The analysis of vascular morphology and functionality enables the assessment of disease activity and therapeutic effects in various pathologies. Raster-scanning optoacoustic mesoscopy (RSOM) is an imaging modality that enables the visualization of superficial vascular networks in vivo. In murine models of colitis, deep vascular networks in the colon wall can be visualized by transrectal absorber guide raster-scanning optoacoustic mesoscopy (TAG-RSOM).
View Article and Find Full Text PDFJ Am Soc Mass Spectrom
October 2024
Electrospray ionization (ESI) enables coupling between liquid chromatography (LC) and mass spectrometry (MS). Since it is a gentle ionization method, it is frequently used for the analysis of large biomolecules. In recent years, several experimental setups have demonstrated that the use of ESI results in the formation of charged droplets that are aspirated into the vacuum systems of mass spectrometers.
View Article and Find Full Text PDFAm Soc Clin Oncol Educ Book
June 2024
Despite improved outcomes in newly diagnosed pediatric AML, relapsed disease remains a therapeutic challenge. Factors contributing to slow progress in improving outcomes include inherent challenges in pediatric clinical trial accrual and the scarcity of novel targeted/immunotherapy agents available for pediatric development. This paradigm is changing, however, as international collaboration grows in parallel with the development of promising targeted agents.
View Article and Find Full Text PDFThe implications of previous central nervous system (CNS) involvement in children with acute myeloid leukemia (AML) undergoing hematopoietic cell transplantation (HCT) remain inadequately understood. Patients with CNS disease require more upfront CNS-directed intrathecal therapy, but little is known about whether transplant conditioning regimens should be intensified or if previous CNS involvement impacts post-HCT outcomes. While total body irradiation (TBI) remains standard for pediatric acute lymphoblastic leukemia myeloablative conditioning, it has been largely replaced with chemotherapy-only myeloablation in pediatric AML, primarily due to toxicity and late effects associated with TBI.
View Article and Find Full Text PDFAcute promyelocytic leukemia (APL) with variant RARA translocation is linked to over 15 partner genes. Recent publications encompassing 6 cases have expanded the spectrum of RARA partners to torque teno mini virus (TTMV). This entity is likely underrecognized due to the lack of clinician and pathologist familiarity, inability to detect the fusion using routine testing modalities, and informatic challenges in its recognition within next-generation sequencing (NGS) data.
View Article and Find Full Text PDFDysregulation of phosphorylation-dependent signaling is a hallmark of tumorigenesis. Protein phosphatase 2 (PP2A) is an essential regulator of cell growth. One scaffold subunit (A) binds to a catalytic subunit (C) to form a core AC heterodimer, which together with one of many regulatory (B) subunits forms the active trimeric enzyme.
View Article and Find Full Text PDFBackground: Acute myeloid leukemia (AML) is a biologically heterogenous disease arising in clonally proliferating hematopoietic stem cells. Sequential acquisition of mutations leads to expanded proliferation of clonal myeloid progenitors and failure of differentiation, leading to fulminant AML.
Summary: Here, we review the pathophysiology of AML with a focus on factors predisposing to AML development, including prior chemo- and radiation therapy, environmental factors, and germline predisposition.
Treatment of recurrent myelodysplastic syndrome (MDS) after hematopoietic cell transplantation (HCT) remains challenging. We present a 4-year-old girl experiencing early MDS relapse post-HCT treated with a multimodal strategy encompassing a second HCT and innovative targeted therapies. We underscore the potential of a comprehensive treatment approach in managing recurrent pediatric MDS.
View Article and Find Full Text PDFTargeted protein degradation relies on small molecules that induce new protein-protein interactions between targets and the cellular protein degradation machinery. Most of these small molecules feature specific ligands for ubiquitin ligases. Recently, the attachment of cysteine-reactive chemical groups to pre-existing small molecule inhibitors has been shown to drive specific target degradation.
View Article and Find Full Text PDFBest Pract Res Clin Haematol
September 2023
One of the consistent features in development of hematopoietic stem cell transplant (HCT) for Acute Lymphoblastic Leukemia (ALL) is the rapidity with which discoveries in the laboratory are translated into innovations in clinical care. Just a few years after murine studies demonstrated that rescue from radiation induced marrow failure is mediated by cellular not humoral factors, E. Donnall Thomas reported on the transfer of bone marrow cells into irradiated leukemia patients.
View Article and Find Full Text PDFBackground: The role of cytoreduction prior to hematopoietic cell transplant (HCT) for patients with pediatric myelodysplastic syndrome (MDS) and related disorders remains unclear.
Procedure: We performed a single-center retrospective analysis of pre-transplant disease management and subsequent HCT outcome for pediatric patients with MDS and related disorders who underwent HCT between 2010 and 2020.
Results: Total 62 patients (median age 11 years) with idiopathic MDS (n = 16), MDS secondary to an underlying germline condition (n = 11), secondary acute myeloid leukemia (n = 9), myeloproliferative neoplasms (n = 8), and treatment-related myeloid neoplasms (n = 18) received an allogeneic HCT.
Unstable gamma globin variants can cause transient neonatal hemolytic anemia. We have identified a novel variant in a newborn who presented with jaundice and anemia requiring phototherapy and red blood cell transfusion. The patient was found to be heterozygous for the mutation HGB2:c.
View Article and Find Full Text PDFObjectives: To compare the risk and intensity of tooth sensitivity (TS) as well the effectiveness of at-home bleaching using two carbamide peroxide bleaching gels, specifically a novel polymeric nanoparticle gel (experimental) and a commercial gel (Opalescence PF, Ultradent, South Jordan, Utah, USA), applied at two application times.
Methods: This multicenter, triple-blind, and split-mouth randomized controlled trial was conducted on 80 healthy adults with canine teeth that were shade A2 or darker. The participants all used the experimental and the control gels on one side of a tray, depending on the group to which they were allocated, for 30 or 60 minutes per day over four weeks.
Acta Odontol Scand
January 2023
Objective: This study aimed to evaluate whether ligature-induced periodontitis and rheumatoid arthritis (RA) potentiate the deleterious effects on functional capacity, periodontal and synovial tissues, leukocyte migration, and interleukin 17 (IL-17) levels, and to investigate the repercussions of single Freund's Complete Adjuvant (FCA) injection associated with periodontitis.
Materials And Methods: Fifty-one male rats were randomised into six groups: control (CG, = 8), RA (RAG, = 9), periodontitis (PG, = 9), periodontitis and RA (PRAG, = 9), periodontitis and intradermal injection (PIDG, = 9), and periodontitis and intra-articular injection (PIAG, = 7). The animals underwent ligature placement and one or two injections with FCA to induce RA.
Objectives: The assessment of SARS-CoV-2 infections in children is still challenging, but essential for appropriate political decisions. The aim of this study was to investigate whether residual blood samples can be used for SARS-CoV-2 seroprevalence monitoring in pediatrics.
Methods: In this repeated cross-sectional cohort study, anonymous residual blood samples from pediatric patients aged 0-17 years were collected in three time-periods (Oct.
Inflammatory myofibroblastic tumor (IMT) is a rare, mesenchymal tumor that has an increased incidence in childhood. Tumors are usually isolated to the chest, abdomen, and retroperitoneum, but metastatic presentations can be seen. Presenting symptoms are nonspecific and include fever, weight loss, pain, shortness of breath, and cough.
View Article and Find Full Text PDFForty Wistar rats were used: (1) control group (CG); (2) group of periodontal disease (PD); (3) type 1 diabetes mellitus group (T1DM); (4) type 1 diabetes mellitus + periodontal disease group (T1DM + PD). In groups T1DM and T1DM + PD, T1DM induction was performed with the administration of streptozotocin (STZ) 80 mg/kg intraperitoneal body weight. The PD and T1DM + PD groups were submitted to PD induction with ligation.
View Article and Find Full Text PDFPeriodontal disease is considered a public health problem because of its high prevalence, while premature birth is a serious perinatal problem, persisting as one of the major causes of perinatal mortality and morbidity. Therefore, the objective of this study was to evaluate the effect of maternal periodontal disease on the occurrence of preterm birth and the birth weight of their babies. The study sample included 45 new mothers, aged 18-35 years, who presented either slight or moderate to severe localized or generalized chronic periodontitis with bleeding on probing and gingival inflammation.
View Article and Find Full Text PDFMalignant rhabdoid tumors (MRT) are highly aggressive pediatric cancers that respond poorly to current therapies. In this study, we screened several MRT cell lines with large-scale RNAi, CRISPR-Cas9, and small-molecule libraries to identify potential drug targets specific for these cancers. We discovered and , the canonical negative regulators of p53, as significant vulnerabilities.
View Article and Find Full Text PDFChemotherapy-induced peripheral neuropathy (CIPN) is a debilitating side effect of many cancer treatments. The hallmark of CIPN is degeneration of long axons required for transmission of sensory information; axonal degeneration causes impaired tactile sensation and persistent pain. Currently the molecular mechanisms of CIPN are not understood, and there are no available treatments.
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