Cyclin-dependent protein kinase regulatory subunit 1 (Cks1) is involved in cell cycle progressionthrough interactions with cyclin-dependent kinases (CDK) and ubiquitination of cyclin-dependentkinase inhibitors (CKI). Dysfunction of CDK dependent associations can affect the entrance of acell into mitosis, particularly the G1-S phase transition. Abnormal assistance from Cks1 with themultiprotein complex SCF (Skp2) in the ubiquitination of CDKN1B (p27Kip1) can disrupt the mitoticregulatory protein levels escalating to cancer development. In this study, we use computationalmethods to investigate interactions in three different complexes sharing Cks1 in order to create atargeted pharmaceutical solution that will assist in regulation. Our analysis is performed using thecrystal structure of Cks1 in three complexes to include involvement between one ubiquitin ligaseand two CDKs. The assessment is based on the intermolecular electrostatic interactions, such ashydrogen bonds and charge-charge interactions. We observe that charge and hydrogen bonding playsa significant role in the stability between Cks1 and adjacent proteins in each complex. Due to largebinding interfaces and varied distribution of charge across the main contact regions, we decided thata condensed pocket on Cks1 that interacts with phosphorylated p27Kip1 should be selected for furtherin-depth examination.

Background

This study aimed to examine the epidemiology of firework-related injuries within a national population between 2012 and 2022, including the severity of injury by year, patient demographics, body region injured, firework type, and diagnosis category of injury.

Methods

Data were collected from the Consumer Product Safety Commission's National Electronic Injury Surveillance System, which is a representative nationwide database that collects data on consumer product-related injuries occurring in the US. Injury rates were calculated based on patient age, sex, body region injured, firework type, and diagnosis category.

Results

A total of 3219 injuries, representing an estimated 122,912 firework-related injuries, were treated in emergency departments within the US from 2012 to 2022. The overall incidence rate of firework-related injuries in the study rose by over 17% from 2012 [2.61 cases per 100,000 people (95% CI 2.03-3.20)] to 2022 and [3.05 cases per 100,000 people (95% CI 2.29-3.80)]. The rate of injuries was highest in adolescents and young adults (age 20-24; 7.13 cases per 100,000 people). Men experienced firework injuries at more than double the rate of women (4.90 versus 2.25 cases per 100,000 people). The upper extremities (41.62%), head/neck (36.40%), and lower extremities (13.78%) were the most commonly injured regions. Over 20% of cases in patients older than 20 were significant injuries requiring hospitalization. Aerial devices (32.11%) and illegal fireworks (21.05%) caused the highest rates of significant injury of any firework type.

Conclusions

The incidence of firework-related injuries has risen over the past decade. Injuries remain the most common among adolescents and young adults. In addition, significant injuries requiring hospitalization occur most often during aerial and illegal firework use. Further targeted sale restrictions, distribution, and manufacturing regulations for high-risk fireworks are required to reduce the incidence of significant injury.

BACKGROUND: Salmonella species are very rarely associated with infective endocarditis, accounting for less than 0.01-2.9 % of total bacterial endocarditis cases. Since 1976, there have less than 90 reported cases of non-Typhoidal Salmonella bacteremia and endocarditis. CASE PRESENTATION: We present the case of a 57-year-old homeless man with a past medical history significant only for polysubstance abuse. He presented to the emergency department with a 3-day history of severe, non-bloody diarrhea, nausea, chills, and oliguria. Due to the patients history of substance use, screening laboratory tests were conducted and were positive for rapid plasma reagin, treponemal antibodies, and hepatitis C. For the profuse diarrhea and severe volume loss, C. difficile, stool white blood cells and stool ova and parasites were ordered but were ultimately negative. Both sets of blood cultures were found to be positive for Salmonella Typhimurium bacteremia. Further workup with transthoracic and transesophageal echocardiogram displayed small mobile masses attached to the aortic surface of the right and non-coronary cusps, confirming endocarditis on the aortic valve. Treatment included penicillin-G once a week for 3 weeks for latent syphilis and ceftriaxone and levofloxacin for bacteremia and endocarditis. CONCLUSIONS: Patients with Salmonella typically present early with gastrointestinal symptoms, but clinicians should consider cardiovascular imaging if blood cultures are found to be positive in order to potentially identify and promptly treat highly fatal Salmonella endocarditis.