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Delayed IL-17RA signaling in early life promotes type I interferon/CXCL10-dependent inhibition of pneumococcal clearance

Idowu, Teniola; Fecko, Daniel P; Eichner, Hannes; Bee, Gavyn Chern Wei; Knoop, Kathryn A; Weiser, Jeffrey N; Lokken-Toyli, Kristen L
Early life is characterized by heightened susceptibility to respiratory pathogens, yet the immune mechanisms that predispose infants to infection remain poorly defined. Using an infant mouse model of Streptococcus pneumoniae (Spn) colonization, we identify an age-dependent delay in IL-17 A production that was associated with prolonged bacterial colonization in infant mice. Consistent with a critical role for this pathway, IL-17 receptor A (IL-17RA)-deficient infant mice exhibited persistent Spn colonization of the upper respiratory tract (URT). Transcriptomic profiling of the URT from Spn-colonized IL-17RA-deficient infant mice revealed an enrichment of antiviral responses compared to WT controls and included increased expression of the interferon-stimulated gene Cxcl10, a chemokine whose expression is positively associated with Spn carriage in humans. These results suggested that IL-17RA signaling constrains the interferon response during URT Spn colonization. WT infant mice exhibited progressively increased expression of Cxcl10 during Spn colonization and was dependent on type 1 interferon (IFNAR1) signaling and the pore forming bacterial toxin, pneumolysin. Genetic deletion of Ifnar1 or Cxcl10, including myeloid cell-specific deletion of Ifnar1, accelerated bacterial clearance in infant mice. In contrast, adult mice exhibited earlier induction of IL-17 A, minimal induction of Cxcl10 expression, and no alteration in bacterial clearance rates following Ifnar1 or Cxcl10 deficiency. Taken together, our results reveal a developmental window in which delayed IL-17 A production postpones the IL-17RA-dependent restraint of the type I interferon/CXCL10 axis, thereby prolonging pneumococcal carriage through impaired myeloid cell-mediated bacterial clearance.
PMID: 42575316
ISSN: 1935-3456
CID: 6071219

Infrared drying characteristics of locust (L. migratoria): physical and techno-functional characterization of locust powder

Barutçu Mazı, Işıl; Mazı, Bekir Gökçen; Sevgili, Hasan
This study examined some physical and techno-functional properties of locust (Locusta migratoria) powder produced by infrared drying at temperatures of 60, 70, and 80 °C. Water activity, pH, Carr's index, Hausner ratio, water holding capacity (WHC), oil holding capacity (OHC), and color parameters of the powders were measured. In addition, infrared drying kinetics were analyzed. Increasing the drying temperature from 60 to 80 °C resulted in a 2.8-fold reduction in drying time, without causing significant changes in the measured properties. Except for WHC, the properties of infrared-dried powders were comparable to those of freeze-dried powder. WHC (2.1-2.3 g water/g) of infrared-dried powders was lower than that of the freeze-dried powder (3.3 g water/g). The locust powder exhibited poor flowability. Drying occurred in the falling rate period, with the Page model best describing the drying behavior. Effective moisture diffusivity (D eff) ranged from 1.17 × 10-10 to 10.9 × 10-7 m2/s, and the activation energy was calculated as 53.81 kJ/mol. The influence of drying temperature on the drying rate was most pronounced during the early stages of drying. Overall, infrared drying, with its shorter processing time, appears to be a promising alternative for the production of locust powder.
PMCID:13476408
PMID: 42603939
ISSN: 0022-1155
CID: 6071201

Respectful Care and Safe Reduction of NTSV Cesarean Delivery Through Standardized QI Interventions at New York University Long Island

Alku, Dajana; Maldonado, Delphina; Eliner, Yael; Russelman, Marie; Walter, Katherine; Gianunzio, Jennifer; Sicuranza, Genevieve; Peskin-Stolze, Melissa; Suhag, Anju
OBJECTIVE:Cesarean delivery (CD) remains a key obstetric quality metric, particularly among nulliparous, term, singleton, vertex (NTSV) pregnancies. In 2024, NTSV CD rate at NYU-LI was 32.9%, exceeding The Joint Commission (TJC) benchmark of ≤30% and demonstrating racial and ethnic disparities. This study aimed to reduce the institutional NTSV CD rate to ≤30% through a multidisciplinary QI initiative while prospectively monitoring safety outcomes and racial disparities. STUDY DESIGN/METHODS:A single-site QI initiative was implemented from 2024-2025 incorporating provider education, patient-centered interventions (TeamBirth and structured labor huddles), standardized labor management, and performance monitoring through monthly case review, clinician feedback, and quarterly equity-focused data review. Outcome measures included monthly overall and quarterly race- and ethnicity-stratified NTSV CD rates. Process measures assessed adherence to evidence-based labor dystocia criteria. Balancing measures included postpartum hemorrhage (PPH) and TJC PC-06 rates. Temporal trends were evaluated using multivariable Poisson regression with adjustment for maternal age, gestational age at delivery, and body mass index. RESULTS:The overall NTSV CD rate decreased from 32.9% in 2024 to 27.8% in 2025, remaining below TJC benchmark in 10 of 12 months. Across the 8-quarter study period, there was a significant decline in the outcome over time (aRR per quarter 0.97, 95% CI 0.95-0.99, p=0.003). Reductions were observed across racial and ethnic groups, including among Black non-Hispanic patients (44.0% to 40.0%) and Asian non-Hispanic patients (37.0% to 29.6%). Adherence to evidence-based labor dystocia criteria remained high, while PPH and PC-06 rates remained stable. CONCLUSIONS:A standardized, multidisciplinary QI initiative was associated with NTSV cesarean delivery rate below the Joint Commission benchmark without increases in maternal or neonatal adverse outcomes. The initiative was also associated with partial reduction in racial disparities in cesarean delivery rates, although persistent inequities remained. Future PDSA cycles will focus on sustaining standardized care and advancing equitable obstetric outcomes.
PMID: 42575496
ISSN: 1098-8785
CID: 6071222

Long-Term Home Storage of Autologous Serum Eye Drops

Waitz, Grit; Sakor, Ibrahim Alhaj; Bergmann-Ewert, Wendy; Thiele, Thomas
INTRODUCTION/UNASSIGNED:Autologous serum eye drops (ASEDs) are used to treat patients with dry eye syndrome. ASED is manufactured by fractionation of autologous whole blood of concerned patients and usually stored under home freezing conditions. METHODS/UNASSIGNED:We analyzed sterility, particle number, protein concentration, and stability of 14 growth factors in ASED for 148 days at -10°C. RESULTS/UNASSIGNED:Total protein concentration was constant showing no significant degradation as assessed by 1D-SDS-PAGE. Slightly increased concentrations of angiopoietin-2, vascular endothelial growth factor, platelet-derived growth factor, and hepatocyte growth factor were observed, while stem cell factor concentration showed only a modest decrease. CONCLUSION/UNASSIGNED:Our data support the feasibility to store ASED for patient use under usual home freezing conditions for up to 148 days.
PMCID:13476086
PMID: 42602779
ISSN: 1660-3796
CID: 6071194

First-in-Class Immuno-Oncology Drug APG157DS Repolarizes Innate Immune Cells and Induces Durable Remission in a Syngeneic Glioblastoma Model

Mohapatra, Shubhasmita; Guerrero, Adrian; Rahman, Neha; Markovic, Stefan; O'Donnell, Lauren; Wadghiri, Youssef Zaim; Zaman, Khondoker Takia; Avila, Luis; Mehta, Parag; Banerjee, Probal
APG157DS is a multi-component investigational drug which is currently the subject of multiple cancer trials. It has shown promising efficacy in patients with head and neck cancer. We report its immuno-modulatory effect in a syngeneic mouse model of glioblastoma (GBM). Long-term treatment with APG157DS led to durable tumor remission in 50% of mice, while all vehicle-treated mice reached humane endpoints within 42 days. Mechanistically, the drug induced selective repolarization of tumor-associated macrophages (TAMs) from an immunosuppressive Arg1high/iNOSlow phenotype to a tumoricidal Arg1low/iNOShigh state, accompanied by increased intratumoral recruitment of activated (NKp46+) natural killer cells and CD8+ cytotoxic T-cells. APG157DS also suppressed vascular endothelial growth factor (VEGF) and Hypoxia-inducible factor 1-alpha (HIF-1α) expression in tumors, further impairing tumor growth. Notably, APG157DS did not elicit off-target macrophage activation in peripheral tissues such as the spleen, highlighting its selective immune targeting. These findings provide a mechanistic rationale for further clinical development of APG157DS in GBM and potentially other immune-evasive cancers.
PMCID:13466085
PMID: 42589344
ISSN: 1422-0067
CID: 6071271

Redefining Progression in a Rapidly Evolving Therapeutic Landscape

Vasan, Neil
PMID: 42593813
ISSN: 2374-2445
CID: 6071288

EUS-guided gastroenterostomy for benign gastric outlet obstruction: Clinical and technical outcomes from a multicenter cohort study

Rizvi, Anam; Hassan, Kamal; Johnson, Kate; Khashab, Mouen A; Fayyaz, Farimah; Al Mardini, Michel; Samanta, Jayanta; Dhar, Jahnvi; Larghi, Alberto; Robles-Medranda, Carlos; Alcivar Vasquez, Juan; Arevalo, Martha; Forti, Edoardo; Cottone, Irene; Vargas, Jorge; Sethi, Amrita; Visrodia, Kavel; Dawod, Enad; Hanscom, Mark; Sampath, Kartik; Mahadev, Srihari; Carr-Locke, David L; Baqain, Laith Eyad; Sharaiha, Reem Z; ,
BACKGROUND AND STUDY AIMS/UNASSIGNED:Endoscopic ultrasound-guided gastroenterostomy (EUS-GE) is emerging as a minimally invasive alternative for benign gastric outlet obstruction (GOO). This study evaluated its safety, efficacy, and long-term outcomes. PATIENTS AND METHODS/UNASSIGNED:This international, multicenter retrospective study included 72 patients who underwent EUS-GE for benign GOO across 13 centers. Clinical success was defined as ability to tolerate solid food based on the GOO scoring system. Secondary outcomes included technical success and adverse events (AEs). RESULTS/UNASSIGNED:< 0.00001). Mean time to oral intake was 20.1 hours. AEs were mild,occurring in 6% intra-procedurally and 10% post-procedurally. Mean follow-up duration was 426.3 days. CONCLUSIONS/UNASSIGNED:EUS-GE demonstrates high technical and clinical success rates with a favorable safety profile for benign GOO, offering a promising alternative to traditional surgical approaches.
PMCID:13077228
PMID: 41988024
ISSN: 2364-3722
CID: 6071166

A National survey of pediatric surgical care coverage models to outlying neonatal intensive care units

Acker, Shannon N; Wolf, Lindsey L; Fisher, Jason; Schermerhorn, Sophia M V; Ignacio, Romeo C; Moriarty, Kevin; Weiss, Richard; Lao, Oliver B; Ahmed, Hira; Gourlay, David; Raval, Mehul V; Rich, Barrie S; ,
BACKGROUND:The delivery of pediatric surgical care to newborns varies based on neonatal intensive care unit (NICU) coverage. We aimed to describe the current national coverage landscape and assess pediatric surgeons' perspectives on the optimal management of infants at outlying NICUs. METHODS:The AAP Delivery of Surgical Care Committee administered a web-based survey to pediatric surgery division chiefs at Children's Hospital Association practices. Responses were analyzed using appropriate nonparametric and categorical statistical tests, with significance set at p<0.05. RESULTS:Fifty-two division chiefs responded (28.9%); 26 (50% reporting covering one or more outlying NICUs. Of these outlying NICUS, 76% were Level III. Just over half (51%) had no affiliation with the surgeons' primary hospital. Case volumes were low, with only 5 NICUs (15%) performing more than 25 operations annually. Factors influencing decisions to operate at outlying NICUs included rapport with neonatologists, NICU level designation, transfer capability, and availability of pediatric anesthesiology. The capacity of outlying NICUs to care for infants with index surgical diagnoses varied based on specific diagnosis. Over half of respondents endorsed transfer to the primary center as the optimal location for care for all procedures except gastrostomy tube placement and central venous access. CONCLUSION/CONCLUSIONS:Half of surveyed pediatric surgery groups provide coverage to one or more outlying NICUs despite low reported case volumes. A clear disconnect exists between pediatric surgeons' views on location for optimal care and sites of current care provision. These findings underscore the need for regionalized strategies to optimize surgical care of these infants.
PMID: 42595044
ISSN: 1531-5037
CID: 6071295

Effects of distinct food preservation methods on the bioactive content and antioxidant capacity of tucumã-do-Amazonas (Astrocaryum aculeatum)

Daleaste, Luana Teixeira; Soares, Lucas de Souza; Argandoña, Eliana Janet Sanjinez; Nascimento, Roberto de Paula do; Filgueiras, Cristina Tostes; Machado, Ana Paula da Fonseca
Tucumã-do-Amazonas (Astrocaryum aculeatum) is a fruit from the Brazilian Amazon with a high potential for processing and bioactive compound extraction. Understanding the chemical composition of different tucumã-processed crops may help create and improve high-quality and safe food products for industrial and health-related purposes. However, studies addressing how preservation methods affect tucumã's bioactive qualities are still lacking. Therefore, this study aimed to compare the bioactive composition and antioxidant capacity of tucumã pulp subjected to four preservation methods convective drying, freeze-drying, acidified preserve, and jelly preparation, with fresh and blanched pulp as controls. Carotenoid content ranged from 26.62 to 557.90 µg/g, total phenolic compounds from 10.01 to 48.54 mg/g, and flavonoids from 0.073 to 0.596 mg/g. Antioxidant activity values were 67.29-215.81 (FRAP) and 0.073-0.596 (ABTS method) µmol of Trolox equivalent/g. Convective drying and freeze-drying preserved carotenoids best, at 101.92% and 77.17% of fresh control levels. Polyphenols were well preserved by freeze-drying and acidified preserve at 137.39% and 80.81% when compared to fresh pulp. Pearson's correlation indicated a strong relationship (r = 0.858-0.931) between total polyphenols, flavonoids, and antioxidant capacity. Preservation methods significantly affected the bioactive compound levels and antioxidant capacity and these results emphasize the potential of tucumã-do-Amazonas pulp for significant bioactive compound extraction.
PMCID:13476202
PMID: 42603871
ISSN: 0022-1155
CID: 6071199

The International Olympic Committee advances a second Consensus Statement on Mental Health in Elite Athletes [Editorial]

Hainline, Brian; Gouttebarge, Vincent; Kroshus-Havril, Emily; Reardon, Claudia L
PMID: 42580853
ISSN: 1473-0480
CID: 6071239