Nanoparticle dose and antigen loading attenuate antigen-specific T-cell responses.

Immune-mediated hypersensitivities such as autoimmunity, allergy, and allogeneic graft rejection are treated with therapeutics that suppress the immune system, and the lack of specificity is associated with significant side effects. The delivery of disease-relevant antigens (Ags) by carrier systems such as poly(lactide-co-glycolide) nanoparticles (PLG-Ag) and carbodiimide (ECDI)-fixed splenocytes (SP-Ag) has demonstrated Ag-specific tolerance induction in model systems of these diseases. Despite therapeutic outcomes by both platforms, tolerance is conferred with different efficacy. This investigation evaluated Ag loading and total particle dose of PLG-Ag on Ag presentation in a coculture system of dendritic cells (DCs) and Ag-restricted T cells, with SP-Ag employed as a control. CD25 expression was observed in nearly all T cells even at low concentrations of PLG-Ag, indicating efficient presentation of Ag by dendritic cells. However, the secretion of IL-2, Th1, and Th2 cytokines (IFNγ and IL-4, respectively) varied depending on PLG-Ag concentration and Ag loading. Concentration escalation of soluble Ag resulted in an increase in IL-2 and IFNγ and a decrease in IL-4. Treatment with PLG-Ag followed a similar trend but with lower levels of IL-2 and IFNγ secreted. Transcriptional Activity CEll ARrays (TRACER) were employed to measure the real-time transcription factor (TF) activity in Ag-presenting DCs. The kinetics and magnitude of TF activity was dependent on the Ag delivery method, concentration, and Ag loading. Ag positively regulated IRF1 activity and, as carriers, NPs and ECDI-treated SP negatively regulated this signaling. The effect of Ag loading and dose on tolerance induction were corroborated in vivo using the delayed-type hypersensitivity (DTH) and experimental autoimmune encephalomyelitis (EAE) mouse models where a threshold of 8 µg/mg Ag loading and 0.5 mg PLG-Ag dose were required for tolerance. Together, the effect of Ag loading and dosing on in vitro and in vivo immune regulation provide useful insights for translating Ag-carrier systems for the clinical treatment of immune disorders.

Mechanisms to Improve Health Through Community Land Trusts.

Community land trusts (CLTs) provide long-term affordable housing and offer a range of mechanisms that may improve the health and well-being of low-income households. We sought to elucidate these mechanisms through thematic analysis of semi-structured interviews with a diverse sample of CLT staff and residents across the USA. Stakeholders most frequently identified improvements in mental health that come through increased housing stability and affordability. Other factors-including the ways that CLTs promote wealth generation, improvements in housing quality and neighborhood amenities, services and partnerships with healthcare organizations, and democratic governance-were raised by respondents though less frequently tied to health benefits. CLTs represent a promising area for future research on housing's impact on health.

Photoactivation of the orange carotenoid protein requires two light-driven reactions mediated by a metastable monomeric intermediate.

The orange carotenoid protein (OCP) functions as a sensor of the ambient light intensity and as a quencher of bilin excitons when it binds to the core of the cyanobacterial phycobilisome. We show herein that the photoactivation mechanism that converts the resting, orange-colored state, OCPO, to the active red-colored state, OCPR, requires a sequence of two reactions, each requiring absorption of a single photon by an intrinsic ketocarotenoid chromophore. Global analysis of absorption spectra recorded during continuous illumination of OCPO preparations from Synechocystis sp. PCC 6803 detects the reversible formation of a metastable intermediate, OCPI, in which the ketocarotenoid canthaxanthin exhibits an absorption spectrum with a partial red shift and a broadened vibronic structure compared to that of the OCPO state. While the dark recovery from OCPR to OCPI is a first-order, unimolecular reaction, the subsequent conversion of OCPI to the resting OCPO state is bimolecular, involving association of two OCPO monomers to form the dark-stable OCPO dimer aggregate. These results indicate that photodissociation of the OCPO dimer to form the monomeric OCPO intermediate is the first step in the photoactivation mechanism. Formation of the OCPO monomer from the dimer increases the mean value and broadens the distribution of the solvent-accessible surface area of the canthaxanthin chromophore measured in molecular dynamics trajectories at 300 K. The second step in the photoactivation mechanism is initiated by absorption of a second photon, by canthaxanthin in the OCPO monomer, which obtains the fully red-shifted and broadened absorption spectrum detected in the OCPR product state owing to displacement of the C-terminal domain and the translocation of canthaxanthin more than 12 Å into the N-terminal domain. Both steps in the photoactivation reaction of OCP are likely to involve changes in the structure of the C-terminal domain elicited by excited-state conformational motions of the ketocarotenoid.

The association between vacant housing demolition and safety and health in Baltimore, MD.

We measured the association between vacant housing demolitions and changes in crime and emergency department (ED) visits in Baltimore, MD. We included 646 block groups in Baltimore, 224 of which experienced at least one demolition from 2012 to 2019. The exposure was the number of demolitions completed in a block group during the previous quarter. Crime (all, property, and violent) and ED visits (all, adults, children, and for specific causes) were examined as the change in the rate per 1000 people from the previous quarter to the current quarter and analyzed using multivariable mixed effects regression models. Demolitions were associated with a small decrease in total ED visits (difference = -0.068 per 1000 people from the previous quarter to the current quarter, 95% CI -0.119, -0.018) but no significant change in crime. For each demolition, the rate of total child ED visits was 0.452 lower compared to the previous quarter (95% CI -0.777, -0.127). Demolitions were associated with small decreases in adult injury-related ED visits in the short term.

Broadband 2DES detection of vibrational coherence in the Sx state of canthaxanthin.

The nonadiabatic mechanism that mediates nonradiative decay of the bright S2 state to the dark S1 state of carotenoids involves population of a bridging intermediate state, Sx, in several examples. The nature of Sx remains to be determined definitively, but it has been recently suggested that Sx corresponds to conformationally distorted molecules evolving along out-of-plane coordinates of the isoprenoid backbone near a low barrier between planar and distorted conformations on the S2 potential surface. In this study, the electronic and vibrational dynamics accompanying the formation of Sx in toluene solutions of the ketocarotenoid canthaxanthin (CAN) are characterized with broadband two-dimensional electronic spectroscopy (2DES) with 7.8 fs excitation pulses and detection of the linear polarization components of the third-order nonlinear optical signal. A stimulated-emission cross peak in the 2DES spectrum accompanies the formation of Sx in <20 fs following excitation of the main absorption band. Sx is prepared instantaneously, however, with excitation of hot-band transitions associated with distorted conformations of CAN's isoprenoid backbone in the low frequency onset of the main absorption band. Vibrational coherence oscillation maps and modulated anisotropy transients show that Sx undergoes displacements from the Franck-Condon S2 state along out-of-plane coordinates as it passes to the S1 state. The results are consistent with the conclusion that CAN's carbonyl-substituted ß-ionone rings impart an intramolecular charge-transfer character that frictionally slows the passage from Sx to S1 compared to carotenoids lacking carbonyl substitution. Despite the longer lifetime, the S1 state of CAN is formed with retention of vibrational coherence after passing through a conical intersection seam with the Sx state.

Microorganisms and Antibiogram Patterns in Fournier's Gangrene: Contemporary Experience from a Single Tertiary Care Center.

PURPOSE: We evaluate the prevalent microorganisms, antibiotic sensitivity patterns and associated outcomes in patients with Fournier's gangrene. MATERIALS AND METHODS: A retrospective chart review of patients with Fournier's gangrene was conducted between October 2011 and April 2018 at our institution. Univariate analysis was performed using the independent t-test or Kruskal-Wallis H test for continuous variables and exact test for categorical variables. RESULTS: Of the 143 patients included in this study, wound culture was available in 131 (92%) patients with a median number of 3 microorganisms per wound. The most commonly grown pathogens were Staphylococcus species (66, 46%), Streptococcus species (53, 37%), Bacteroides species (34, 24%), Candida species (31, 22%), Escherichia coli (28, 20%) and Prevotella species (26, 18%). Most bacteria were sensitive to ampicillin-sulbactam, ceftriaxone, piperacillin-tazobactam, amikacin and cefepime, and resistant to ampicillin, trimethoprim-sulfamethoxazole, levofloxacin and clindamycin. Enterococcus faecalis and Streptococcus anginosus were resistant to vancomycin. The overall Fournier's gangrene mortality count was 14 (10%) patients. No association was noted between the type of infection and Fournier's gangrene severity index, length of hospital stay or mortality. CONCLUSIONS: At our institution Candida is a prevalent pathogen in the wound culture of patients with Fournier's gangrene. The resistance patterns for clindamycin and vancomycin are concerning. Addition of an antifungal agent to the empiric treatment should be considered based on clinical presentation.

The Impact of Ureteral Access Sheath Use on the Development of Abnormal Postoperative Upper Tract Imaging after Ureteroscopy.

PURPOSE: Ureteral access sheaths are commonly used during ureteroscopy to facilitate stone removal, improve visibility and maintain low intrarenal pressures. However, the use of a ureteral access sheath can cause ureteral wall ischemia and ureteral tears, potentially increasing the risk of postoperative ureteral stricture and obstruction. We studied the impact of ureteral access sheath use on postoperative imaging studies. Secondary objectives included studying the impact of other intraoperative parameters on postoperative imaging studies. MATERIALS AND METHODS: A retrospective chart review was conducted of cases that underwent ureteroscopy for nephroureterolithiasis across 2 high volume institutions between January 2012 and September 2016. Patient demographics, cumulative stone size, operative time, use of ureteral access sheath, laser lithotripsy, basket extraction, preoperative ureteral stent and postoperative ureteral stent placement were extracted from the electronic medical record. Findings of followup renal ultrasound, kidney-ureter-bladder x-ray and/or computerized tomography at approximately 8 weeks after surgery were recorded. RESULTS: A total of 1,332 ureteroscopies were performed with 1,060 cases (79.6%) returning for routine upper tract imaging after ureteroscopy. Postoperative hydronephrosis was noted following 127 cases (12.0%). Factors predicting presence of hydronephrosis after ureteroscopy include lower body mass index (p=0.0016), greater cumulative stone size (p=0.0003), increased operative time (p <0.0001), preoperative ureteral stent (OR 1.49, p=0.0299) and postoperative ureteral stent placement (OR 6.43, p=0.0031). Postoperative hydronephrosis was not associated with use of ureteral access sheath, age, laser lithotripsy or basket extraction. CONCLUSIONS: Use of ureteral access sheath did not have a significant impact on development of postoperative hydronephrosis, suggesting ureteral access sheath is safe for use during ureteroscopy. Ureteral strictures remain rare following ureteroscopy, seen in only 1.0% of our cohort. With an observed prevalence of hydronephrosis of 12.0% on followup imaging at 8 weeks, routine upper tract imaging after ureteroscopy remains a valuable prognostic tool.

Conjugation of Transforming Growth Factor Beta to Antigen-Loaded Poly(lactide- co-glycolide) Nanoparticles Enhances Efficiency of Antigen-Specific Tolerance.

Current strategies for treating autoimmunity involve the administration of broad-acting immunosuppressive agents that impair healthy immunity. Intravenous (i.v.) administration of poly(lactide- co-glycolide) nanoparticles (NPs) containing disease-relevant antigens (Ag-NPs) have demonstrated antigen (Ag)-specific immune tolerance in models of autoimmunity. However, subcutaneous (s.c.) delivery of Ag-NPs has not been effective. This investigation tested the hypothesis that codelivery of the immunomodulatory cytokine, transforming growth factor beta 1 (TGF-ß), on Ag-NPs would modulate the immune response to Ag-NPs and improve the efficiency of tolerance induction. TGF-ß was coupled to the surface of Ag-NPs such that the loadings of Ag and TGF-ß were independently tunable. The particles demonstrated bioactive delivery of Ag and TGF-ß in vitro by reducing the inflammatory phenotype of bone marrow-derived dendritic cells and inducing regulatory T cells in a coculture system. Using an in vivo mouse model for multiple sclerosis, experimental autoimmune encephalomyelitis, TGF-ß codelivery on Ag-NPs resulted in improved efficacy at lower doses by i.v. administration and significantly reduced disease severity by s.c. administration. This study demonstrates that the codelivery of immunomodulatory cytokines on Ag-NPs may enhance the efficacy of Ag-specific tolerance therapies by programming Ag presenting cells for more efficient tolerance induction.

High-Dose Adenosine for Treatment of Refractory Supraventricular Tachycardia in an Emergency Department of an Academic Medical Center: A Case Report and Literature Review.

BACKGROUND: Symptomatic tachycardia is a common admission diagnosis in the emergency department (ED). This can be a life-threatening condition and requires immediate attention. Supraventricular tachycardia (SVT) is commonly treated with adenosine, and successful treatment is limited to atrioventricular (AV) node-dependent SVTs as adenosine causes a transient heart block. However, there are limited data available for instances when the recommended dosing regimen (6 mg, 12 mg, 12 mg) fails to terminate SVT. CASE REPORT: A 33-year old man was evaluated in the ED with an electrocardiogram revealing a regular narrow complex tachycardia with a heart rate of 180 beats/min and a rhythm consistent with SVT. He reported experiencing 3 days of fatigue, myalgias, palpitations, and dyspnea on exertion, but was otherwise hemodynamically stable. Attempts at chemical cardioversion with standard doses of adenosine (6 mg, 12 mg, and 12 mg) were given without success. After consultation with the cardiology service, additional doses of 24 mg and then 36 mg of adenosine were administered. The last dose of 36 mg produced sustained conversion and return to a normal sinus rhythm. The patient later underwent radiofrequency ablation of a left-sided orthodromic reciprocating accessory pathway. After 3 months of medical management, the patient had an implantable cardiac defibrillator placed for prevention of sudden cardiac death. WHY SHOULD AN EMERGENCY PHYSICIAN BE AWARE OF THIS?: Each case of SVT demands immediate attention from an emergency physician. It is imperative that providers be aware of the limitations of adenosine and when it may be appropriate to deviate from standard dosing recommendations. This is in addition to collaborating with an expert in cardiac electrophysiology when initial management tactics are not successful.

Advanced Urology Boot Camp: A Simulation-based Curriculum to Enhance Fourth-year Medical Student Procedural Competency.

INTRODUCTION: Simulation-based medical education continues to gain popularity as the clinical environment requires exemplary patient safety while simultaneously maximizing the learner's educational experience. There is a current lack of urology-focused medical student education curricula in the literature. Here, we present the findings of a didactic and simulation-based medical student advanced "urology boot camp" curriculum, which was designed for learners interested in pursuing careers in urology. METHODS: Twenty-nine fourth-year urology-dedicated medical students completing their subinternship at our institution during the 2018-2019 academic year participated in an advanced hands-on simulation "boot camp," which taught both simple and advanced Foley catheter placement, manual and continuous bladder irrigation, and diagnostic cystoscopy. Knowledge acquisition was assessed through quizzes administered before and after completing electronic modules, and a post-simulation survey assessing learners' confidence in their knowledge and skill set, as well as their satisfaction with the curriculum. RESULTS: Medical students demonstrated significant gains in knowledge from pre-test (mean 73.7%) to post-test (mean 94.5%, P < .001), which was consistent across each simulation procedure. Participants self-reported significant improvement in confidence with the procedures from before to after the educational intervention (P < .001). Students also found the curriculum to be beneficial to their understanding of the subject matter (P < .001), would recommend this curriculum to other medical students (P < .001), and thought it better prepared them to meet expected ACGME (Accreditation Council for Graduate Medical Education) milestones (P < .001). CONCLUSIONS: Findings from our advanced "boot camp" simulation curriculum demonstrated successful gains in knowledge and confidence following learning modules and hands-on simulation, indicating that this type of educational intervention could be beneficial in improving exposure to skills and developing confidence prior to urology internship and junior residency.

Characterization of the [2Fe-2S] cluster of Escherichia coli transcription factor IscR.

IscR is an Fe-S cluster-containing transcription factor involved in a homeostatic mechanism that controls Fe-S cluster biogenesis in Escherichia coli. Although IscR has been proposed to act as a sensor of the cellular demands for Fe-S cluster biogenesis, the mechanism by which IscR performs this function is not known. In this study, we investigated the biochemical properties of the Fe-S cluster of IscR to gain insight into the proposed sensing activity. Mössbauer studies revealed that IscR contains predominantly a reduced [2Fe-2S](+) cluster in vivo. However, upon anaerobic isolation of IscR, some clusters became oxidized to the [2Fe-2S](2+) form. Cluster oxidation did not, however, alter the affinity of IscR for its binding site within the iscR promoter in vitro, indicating that the cluster oxidation state is not important for regulation of DNA binding. Furthermore, characterization of anaerobically isolated IscR using resonance Raman, Mössbauer, and nuclear magnetic resonance spectroscopies leads to the proposal that the [2Fe-2S] cluster does not have full cysteinyl ligation. Mutagenesis studies indicate that, in addition to the three previously identified cysteine residues (Cys92, Cys98, and Cys104), the highly conserved His107 residue is essential for cluster ligation. Thus, these data suggest that IscR binds the cluster with an atypical ligation scheme of three cysteines and one histidine, a feature that may be relevant to the proposed function of IscR as a sensor of cellular Fe-S cluster status.

Fluorescence of carotenoids: Probing binding site interactions and conformational motion in carotenoproteins.

The function of carotenoids in carotenoproteins is optimized by the electrostatic and steric interactions between the carotenoid and its surrounding binding site. Binding to the protein distorts the conformation of the carotenoid and induces a charge-transfer character. This chapter shows how the line shape of the fluorescence spectrum, the fluorescence quantum yield, and the fluorescence anisotropy of the second excited singlet state of a carotenoid, S2, can be used to probe the structure and dynamics of carotenoids in carotenoproteins. The experimental approach and a brief introduction to the theory we used to detect hydrogen bonding interactions with the active ketocarotenoids in the orange carotenoid protein are discussed here as an example. Fluorescence anisotropy is then introduced as a probe of the conformational motions that follow optical excitation of a carotenoid using results from a study of ß-carotene in solution over a range of temperatures.

Fellowship training in endourology: Impact on percutaneous nephrolithotomy access patterns.

INTRODUCTION: Percutaneous nephrolithotomy (PCNL) remains the treatment of choice for kidney stones larger than 2 cm. Few studies have examined the reasons why some urologists obtain their own PCNL access while others prefer to have interventional radiology (IR) obtain access. The objective of this study was to investigate what factors influence this decision. METHODS: A survey was posted to the American Urological Association's (AUA) Young Urologist Community. Descriptive statistics and exploratory analyses were used to summarize practice trends and motivating factors. RESULTS: All 99 respondents began practicing within the past 11 years. Ninety-two currently perform PCNLs and 47% of them obtain their own access. Endourology fellowship-trained physicians were more likely to currently obtain their own access (75%) compared to urologists who completed non-endourology fellowships (75% vs. 23%, p=0.58) and non-fellowship-trained urologists (75% vs. 45%, p=0.01). Logging >50 cases during training also predicted physicians obtaining their own access and having a larger annual number of PCNL cases. The most common motivator for obtaining one's own access was preference to control their own access point (95%). CONCLUSIONS: Urologist-obtained PCNL access was associated with greater training experience (endourology fellowship) and current annual PCNL case volume. Urologist-reported factors that influenced the decision to obtain one's own access include control of access, comfort level, and both physician and patient convenience. By identifying the factors that influence practice patterns, we may better address barriers, improve education to make urologistobtained PCNL access feasible even without fellowship training, and ultimately improve outcomes and quality of care.

Urology Boot Camp: A Pilot Medical Student Curriculum for Common Bedside Urologic Procedures.

OBJECTIVES: To develop a novel "bootcamp" simulation-based curriculum to introduce common urologic procedures and to improve readiness for performing them at bedside. METHODS: Three hundred twenty-five third-year medical students at our single institution participated in a hands-on simulation "boot camp" over a 2-year accrual period. This curriculum was designed to teach basic urologic bedside procedures (ie, Foley catheter placement, Bladder irrigation) to third year medical students prior to the start of their surgical clerkships in a live instructional setting with direct feedback from instructors. The objective aspects of the study consisted of a survey administered to study participants following participation in the simulation boot camp, as well as pre- and post-module assessments. RESULTS: Medical students self-reported knowledge gains following the simulation session (P < .001), with 45.8% increase in procedural confidence. Additionally, students reported that the educational intervention was beneficial to their understanding of the subject matter (P < .001), were "very likely" to recommend the session to another medical student (P < .001), and felt that educational intervention better prepared them for an upcoming national exam (P < .001). Finally, the greatest gains were seen for those students who self-reported lower precurriculum knowledge (P < .001). CONCLUSIONS: Findings from our M3 "boot camp" led to self-reported gains in subject matter knowledge following the hands-on simulation curriculum, indicating that this type of educational intervention can be beneficial in preparing medical students for common bedside procedures.

Excitation energy transfer and vibronic coherence in intact phycobilisomes.

The phycobilisome is an oligomeric chromoprotein complex that serves as the principal mid-visible light-harvesting system in cyanobacteria. Here we report the observation of excitation-energy-transfer pathways involving delocalized optical excitations of the bilin (linear tetrapyrrole) chromophores in intact phycobilisomes isolated from Fremyella diplosiphon. By using broadband multidimensional electronic spectroscopy with 6.7-fs laser pulses, we are able to follow the progress of excitation energy from the phycoerythrin disks at the ends of the phycobilisome's rods to the C-phycocyanin disks along their length in <600 fs. Oscillation maps show that coherent wavepacket motions prominently involving the hydrogen out-of-plane vibrations of the bilins mediate non-adiabatic relaxation of a manifold of vibronic exciton states. However, the charge-transfer character of the bilins in the allophycocyanin-containing segments localizes the excitations in the core of the phycobilisome, yielding a kinetic bottleneck that enables photoregulatory mechanisms to operate efficiently on the >10-ps timescale.

Assessment of a Novel Urology Resident Simulation-Based Curriculum.

INTRODUCTION: Interactive simulation training during residency is a rapidly growing initiative due to work-hour restrictions, improved simulation model fidelity and an evolving technological field. We designed and implemented a simulation curriculum for urology residents. The objective of this study was to assess its impact on trainee confidence and knowledge. METHODS: This was a prospective nonblinded case series analyzing the use of simulation education with entrance and exit surveys. We developed and implemented monthly workshops featuring fundamental urological procedures and skills. Residents from a single academic urology residency program received didactic instruction as well as supervised simulation training from an expert faculty member. RESULTS: The majority of residents highly rated all topics and affirmed that they would repeat the simulation topic in the future. Overall, junior residents averaged a 27% gain in base knowledge (p <0.001), and senior residents reported a 15.5% gain in base knowledge (p <0.001). Didactic and mentored simulation portions of the sessions were considered equally valuable (p >0.5). Of the residents 84% felt the sessions better prepared them to be in the operating room and 94% reported that they would recommend the simulation sessions to a peer (p <0.001). CONCLUSIONS: Simulation is a valuable tool that prepares residents for operating room experiences. We have developed a robust simulation curriculum that serves as a feasible and valuable model for other training programs, and has led to increased resident confidence and knowledge in urological procedures and skills.

Risk factors, demographic profiles, and management of uncomplicated recurrent urinary tract infections: a single institution study.

OBJECTIVE: Recurrent urinary tract infections (rUTI) are a common urologic chief complaint. Although rUTIs are a significant burden on the healthcare system, until recently there were no published guidelines to delineate optimal management of this condition. The objective of this study was to describe the demographic profile of rUTI patients and summarize practice patterns at a single tertiary health center, as well as to assess whether our real-life practice patterns parallel the recently published guidelines. METHODS: We conducted a retrospective record review of female patients presenting for diagnosis of uncomplicated rUTI/cystitis between October 2010 and September 2018. Analyses were conducted to investigate (a) whether pre- versus postmenopausal women differed in their risk factors for rUTI, (b) whether providers adjust their practice patterns when treating pre- versus postmenopausal women with rUTIs, and (c) whether certain treatment regimens led to lower rates of rUTI than others. RESULTS: Of the 125 cases included in the final analysis, pre- versus postmenopausal women did differ in their risk factors for rUTI, specifically age, Charlson Comorbidity Index score, and comorbidities. Although common treatments were found across menopausal status, providers did adjust their practice patterns when treating pre- versus postmenopausal women, including the use of postcoital suppression, conservative measures, cranberry juice/extract, and probiotics for premenopausal women and daily suppression and vaginal estrogens for postmenopausal women. rUTI after treatment (<40%) was highest after the use of conservative measures for all women and rates of rUTI after treatment generally did not differ as a function of menopausal status, but rather by treatment option. CONCLUSIONS: This single institution report sheds light on practice patterns at a major academic center, specifically as it compares to the new American Urological Association guidelines and the use of estrogen cream for postmenopausal women.

Fournier's Gangrene in Females: Presentation and Management at a Tertiary Center.

OBJECTIVE: To report and compare presentation and management of Fournier's Gangrene (FG) in female vs male patients at a single tertiary care center. METHODS: Patient demographics, clinical characteristics, treatments and outcomes were summarized and compared between males and females who were treated for FG from 2011 to 2018 at a single institution. RESULTS: Of the 143 patients treated for FG at our institution, 33 (23%) were female. Female patients were predominantly white (82%), with a median (IQR) age of 55 (46, 59). Median female boby mass index (BMI) was 42.1 (32, 50.4). Female patients' wound cultures were polymicrobial mix of gram positive and gram negative organisms. Median number of debridements for females was 2 (1,3). The most common anatomic region of gangrene involvement in females was labia (76%) followed by perineum (55%) and gluteus/buttocks (42%). Mortality rate during initial admission was 6% for females. Female patients had a higher median BMI than males (42.1 vs 33.7 respectively; P = .003). FG severity index, length of hospital stay, number of debridements, and wound cultures were comparable to males. The surgical team managing initial debridements differed with females managed primarily by general surgery and males primarily by urology. Mortality rate was comparable to men (6% vs 7%, P >.05). CONCLUSION: Female patients with FG have greater BMI but similar clinical presentation, microbiologic characteristics and mortality rate compared to men. Urologists have little involvement during initial management for females at our institution.

Trends in Acute Pain Management for Renal Colic in the Emergency Department at a Tertiary Care Academic Medical Center.

Introduction: Renal colic secondary to kidney stone disease is a common reason for emergency department (ED) visits and often leads to patients receiving narcotic medications. The objective of this study was to describe longitudinal analgesia prescribing patterns for kidney stone patients acutely managed in the ED. Methods: This was a retrospective chart review of patients who presented to the ED between 2013 and 2018 and were subsequently diagnosed with a kidney stone. Encounters during which opioids and nonopioids were administered in the ED and prescribed at discharge were stratified by year, race, ethnicity, insurance status, gender, and location of ED (main academic campus and community-based campus). Patients were excluded if they required hospital admission or a stone-related procedure related to the ED encounter. Results: We reviewed 1620 total encounters for 1376 unique patients. Frequency of patients receiving opioids in the ED decreased from 81% in 2013 to 57% in 2018 (p < 0.001). During the same time period, nonopioid administration in the ED remained relatively unchanged (64% vs 67%). The proportion of patients prescribed opioids at discharge decreased from 77% to 59% (p < 0.001), while nonopioid prescriptions at discharge increased from 32% to 41% (p = 0.010). Frequency of administering both a narcotic and non-narcotic during the same ED encounter decreased over the 5-year period from 27% to 8% (p < 0.001). Conclusion: Opioids are being given less both during the ED encounter and at discharge for acute renal colic, while nonopioid prescribing is increasing. These trends may be due to increasing physician awareness to opioid addiction, or as a result of stricter legislation prohibiting opioid prescribing.

Fluorescence Anisotropy Detection of Barrier Crossing and Ultrafast Conformational Dynamics in the S2 State of ß-Carotene.

Carotenoids are usually only weakly fluorescent despite being very strong absorbers in the mid-visible region because their first two excited singlet states, S1 and S2, have very short lifetimes. To probe the structural mechanisms that promote the nonradiative decay of the S2 state to the S1 state, we have carried out a series of fluorescence lineshape and anisotropy measurements with a prototype carotenoid, ß-carotene, in four aprotic solvents. The anisotropy values observed in the fluorescence emission bands originating from the S2 and S1 states reveal that the large internal rotations of the emission transition dipole moment, as much as 50° relative to that of the absorption transition dipole moment, are initiated during ultrafast evolution on the S2 state potential energy surface and persist upon nonradiative decay to the S1 state. Electronic structure calculations of the orientation of the transition dipole moment account for the anisotropy results in terms of torsional and pyramidal distortions near the center of the isoprenoid backbone. The excitation wavelength dependence of the fluorescence anisotropy indicates that these out-of-plane conformational motions are initiated by passage over a low-activation energy barrier from the Franck-Condon S2 structure. This conclusion is consistent with detection over the 80-200 K range of a broad, red-shifted fluorescence band from a dynamic intermediate evolving on a steep gradient of the S2 state potential energy surface after crossing the activation barrier. The temperature dependence of the oscillator strength and anisotropy indicate that nonadiabatic passage from S2 through a conical intersection seam to S1 is promoted by the out-of-plane motions of the isoprenoid backbone with strong hindrance by solvent friction.