Contribution of Streptococcus pseudopneumoniae and Streptococcus salivarius to vocal fold mucosal integrity and function.

Structural changes to the vocal fold (VF) epithelium, namely, loosened intercellular junctions, have been reported in VF benign lesions. The potential mechanisms responsible for the disruption of cell junctions do not address the contribution of resident microbial communities to this pathological phenomenon. In this study, we focused on determining the relationship between Streptococcus pseudopneumoniae (SP), a dominant bacterial species associated with benign lesions, and Streptococcus salivarius (SS), a commensal bacterium, with human VF epithelial cells in our three-dimensional model of the human VF mucosa.

The Impact of Neighborhood and Socioeconomic Disparities on Distal Radius Fracture Follow-Up Adherence.

Background: The aims of this retrospective cohort study were (1) to assess whether the Area Deprivation Index (ADI), a novel neighborhood-level socioeconomic disparities metric, is associated with follow-up nonadherence, and (2) to determine the individual-level socioeconomic factors associated with follow-up nonadherence after treatment of distal radius fractures (DRFs).

Methods: The authors included all patients who underwent nonoperative or operative management of DRFs at an academic level I trauma center between 2019 and 2021. A manual chart review was performed to collect data on ADI, sociodemographic factors, injury characteristics, conservative and surgical interventions, and health care utilization.

Selective Bacterial Colonization of the Murine Larynx in a Gnotobiotic Model.

The larynx is a mucosal organ situated between the respiratory and gastrointestinal tracts. Little is known about microbial contributions to laryngeal epithelial health and pathogenesis. Developing a gnotobiotic laryngeal model will introduce new avenues for targeted explorations of microbes in laryngeal mucosal biology, allowing for enhanced understanding of host-microbe interaction in the upper airway.

Change Theory Contributes to Choosing Wisely for Immune Thrombocytopenia.

Objectives: Despite 2011 guidelines in which it is suggested that treatment of acute immune thrombocytopenia purpura (aITP) is not needed for patients without significant bleeding, only 14% of children treated for aITP have bleeding symptoms. Our aim was to decrease the percentage of children with first-episode aITP who were unnecessarily treated by 50% within 12 months of guideline implementation.

Methods: An intervention was designed by using the precaution-adoption-process model.

Outcomes of Measurable Residual Disease in Pediatric Acute Myeloid Leukemia before and after Hematopoietic Stem Cell Transplant: Validation of Difference from Normal Flow Cytometry with Chimerism Studies and Wilms Tumor 1 Gene Expression.

We enrolled 150 patients in a prospective multicenter study of children with acute myeloid leukemia undergoing hematopoietic stem cell transplantation (HSCT) to compare the detection of measurable residual disease (MRD) by a "difference from normal" flow cytometry (ΔN) approach with assessment of Wilms tumor 1 (WT1) gene expression without access to the diagnostic specimen. Prospective analysis of the specimens using this approach showed that 23% of patients screened for HSCT had detectable residual disease by ΔN (.04% to 53%).

Targeted inhibition of histone H3K27 demethylation is effective in high-risk neuroblastoma.

High-risk neuroblastoma is often distinguished by amplification of and loss of differentiation potential. We performed high-throughput drug screening of epigenetic-targeted therapies across a large and diverse tumor cell line panel and uncovered the hypersensitivity of neuroblastoma cells to GSK-J4, a small-molecule dual inhibitor of lysine 27 of histone 3 (H3K27) demethylases ubiquitously transcribed tetratricopeptide repeat, X chromosome (UTX), and histone demethylase Jumonji D3 (JMJD3). Mechanistically, GSK-J4 induced neuroblastoma differentiation and endoplasmic reticulum (ER) stress, with accompanying up-regulation of p53 up-regulated modulator of apoptosis (PUMA) and induction of cell death.

Insights Into the Role of Collagen in Vocal Fold Health and Disease.

As one of the key fibrous proteins in the extracellular matrix, collagen plays a significant role in the structural and biomechanical characteristics of the vocal fold. Anchored fibrils of collagen create secure structural regions within the vocal folds and are strong enough to sustain vibratory impact and stretch during phonation. This contributes tensile strength, density, and organization to the vocal folds and influences health and pathogenesis.

Exploitation of the Apoptosis-Primed State of MYCN-Amplified Neuroblastoma to Develop a Potent and Specific Targeted Therapy Combination.

Fewer than half of children with high-risk neuroblastoma survive. Many of these tumors harbor high-level amplification of MYCN, which correlates with poor disease outcome. Using data from our large drug screen we predicted, and subsequently demonstrated, that MYCN-amplified neuroblastomas are sensitive to the BCL-2 inhibitor ABT-199.

HLA-DR expression on myeloid cells is a potential prognostic factor in patients with high-risk neuroblastoma.

The adaptive immune system has been reported to play a dual role in many cancers, on one hand inhibiting tumor growth and, on the other hand, promoting disease progression, escape from cancer immunosurveillance and relapse. We have previously reported that the suppression of the adaptive immune response associated with high levels of myeloid-derived suppressor cells (MDSC) was evident in patients with low-risk neuroblastoma. Here, we report the results of a pilot study demonstrating that the amounts of HLA-DR-positive or negative myeloid cells in the peripheral blood might predict disease outcome among individuals affected by high-risk neuroblastoma.

Distinct signatures of the immune responses in low risk versus high risk neuroblastoma.

Background: Over 90% of low risk (LR) neuroblastoma patients survive whereas less than 30% of high risk (HR) patients are long term survivors. Age (children younger than 18 months old) is associated with LR disease. Considering that adaptive immune system is well developed in older children, and that T cells were shown to be involved in tumor escape and progression of cancers, we sought to determine whether HR patients may tend to show a signature of adaptive immune responses compared to LR patients who tend to have diminished T-cell responses but an intact innate immune response.

CD4+ T cells inhibit the neu-specific CD8+ T-cell exhaustion during the priming phase of immune responses against breast cancer.

Studies conducted in animal model of infectious diseases or H-Y antigen model suggest a crucial role for CD4+ T cells in providing help for CD8+ T-cell memory responses. This concept suggests that inclusion of T helper epitopes in vaccine formulation will result in improved CD8+ T-cell responses. Although this concept has been applied to cancer vaccine design, the role of CD4+ T cells in the memory differentiation of CD8+ T cells and retention of their anti-tumor function have never been tested in breast cancer model.

Human T cells express CD25 and Foxp3 upon activation and exhibit effector/memory phenotypes without any regulatory/suppressor function.

Background: Foxp3 has been suggested to be a standard marker for murine Tregs whereas its role as marker for human Tregs is controversial. While some reports have shown that human Foxp3+ T cells had no regulatory function others have shown their role in the inhibition of T cell proliferation.

Methods: T cell activation was performed by means of brayostatin-1/ionomycin (B/I), mixed lymphocyte reaction (MLR), and CD3/CD28 activation.