Comparing self-reported physical activity and sedentary time to objective fitness measures in a military cohort.

Objectives: Regular vigorous physical activity (PA) and high levels of physical fitness (PF) confer health benefits. Conversely, sedentary time is a risk factor for chronic illness, independent of PA. We evaluated associations between self-reported PA, sedentary time, and objective PF measures in military Service members.

Synthetic high-density lipoprotein nanoconjugate targets neuroblastoma stem cells, blocking migration and self-renewal.

Background: Pathways critical for neuroblastoma cancer stem cell function are targeted by 4,19,27-triacetyl withalongolide A (WGA-TA). Because neuroblastoma cells and their cancer stem cells highly overexpress the scavenger receptor class B type 1 receptor that binds to synthetic high-density lipoprotein, we hypothesized that a novel mimetic synthetic high-density lipoprotein nanoparticle would be an ideal carrier for the delivery of 4,19,27-triacetyl withalongolide to neuroblastoma and neuroblastoma cancer stem cells.

Methods: Expression of scavenger receptor class B type 1 in validated human neuroblastoma cells was evaluated by quantitative polymerase chain reaction (qPCR) and Western blot.

Integrative Clinical Sequencing in the Management of Refractory or Relapsed Cancer in Youth.

Importance: Cancer is caused by a diverse array of somatic and germline genomic aberrations. Advances in genomic sequencing technologies have improved the ability to detect these molecular aberrations with greater sensitivity. However, integrating them into clinical management in an individualized manner has proven challenging.

Imatinib Treatment in PDGFRA-Negative Childhood Hypereosinophilic Syndrome.

We report a 4-year-old female who presented with severe hypereosinophilia (215.7 K/μl) and end-organ dysfunction. Extensive evaluation including whole exome sequencing was performed, revealing no causative mutation.

Alternative NHEJ Pathway Components Are Therapeutic Targets in High-Risk Neuroblastoma.

Unlabelled: In neuroblastoma, MYCN genomic amplification and segmental chromosomal alterations including 1p or 11q loss of heterozygocity and/or 17q gain are associated with progression and poor clinical outcome. Segmental alterations are the strongest predictor of relapse and result from unbalanced translocations attributable to erroneous repair of chromosomal breaks. Although sequence analysis of affected genomic regions suggests that these errors arise by nonhomologous end-joining (NHEJ) of DNA double-strand breaks (DSB), abnormalities in NHEJ have not been implicated in neuroblastoma pathogenesis.

CREB-binding protein regulates Ku70 acetylation in response to ionization radiation in neuroblastoma.

Ku70 was originally described as an autoantigen, but it also functions as a DNA repair protein in the nucleus and as an antiapoptotic protein by binding to Bax in the cytoplasm, blocking Bax-mediated cell death. In neuroblastoma (NB) cells, Ku70's binding with Bax is regulated by Ku70 acetylation such that increasing Ku70 acetylation results in Bax release, triggering cell death. Although regulating cytoplasmic Ku70 acetylation is important for cell survival, the role of nuclear Ku70 acetylation in DNA repair is unclear.

Thalidomide therapy for aggressive histiocytic lesions in the pediatric population.

Aggressive histiocytic lesions are uncommon in the pediatric population. These neoplasms occur in isolation or after therapy for other types of hematopoietic malignancy such as T-cell acute lymphoblastic leukemia. The etiology of these lesions is poorly understood, and no definitive standard of care has been established for patients with these diagnoses.

HDAC6 deacetylates Ku70 and regulates Ku70-Bax binding in neuroblastoma.

Ku70 was first characterized as a nuclear factor that binds DNA double-strand breaks in nonhomolog end-joining DNA repair. However, recent studies have shown that Ku70 is also found in the cytoplasm and binds Bax, preventing Bax-induced cell death. We have shown that, in neuroblastoma cells, the binding between Ku70 and Bax depends on the acetylation status of Ku70, such that, when Ku70 is acetylated, Bax is released from Ku70, triggering cell death.

CLU blocks HDACI-mediated killing of neuroblastoma.

Clusterin is a ubiquitously expressed glycoprotein with multiple binding partners including IL-6, Ku70, and Bax. Clusterin blocks apoptosis by binding to activated Bax and sequestering it in the cytoplasm, thereby preventing Bax from entering mitochondria, releasing cytochrome c, and triggering apoptosis. Because increased clusterin expression correlates with aggressive behavior in tumors, clusterin inhibition might be beneficial in cancer treatment.

Isolated infrarenal caval disruption secondary to minimal blunt trauma.

Injuries to the inferior vena cava (IVC) are highly lethal and are usually associated with gunshot wounds. Blunt injury to the IVC is a rare entity that is usually located in the retrohepatic space. We present the case of an infrarenal caval disruption in a 9-year-old as a result of minimal blunt trauma.

Ku70 acetylation in neuroblastoma pathogenesis and therapy.

Neuroblastoma is a cancer that occurs in children. It develops from stem cells that normally give rise to parts of the peripheral nervous system and adrenal glands. Although most children with localized neuroblastoma are cured, children with wide-spread disease have a small chance of survival even after surgery, chemotherapy, radiation and bone marrow transplantation.

Microscopic polyangiitis in an adolescent presenting as severe anemia and syncope.

Microscopic polyangiitis (MPA) is an autoimmune systemic vasculitis of small vessels. The condition has been best characterized in older adults and little is known of the natural history of this disease in children and adolescents. In this report, a case of an adolescent presenting with symptomatic anemia and syncopal episodes is described.

FDG PET imaging of childhood sarcomas.

Background: Positron-emission tomography (PET) imaging using [(18)F]fluorodeoxyglucose (FDG) is useful for detection, staging, and monitoring a variety of malignancies, including lymphoma, in adults, but its utility in sarcomas, especially soft tissue sarcomas (STS), in children and young adults is not clear.

Procedure: To evaluate the potential utility of FDG PET in the care of STS in children and young adults, we analyzed 46 PET scans in 25 patients acquired over 12 years. Scans were interpreted by two imaging physicians blinded to findings from other imaging studies and clinical information.

Bcl6 is expressed in neuroblastoma: tumor cell type-specific expression predicts outcome.

Neuroblastoma (NB) is the most common extracranial solid neoplasm of infancy and childhood. Whereas most low-risk patients do well, children with high-risk tumors often fail intensive treatment. Identification of novel biomarkers is critical to improve prognostication, tailor therapy, and develop new therapeutic targets.

Bortezomib as a therapeutic candidate for neuroblastoma.

Outcomes remain poor in neuroblastoma despite intensive treatment. Agents with potential efficacy can be drawn from anti-neoplastic drugs introduced for other malignancies. Bortezomib, a proteasome inhibitor, modulates cell-signaling molecules leading to apoptosis.

CREB-binding protein is a mediator of neuroblastoma cell death induced by the histone deacetylase inhibitor trichostatin A.

The cytotoxic mechanism of the histone deacetylase inhibitor (HDACI) Trichostatin A (TSA) was explored in a neuroblastoma (NB) model. TSA induces cell death in neuroblastic-type NB cells by increasing the acetylation of Ku70, a Bax-binding protein. Ku70 acetylation causes Bax release and activation, triggering cell death.

Epstein-Barr virus-induced hemophagocytic lymphohistiocytosis and X-linked lymphoproliferative disease: a mimicker of sepsis in the pediatric intensive care unit.

A rare complication of infection with the Epstein-Barr virus is the development of hemophagocytic lymphohistiocytosis. Although most cases of Epstein-Barr virus-induced hemophagocytic lymphohistiocytosis develop in immunocompetent individuals, the rare immunodeficiency X-linked lymphoproliferative disease is often unmasked by Epstein-Barr virus infection and is clinically indistinguishable from Epstein-Barr virus-induced hemophagocytic lymphohistiocytosis. We describe the clinical course and management of a previously healthy 17-year-old boy who presented with hemodynamic collapse and severe systemic inflammatory response syndrome resulting from overwhelming hemophagocytosis in the setting of X-linked lymphoproliferative disease.