',4'-Trimethoxyflavone (TMF) had the lowest IC50 value of 0.34 µM for 15-PGDH inhibition but >400 µM for cytotoxicity, indicating a high therapeutic index. TMF elevated PGE2 levels in a concentration-dependent manner in both A549 lung cancer and HaCaT cells. It also significantly increased mRNA expression of multidrug resistance-associated protein 4 (MRP4) and of prostaglandin transporter (PGT) slightly in HaCaT cells. In addition, TMF facilitated in vitro wound healing in a HaCaT scratch model, which was completely inhibited by adding both 15-PGDH and NAD+ as cofactor, confirming the involvement of PGE2 in its wound healing effect. CONCLUSION: TMF with a high therapeutic index can facilitate wound healing through PGE2 elevation by 15-PGDH inhibition.

Prediction of Long-Term Mortality Based on Neutrophil-Lymphocyte Ratio After Percutaneous Coronary Intervention.

BACKGROUND: The preprocedural neutrophil-lymphocyte ratio (NLR) is related to adverse outcomes in patients with coronary artery disease. We hypothesized that high NLR is a predictor of cardiac death after percutaneous coronary intervention (PCI). The objective of this investigation was to assess the associations of NLR, high-sensitivity cardiac troponin T (hs-cTnT) and N-terminal pro-B type natriuretic peptide (NT-proBNP) with the occurrence of cardiac death after PCI. MATERIALS AND METHODS: The NLR, hs-cTnT and NT-proBNP were analyzed in 372 patients who underwent PCI. The primary end point was cardiac death. RESULTS: The median NLR was 2.3 (interquartile range: 1.5-4.1). There were 21 cardiac death events during a mean follow-up duration of 25.8 months. With the NLR cutoff level set to 3.3 using the receiver-operating characteristic curve, the sensitivity and specificity for differentiating between the group with cardiac death and the group without cardiac death were 85.7% and 59.3%, respectively. Kaplan-Meier analysis revealed that the higher NLR group (≥3.3) had a significantly higher cardiac death rate than the lower NLR group (<3.3) (11.1% versus 1.4%, log-rank: P < 0.0001). This value was more useful in patients with heart failure (NT-proBNP ≥ 300ng/L) or myocardial injury (hs-cTnT ≥ 100ng/L). CONCLUSIONS: The outcomes of the current study demonstrate that high NLR is a predictor of cardiac death after PCI, especially in patients with heart failure or myocardial injury.

Reversal of P-glycoprotein-mediated multidrug resistance by 5,6,7,3',4'-pentamethoxyflavone (Sinensetin).

Multidrug resistance (MDR) cells can be sensitized to anticancer drugs when treated concomitantly with chemosensitizers. In this study, chemosensitizing effects of 5,6,7,3',4'-pentamethoxyflavone (sinensetin) and its analogs were investigated with respect to in vitro efficacy and structure-activity relationship. Sinensetin reversed the resistance of P-glycoprotein (Pgp)-overexpressing AML-2/D100 to vincristine in a concentration-dependent manner. Chemosensitizing effect of sinensetin was 10- and 18-fold higher than those of 5,7,3',4'-tetramethoxyflavone and 3,7-dihydroxy-3',4'-dimethoxyflavone, respectively. Sinensetin cytotoxicity in AML-2/D100 was not changed by the complete inhibition of Pgp, suggesting that it is not a substrate for Pgp. Flow cytometry showed that sinensetin increased drug accumulation in the AML-2/D100 in a concentration-dependent manner. Unlike verapamil and cyclosporin A, the maximum non-cytotoxic concentrations of sinensetin were found to decrease the Pgp levels. Azidopine-binding assay showed that cyclosporin A or verapamil inhibited azidopine binding on Pgp partially but sinensetin did not. Taken together, these results suggest that sinensetin has a chemosensitizing effect in reversing Pgp-mediated MDR by increasing the intracellular accumulation of drugs without competition in a binding site of azidopine. Thus, sinensetin is anticipated as a novel and highly potent second-generation flavonoid chemosensitizer, since sinensetin has significant advantages of having a high therapeutic index, of being a non-transportable inhibitor, and of effecting no induction of Pgp.