Altering the Anti-inflammatory Lipoxin Microenvironment: a New Insight into Kaposi's Sarcoma-Associated Herpesvirus Pathogenesis.

Lipoxins are host anti-inflammatory molecules that play a vital role in restoring tissue homeostasis. The efficacy of lipoxins and their analog epilipoxins in treating inflammation and its associated diseases has been well documented. Kaposi's sarcoma (KS) and primary effusion lymphoma (PEL) are two well-known inflammation related diseases caused by Kaposi's sarcoma-associated herpesvirus (KSHV). Controlling inflammation is one of the strategies adopted to treat KS and PEL, a primary motivation for exploring and evaluating the therapeutic potential of using lipoxins. This study documents how KSHV manipulates and downregulates the secretion of the anti-inflammatory lipoxin A4 in host cells and the viral factors involved in this process using in vitro KS and PEL cells as models. The presence of the lipoxin A4 receptor/formyl peptidyl receptor (ALX/FPR) in KS patient tissue sections and in vitro KS and PEL cell models offers a novel possibility for treating KS and PEL with lipoxins. Treating de novo KSHV-infected endothelial cells with lipoxin and epilipoxin creates an anti-inflammatory environment by decreasing the levels of NF-κB, AKT, ERK1/2, COX-2, and 5-lipoxygenase. Lipoxin treatment on CRISPR/CAS9 technology-mediated ALX/FPR gene deletion revealed the importance of the lipoxin receptor ALX for effective lipoxin signaling. A viral microRNA (miRNA) cluster was identified as the primary factor contributing to the downregulation of lipoxin A4 secretion in host cells. The KSHV miRNA cluster probably targets enzyme 15-lipoxygenase, which is involved in lipoxin A4 synthesis. This study provides a new insight into the potential treatment of KS and PEL using nature's own anti-inflammatory molecule, lipoxin. IMPORTANCE: KSHV infection has been shown to upregulate several host proinflammatory factors, which aid in its survival and pathogenesis. The influence of KSHV infection on anti-inflammatory molecules is not well studied. Since current treatment methods for KS and PEL are fraught with unwanted side effects and low efficiency, the search for new therapeutics is therefore imperative. The use of nature's own molecule lipoxin as a drug is promising. This study opens up new domains in KSHV research focusing on how the virus modulates lipoxin secretion and warrants further investigation of the therapeutic potential of lipoxin using in vitro cell models for KS and PEL.

Racial Disparities in Opioid Analgesia Administration Among Adult Emergency Department Patients with Abdominal Pain.

INTRODUCTION: Racial disparities in pain management have been reported among emergency department (ED) patients. In this study we evaluated the association between patients' self-identified race/ethnicity and the administration of opioid analgesia among ED patients with abdominal pain, the most common chief complaint for ED presentations in the United States. METHODS: This was a retrospective cohort study of adult (age ≥18 years) patients who presented to the ED of a single center with abdominal pain from January 1, 2019-December 31, 2020. We collected demographic and clinical information, including patients' race and ethnicity, from the electronic health record. The primary outcome was the ED administration of any opioid analgesic (binary). Secondary outcomes included the administration of non-opioid analgesia (binary) and administration of any analgesia (binary). We used logistic regression models to estimate odds ratios (OR) of the association between a patient's race/ethnicity and analgesia administration. Covariates included age, sex, initial pain score, Emergency Severity Index, and ED visits in the prior 30 days. Subgroup analyses were performed in non-pregnant patients, those who underwent any imaging study, were admitted to the hospital, and who underwent surgery within 24 hours of ED arrival. RESULTS: We studied 7,367 patients: 45% (3,314) were non-Hispanic (NH) White; 28% (2,092) were Hispanic/Latinx; 19% (1,384) were NH Black, and 8% (577) were Asian. Overall, 44% (3,207) of patients received opioid analgesia. In multivariable regression models, non-White patients were less likely to receive opioid analgesia compared with White patients (OR 0.73, 95% CI 0.65-0.83 for Hispanic/Latinx patients; OR 0.62, 95% CI 0.54-0.72 for Black patients; and OR 0.64, 95% CI 0.52-0.78 for Asian patients). Black patients were also less likely to receive non-opioid analgesia, and Black and Hispanic/Latinx patients were less likely than White patients to receive any analgesia. The associations were similar across subgroups; however, the association was attenuated among patients who underwent surgery within 24 hours of ED arrival. CONCLUSION: Hispanic/Latinx, Black, and Asian patients were significantly less likely to receive opioid analgesia than White patients when presenting to the ED with abdominal pain. Black patients were also less likely than White patients to receive non-opioid analgesia.

Pouring and running a protein gel by reusing commercial cassettes.

The evaluation of proteins using sodium dodecyl sulfate polyacrylamide gel electrophoresis (SDS-PAGE) analysis is a common technique used by biochemistry and molecular biology researchers. For laboratories that perform daily analyses of proteins, the cost of commercially available polyacrylamide gels (~$10/gel) can be considerable over time. To mitigate this cost, some researchers prepare their own polyacrylamide gels. Traditional methods of pouring these gels typically utilize specialized equipment and glass gel plates that can be expensive and preclude pouring many gels and storing them for future use. Furthermore, handling of glass plates during cleaning or gel pouring can result in accidental breakage creating a safety hazard, which may preclude their use in undergraduate laboratory classes. Our protocol demonstrates how to pour multiple protein gels simultaneously by recycling Invitrogen Nupage Novex minigel cassettes, and inexpensive materials purchased at a home improvement store. This economical and streamlined method includes a way to store the gels at 4°C for a few weeks. By re-using the plastic gel cassettes from commercially available gels, labs that run frequent protein gels can save significant costs and help the environment. In addition, plastic gel cassettes are extremely resistant to breakage, which makes them ideal for undergraduate laboratory classrooms.