REST-dependent glioma progression occurs independently of the repression of the long non-coding RNA HAR1A.

The long non-coding RNA (lncRNA), HAR1A is emerging as a putative tumour suppressor. In non-neoplastic brain cells, REST suppresses HAR1A expression. In gliomas REST acts as an oncogene and is a potential therapeutic target.

Equity and justice in medical education: mapping a longitudinal curriculum across 4 years.

Background: In 2024 in the United States there is an attack on diversity, equity, and inclusion initiatives within education. Politics notwithstanding, medical school curricula that are current and structured to train the next generation of physicians to adhere to our profession's highest values of fairness, humanity, and scientific excellence are of utmost importance to health care quality and innovation worldwide. Whereas the number of anti-racism, diversity, equity, and inclusion (ARDEI) curricular innovations have increased, there is a dearth of published longitudinal health equity curriculum models.

Evaluating Dual Process Decision-Making Along the PrEP Consumer Journey: New Insights for Supporting PrEP Use.

With the rise of new and emerging Pre-Exposure Prophylaxis (PrEP) modalities, greater attention is needed to better understand how people who could benefit from PrEP make decisions to initiate, stop, pause, or switch PrEP regimens. In this study we borrow from the field of consumer research to create a consumer-derived PrEP Consumer Journey Model that describes key decision-making touchpoints a PrEP consumer moves through within and outside of a clinical context. Using in-depth interviews (n = 29) with gay and bisexual men who have sex with men, we evaluate which system 1 (emotional) and system 2 (cognitive) attributes are used for decision-making at different touchpoints along the PrEP Consumer Journey.

UK Healthcare Workers' Experiences of Major System Change in Elective Surgery During the COVID-19 Pandemic: Reflections on Rapid Service Adaptation.

Background: The coronavirus disease 2019 (COVID-19) pandemic disrupted the delivery of elective surgery in the United Kingdom. The majority of planned surgery was cancelled or postponed in March 2020 for the duration of the first wave of the pandemic. We investigated the experiences of staff responsible for delivering rapid changes to surgical services during the first wave of the pandemic in the United Kingdom, with the aim of developing lessons for future major systems change (MSC).

The Long Non-Coding RNA H19 Drives the Proliferation of Diffuse Intrinsic Pontine Glioma with H3K27 Mutation.

Diffuse intrinsic pontine glioma (DIPG) is an incurable paediatric malignancy. Identifying the molecular drivers of DIPG progression is of the utmost importance. Long non-coding RNAs (lncRNAs) represent a large family of disease- and tissue-specific transcripts, whose functions have not yet been elucidated in DIPG.

Perceptions and experiences of healthcare workers during the COVID-19 pandemic in the UK.

Objective: The COVID-19 pandemic has set unprecedented demand on the healthcare workforce around the world. The UK has been one of the most affected countries in Europe. The aim of this study was to explore the perceptions and experiences of healthcare workers (HCWs) in relation to COVID-19 and care delivery models implemented to deal with the pandemic in the UK.

Human Sialic acid O-acetyl esterase (SIAE) - mediated changes in sensitivity to etoposide in a medulloblastoma cell line.

Medulloblastoma (MB), the most common malignant paediatric brain tumour occurs in the cerebellum. Advances in molecular genomics have led to the identification of defined subgroups which are associated with distinct clinical prognoses. Despite this classification, standard therapies for all subgroups often leave children with life-long neurological deficits.

Fucosyltransferase 4 and 7 mediates adhesion of non-small cell lung cancer cells to brain-derived endothelial cells and results in modification of the blood-brain-barrier: in vitro investigation of CD15 and CD15s in lung-to-brain metastasis.

Purpose: Metastatic non-small cell lung (NSCLC) cancer represents one of the most common types of brain metastasis. The mechanisms involved in how circulating cancer cells transmigrate into brain parenchyma are not fully understood. The aim of this work was to investigate the role of fucosylated carbohydrate epitopes CD15 and sialyated CD15s in cancer adhesion to brain-derived endothelial cells and determine their influence in blood-brain barrier (BBB) disruption METHODS: Three distinct, independent methods were used to measure brain endothelial integrity and include voltohmmeter (EVOM™), impedance spectroscopy (CellZscope®) and electric cell-substrate impedance sensing system (ECIS™).

The Leadership Style of "The People's Doctor": A Contemporary Look Back at New York State Commissioner of Health David Axelrod, MD.

David Axelrod, MD, New York State's commissioner of health from 1979 to 1991, had a panoramic view of public health and a legendary track record of tackling complex issues ranging from the Love Canal environmental disaster to HIV/AIDS and end-of-life ethics. Many raved about Axelrod's leadership, whereas others criticized his response and style. Two decades later, we describe his leadership attributes.

Intersection of Brain Development and Paediatric Diffuse Midline Gliomas: Potential Role of Microenvironment in Tumour Growth.

Diffuse intrinsic pontine glioma (DIPG) is a devastating and incurable paediatric brain tumour with a median overall survival of 9 months. Until recently, DIPGs were treated similarly to adult gliomas, but due to the advancement in molecular and imaging technologies, our understanding of these tumours has increased dramatically. While extensive research is being undertaken to determine the function of the molecular aberrations in DIPG, there are significant gaps in understanding the biology and the influence of the tumour microenvironment on DIPG growth, specifically in regards to the developing pons.

Oxamate, but Not Selective Targeting of LDH-A, Inhibits Medulloblastoma Cell Glycolysis, Growth and Motility.

Medulloblastoma is the most common malignant paediatric brain tumour and current therapies often leave patients with severe neurological disabilities. Four major molecular groups of medulloblastoma have been identified (Wnt, Shh, Group 3 and Group 4), which include additional, recently defined subgroups with different prognosis and genetic characteristics. Lactate dehydrogenase A (LDHA) is a key enzyme in the aerobic glycolysis pathway, an abnormal metabolic pathway commonly observed in cancers, associated with tumour progression and metastasis.

Real-time acquisition of transendothelial electrical resistance in an all-human, , 3-dimensional, blood-brain barrier model exemplifies tight-junction integrity.

The blood-brain barrier (BBB) consists of endothelial cells, astrocytes, and pericytes embedded in basal lamina (BL). Most models use nonhuman, monolayer cultures for therapeutic-delivery studies, relying on transendothelial electrical resistance (TEER) measurements without other tight-junction (TJ) formation parameters. We aimed to develop reliable, reproducible, 3-dimensional (3D) models incorporating relevant human, cell types and BL proteins.

CD15s/CD62E Interaction Mediates the Adhesion of Non-Small Cell Lung Cancer Cells on Brain Endothelial Cells: Implications for Cerebral Metastasis.

Expression of the cell adhesion molecule (CAM), Sialyl Lewis X (CD15s) correlates with cancer metastasis, while expression of E-selectin (CD62E) is stimulated by TNF-α. CD15s/CD62E interaction plays a key role in the homing process of circulating leukocytes. We investigated the heterophilic interaction of CD15s and CD62E in brain metastasis-related cancer cell adhesion.

TNF-α enhancement of CD62E mediates adhesion of non-small cell lung cancer cells to brain endothelium via CD15 in lung-brain metastasis.

Background: CD15, which is overexpressed on various cancers, has been reported as a cell adhesion molecule that plays a key role in non-CNS metastasis. However, the role of CD15 in brain metastasis is largely unexplored. This study provides a better understanding of CD15/CD62E interaction, enhanced by tumor necrosis factor-α (TNF-α), and its correlation with brain metastasis in non-small cell lung cancer (NSCLC).

The Regulation and Function of Lactate Dehydrogenase A: Therapeutic Potential in Brain Tumor.

There are over 120 types of brain tumor and approximately 45% of primary brain tumors are gliomas, of which glioblastoma multiforme (GBM) is the most common and aggressive with a median survival rate of 14 months. Despite progress in our knowledge, current therapies are unable to effectively combat primary brain tumors and patient survival remains poor. Tumor metabolism is important to consider in therapeutic approaches and is the focus of numerous research investigations.

Identification and functional prediction of mitochondrial complex III and IV mutations associated with glioblastoma.

Background: Glioblastoma (GBM) is the most common primary brain tumor in adults, with a dismal prognosis. Treatment is hampered by GBM's unique biology, including differential cell response to therapy. Although several mitochondrial abnormalities have been identified, how mitochondrial DNA (mtDNA) mutations contribute to GBM biology and therapeutic response remains poorly described.

Dual targeting NG2 and GD3A using Mab-Zap immunotoxin results in reduced glioma cell viability in vitro.

Background: Effective treatments for glioblastoma multiforme (GBM) are lacking due, in part, to cellular heterogeneity. Consequently, single-target therapeutic strategies are unlikely to succeed. Simultaneous targeting of different neoplastic cell populations within the same tumour may, therefore, prove of value.

Expression of the chondroitin sulphate proteoglycan, NG2, in paediatric brain tumors.

Background/aim: While neuron-glia 2 (NG2) is well-characterized in the developing brain and in adult high-grade gliomas, little is known about NG2 expression in paediatric brain tumors. Here, NG2 expression was examined in a range of paediatric brain tumors.

Materials And Methods: A retrospective immunohistopathological analysis of 57 paediatric brain tumor biopsies of various tumor types was carried out.

Wilms tumor 1 gene, CD97, and the emerging biogenetic profile of glioblastoma.

Glioblastoma multiforme (GBM) is the most common type of primary brain tumor, and current treatment regimens are only marginally effective. One of the most vexing and malignant aspects of GBM is its pervasive infiltration into surrounding brain tissue. This review describes the role of the Wilms tumor 1 gene (WT1) and its relationship to GBM.

Brain tumor cell line authentication, an efficient alternative to capillary electrophoresis by using a microfluidics-based system.

Background: The current method for cell line authentication is genotyping based on short tandem repeat (STR)-PCR involving coamplification of a panel of STR loci by multiplex PCR and downstream fragment length analysis (FLA), usually performed by capillary electrophoresis. FLA by capillary electrophoresis is time-consuming and can be expensive, as the facilities are generally not accessible for many research laboratories.

Methods: In the present study, a microfluidic electrophoresis system, the Agilent 2100 Bioanalyzer, was used to analyze the STR-PCR fragments from 10 human genomic loci of a number of human cell lines, including 6 gliomas, 1 astrocyte, 1 primary lung cancer, 1 lung brain metastatic cancer, and 1 rhabdomyosarcoma; and this was compared with the standard method, that is, capillary electrophoresis, using the Applied Biosystems 3130xl Genetic Analyzer.

Health care savings with the patient-centered medical home: Community Care of North Carolina's experience.

This study evaluated the financial impact of integrating a systemic care management intervention program (Community Care of North Carolina) with person-centered medical homes throughout North Carolina for non-elderly Medicaid recipients with disabilities during almost 5 years of program history. It examined Medicaid claims for 169,676 non-elderly Medicaid recipients with disabilities from January 2007 through third quarter 2011. Two models were used to estimate the program's impact on cost, within each year.

Novel report of expression and function of CD97 in malignant gliomas: correlation with Wilms tumor 1 expression and glioma cell invasiveness.

Object: The Wilms tumor 1 (WT1) protein-a developmentally regulated transcription factor-is aberrantly expressed in gliomas and promotes their malignant phenotype. However, little is known about the molecular allies that help it mediate its oncogenic functions in glioma cells.

Methods: The authors used short interfering RNA (siRNA) to suppress WT1 expression in glioblastoma (GBM) cells and evaluated the effect of this on GBM cell invasiveness.

Matrix metalloproteinase-1 expression enhances tumorigenicity as well as tumor-related angiogenesis and is inversely associated with TIMP-4 expression in a model of glioblastoma.

Herein we continue the study of matrix metalloproteinase-1 (MMP-1) with respect to glioblastoma multiforme (GBM) cell tumorigenicity and angiogenesis. A model of tumorigenicity with cells stably altered to over-express or knock-down MMP-1 revealed that it significantly increases tumor incidence and size. Organized endothelial growth in human umbilical vein endothelial cell (HUVEC)-GBM co-cultures was significantly increased in the presence of MMP-1.

Protein pathway activation mapping of brain metastasis from lung and breast cancers reveals organ type specific drug target activation.

Brain metastases are the most common fatal complication of systemic cancer, especially of lung (40-50%) and breast (20-30%) cancers. In this era of personalized therapy, there is a critical need to uncover the signaling architecture of brain metastases; however, little is known about what signaling pathways are activated in the context of the brain microenvironment. Using a unique study set of 42 brain metastases from patients with breast or nonsmall cell lung cancer (NSCLC), the phosphorylation/activation states of 128 key signaling proteins involved in cancer signaling were measured in laser capture microdissected tumor epithelium using reverse phase protein microarray (RPMA) technology.