Environmentally persistent free radicals lead to selective inhibition of CYP1 monooxygenase activities, and increased production of reactive oxygen species by reaction uncoupling

This study focuses on the effect of Environmentally Persistent Free Radicals (EPFRs) on the P450 enzymes of the CYP1 family. EPFRs are a component of particulate pollutants, that are stable in the environment, but can generate free radicals, leading to oxidative stress and subsequent toxicity of the respiratory, cardiovascular, and immune systems once they enter an organism. The results show differences in the ability of EPFRs to inhibit CYP1-dependent substrate metabolism, with CYP1B1 being inhibited to the greatest extent. There also were differences in the ability of EPFRs to disrupt the POR•CYP1 complex, with CYP1B1 being the only form where EPFRs disrupted POR•CYP1B1 complex formation. Despite the inhibition of substrate metabolism, each CYP1 enzyme, when reconstituted with NADPH-cytochrome P450 reductase (POR) was able to synergistically stimulate the generation of reactive oxygen (ROS) in the presence of particulate matter. Interestingly, both POR and the CYP1 enzymes were able to stimulate ROS generation, even when in partial reconstituted systems where only one of the proteins was present. However, when both POR and CYP1 were combined in a complete reconstituted system, ROS generation was synergistically stimulated

Video vs Direct Laryngoscopy for Tracheal Intubation After Cardiac Arrest: A Secondary Analysis of the Direct vs Video Laryngoscope Trial

BACKGROUND: Airway management is a critical component of the care of patients experiencing cardiac arrest, but data from randomized trials on the use of video vs direct laryngoscopy for intubation in the setting of cardiac arrest are limited. Current American Heart Association guidelines recommend placement of an endotracheal tube either during CPR or shortly after return of spontaneous circulation, but do not provide guidance around intubation methods, including the choice of laryngoscope. RESEARCH QUESTION: Does use of video laryngoscopy improve the incidence of successful intubation on the first attempt, compared with use of direct laryngoscopy, among adults undergoing tracheal intubation after experiencing cardiac arrest? STUDY DESIGN AND METHODS: This secondary analysis of the Direct vs Video Laryngoscope (DEVICE) trial compared video laryngoscopy vs direct laryngoscopy in the subgroup of patients who were intubated after cardiac arrest. The primary outcome was the incidence of successful intubation on the first attempt. Additional outcomes included the duration of laryngoscopy. RESULTS: Among the 1,417 patients in the DEVICE trial, 113 patients (7.9%) experienced cardiac arrest before intubation, of whom 48 patients were randomized to the video laryngoscopy group and 65 patients were randomized to the direct laryngoscopy group. Successful intubation on the first attempt occurred in 40 of 48 patients (83.3%) in the video laryngoscopy group and in 42 of 65 patients (64.6%) in the direct laryngoscopy group (absolute risk difference, 18.7 percentage points; 95% CI, 1.2-36.2 percentage points; P = .03). The mean duration of laryngoscopy was 48.0 seconds (SD, 37.3 seconds) in the video laryngoscope group and 98.0 seconds (SD, 122.4 seconds) in the direct laryngoscopy group (mean difference, -50.0 seconds; 95% CI, -86.8 to -13.3 seconds; P = .004). INTERPRETATION: Among adults undergoing tracheal intubation after experiencing cardiac arrest, use of video laryngoscopy was associated with increased incidence of successful intubation on the first attempt and shortened duration of laryngoscopy, compared with use of direct laryngoscopy

Effect of Endodontic Access Preparation on the Retention of Zirconia Crowns with Temporary or Permanent Access Hole Restorations: An In Vitro Study

Objectives: To evaluate the effect endodontic access preparation had on the retention of anterior zirconia crowns after restoring the access hole with temporary versus permanent restorative materials. Methods: 30 anterior zirconia crowns were milled from 5Y-TZP zirconia and bonded to a 3D printed die with resin cement. Crowns were randomly divided into three groups including negative control (NC, n = 10) with no endodontic access preparation; positive control (PC, N = 10) received endodontic access preparation and was restored with a temporary restorative material (Cavit); composite restoration (CR, N = 10) received an endodontic access preparation and then the access hole was restored with composite resin. Results: Considering the retention of crowns in NC group, PC group lost approximately 50% of its retention while the CR group had approximately 150% increase in the retention. The difference between the three groups was statistically significant (P \u3c 0.05). Conclusion: Restoring the endodontic access hole of a central incisor zirconia crown with composite resin improves the retention of the crown

Dance in the Darkness by L. Birke

22 x 15 Watercolor on Paperhttps://digitalscholar.lsuhsc.edu/art_med/1035/thumbnail.jp

Molecular Dissection of the Role of ACE2 in Glucose Homeostasis

Angiotensin Converting Enzyme 2 (ACE2) was discovered 25 years ago as a negative regulator of renin-angiotensin system, opposing the effects of angiotensin-II. Beyond its well-demonstrated roles in cardiovascular regulation and Covid-19 pathology, ACE2 is involved in a plethora of physio-pathological processes. In this review, we summarize the latest discoveries on the role of ACE2 in glucose homeostasis and regulation of metabolism. In the endocrine pancreas, ACE2 is expressed at low levels in β cells, but loss of its expression inhibits glucose-stimulated insulin secretion and impairs glucose tolerance. Conversely, overexpression of ACE2 improved glycemia and suggests that recombinant ACE2 might be a future therapy for diabetes. In the skeletal muscle of ACE2-deficient mice, a progressive triglyceride accumulation was observed, whereas in diabetic kidney the initial increase in ACE2 is followed by a chronic reduction of expression in kidney tubules and impairment of glucose metabolism. At the intestinal level, dysregulation of the enzyme alters the amino acid absorption and intestinal microbiome, while at the hepatic level, ACE2 protects against diabetic fatty liver disease. Not least, ACE2 is upregulated in adipocytes in response to nutritional stimuli and administration of recombinant ACE2 decreased body weight and increased thermogenesis. In addition to tissue-specific regulation of ACE2 function, the enzyme undergoes complex cellular posttranslational modifications which are changed during diabetes evolution, with at least proteolytic cleavage and ubiquitination leading to modifications in ACE2 activity. Detailed characterization of ACE2 in specific cellular- and tissue-manner holds promise for improving therapeutic outcomes in diabetes and metabolic disorders

Rectus Abdominis Repair Compared to Posterior Wall Mesh Reinforcement in Athletes With Sportsman\u27s Hernia: A Systematic Review

Athletic pubalgia is a relatively uncommon injury that is not fully understood. There are few high-level studies comparing treatments of athletic pubalgia, and this investigation seeks to utilize original articles to compare two common techniques for treatment of athletic pubalgia. The purpose of this study is to compare two prominent procedures, i.e., rectus abdominus repair and posterior wall reinforcement, through a systematic review. Inclusion/exclusion criteria were identified and then applied to search strategies in PubMed and MEDLINE. Two reviewers screened articles based on the agreed-upon criteria in a primary screen of titles and abstracts and a secondary screen of full-text articles. A total of 59 full-text articles were reviewed, and 13 were selected for this study. The study designs included seven prospective cohort studies, five retrospective cohort studies, and one randomized control trial. There were five studies with rectus abdominus repair intervention and eight studies with posterior wall reinforcement intervention. The median age range was 22-32. The mean follow-up time ranged from one month to 12.5 years. The success rate ranged from 76% to 96% for rectus abdominus repair and from 72% to 98% for posterior wall reinforcement. The two procedures performed about the same as the success rate for both procedures ranged from about 70% to 90%. The lack of standardization in clinical outcomes makes comparison across studies difficult. It is hard to discern which procedure actually performs better, and thus future research in this area needs to be conducted to focus on more specific outcomes, frequent follow-up, and standardization of outcome measures

A Sex Comparison of Fall and Fracture Occurrence in the Elderly Diabetic Population: A Quantitative Study

AIMS: To assess differences in falls and fractures in men and women with type 2 diabetes mellitus (T2DM) within a diverse population in Southeast Louisiana. METHODS: A list of 1200 patients was generated through an electronic health record system using keywords: diabetic diagnosis, falls, and fractures to conduct this retrospective cohort study. This chart review included adults with T2DM who experienced at least one fall and/or fracture between January 2018 and May 2023 at East Jefferson General Hospital located in Metairie, Louisiana. Only falls and fractures that resulted in a hospital visit were included. Results were compared between males and females. RESULTS: Patient data were collected from 100 randomly selected patients: 50 females and 50 males (mean age 67 years, 97% of patients were non-Hispanic, and 72% Black). Statistical analysis was conducted using the Student\u27s t test, Fisher\u27s exact, and Pearson correlation. An average of 3-4 falls occurred per patient, with no significant sex difference observed (p = 0.97). Thirty-eight percent of patients experienced a fracture with a significant sex difference (50% of female vs. 26% of male patients [p = 0.02]). Positive correlations between comorbid conditions and falls and fractures were seen, particularly in women: a moderate correlation for falls (r = 0.48, p \u3c 0.01) and a strong correlation for fractures (r = 0.52, p \u3c 0.01). Patients not on insulin treatment experienced a greater occurrence of fractures than insulin-dependent patients (46% vs. 22%, p = 0.03). CONCLUSIONS: Our findings suggest that in a diverse population, women with T2DM are at an increased risk of experiencing fractures, and specialized care should be given to this population to reduce the risk of fracture occurrence. Additional comorbidities increase the risk of falls and fractures

Silencing FAF2 mitigates alcohol-induced hepatic steatosis by modulating lipolysis and PCSK9 pathway

BACKGROUND: Chronic alcohol consumption leads to lipid accumulation, oxidative stress, cellular damage, and inflammation in the liver, collectively referred to as alcohol-associated liver disease (ALD). FAF2/UBXD8/ETEA (Fas-associated factor 2) is a ubiquitin ligase adaptor protein that plays a crucial role in the ubiquitin-mediated degradation of misfolded proteins in the endoplasmic reticulum. A recent genome-wide association study indicated an association between FAF2 and ALD; however, the exact contribution of FAF2 to ALD pathogenesis remains unclear. METHODS: FAF2 was knocked down using AAV-delivered shRNA in C57/BL6 mice. Mice were subjected to a chronic-plus-single binge ethanol feeding (NIAAA) model. Nine hours after gavage, liver, blood, and other organs of interest were collected for gene expression and biochemical analyses. RESULTS: We first observed a significant elevation in hepatic FAF2 protein expression in individuals with ALD and in mice subjected to an ethanol-binge model. Interestingly, knocking down FAF2 in the liver using adeno-associated virus serotype 8-delivered short hairpin RNA conferred a protective effect against alcohol-induced liver steatosis in ethanol-binged mice. Transcriptomic analysis revealed that differentially expressed genes were enriched in multiple lipid metabolism regulation pathways. Further analysis of transcription factors regulating these differentially expressed genes suggested potential regulation by SREBP1. Several SREBP1 target genes, including Fasn, Scd1, Lpin1, and Pcsk9 (proprotein convertase subtilisin/kexin type 9), were dysregulated in the livers of ethanol-fed FAF2 knockdown mice. Additionally, Pcsk9 could be regulated through the FOXO3-SIRT6 pathway in the livers of ethanol-fed FAF2 knockdown mice, leading to increased liver low-density lipoprotein receptor expression and reduced plasma LDL cholesterol levels. Furthermore, FAF2 knockdown in mouse liver enhanced adipose triglyceride lipase lipolytic activity by upregulating the adipose triglyceride lipase activator, comparative gene identification-58, and downregulating the adipose triglyceridelipase transport inhibitor, Elmod2, contributing to the alleviation of liver steatosis. CONCLUSIONS: Our study uncovers a novel mechanism involving FAF2 in the pathogenesis of ALD