Curr Probl Diagn Radiol
April 2024
Objective: The purpose of this research is to more precisely quantify the positivity rate for conventional radiographs (CR) of the orbit performed for the purpose of pre-MR screening in patients at risk of having a radio-opaque orbital foreign body (ROFB).
Methods: By review of electronic medical records, we identified 47,237 patients who had undergone orbital CR for clearance of ROFB prior to MRI. The reports from these examinations were manually reviewed, and the examinations with positive findings were re-interpreted by a CAQ-certified head and neck radiologist.
Curr Probl Pediatr Adolesc Health Care
August 2023
Quality Improvement (QI) knowledge and skills are required at all levels of physician training. System improvement efforts need to include understanding of health disparities and design of interventions to reduce those disparities, thus health equity needs to be integrated into QI education. Payors, accreditation bodies and health systems' emphases on QI result in the need for QI curricula that meet the needs of diverse learners.
View Article and Find Full Text PDFBackground/purpose: Neoadjuvant chemotherapy (NAC) is gaining popularity over a surgery-first (SF) approach in treating resectable and borderline resectable pancreatic ductal adenocarcinoma (PDAC). However, what constitutes effective neoadjuvant chemotherapy is unknown.
Methods: We retrospectively analyzed resectable and borderline resectable PDAC patients who underwent pancreaticoduodenectomy (2010-2019) at a single institution.
Background: Activities and inhibition of the Renin-Angiotensin-Aldosterone System (RAAS) may affect the survival of resected pancreatic ductal adenocarcinoma (PDAC) patients METHOD: A single-institution retrospective analysis of resected PDAC patients between 2010 and 2019. To estimate the effect of angiotensin system inhibitors (ASIs) on patient survival, we performed Kaplan Meier analysis, Cox Proportional Hazards model, Propensity Score Matching (PSM), and inverse probability weighting (IPW) analysis.
Results: 742 patients were included in the analysis.
T cells are critical mediators of antitumor immunity and a major target for cancer immunotherapy. Antibody blockade of inhibitory receptors such as PD-1 can partially restore the activity of tumor-infiltrating lymphocytes (TILs). However, the activation signals required to promote TIL responses are less well characterized.
View Article and Find Full Text PDFTranscriptional coregulators, which mediate chromatin-dependent transcriptional signaling, represent tractable targets to modulate tumorigenic gene expression programs with small molecules. Genetic loss-of-function studies have recently implicated the transcriptional coactivator, ENL, as a selective requirement for the survival of acute leukemia and highlighted an essential role for its chromatin reader YEATS domain. Motivated by these discoveries, we executed a screen of nearly 300,000 small molecules and identified an amido-imidazopyridine inhibitor of the ENL YEATS domain (IC = 7 μM).
View Article and Find Full Text PDFSchool-based guidelines often require that treatment focuses on minimizing or eliminating stuttered speech. The purpose of this study was to examine the benefits of explicit training in communication competencies to children who stutter without targeting stuttered speech. Thirty-seven children (ages 4-16) completed Camp Dream.
View Article and Find Full Text PDFScurvy is a rare disease in developed nations. In the field of pediatrics, it primarily is seen in children with developmental and behavioral issues, malabsorptive processes, or diseases involving dysphagia. We present the case of an otherwise developmentally appropriate 4-year-old boy who developed scurvy after gradual self-restriction of his diet.
View Article and Find Full Text PDFProc Natl Acad Sci U S A
November 2018
Chimeric antigen receptor (CAR) T cells with a long-lived memory phenotype are correlated with durable, complete remissions in patients with leukemia. However, not all CAR T cell products form robust memory populations, and those that do can induce chronic B cell aplasia in patients. To address these challenges, we previously developed a switchable CAR (sCAR) T cell system that allows fully tunable, on/off control over engineered cellular activity.
View Article and Find Full Text PDFObjective: Pancreatic ductal adenocarcinoma (PDAC) is a disease of unmet medical need. While immunotherapy with chimeric antigen receptor T (CAR-T) cells has shown much promise in haematological malignancies, their efficacy for solid tumours is challenged by the lack of tumour-specific antigens required to avoid on-target, off-tumour effects. Switchable CAR-T cells whereby activity of the CAR-T cell is controlled by dosage of a tumour antigen-specific recombinant Fab-based 'switch' to afford a fully tunable response may overcome this translational barrier.
View Article and Find Full Text PDFPurpose: The purpose of the present study was to explore the clinical utility of self-disclosure, particularly, whether disclosing in an informative manner would result in more positive observer ratings of the speaker who stutters than either disclosing in an apologetic manner or choosing not to self-disclose at all.
Method: Observers (N=338) were randomly assigned to view one of six possible videos (i.e.
The treatment of patients with acute myeloid leukemia (AML) with targeted immunotherapy is challenged by the heterogeneity of the disease and a lack of tumor-exclusive antigens. Conventional immunotherapy targets for AML such as CD33 and CD123 have been proposed as targets for chimeric antigen receptor (CAR)-engineered T-cells (CAR-T-cells), a therapy that has been highly successful in the treatment of B-cell leukemia and lymphoma. However, CD33 and CD123 are present on hematopoietic stem cells, and targeting with CAR-T-cells has the potential to elicit long-term myelosuppression.
View Article and Find Full Text PDFBronchiolitis is a common cause of outpatient visits and hospitalization in children younger than age 2 years. Despite the frequency with which pediatricians manage this diagnosis, there is significant variability in care in both the inpatient and outpatient setting. This may be due in part to changing guidelines set forth by leading pediatric organizations such as the American Academy of Pediatrics, as increasing evidence emerges that traditional therapies are not effective.
View Article and Find Full Text PDFPhosphodiesterase 4 (PDE4) inhibitors are approved for the treatment of some moderate to severe inflammatory conditions. However, dose-limiting side effects in the central nervous system and gastrointestinal tract, including nausea, emesis, headache, and diarrhea, have impeded the broader therapeutic application of PDE4 inhibitors. We sought to exploit the wealth of validation surrounding PDE4 inhibition by improving the therapeutic index through generation of an antibody-drug conjugate (ADC) that selectively targets immune cells through the CD11a antigen.
View Article and Find Full Text PDFAngew Chem Int Ed Engl
June 2016
Chimeric antigen receptor T (CAR-T) cells have demonstrated promising results against hematological malignancies, but have encountered significant challenges in translation to solid tumors. To overcome these hurdles, we have developed a switchable CAR-T cell platform in which the activity of the engineered cell is controlled by dosage of an antibody-based switch. Herein, we apply this approach to Her2-expressing breast cancers by engineering switch molecules through site-specific incorporation of FITC or grafting of a peptide neo-epitope (PNE) into the anti-Her2 antibody trastuzumab (clone 4D5).
View Article and Find Full Text PDFProc Natl Acad Sci U S A
January 2016
Chimeric antigen receptor T (CAR-T) cell therapy has produced impressive results in clinical trials for B-cell malignancies. However, safety concerns related to the inability to control CAR-T cells once infused into the patient remain a significant challenge. Here we report the engineering of recombinant antibody-based bifunctional switches that consist of a tumor antigen-specific Fab molecule engrafted with a peptide neo-epitope, which is bound exclusively by a peptide-specific switchable CAR-T cell (sCAR-T).
View Article and Find Full Text PDFCompetitive enzyme-linked immunosorbent assay was used to quantify the amounts of the neonicotinoids clothianidin and imidacloprid in Poa annua L. clippings from treated golf course fairways. Average clothianidin residues 7 d after application ranged from 674 to 1,550 ng/g tissue in 2012 and 455-2,220 ng/g tissue in 2013.
View Article and Find Full Text PDFUse of early ripening highbush blueberry cultivars to avoid infestation and mass trapping were evaluated for managing spotted wing drosophila, Drosophila suzukii (Matsumura). Fourteen highbush blueberry cultivars were sampled for spotted wing drosophila infestation. Most 'Earliblue', 'Bluetta', and 'Collins' fruit were harvested before spotted wing drosophila oviposition commenced, and so escaped injury.
View Article and Find Full Text PDFObjective: The aim of this study was to investigate the effect of chronic heart failure (HF; 16 weeks post left coronary artery ligation) on the brain's orexin (ORX) and related neuropeptide systems.
Methods: Indicators of cardiac function, including the percent fractional shortening (%FS) left ventricular posterior wall shortening velocity (LVPWSV) were assessed via echocardiography at 16 weeks post myocardial infarction or sham treatment in male Lewis rats (n=5/group). Changes in gene expression in HF versus control (CON) groups were quantified by real-time PCR in the hypothalamus, amygdala and dorsal pons.
Background: SIRT1 is likely to play a role in the extension in healthspan induced by dietary restriction. Actions of SIRT1 are pleiotropic, and effects on healthspan may include effects on DNA methylation. Polycomb group protein target genes (PCGTs) are suppressed by epigenetic mechanisms in stem cells, partly through the actions of the polycomb repressive complexes (PRCs), and have been shown previously to correspond with loci particularly susceptible to age-related changes in DNA methylation.
View Article and Find Full Text PDFUnlabelled: PHENOMENON: Mental health (MH) problems are prevalent in the pediatric population, and in a setting of limited resources, pediatricians need to provide MH care in the primary medical home yet are uncomfortable doing so citing a lack of training during residency as one barrier.
Approach: The purpose of this study is to describe pediatric residents' experiences and perspectives on the current and ideal states of MH training and ideas for curriculum development to bridge this gap. A qualitative study using focus groups of pediatric residents from an urban academic medical center was performed.
Objective: To assess pediatric residency program director (PD) perceptions of the current state of mental health (MH) training, their receptivity to curricular changes, and perceptions of their residents' knowledge and skills in MH care.
Methods: We performed a cross-sectional study utilizing a Web-based survey of pediatric residency PDs to assess program characteristics, learning modalities PDs currently had or would implement, and their knowledge of the new American Academy of Pediatrics' MH competencies. PDs then ranked their residents' knowledge and skills for 29 MH competencies.