Age-Related Gliosis Promotes Central Nervous System Lymphoma through CCL19-Mediated Tumor Cell Retention.

How lymphoma cells (LCs) invade the brain during the development of central nervous system lymphoma (CNSL) is unclear. We found that NF-κB-induced gliosis promotes CNSL in immunocompetent mice. Gliosis elevated cell-adhesion molecules, which increased LCs in the brain but was insufficient to induce CNSL.

Which Student Characteristics Are Most Important in Determining Clinical Honors in Clerkships? A Teaching Ward Attending Perspective.

Purpose: To explore faculty perspectives on which characteristics of high-performing clerkship students are most important when determining an honors or top grade designation for clinical performance.

Method: In 2016-2017, the authors surveyed faculty (teaching ward attendings) for internal medicine clerkships and 1 pediatrics clerkship in inpatient settings at 5 U.S.

Design, synthesis and biological activity of N-phenylsubstituted-7H-pyrrolo[2,3-d]pyrimidin-4-amines as dual inhibitors of aurora kinase A and epidermal growth factor receptor kinase.

Simultaneous inhibition of multiple kinases has been suggested to provide synergistic effects on inhibition of tumour growth and resistance. This study describes the design, synthesis and evaluation of 18 compounds incorporating a pyrrolo[2,3-d]pyrimidine scaffold for dual inhibition of epidermal growth factor receptor kinase (EGFR) and aurora kinase A (AURKA). Compounds 1-18 of this study demonstrate nanomolar inhibition of EGFR and micromolar inhibition of AURKA.

Moderating effects of immunosuppressive medications and risk factors for post-operative joint infection following total joint arthroplasty in patients with rheumatoid arthritis or osteoarthritis.

Objective: Inconclusive findings about infection risks, importantly the use of immunosuppressive medications in patients who have undergone large-joint total joint arthroplasty, challenge efforts to provide evidence-based perioperative total joint arthroplasty recommendations to improve surgical outcomes. Thus, the aim of this study was to describe risk factors for developing a post-operative infection in patients undergoing TJA of a large joint (total hip arthroplasty, total knee arthroplasty, or total shoulder arthroplasty) by identifying clinical and demographic factors, including the use of high-risk medications (i.e.

Serious outbreak of human metapneumovirus in patients with hematologic malignancies.

Human metapneumovirus (hMPV) is an important cause of lower respiratory tract infection. In healthy subjects infections are usually mild and rarely necessitate hospitalization. However, more serious outcomes have been described for allogeneic stem cell transplant recipients.

Cks1 is a critical regulator of hematopoietic stem cell quiescence and cycling, operating upstream of Cdk inhibitors.

Cyclin-dependent kinase subunit 1 (Cks1) is a critical rate-limiting component of the Skp1-Cullin1-Skp2 (SCF(Skp2)) ubiquitin ligase that controls cell cycle inhibitor abundance. Cyclin-dependent kinase (Cdk) inhibitors (CKIs) regulate hematopoietic stem cell (HSC) self-renewal, regeneration after cytotoxic stress and tumor cell proliferation. We thus studied the role of Cks1 in HSC and in a prototypic stem cell disorder, chronic myeloid leukemia (CML).

Myc-induced SUMOylation is a therapeutic vulnerability for B-cell lymphoma.

Myc oncogenic transcription factors (c-Myc, N-Myc, and L-Myc) coordinate the control of cell growth, division, and metabolism. In cancer, Myc overexpression is often associated with aggressive disease, which is in part due to the destruction of select targets by the ubiquitin-proteasome system (eg, SCF(Skp2)-directed destruction of the Cdk inhibitor p27(Kip1)). We reasoned that Myc would also regulate SUMOylation, a related means of posttranslational modification of proteins, and that this circuit would play essential roles in Myc-dependent tumorigenesis.

End-of-life and palliative care curricula in internal medicine clerkships: a report on the presence, value, and design of curricula as rated by clerkship directors.

Purpose: End-of-life and palliative care (EOL/PC) education is a necessary component of undergraduate medical education. The extent of EOL/PC education in internal medicine (IM) clerkships is unknown. The purpose of this national study was to investigate the presence of formal EOL/PC curricula within IM clerkships; the value placed by IM clerkship directors on this type of curricula; curricular design and implementation strategies; and related barriers and resources.

Efficacy of repeat myeloablative chemotherapy with autologous stem-cell support in multiple myeloma.

Objective: Induction high-dose chemotherapy followed by myeloablative melphalan (HD-Mel) treatment and autologous hematopoietic stem-cell support (autoSCT) is a standard treatment for multiple myeloma (MM) either upfront or in relapse after conventional treatment. We performed a retrospective analysis of consecutive patients undergoing a late repeat HD-Mel/autoSCT treatment for MM.

Methods: Data from 24 consecutive patients with MM who underwent a myeloablative treatment with HD-Mel late after completion of upfront first high-dose therapy were assessed for toxicity, response, progression-free survival (PFS) and time to next treatment (TTNT).

Cks1 is required for tumor cell proliferation but not sufficient to induce hematopoietic malignancies.

The Cks1 component of the SCF(Skp2) complex is necessary for p27(Kip1) ubiquitylation and degradation. Cks1 expression is elevated in various B cell malignancies including Burkitt lymphoma and multiple myeloma. We have previously shown that loss of Cks1 results in elevated p27(Kip1) levels and delayed tumor development in a mouse model of Myc-induced B cell lymphoma.

Cks1 promotion of S phase entry and proliferation is independent of p27Kip1 suppression.

Cks1 is an activator of the SCF(Skp2) ubiquitin ligase complex that targets the cell cycle inhibitor p27(Kip1) for degradation. The loss of Cks1 results in p27(Kip1) accumulation and decreased proliferation and inhibits tumorigenesis. We identify here a function of Cks1 in mammalian cell cycle regulation that is independent of p27(Kip1).

Aurora kinase inhibition overcomes cetuximab resistance in squamous cell cancer of the head and neck.

Squamous cell cancer of the head and neck (SCCHN) is the sixth leading cause for cancer deaths worldwide. Despite extense knowledge of risk factors and pathogenesis about 50 percent of all patients and essentially every patient with metastatic SCCHN eventually die from this disease. We analyzed the clinical data and performed immunohistochemistry for Epidermal growth factor receptor (EGFR) and Aurora kinase A (Aurora-A) expression in 180 SCCHN patients.

Are primary care providers uncomfortable providing routine preventive care for inflammatory bowel disease patients?

Background And Aims: Those with chronic diseases, including inflammatory bowel disease (IBD), often do not receive preventive care at the same rate as the general population. Attitudes of primary care providers could be key factors in the receipt of preventive care.

Methods: We surveyed attendees of a family medicine review course.

Aurora kinases A and B are up-regulated by Myc and are essential for maintenance of the malignant state.

Myc oncoproteins promote continuous cell growth, in part by controlling the transcription of key cell cycle regulators. Here, we report that c-Myc regulates the expression of Aurora A and B kinases (Aurka and Aurkb), and that Aurka and Aurkb transcripts and protein levels are highly elevated in Myc-driven B-cell lymphomas in both mice and humans. The induction of Aurka by Myc is transcriptional and is directly mediated via E-boxes, whereas Aurkb is regulated indirectly.

Skp2 directs Myc-mediated suppression of p27Kip1 yet has modest effects on Myc-driven lymphomagenesis.

The universal cyclin-dependent kinase inhibitor p27(Kip1) functions as a tumor suppressor, and reduced levels of p27(Kip1) connote poor prognosis in several human malignancies. p27(Kip1) levels are predominately regulated by ubiquitin-mediated turnover of the protein, which is marked for destruction by the E3 ubiquitin ligase SCF(Skp2) complex following its phosphorylation by the cyclin E-cyclin-dependent kinase 2 complex. Binding of phospho-p27(Kip1) is directed by the Skp2 F-box protein, and this is greatly augmented by its allosteric regulator Cks1.

A complementary and alternative medicine workshop using standardized patients improves knowledge and clinical skills of medical students.

Objectives: As the use of complementary and alternative medicine (CAM) has increased in the general population, so has the interest in CAM education among medical students and medical educators. The purpose of this study is to determine the impact of a CAM workshop using standardized patients (SP) on knowledge and clinical skills of third-year medical students.

Design: A 4-hour CAM workshop was developed as part of a new curriculum for a required third-year 4-week primary care internal medicine clerkship.