A multi-biomarker panel for predicting Tocilizumab response in Rheumatoid arthritis patients.

Rheumatoid arthritis (RA) is a chronic systemic autoimmune disease characterized by inflammation in the synovial lining of the joints. Key inflammatory cytokines such as interleukin-6 (IL-6), TNF-α, and others play a critical role in the activation of local synovial leukocytes and the induction of chronic inflammation. Tocilizumab (TCZ), a humanized anti-IL-6 receptor monoclonal antibody, has demonstrated significant clinical efficacy in treating RA patients. However, similar to other inflammatory cytokine blockers, such as TNF-alpha inhibitors, Interleukin-1 inhibitors, or CD20 inhibitors, some patients do not respond to treatment. To address this challenge, our study employed a high-precision proteomics approach to identify protein biomarkers capable of predicting clinical responses to Tocilizumab in RA patients. Through the use of data-independent acquisition (DIA) mass spectrometry, we analyzed serum samples from both TCZ responders and non-responders to discover potential biomarker candidates. These candidates were subsequently validated using individual serum samples from two independent cohorts: a training set (N = 70) and a test set (N = 18), allowing for the development of a robust multi-biomarker panel. The constructed multi-biomarker panel demonstrated an average discriminative power of 86 % between response and non-response groups, with a high area under the curve (AUC) value of 0.84. Additionally, the panel exhibited 100 % sensitivity and 60 % specificity. Collectively, our multi-biomarker panel holds promise as a diagnostic tool to predict non-responders to TCZ treatment in RA patients.

Radiographic and Clinical Outcomes of Transverse Process Hook Placement at the Proximal Thoracic Upper Instrumented Vertebra in Adult Spinal Deformity Surgery.

OBJECTIVE: Few studies have reported radiographic and clinical outcomes of transverse process hook (TPH) placement at the proximal thoracic upper instrumented vertebra (UIV) in adult spinal deformity (ASD) surgery. This study aims to investigate radiographic and clinical outcomes of TPH placement at the UIV for ASD surgery. METHODS: This is a retrospective cohort of 56 patients with ASD (age, 59 ± 13 years; followup, 44 ± 19 months) from Johns Hopkins Hospital, who underwent long posterior spinal fusion to the proximal thoracic spine (T2-5). Visual analogue scale (VAS) for back pain, Oswestry Disability Index (ODI), 36-item Short Form health survey scores, thoracic kyphosis (TK), lumbar lordosis, sacral slope, pelvic tilt, pelvic incidence, proximal junctional kyphosis (PJK) angle, PJK incidence, pattern of PJK, grades of TPH dislodgement, revision surgery, and factors associated with high-grade TPH dislodgement were analyzed. RESULTS: VAS for back pain and ODI values improved significantly from preoperatively to final follow-up. Mean change in PJK angle was 12° (range, 0.5°-43°). Twenty patients (36%) developed PJK, of whom 13 had compression fractures at 1 vertebra distal to the UIV (UIV-1). Final TPH position was stable in 42 patients (75%). In most patients (86%), TPH dislodgement did not progress after 6-month postoperative follow-up. Three patients (5.3%) underwent revision surgery to extend the fusion because of symptomatic PJK. Unstable TPH position was associated only with revision surgery and TK. CONCLUSION: TPH placement at the proximal thoracic UIV for long fusion showed favorable clinical and radiographic outcomes in terms of the incidence of PJK and mean PJK angle at mean 44-month follow-up. TPHs placed in the proximal thoracic UIV were in stable position in 75% of patients. Compression fracture at UIV-1 was the most common pattern of PJK. PJK angle progression was greater in revision cases and in patients with greater preoperative thoracic kyphosis.

Caregiver preferences for physically harsh discipline of children in rural Uganda.

Purpose: Physically harsh discipline is associated with poor developmental outcomes among children. These practices are more prevalent in areas experiencing poverty and resource scarcity, including in low- and middle-income countries. Designed to limit social desirability bias, this cross-sectional study in rural Uganda estimated caregiver preferences for physically harsh discipline; differences by caregiver sex, child sex, and setting; and associations with indicators of household economic stress and insecurity. Method: Three-hundred-fifty adult caregivers were shown six hypothetical pictographic scenarios depicting children whining, spilling a drink, and kicking a caregiver. Girls and boys were depicted engaging in each of the three behaviors. Approximately half of the participants were shown scenes from a market setting and half were shown scenes from a household setting. For each scenario, caregivers reported the discipline strategy they would use (time out, beating, discussing, yelling, ignoring, slapping). Results: Two thirds of the participants selected a physically harsh discipline strategy (beating, slapping) at least once. Women selected more physically harsh discipline strategies than men (b = 0.40; 95% confidence interval [CI], 0.26 to 0.54). Participants shown scenes from the market selected fewer physically harsh discipline strategies than participants shown scenes from the household (b = -0.51; 95% CI, -0.69 to -0.33). Finally, caregivers selected more physically harsh discipline strategies in response to boys than girls. Indicators of economic insecurity were inconsistently associated with preferences for physically harsh discipline. Conclusions: The high prevalence of physically harsh discipline preferences warrant interventions aimed at reframing caregivers' approaches to discipline.

Cerebrospinal Fluid Leaks: Challenges in Localizing Spontaneous Spinal Leak Sites and Minimally Invasive Treatment.

The confirmation of cerebrospinal fluid (CSF) leaks in the setting of spontaneous intracranial hypotension (SIH) by imaging involves a growing toolset of multimodal advanced spinal and skull base imaging techniques, for which exists a unique set of challenges for each CSF leak type. Furthermore, the repertoire of minimally invasive CSF leak treatment beyond nontargeted epidural blood patch administration has grown widely, with varied practices across institutions. This review describes current diagnostic imaging and treatment modalities as they apply to the challenges of CSF leak localization and management.

Inhibition of Mast Cell Degranulation by Novel Small Molecule MRGPRX2 Antagonists.

BACKGROUND: Mas-related G-protein coupled receptor X2 (MRGPRX2) is a promiscuous receptor on mast cells that mediates IgE-independent degranulation and has been implicated in multiple mast cell-mediated disorders, including chronic urticaria, atopic dermatitis, and pain disorders. Although it is a promising therapeutic target, few potent, selective, small molecule antagonists have been identified, and functional effects of human MRGPRX2 inhibition have not been evaluated in vivo. OBJECTIVE: We identified and characterized novel, potent, and selective orally active small molecule MRGPRX2 antagonists for potential treatment of mast cell-mediated disease. METHODS: Antagonists were identified using multiple functional assays in cell lines overexpressing human MRGPRX2, LAD2 mast cells, human peripheral stem cell-derived mast cells, and isolated skin mast cells. Skin mast cell degranulation was evaluated in Mrgprb2em(-/-) knockout (KO) and Mrgprb2em(MRGPRX2) transgenic human MRGPRX2 knock-in (KI) mice by assessment of agonist-induced skin vascular permeability. Ex vivo skin mast cell degranulation and associated histamine release was evaluated by microdialysis of human skin tissue samples. RESULTS: MRGPRX2 antagonists potently inhibited agonist-induced MRGPRX2 activation and mast cell degranulation in all mast cell types tested, in an IgE-independent manner. Orally administered MRGPRX2 antagonists also inhibited agonist-induced degranulation and resulting vascular permeability in MRGPRX2 KI mice. In addition, antagonist treatment dose dependently inhibited agonist-induced degranulation in ex vivo human skin. CONCLUSION: MRGPRX2 small molecule antagonists potently inhibited agonist-induced mast cell degranulation in vitro and in vivo as well as ex vivo in human skin, supporting potential therapeutic utility as a novel treatment for multiple human diseases involving clinically relevant mast cell activation.

Transdermal bisoprolol for prevention of postoperative atrial fibrillation: A systematic review and meta-analysis.

Background: The transdermal patch of bisoprolol available in Japan has been reported to demonstrate superior efficacy in preventing postoperative atrial fibrillation, possibly surpassing its oral counterpart. However, there has been no systematic review and meta-analysis assessing the efficacy of transdermal bisoprolol. Methods: A comprehensive systematic literature search was conducted on PubMed, Embase, and Cochrane to identify all relevant studies assessing the efficacy of transdermal bisoprolol in preventing postoperative atrial fibrillation. The search covered studies from inception up to December 4, 2023. For data analysis, Review Manager (RevMan) 5.4 software was employed, using a random-effects model to calculate risk ratios (RR) and 95% confidence intervals (CI). Results: Three studies, comprising a total of 551 patients (transdermal bisoprolol 228 and control 323), were included. There was a decreased risk of postoperative atrial fibrillation or atrial tachyarrhythmias in patients treated with transdermal bisoprolol (RR 0.43, 95% CI 0.27-0.67, p = .0002, I 2 = 0%). Conclusion: Transdermal administration of bisoprolol has consistently shown efficacy, and this pooled analysis supports its effectiveness. The heterogeneity of the included studies limits certain interpretations. Future randomized clinical trials may elucidate the superiority of transdermal administration over oral administration.

Psychosocial correlates of parents' willingness to vaccinate their children against COVID-19.

BACKGROUND: Public health guidance recommended that children who are 6 months or older be vaccinated against COVID-19 in June of 2022. In the U.S., 56% of children under 17 had not received the COVID-19 vaccination in 2023. We examine parents' willingness to vaccinate their children against COVID-19 using the theory of planned behavior in order to design effective strategies to promote vaccine uptake. METHODS: The Philadelphia Community Engagement Alliance is part of an NIH community-engaged consortium focused on addressing COVID-19 disparities across the U.S. We surveyed 1,008 Philadelphia parents (mean age 36.86, SD 6.55; 42.3% racial/ethnic minorities) between September 2021 and February 2022, a period when guidance for child vaccination was anticipated. Structural Equation Modeling analysis examined associations between parental willingness and vaccine-related attitudes, norms, and perceived control. Covariates included parents' COVID-19 vaccination status, race/ethnicity, gender, and survey completion post-CDC pediatric COVID-19 vaccination guidelines. Subgroup analyses by race/ethnicity and gender were conducted. RESULTS: Our model demonstrated good fit (χ2 = 907.37, df = 419, p<0.001; comparative fit index [CFI] = 0.951; non-normed fit index [NNFI] = 0.946; root mean square error of approximation [RMSEA] = 0.034 with 95% CI = 0.030-0.038). Attitudes ([Formula: see text] = 0.447, p<0.001) and subjective norms ([Formula: see text] = 0.309, p = 0.002) were predictors of intention. Racial/ethnic minority parents exhibited weaker vaccination intentions ([Formula: see text] = -0.053, p = 0.028) than non-Hispanic White parents. CONCLUSIONS: Parents' attitudes and norms influence their vaccination intentions. Despite the survey predating widespread child vaccine availability, findings are pertinent given the need to increase and sustain pediatric vaccinations against COVID-19. Interventions promoting positive vaccine attitudes and prosocial norms are warranted. Tailored interventions and diverse communication strategies for parental subgroups may be useful to ensure comprehensive and effective vaccination initiatives.

Risk Factors for Progression of Cervical Congenital Scoliosis and Associated Compensatory Curve Behavior.

Background: This study investigated risk factors for progression of deformity in pediatric congenital cervical scoliosis (CCS) and evaluated the correlation between congenital cervical curves and compensatory thoracic and lumbar curves. Methods: Medical records were retrospectively reviewed for 38 pediatric patients with CCS with a minimum 2-year follow-up. Curve progression was defined as >10° increase in cervical coronal curve angle between presentation and last follow-up. Results: A total of 38 patients (16 girls, 22 boys) with a mean age at presentation of 5.6 ± 4.1 years met the inclusion criteria. Sixteen patients (42%) had curve progression with a mean follow-up of 3.1 ± 3.0 years. At presentation, T1 slope was significantly larger among children with progressive deformities (p = 0.041). A total of 18 of the 38 patients with strictly cervical spine deformity were then selected for subanalysis to evaluate the progression of compensatory curves. Cervical major coronal curves were found to significantly correlate with lumbar major coronal curves (r = 0.409), C2 central sacral vertical line (CSVL) (r = 0.407), and C7-CSVL (r = 0.403) (p < 0.05). Thoracic major coronal curves did not significantly correlate with cervical major coronal curves (r = 0.218) (p > 0.05). Conclusion: In conclusion, 42% of osseous CCS curves progressed over time in the overall cohort, and high initial T1 slope was found to be most highly correlated with progression of cervical deformity. Cervical major coronal curves significantly correlated with lumbar curve magnitude but not with thoracic curve size in isolated CCS, possibly due to the increased flexibility of the lumbar spine which may allow greater compensatory balance and thus have a greater correlation with cervical curve magnitude and possibly progression.

The association between street construction projects and community violence in New York City.

Introduction: Community violence is a major cause of injury and death in the United States. Empirical studies have identified that some place-based interventions of urban private places, such as remediations of vacant lots and buildings, are associated with reductions in community violence in surrounding areas. The aim of this study was to examine whether routine maintenance and repair of urban public places (e.g., street construction projects) are also associated with reductions in community violence, proxied by violent crime. Method: This staggered adoption difference-in-difference analysis investigated the association between street construction projects and community violence in New York City from 2010-2019, divided into 40 calendar quarters. The units of analysis were street-quarters (n = 155,280). Intervention street-quarters were those with completed projects in 2010-2019; control streets were those where projects were scheduled but not completed before 2019. The outcome of community violence was proxied by counts of crime and violence incidents reported to the New York Police Department, within street-quarters. Results: There were 79,592 street-quarters with any community violence incidents (51.2%). We found that street construction projects were associated with a decrease in reckless endangerment (ATT = -0.013; 95% CI = -0.021, -0.004), robbery (ATT = -0.035; 95% CI = -0.063, -0.007), and weapons offenses (ATT = -0.016; 95% CI = -0.031, -0.001) occurring on street-quarters. Conclusion: Street construction projects may be yet another type of place-based intervention to reduce community violence.

Spatial and Temporal Resolution of Cyanobacterial Bloom Chemistry Reveals an Open-Ocean Trichodesmium thiebautii as a Talented Producer of Specialized Metabolites.

While the ecological role that Trichodesmium sp. play in nitrogen fixation has been widely studied, little information is available on potential specialized metabolites that are associated with blooms and standing stock Trichodesmium colonies. While a collection of biological material from a T. thiebautii bloom event from North Padre Island, Texas, in 2014 indicated that this species was a prolific producer of chlorinated specialized metabolites, additional spatial and temporal resolution was needed. We have completed these metabolite comparison studies, detailed in the current report, utilizing LC-MS/MS-based molecular networking to visualize and annotate the specialized metabolite composition of these Trichodesmium blooms and colonies in the Gulf of Mexico (GoM) and other waters. Our results showed that T. thiebautii blooms and colonies found in the GoM have a remarkably consistent specialized metabolome. Additionally, we isolated and characterized one new macrocyclic compound from T. thiebautii, trichothilone A (1), which was also detected in three independent cultures of T. erythraeum. Genome mining identified genes predicted to synthesize certain functional groups in the T. thiebautii metabolites. These results provoke intriguing questions of how these specialized metabolites affect Trichodesmium ecophysiology, symbioses with marine invertebrates, and niche development in the global oligotrophic ocean.

Resilience as a psychiatric factor affecting outcomes after total joint arthroplasty: a systematic review.

INTRODUCTION: Mental and psychiatric status continue to be underscreened prior to total joint arthroplasty (TJA). Research on the role of resilience as a psychiatric factor affecting TJA outcomes remains limited. Therefore, our systematic review sought to evaluate the impact of patient resilience in TJA. METHODS: A systematic review of the literature from the Pubmed, MEDLINE, EBSCOhost, and Google Scholar online databases was performed in abidance with Preferred Reporting Items for Systematic Review and Meta-Analyses (PRISMA) guidelines. Studies reporting on outcomes following primary total hip arthroplasty (THA) and/or total knee arthroplasty (TKA) segregated by patient resilience were included. Case reports, reviews, meta-analyses, and conference abstracts were excluded. Primary outcomes of interest included patient-reported outcomes (PROs), surgical outcomes, and postoperative opioid consumption. RESULTS: Twelve articles were included reporting on a total of 1,577 TJAs. There was a strong agreement that the Patient Reported Outcomes Measurement Information System (PROMIS)-Physical Health and Mental Health components were strongly predicted by patient resilience. However, there was inconclusive evidence regarding the impact of resilience on UCLA Activity Scales (UCLA) and Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) outcomes as well as postoperative hip and knee function. Similarly, conflicting evidence was presented regarding the effect of resilience on length of stay (LOS). Greater resilience was associated with reduced opioid usage in the immediate inpatient postoperative period. However, resilience had no significant effect on opioid requirements in the postoperative outpatient follow-up time frame. CONCLUSION: The present analysis demonstrated mixed, inconclusive evidence regarding the impact of resilience on postoperative outcomes. The paucity of research evaluating this relationship warrants further investigation, examining both short and long-term outcomes. Due to the limited literature evaluating resilience as a predictor of outcomes following TJA, we cannot definitively rule out resilience as a valuable metric and must further examine its utility as a preoperative screening tool. LEVEL OF EVIDENCE: III.

Declining Inflation-Adjusted Medicare Physician Fees: An Unsustainable Trend in Hip Arthroscopy.

INTRODUCTION: Although hip arthroscopy continues to be one of the most used arthroscopic procedures, no focused, comprehensive evaluation of reimbursement trends has been conducted. The purpose of this study was to analyze the temporal Medicare reimbursement trends for hip arthroscopy procedures. METHODS: From 2011 to 2021, the Medicare Physician Fee Schedule Look-Up Tool was queried for Current Procedural Terminology (CPT) codes related to hip arthroscopy (29860 to 29863, 29914 to 29916). All monetary data were adjusted to 2021 US dollars. The compound annual growth rate and total percentage change were calculated. Mann-Kendall trend tests were used to evaluate the reimbursement trends. RESULTS: Based on the unadjusted values, a significant increase in physician fee was observed from 2011 to 2021 for CPT codes 29861 (removal of loose or foreign bodies; % change: 3.49, P = 0.03) and 29862 (chondroplasty, abrasion arthroplasty, labral resection; % change: 3.19, P = 0.03). The remaining CPT codes experienced no notable changes in reimbursement based on the unadjusted values. After adjusting for inflation, all seven of the hip arthroscopy CPT codes were observed to experience a notable decline in Medicare reimbursement. Hip arthroscopy with acetabuloplasty (CPT: 29915) and labral repair (CPT: 29916) exhibited the greatest reduction in reimbursement with a decrease in physician fee of 24.69% ( P < 0.001) and 24.64% ( P < 0.001), respectively, over the study period. DISCUSSION: Medicare reimbursement for all seven of the commonly used hip arthroscopy services did not keep up with inflation, demonstrating marked reductions from 2011 to 2021. Specifically, the inflation-adjusted reimbursements decreased between 19.23% and 24.69% between 2011 and 2021.

Post-myocardial Infarction Left Ventricular Aneurysm With Contained Rupture and Hemopericardium.

Left ventricular aneurysms (LVAs) represent a rare yet critical complication arising from late-presenting myocardial infarction (MI). Here, we present the case of an 88-year-old male with chest pressure, elevated troponin, B-type natriuretic peptide, and lactate. The electrocardiogram showed sinus tachycardia and an old right bundle branch block. The patient was started on heparin infusion, but progressively worsening hypotension necessitated transfer to the intensive care unit and the initiation of vasopressors. The echocardiogram identified a focal aneurysm in the mid-anterolateral wall, moderate pericardial effusion with a coagulum, and tamponade physiology. Computed tomography angiography of the chest confirmed a moderate pericardial effusion with density consistent with hemopericardium. LVAs pose a substantial threat of cardiovascular morbidity and mortality. While echocardiography serves as the initial assessment method, supplemental imaging modalities may need to be utilized. Various complications have been reported with LVA, including thromboembolization, ventricular arrhythmias, pericardial effusion with tamponade, and left ventricular rupture which accounts for 5%-24% of all in-hospital deaths related to MI. Although LVAs are the most common mechanical complications following an MI, instances of contained aneurysm rupture leading to hemopericardium are infrequent and scarcely reported. High clinical suspicion and prompt imaging with echocardiography are essential for diagnosis. Determining the optimal timing and selection between surgical and percutaneous interventions necessitates additional research for informed decision-making.

Cardiac Challenges in Immune Checkpoint Therapy: Complete Heart Block With Pembrolizumab.

Immune checkpoint inhibitors (ICIs) have revolutionized cancer treatment, yet they come with a spectrum of immune-related adverse events, including cardiac complications. We present the case of a 72-year-old male with metastatic renal cell carcinoma who developed complete heart block and ventricular arrhythmias following pembrolizumab therapy. Despite no evidence of myocarditis, the patient's condition rapidly deteriorated, ultimately resulting in his demise. This case underscores the critical need for vigilance in recognizing and managing potential cardiotoxicity associated with ICIs. Additionally, it highlights the importance of multidisciplinary collaboration in optimizing diagnostic and therapeutic strategies for patients undergoing immune checkpoint inhibitor therapy.

5-Factor Modified Frailty Index as a Predictor of Outcomes After Hemiarthroplasty or Total Hip Arthroplasty for Femoral Neck Fracture.

INTRODUCTION: Although the 5-factor modified frailty index (mFI-5) has been shown to be an independent predictor of complications after primary total hip arthroplasty (THA), its predictive value has not been evaluated in the setting of hip fracture. We therefore assessed the utility of mFI-5 score as an independent predictor of morbidity and mortality in patients who underwent THA or hemiarthroplasty for femoral neck fracture. METHODS: The American College of Surgeons National Surgical Quality Improvement database was queried for all patients with femoral neck fractures treated with THA or hemiarthroplasty between 2006 and 2020. A multivariate logistic regression analysis was done using mFI-5 as a predictor while controlling for baseline demographic and clinical variables. RESULTS: In total, 45,185 patients (hemiarthroplasty: 37,645; THA: 7,540) were identified. For hemiarthroplasty patients, the mFI-5 strongly predicted risk of any complication (OR, 1.1; 95% CI, 1.1 to 1.2; P < 0.001), bleeding (OR, 1.2; 95% CI, 1.1 to 1.3; P < 0.001), and readmission (OR, 1.2; 95% CI, 1.1 to 1.3; P < 0.001). For THA patients, the mFI-5 was a strong predictor of any complication (OR, 1.2; 95% CI, 1.0 to 1.3; P = 0.023), pneumonia (OR, 1.4; 95% CI, 1.0 to 2.0; P = 0.047), and readmission (OR, 1.3; 95% CI, 1.1 to 1.6; P = 0.004). DISCUSSION: The mFI-5 is an independent predictor of morbidity and complications after hemiarthroplasty and THA for femoral neck fracture. Importantly, readmission risk was predicted by the mFI-5. The mFI-5 may present a valuable clinical tool for assessment of high-risk patients who might require additional resources and specialized care after femoral neck fracture.

A Case of Gemella morbillorum Causing Multi-valvular Endocarditis.

This is the case of a 31-year-old man with no significant past medical history who presented to the emergency department experiencing persistent fevers, chills, and malaise for the past 2-3 weeks. During this period, he had multiple urgent care visits for possible left-sided otitis media which was treated with short a course of Augmentin. While on antibiotics his symptoms would improve, but they would reappear once he had finished treatment. The patient also had significant dental carries with a chronic right molar infection. At the emergency department, blood cultures grew two out of two Gemella morbillorum. Transthoracic echocardiography showed a 1 cm x 0.5 cm mobile density on the left coronary cusp of the aortic valve with moderate-severe aortic insufficiency. The patient was started on empiric IV vancomycin. Further workup revealed that the source of infection was dental carries. While proceeding with a transesophageal echocardiogram, the patient went into flash pulmonary edema requiring ICU admission. Imaging revealed an elongated 1.7 cm x 0.6 cm vegetation attached to the base of the left coronary cusp on the left ventricular outflow tract side with severe aortic regurgitation and a small 0.8 cm x 0.8 cm vegetation on the atrial side of the anterior mitral leaflet at A2 associated with mitral leaflet perforation with severe mitral regurgitation. Oral surgery removed the infected teeth. Cardiothoracic surgery performed open heart valve replacement which revealed a completely destroyed aortic valve, droplet vegetation, and destruction of the mitral valve leading to mechanical valve replacement. The patient received a two-week course of gentamycin while in the ICU with meropenem. Once sensitivities were back, he was switched to IV penicillin therapy for a total of six weeks.

Phototransformation of achiral metasurfaces into handedness-selectable transient chiral media.

Chirality is a geometric property describing the lack of mirror symmetry. This unique feature enables photonic spin-selectivity in light-matter interaction, which is of great significance in stereochemistry, drug development, quantum optics, and optical polarization control. The versatile control of optical geometry renders optical metamaterials as an effective platform for engineered chiral properties at prescribed spectral regimes. Unfortunately, geometry-imposed restrictions only allow one circular polarization state of photons to effectively interact with chiral meta-structures. This limitation motivates the idea of discovering alternative techniques for dynamically reconfiguring the chiroptical responses of metamaterials in a fast and facile manner. Here, we demonstrate an approach that enables optical, sub-picosecond conversion of achiral meta-structures to transient chiral media in the visible regime with desired handedness upon the inhomogeneous generation of plasmonic hot electrons. As a proof of concept, we utilize linearly polarized laser pulse to demonstrate near-complete conversion of spin sensitivity in an achiral meta-platform-a functionality yet achieved in a non-mechanical fashion. Owing to the generation, diffusion, and relaxation dynamics of hot electrons, the demonstrated technique for all-optical creation of chirality is inherently fast, opening new avenues for ultrafast spectro-temporal construction of chiral platforms with on-demand spin-selectivity.

The Cost-Effectiveness of Smoking Cessation Programs for Prevention of Wound Complications Following Total Ankle Arthroplasty: A Break-Even Analysis.

Background: Tobacco use significantly increases the rate of wound complications in patients undergoing total ankle arthroplasty (TAA). Preoperative optimization through smoking cessation programs significantly minimizes the rate of infection and improves wound healing in arthroplasty procedures. Despite its utility, minimal research has examined the cost-effectiveness of preoperative smoking cessation programs to reduce the need for extracapsular irrigation and debridement (I&D) due to wound complications following TAA. Methods: The cost of an I&D procedure was obtained from our institution's purchasing records. Baseline wound complication rates among tobacco users who have undergone TAA and smoking cessation program cost were obtained from literature. A break-even economic analysis was performed to determine the absolute risk reduction (ARR) to economically justify the implementation of preoperative smoking cessation programs. Different smoking cessation program and I&D costs were tested to account for variations in each factor. ARR was then used to calculate the number needed to treat (NNT) to prevent a single I&D while remaining cost-effective. Results: Smoking cessation programs were determined to be economically justified if it prevents 1 I&D surgery out of 8 TAAs among tobacco users (ARR = 12.66%) in the early postoperative period (<30 days). ARR was the same at the literature high (27.3%) and weighted literature average (13.3%) complication rates when using the cost of I&D surgery at our institution ($1757.13) and the literature value for a smoking cessation program ($222.45). Cost-effectiveness was maintained with higher I&D surgery costs and lower costs of smoking cessation treatment. Conclusion: Our model's input data suggest that the routine use of smoking cessation programs among tobacco users undergoing TAA is cost-effective for risk reduction of I&D surgery in the early postoperative period. This intervention was also found to be economically warranted with higher I&D costs and lower smoking cessation program costs than those found in the literature and at our institution.Level of Evidence: Level III, economic and decision analysis.

Temporal Dynamics of Cyanobacterial Bloom Community Composition and Toxin Production from Urban Lakes.

With a long evolutionary history and a need to adapt to a changing environment, cyanobacteria in freshwater systems use specialized metabolites for communication, defense, and physiological processes. However, the role that these metabolites play in differentiating species, maintaining microbial communities, and generating niche persistence and expansion is poorly understood. Furthermore, many cyanobacterial specialized metabolites and toxins present significant human health concerns due to their liver toxicity and their potential impact to drinking water. Gaps in knowledge exist with respect to changes in species diversity and toxin production during a cyanobacterial bloom (cyanoHAB) event; addressing these gaps will improve understanding of impacts to public and ecological health. In the current project, we utilized a multiomics strategy (DNA metabarcoding and metabolomics) to determine the cyanobacterial community composition, toxin profile, and the specialized metabolite pool at three freshwater lakes in Providence, RI during summer-fall cyanoHABs. Species diversity decreased at all study sites over the course of the bloom event, and toxin production reached a maximum at the midpoint of the event. Additionally, LC-MS/MS-based molecular networking identified new toxin congeners. This work provokes intriguing questions with respect to the use of allelopathy by organisms in these systems and the presence of emerging toxic compounds that can impact public health.