A novel radiation-induced p53 mutation is not implicated in radiation resistance via a dominant-negative effect.

Understanding the mutations that confer radiation resistance is crucial to developing mechanisms to subvert this resistance. Here we describe the creation of a radiation resistant cell line and characterization of a novel p53 mutation. Treatment with 20 Gy radiation was used to induce mutations in the H460 lung cancer cell line; radiation resistance was confirmed by clonogenic assay. Limited sequencing was performed on the resistant cells created and compared to the parent cell line, leading to the identification of a novel mutation (del) at the end of the DNA binding domain of p53. Levels of p53, phospho-p53, p21, total caspase 3 and cleaved caspase 3 in radiation resistant cells and the radiation susceptible (parent) line were compared, all of which were found to be similar. These patterns held true after analysis of p53 overexpression in H460 cells; however, H1299 cells transfected with mutant p53 did not express p21, whereas those given WT p53 produced a significant amount, as expected. A luciferase assay demonstrated the inability of mutant p53 to bind its consensus elements. An MTS assay using H460 and H1299 cells transfected with WT or mutant p53 showed that the novel mutation did not improve cell survival. In summary, functional characterization of a radiation-induced p53 mutation in the H460 lung cancer cell line does not implicate it in the development of radiation resistance

The Efficacy and Safety Profile of Netarsudil 0.02% in Glaucoma Treatment: Real-World Outcomes

Introduction: More effective glaucoma medications are necessary as medication intolerance and non-adherence remain problematic. Netarsudil is a newly FDA-approved Rho kinase inhibitor. We hypothesize that netarsudil will safely reduce intraocular pressure (IOP) compared to baseline even while other glaucoma medications are used. Methods: This retrospective observational study was conducted on glaucoma patients seen at the Wills Eye Hospital Glaucoma Service who received netarsudil 0.02% between March and September of 2018. Intraocular pressure (IOP, via Goldmann applanation tonometry) and best corrected visual acuity (BCVA, via Snellen visual acuity charts) comparisons between baseline and 1- and 3-month follow-up visits were performed using Student’s t-tests. Results: This study included 172 eyes of 108 patients. Compared to baseline, a mean±SD decrease in IOP of 3.67±4.91 and 3.91±4.83 mmHg was noted at 1- and 3-month follow-up visits, respectively (both p\u3c0.001). No statistically significant difference in IOP change between patients on ≥3 and \u3c3 glaucoma medications at month 1 was observed (p=0.667). Conjunctival hyperemia was the most common side effect at months 1 and 3 (15.7% and 23.0% of patients, respectively). Blurred vision was reported at 1- and 3-month follow-up (5.8% and 8.0% of patients, respectively), but no significant difference in BCVA was observed (p= 0.723 and 0.611, respectively). Discussion: With a mild side effect profile, netarsudil yielded a significant IOP reduction in glaucoma patients, including significant reductions in patients on ≥3 medications. Given its efficacy and unique mechanism of action, earlier-line use of netarsudil may be considered

Adolescent Bariatric Surgery Programs: Progress in Pennsylvania

Objective: In 2019 the American Academy of Pediatrics (AAP) called for increased access to Metabolic and Bariatric Surgery (MBS). To understand adolescent weight loss programs offering MBS in Pennsylvania, a survey was completed. Methods: Adolescent weight loss centers in Pennsylvania offering MBS were identified using the American Society for Metabolic and Bariatric Surgery (ASMBS) on-line directory and Google search. Phone interviews were conducted with the director of each program. Results: Eight programs were identified. Operations were performed in seven adult hospitals. Six had Comprehensive Adolescent Accreditation through the Metabolic and Bariatric Surgery Accreditation and Quality Improvement Program (MBSAQIP). A total of 92 adolescents were operated on in the year from June 2021 to July 2022 which is an 84% increase from the preceding year. Ninety patients received a sleeve gastrectomy. Adult bariatric surgeons were involved in all operations. Six of the programs were led by diplomates of the American Board of Obesity Medicine. Each clinic had a psychologist. No program had all eight of the health care professionals recommended by the authors, but two programs had seven of the eight. In addition, three included a social worker, two an exercise physiologist and two had pediatric subspecialists incorporated into the clinic. Two programs had the operating surgeon caring for patients in the multidisciplinary clinic. Conclusion: This survey of programs across Pennsylvania shows an increase in the number of bariatric operations. More progress is necessary to improve access to this service and improve the quality of programs in Pennsylvania. Keywords: Metabolic, Obesity, Weight Los

Ahmed vs Baerveldt Glaucoma Drainage Device in Uveitic Glaucoma

Introduction: Uveitis is an inflammatory eye disorder which may elevate intraocular pressure (IOP), causing sight-threatening glaucoma. Treatment of refractory uveitic glaucoma involves implantation of a glaucoma drainage device (GDD). Uveitic glaucoma has been a minority diagnosis in prior studies comparing the valved Ahmed GDD and non-valved Baerveldt GDD. Here we compare the safety and efficacy of the Ahmed and Baerveldt GDD in uveitic glaucoma. Methods: This retrospective comparative study was conducted on patients with uveitic glaucoma (≥14 years old) who underwent Ahmed or Baerveldt GDD implantation between 2006–2018 with a minimum follow-up of 3 months. Success was defined as IOP of 6-21 mmHg with (complete success) or without (qualified success) medications, with at least light perception vision and no further glaucoma surgery. Pearson Chi-squared test, independent t test, and Kaplan-Meier survival model were utilized for statistical analysis. Results: 137 eyes of 122 patients (67 Ahmed and 70 Baerveldt) were included. Baseline characteristics were comparable in both groups. The Baerveldt group experienced greater IOP reduction (60.3% vs. 44.5%), higher complete success rate (28.6% vs. 10.4%), higher complication rate (44.3% vs. 20.9%), and higher hypotony rate (10% vs. 0%) than the Ahmed group (all p values \u3c0.05). Discussion: Our results are in line with pooled analysis of previous GDD comparison studies on various types of glaucoma. For patients with uveitic glaucoma, the Baerveldt implant provided a significantly higher success rate and greater IOP reduction with fewer medications, but was associated with a higher complication rate, compared to the Ahmed implant

The North Carolina Automated External Defibrillator Location Project: Recommendations for Use of Automated External Defibrillators in the Resuscitation of Victims of Out-of-Hospital Sudden Cardiac Death

Purpose: The study was undertaken to determine the current level of Automated External Defibrillator (AED) preparedness in North Carolina and to evaluate potential alternatives for future actions in the area of AED deployment and Public Access Defibrillation (PAD). Methods: A literature review was conducted to evaluate the efficacy and costeffectiveness of treatment options for out-of-hospital sudden cardiac death (SCD). Primary data were obtained via phone and electronic mail surveys of state and county EMS officials, commercial AED vendors, and American Heart Association Training Centers. Results: Review of the literature indicates successful defibrillatory treatment of SCD must be accomplished within 10 minutes of collapse. With few exceptions, most communities cannot achieve such a prompt response with traditional EMS service. Communities with AED-equipped first responders accomplish such a prompt response with greater frequency than those without such responders. PAD allows for prompt defibrillation and a markedly increased probability of survival for SCD victims in public places; only 3% of all SCDs occur in such public places. In North Carolina, in addition to 282 EMS agencies and Fire Departments, 600 locations were found to have at least 1 AED, many of which have the possibility of PAD. None of the 9-1-1 centers in the state had the locations of AEDs entered into Computer Automated Dispatch (CAD), 33% percent of counties did not have an AED or other defibrillator on all first-responding fire or EMS vehicles, and 45% of counties are unable to provide instructions for use of an AED over the phone. Conclusions: All first-responding EMS units and fire engines need to be equipped with AEDs. Those AEDs located in areas for potential PAD need to have their location registered with 9-1-1 dispatch in order to ensure they are used in the event of a near-by SCD. Emergency Medical Dispatchers must be prepared to provide instructions for use of an AED to the untrained bystander. More research is needed before recommendations regarding placement of additional AEDs for PAD can be made.Master of Public Healt