A New Class of Mechano-Responsive PolyureThane Via Anthracene -TAD Diels-Alder (DA) Click Chemistry.

Smart or stimuli-responsive polymers have garnered significant interest in the scientific community due to their response to different stimuli like pH, temperature, light, mechanical force, etc. Mechanophoric polymer is an intriguing class of smart polymers that respond to external mechanical force by producing fluorescent moieties and can be utilized for damage detection and stress-sensing assessment. In recent reports on mechanophoric polymers, different mechanophoric motifs such as spiropyran, rhodamine, coumarin, etc. are explored. This investigation reports a new kind of mechanophoric polyurethane (PU) adduct based on Diels-Alder (DA) click chemistry. Here, an anthracene(An)-end capped tri-armed urethane system is synthesized, followed by a DA reaction using bis-(1,2,4-triazoline-3,5-dione) (bis-TAD) derivative. The incorporation of bis-TAD in the urethane system renders the anthracene inactive ("turn-off") by dismantling its conjugation as a result of a successful DA reaction. The soft PU translated into a harder material through bis-TAD linkages between polymer chains as evident from nanoindentation (NINT) analysis. The resulting material reverts back to its fluorescent "turned-on" mode owing to a force-accelerated retro-Diels-Alder (r-DA) reaction. Besides the mechanophoric attributes, the material demonstrates self-healing behavior examined by microscopic investigations. This innovative approach can be a potential route to design responsive polymers with dynamic functionalities for advanced material applications.

Isoform-specific C-terminal phosphorylation drives autoinhibition of Casein Kinase 1.

Casein kinase 1 δ (CK1δ) controls essential biological processes including circadian rhythms and Wnt signaling, but how its activity is regulated is not well understood. CK1δ is inhibited by autophosphorylation of its intrinsically disordered C-terminal tail. Two CK1 splice variants, δ 1 and δ 2 , are known to have very different effects on circadian rhythms. These variants differ only in the last 16 residues of the tail, referred to as the extreme C-termini (XCT), but with marked changes in potential phosphorylation sites. Here we test if the XCT of these variants have different effects in autoinhibition of the kinase. Using NMR and HDX-MS, we show that the δ 1 XCT is preferentially phosphorylated by the kinase and the δ 1 tail makes more extensive interactions across the kinase domain. Mutation of δ1 -specific XCT phosphorylation sites increases kinase activity both in vitro and in cells and leads to changes in circadian period, similar to what is reported in vivo. Mechanistically, loss of the phosphorylation sites in XCT disrupts tail interaction with the kinase domain. δ1 autoinhibition relies on conserved anion binding sites around the CK1 active site, demonstrating a common mode of product inhibition of CK1δ . These findings demonstrate how a phosphorylation cycle controls the activity of this essential kinase.

A circadian behavioral analysis suite for real-time classification of daily rhythms in complex behaviors.

Measuring animal behavior over long timescales has been traditionally limited to behaviors that are easily measurable with real-time sensors. More complex behaviors have been measured over time, but these approaches are considerably more challenging due to the intensive manual effort required for scoring behaviors. Recent advances in machine learning have introduced automated behavior analysis methods, but these often overlook long-term behavioral patterns and struggle with classification in varying environmental conditions. To address this, we developed a pipeline that enables continuous, parallel recording and acquisition of animal behavior for an indefinite duration. As part of this pipeline, we applied a recent breakthrough self-supervised computer vision model to reduce training bias and overfitting and to ensure classification robustness. Our system automatically classifies animal behaviors with a performance approaching that of expert-level human labelers. Critically, classification occurs continuously, across multiple animals, and in real time. As a proof-of-concept, we used our system to record behavior from 97 mice over two weeks to test the hypothesis that sex and estrogen influence circadian rhythms in nine distinct home cage behaviors. We discovered novel sex- and estrogen-dependent differences in circadian properties of several behaviors including digging and nesting rhythms. We present a generalized version of our pipeline and novel classification model, the "circadian behavioral analysis suite," (CBAS) as a user-friendly, open-source software package that allows researchers to automatically acquire and analyze behavioral rhythms with a throughput that rivals sensor-based methods, allowing for the temporal and circadian analysis of behaviors that were previously difficult or impossible to observe.

Ambivalent Sexism and Tolerance of Violence Against Women in India.

We examined associations between sexist beliefs and tolerance of violence against women in India using a nationally representative probability sample of adults (n = 133,398). Research consistently indicates that hostile sexism fosters tolerance of violence against women. However, benevolent sexism is sometimes associated with higher tolerance and sometimes with lower tolerance of violence. We proposed that this inconsistency could be resolved by considering the source of violence: Is violence perpetrated by outsiders or intimate partners? Results of a multigroup structural equation model showed that endorsement of hostile sexism was related to greater tolerance of violence regardless of the source. In contrast, endorsement of benevolent sexism was associated with lower tolerance of violence from outsiders but was simultaneously associated with higher tolerance of spousal violence. These opposing processes indicate that although benevolent sexism promises women protection from violence, the very same ideology legitimizes spousal violence, thereby reinforcing men's power within intimate relationships.

Secreted dengue virus NS1 from infection is predominantly dimeric and in complex with high-density lipoprotein.

Severe dengue infections are characterized by endothelial dysfunction shown to be associated with the secreted nonstructural protein 1 (sNS1), making it an attractive vaccine antigen and biotherapeutic target. To uncover the biologically relevant structure of sNS1, we obtained infection-derived sNS1 (isNS1) from dengue virus (DENV)-infected Vero cells through immunoaffinity purification instead of recombinant sNS1 (rsNS1) overexpressed in insect or mammalian cell lines. We found that isNS1 appeared as an approximately 250 kDa complex of NS1 and ApoA1 and further determined the cryoEM structures of isNS1 and its complex with a monoclonal antibody/Fab. Indeed, we found that the major species of isNS1 is a complex of the NS1 dimer partially embedded in a high-density lipoprotein (HDL) particle. Crosslinking mass spectrometry studies confirmed that the isNS1 interacts with the major HDL component ApoA1 through interactions that map to the NS1 wing and hydrophobic domains. Furthermore, our studies demonstrated that the sNS1 in sera from DENV-infected mice and a human patient form a similar complex as isNS1. Our results report the molecular architecture of a biological form of sNS1, which may have implications for the molecular pathogenesis of dengue.

The Evolving Classification of Meningiomas: Integration of Molecular Discoveries to Inform Patient Care.

Meningioma classification and treatment have evolved over the past eight decades. Since Bailey, Cushing, and Eisenhart's description of meningiomas in the 1920s and 1930s, there have been continual advances in clinical stratification by histopathology, radiography and, most recently, molecular profiling, to improve prognostication and predict response to therapy. Precise and accurate classification is essential to optimizing management for patients with meningioma, which involves surveillance imaging, surgery, primary or adjuvant radiotherapy, and consideration for clinical trials. Currently, the World Health Organization (WHO) grade, extent of resection (EOR), and patient characteristics are used to guide management. While these have demonstrated reliability, a substantial number of seemingly benign lesions recur, suggesting opportunities for improvement of risk stratification. Furthermore, the role of adjuvant radiotherapy for grade 1 and 2 meningioma remains controversial. Over the last decade, numerous studies investigating the molecular drivers of clinical aggressiveness have been reported, with the identification of molecular markers that carry clinical implications as well as biomarkers of radiotherapy response. Here, we review the historical context of current practices, highlight recent molecular discoveries, and discuss the challenges of translating these findings into clinical practice.

Atmospheric gaseous mercury and associated health risk assessment in the economic capital of India.

Mercury cycling in coastal metropolitan areas on the west coast of India becomes complex due to the combined effects of both intensive domestic anthropogenic emissions and marine air masses. The present study is based on yearlong data of continuous measurements of gaseous elemental mercury (GEM) concentration concurrent with meteorological parameters and some air pollutants at a coastal urban site in Mumbai, on the west coast of India, for the first time. The concentration of GEM was found in a range between 2.2 and 12.3 ng/m3, with a mean of 3.1 ± 1.1 ng/m3, which was significantly higher than the continental background values in the Northern Hemisphere (~ 1.5 ng/m3). Unlike particulates, GEM starts increasing post-winter to peak during the monsoon and decrease towards winter. July had the highest concentration of GEM followed by October, and a minimum in January. GEM exhibited a distinct diurnal cycle, mainly with a broad peak in the early morning, a narrow one by nightfall, and a minimum in the afternoon. The peaks and their timing suggest the origin of urban mobility and the start of local activities. A positive correlation between SO2, PM2.5, temperature, relative humidity, and GEM indicates that emissions from local industrial plants in the Mumbai coastal area. Principal component analysis (PCA) and cluster analysis (CA) confirm this fact. Monthly back trajectory analysis showed that air mass flows are predominantly from the Arabian Sea and local human activities. Assessment of human health risks by USEPA model reveals that the hazardous quotient, HQ < 1, implies negligible carcinogenic risk. GEM observations in Mumbai during the study period are below the World Health Organization's (WHO) safe limit (200 ng/m3) for long-term inhalation.

Synthesis of ultra-high molecular weight homo- and copolymers via an ultrasonic emulsion process with a fast rate.

In the forefront of advanced materials, ultra-high molecular weight (UHMW) polymers, renowned for their outstanding mechanical properties, have found extensive applications across various domains. However, their production has encountered a significant challenge: the attainment of UHMW polymers with a low dispersity (Ɖ). Herein, we introduce the pioneering technique of ultrasound (US) initiated polymerization, which has garnered attention for its capability to successfully polymerize a multitude of monomers. This study showcases the synthesis of UHMW polymers with a comparatively low Ɖ ( ≤ 1.1) within a remarkably short duration ( ~ 15 min) through the amalgamation of emulsion polymerization and high-frequency ultrasound-initiated polymerization. Particularly noteworthy is the successful copolymerization of diverse monomers, surpassing the molecular weight and further narrowing the Ɖ compared to their respective homopolymers. Notably, this includes monomers like vinyl acetate, traditionally deemed unsuitable for controlled polymerization. The consistent production and uniform dispersion of radicals during ultrasonication have been identified as key factors facilitating the swift fabrication of UHMW polymers with exceptionally low Ɖ.

Neutrophil lymphocyte ratio and heart type fatty acid binding protein as a prognostic marker in Myocardial infarction within 48 h of admission.

BACKGROUND: The neutrophil to lymphocyte ratio (NLR) is a measure of systemic inflammation, whereas Heart type fatty acid protein (HFABP) is a cytosolic protein released early after acute coronary syndrome (ACS). The aim of this research study is to determine whether NLR and H-FAB are useful in predicting the prognosis in patients with ST segment elevation myocardial infarction (STEMI) 48 h after admission. This is a prospective observational study conducted on 97 patients who had been admitted to emergency room with ST-elevation myocardial infarction in their ECG in a tertiary care centre of south India. The neutrophil-lymphocyte ratio was measured at the time of admission, 24th hour and 48th hour, and then compared with the outcome. To determine their significance in the MI episode, troponin-I and H-FABP were also measured. RESULTS: A significant correlation was found in the final outcomes of patients and the NLR at the time of admission and at 48 h (p = 0.01). Additionally, a substantial correlation between NLR and various degrees of LV dysfunction was also observed (p = 0.01). H-FABP was found to be positive in all 97 of the patients examined, whereas Troponin-I was only found to be positive in 56.7%. CONCLUSION: The study's findings, indicated strong correlations between NLR and LVEF, indicated that NLR might serve as an early predictor of cardiac events which could be either poor prognosis or higher mortality. This research found that H-FABP may serve as an early MI diagnostic marker.

Critical appraisal of machine learning prognostic models for acute pancreatitis: protocol for a systematic review.

Acute pancreatitis (AP) is an acute inflammatory disorder that is common, costly, and is increasing in incidence worldwide with over 300,000 hospitalizations occurring yearly in the United States alone. As its course and outcomes vary widely, a critical knowledge gap in the field has been a lack of accurate prognostic tools to forecast AP patients' outcomes. Despite several published studies in the last three decades, the predictive performance of published prognostic models has been found to be suboptimal. Recently, non-regression machine learning models (ML) have garnered intense interest in medicine for their potential for better predictive performance. Each year, an increasing number of AP models are being published. However, their methodologic quality relating to transparent reporting and risk of bias in study design has never been systematically appraised. Therefore, through collaboration between a group of clinicians and data scientists with appropriate content expertise, we will perform a systematic review of papers published between January 2021 and December 2023 containing artificial intelligence prognostic models in AP. To systematically assess these studies, the authors will leverage the CHARMS checklist, PROBAST tool for risk of bias assessment, and the most current version of the TRIPOD-AI. (Research Registry ( http://www.reviewregistry1727 .).

Co-relation of Portal Vein Tumour Thrombus Response With Survival Function Following Robotic Radiosurgery in Vascular Invasive Hepatocellular Carcinoma.

Background/aims: The aim of this study was to prospectively evaluate stereotactic body radiotherapy (SBRT) with robotic radiosurgery in hepatocellular carcinoma patients with macrovascular invasion (HCC-PVT). Materials and methods: Patients with inoperable HCC-PVT, good performance score (PS0-1) and preserved liver function [up to Child-Pugh (CP) B7] were accrued after ethical and scientific committee approval [Clinical trial registry-India (CTRI): 2022/01/050234] for treatment on robotic radiosurgery (M6) and planned with Multiplan (iDMS V2.0). Triple-phase contrast computed tomography (CT) scan was performed for contouring, and gross tumour volume (GTV) included contrast-enhancing mass within main portal vein and adjacent parenchymal disease. Dose prescription was as per risk stratification protocol (22-50 Gy in 5 fractions) while achieving the constraints of mean liver dose <15 Gy, 800 cc liver <8 Gy and the duodenum max of <24 Gy). Response assessment was done at 2 months' follow-up for recanalization. Patient- and treatment-related factors were evaluated for influence in survival function. Results: Between Jan 2017 and May 2022, 318 consecutive HCC with PVT patients were screened and 219 patients were accrued [male 92%, CP score: 5-7 90%, mean age: 63 years (38-85 yrs), Cancer of the Liver Italian Program <3: 84 (40%), 3-6117 (56%), infective aetiology 9.5%, performance status (PS): 0-37%; 1-56%]. Among 209 consecutive patients accrued for SBRT treatment (10 patients were excluded after accrual due to ascites and decompensation), 139 were evaluable for response assessment (>2 mo follow-up). At mean follow-up of 12.21 months (standard deviation: 10.66), 88 (63%) patients expired and 51 (36%) were alive. Eighty-two (59%) patients had recanalization of PVT (response), 57 (41%) patients did not recanalize and 28 (17%) had progressive/metastatic disease prior to response evaluation (<2 months). Mean overall survival (OS) in responders and non-responders were 18.4 [standard error (SE): 2.52] and 9.34 month (SE 0.81), respectively (P < 0.001). Mean survival in patients with PS0, PS1 and PS2 were 17, 11.7 and 9.7 months (P = 0.019), respectively. OS in partial recanalization, bland thrombus and complete recanalization was 12.4, 14.1 and 30.3 months, respectively (P-0.002). Adjuvant sorafenib, Barcelona Clinic Liver Classification stage, gender, age and RT dose did not influence response to treatment. Recanalization rate was higher in good PS patients (P-0.019). OS in patients with response to treatment, in those with no response to treatment, in those who are fit but not accrued and in those who are not suitable were 18.4, 9.34, 5.9 and 2.6 months, respectively (P-<0.001). Thirty-six of 139 patients (24%) had radiation-induced liver disease (RILD) [10 (7.2%) had classic RILD & 26 (19%) had non-classic RILD]. Derangement in CP score (CP score change) by more than 2 was seen in 30 (24%) within 2-month period after robotic radiosurgery. Eighteen (13%) had unplanned admissions, two patients required embolization due to fiducial-related bleeding and 20 (14%) had ascites, of which 9 (6%) patients required abdominocentesis. Conclusion: PVT response or recanalization after SBRT is a statistically significant prognostic factor for survival function in HCC-PVT.

Provider-ordered viral testing and antibiotic administration practices among children with acute respiratory infections across healthcare settings in Nashville, Tennessee.

Objective: Evaluate the association between provider-ordered viral testing and antibiotic treatment practices among children discharged from an ED or hospitalized with an acute respiratory infection (ARI). Design: Active, prospective ARI surveillance study from November 2017 to February 2020. Setting: Pediatric hospital and emergency department in Nashville, Tennessee. Participants: Children 30 days to 17 years old seeking medical care for fever and/or respiratory symptoms. Methods: Antibiotics prescribed during the child's ED visit or administered during hospitalization were categorized into (1) None administered; (2) Narrow-spectrum; and (3) Broad-spectrum. Setting-specific models were built using unconditional polytomous logistic regression with robust sandwich estimators to estimate the adjusted odds ratios and 95% confidence intervals between provider-ordered viral testing (ie, tested versus not tested) and viral test result (ie, positive test versus not tested and negative test versus not tested) and three-level antibiotic administration. Results: 4,107 children were enrolled and tested, of which 2,616 (64%) were seen in the ED and 1,491 (36%) were hospitalized. In the ED, children who received a provider-ordered viral test had 25% decreased odds (aOR: 0.75; 95% CI: 0.54, 0.98) of receiving a narrow-spectrum antibiotic during their visit than those without testing. In the inpatient setting, children with a negative provider-ordered viral test had 57% increased odds (aOR: 1.57; 95% CI: 1.01, 2.44) of being administered a broad-spectrum antibiotic compared to children without testing. Conclusions: In our study, the impact of provider-ordered viral testing on antibiotic practices differed by setting. Additional studies evaluating the influence of viral testing on antibiotic stewardship and antibiotic prescribing practices are needed.

The Impact of Health Care Algorithms on Racial and Ethnic Disparities : A Systematic Review.

BACKGROUND: There is increasing concern for the potential impact of health care algorithms on racial and ethnic disparities. PURPOSE: To examine the evidence on how health care algorithms and associated mitigation strategies affect racial and ethnic disparities. DATA SOURCES: Several databases were searched for relevant studies published from 1 January 2011 to 30 September 2023. STUDY SELECTION: Using predefined criteria and dual review, studies were screened and selected to determine: 1) the effect of algorithms on racial and ethnic disparities in health and health care outcomes and 2) the effect of strategies or approaches to mitigate racial and ethnic bias in the development, validation, dissemination, and implementation of algorithms. DATA EXTRACTION: Outcomes of interest (that is, access to health care, quality of care, and health outcomes) were extracted with risk-of-bias assessment using the ROBINS-I (Risk Of Bias In Non-randomised Studies - of Interventions) tool and adapted CARE-CPM (Critical Appraisal for Racial and Ethnic Equity in Clinical Prediction Models) equity extension. DATA SYNTHESIS: Sixty-three studies (51 modeling, 4 retrospective, 2 prospective, 5 prepost studies, and 1 randomized controlled trial) were included. Heterogenous evidence on algorithms was found to: a) reduce disparities (for example, the revised kidney allocation system), b) perpetuate or exacerbate disparities (for example, severity-of-illness scores applied to critical care resource allocation), and/or c) have no statistically significant effect on select outcomes (for example, the HEART Pathway [history, electrocardiogram, age, risk factors, and troponin]). To mitigate disparities, 7 strategies were identified: removing an input variable, replacing a variable, adding race, adding a non-race-based variable, changing the racial and ethnic composition of the population used in model development, creating separate thresholds for subpopulations, and modifying algorithmic analytic techniques. LIMITATION: Results are mostly based on modeling studies and may be highly context-specific. CONCLUSION: Algorithms can mitigate, perpetuate, and exacerbate racial and ethnic disparities, regardless of the explicit use of race and ethnicity, but evidence is heterogeneous. Intentionality and implementation of the algorithm can impact the effect on disparities, and there may be tradeoffs in outcomes. PRIMARY FUNDING SOURCE: Agency for Healthcare Quality and Research.

Associations between Child Opportunity Index and Pediatric Cardiac Surgical Outcomes.

OBJECTIVE: To assess the relationship between the Child Opportunity Index (COI), a comprehensive measurement of social determinants of health, and specific COI domains on patient-specific outcomes following congenital cardiac surgery in the metropolitan region of Atlanta, Georgia. STUDY DESIGN: In this retrospective chart review, we included patients who underwent an index operation for congenital heart disease between 2010 and 2020 in a single pediatric health care system. Patients' addresses were geocoded and mapped to census tracts. Descriptive statistics, univariable analysis, and multivariable regression models were employed to assess associations between variables and outcomes. RESULTS: Of the 7460 index surgeries, 3798 (51%) met eligibility criteria. Presence of an adverse outcome, defined as either mortality or 1 of several other major postoperative morbidities, was significantly associated with COI in the univariable model (P = .008), but not the multivariable regression model (P = .39). Postoperative hospital length of stay was significantly associated with COI (P < .001) in univariable and multivariable regression models. There was no significant association between COI and readmission within 30 days of hospital discharge in univariable (P < .094) and multivariable (P = .49) models. CONCLUSION: COI is associated with postoperative hospital length of stay but not all outcomes in patients after congenital heart surgery. By understanding the role of COI in outcomes related to cardiac surgery, targeted interventions can be developed to improve health equity.

Designing a New Class of Mechanophoric Polymer Based on Epoxy-Functionalized Rhodamine Derivative.

Mechanophoric polymers are an interesting class of smart polymers which contains a special force-sensitive molecular motif that can lead to a chemical change within the polymer network in response to mechanical force. This investigation reports the design of a mechanophoric polymer based on epoxy-functionalized rhodamine via a monomeric approach. In this case, rhodamine (Rh) is modified with glycidyl methacrylate (GMA) through an epoxy-amine reaction to design a vinyl-functionalized multi-armed macromonomer (Rh-GMA), which is reacted with butyl acrylate (BA) to prepare the crosslinked polymeric film. The crosslinked polymeric film demonstrates mechanophoric properties under UV and stretching conditions.

Antimicrobial Stewardship and Improved Antibiotic Utilization in the Pediatric Cardiac Intensive Care Unit.

Background: We developed a multidisciplinary antimicrobial stewardship team to optimize antimicrobial use within the Pediatric Cardiac Intensive Care Unit. A quality improvement initiative was conducted to decrease unnecessary broad-spectrum antibiotic use by 20%, with sustained change over 12 months. Methods: We conducted this quality improvement initiative within a quaternary care center. PDSA cycles focused on antibiotic overuse, provider education, and practice standardization. The primary outcome measure was days of therapy (DOT)/1000 patient days. Process measures included electronic medical record order-set use. Balancing measures focused on alternative antibiotic use, overall mortality, and sepsis-related mortality. Data were analyzed using statistical process control charts. Results: A significant and sustained decrease in DOT was observed for vancomycin and meropenem. Vancomycin use decreased from a baseline of 198 DOT to 137 DOT, a 31% reduction. Meropenem use decreased from 103 DOT to 34 DOT, a 67% reduction. These changes were sustained over 24 months. The collective use of gram-negative antibiotics, including meropenem, cefepime, and piperacillin-tazobactam, decreased from a baseline of 323 DOT to 239 DOT, a reduction of 26%. There was no reciprocal increase in cefepime or piperacillin-tazobactam use. Key interventions involved electronic medical record changes, including automatic stop times and empiric antibiotic standardization. All-cause mortality remained unchanged. Conclusions: The initiation of a dedicated antimicrobial stewardship initiative resulted in a sustained reduction in meropenem and vancomycin usage. Interventions did not lead to increased utilization of alternative broad-spectrum antimicrobials or increased mortality. Future interventions will target additional broad-spectrum antimicrobials.

Associations of plasma omega-6 and omega-3 fatty acids with overall and 19 site-specific cancers: a population-based cohort study in UK Biobank.

Background: Previous epidemiological studies of the associations between polyunsaturated fatty acids (PUFAs) and cancer incidence have been inconsistent. We investigated the associations of plasma omega-3 and omega-6 PUFAs with the incidence of overall and 19 site-specific cancers in a large prospective cohort. Methods: 253,138 eligible UK Biobank participants were included in our study. With a mean follow-up of 12.9 years, 29,838 participants were diagnosed with cancer. The plasma levels of omega-3 and omega-6 PUFAs were expressed as percentages of total fatty acids (omega-3% and omega-6%). Results: In our main models, both omega-6% and omega-3% were inversely associated with overall cancer incidence (HR per SD = 0.98, 95% CI = 0.96-0.99; HR per SD = 0.99, 95% CI = 0.97-1.00; respectively). Of the 19 site-specific cancers available, 14 were associated with omega-6% and five with omega-3%, all indicating inverse associations, with the exception that prostate cancer was positively associated with omega-3% (HR per SD = 1.03, 95% CI = 1.01 - 1.05). Conclusions: Our population-based cohort study in UK Biobank indicates small inverse associations of plasma omega-6 and omega-3 PUFAs with the incidence of overall and most site-specific cancers, although there are notable exceptions, such as prostate cancer.

Enhanced durability and evolution of retreatment criteria of intravitreal antivascular endothelial growth factor agents for diabetic macular edema.

PURPOSE OF REVIEW: The increasing prevalence of diabetic macular edema (DME) necessitates an updated review of treatment modalities. While the shift from laser to anti-vascular endothelial growth factor (anti-VEGF) therapy has transformed patient outcomes, benefits of these agents are not fully realized in real-world implementation relative to the setting of controlled clinical trials. This review outlines the evolution of intravitreal anti-VEGF treatment extension protocols for DME that reflect efforts to address treatment adherence challenges while optimizing visual outcomes. RECENT FINDINGS: Recent studies highlight the efficacy of extended-interval dosing with anti-VEGF agents in managing DME. Trials such as RISE/RIDE, VISTA/VIVID, and LUCIDATE have established the foundation of these regimens by demonstrating sustained visual gains with continuous treatment. However, newer trials including PROTOCOL T, KESTREL/KITE, YOSEMITE/RHINE, and PHOTON have furthered this concept, revealing that less frequent dosing of various anti-VEGF agents can maintain similar visual acuity and anatomical outcomes to traditional monthly injections. SUMMARY: The reviewed findings suggest a paradigm shift in DME treatment toward less frequent anti-VEGF injections. This has significant implications for clinical practice, potentially leading to greater adherence to treatment regimens and sustained visual function in patients, while minimizing treatment burden and healthcare costs. Further investigation into the long-term effects of extended dosing intervals is required.

Principal Component Patterns of Pediatric Respiratory Viral Testing Across Health Care Settings.

BACKGROUND AND OBJECTIVES: Factors prompting clinicians to request viral testing in children are unclear. We assessed patterns prompting clinicians to perform viral testing in children discharged from an emergency department (ED) or hospitalized with an acute respiratory infection (ARI). METHODS: Using active ARI surveillance data collected from November 2017 through February 2020, children aged between 30 days and 17 years with fever or respiratory symptoms who had a research respiratory specimen tested were included. Children's presentation patterns from their initial evaluation at each health care setting were analyzed using principal components (PCs) analysis. PC-specific models using logistic regression with robust sandwich estimators were used to estimate odds ratios (ORs) and 95% confidence intervals (CIs) between PCs and provider-ordered viral testing. PCs were assigned respiratory virus/viruses names a priori based on the patterns represented. RESULTS: In total, 4107 children were enrolled and tested, with 2616 (64%) discharged from the ED and 1491 (36%) hospitalized. In the ED, children with a coviral presentation pattern had a 1.44-fold (95% CI, 1.24-1.68) increased odds of receiving a provider-ordered viral test than children showing clinical symptoms less representative of coviral-like infection. Whereas children in the ED and hospitalized with rhinovirus-like symptoms had 71% (OR, 0.29; 95% CI, 0.24-0.34) and 39% (OR, 0.61; 95% CI, 0.49-0.76) decreased odds, respectively, of receiving a provider-ordered viral test during their medical encounter. CONCLUSIONS: Viral tests are frequently ordered by clinicians, but presentation patterns vary by setting and influence the initiation of testing. Additional assessments of factors affecting provider decisions to use viral testing in pediatric ARI management are needed to maximize patient benefits of testing.