Interactions between Adipocytes and Breast Cancer Cells Stimulate Cytokine Production and Drive Src/Sox2/miR-302b-Mediated Malignant Progression.

Consequences of the obesity epidemic on cancer morbidity and mortality are not fully appreciated. Obesity is a risk factor for many cancers, but the mechanisms by which it contributes to cancer development and patient outcome have yet to be fully elucidated. Here, we examined the effects of coculturing human-derived adipocytes with established and primary breast cancer cells on tumorigenic potential.

Early intervention with Interleukin-1 Receptor Antagonist Protein modulates catabolic microRNA and mRNA expression in cartilage after impact injury.

Objective: The purpose of this controlled laboratory study was to determine the efficacy of Interleukin-1 Receptor Antagonist Protein (IRAP) treatment as an early intervention strategy by examining the changes in microRNA and mRNA expression in cartilage in an ex-vivo porcine knee joint impact model.

Methods: Custom impact device was used to create replicable injury ex-vivo to intact porcine knee joint. Injury was caused by dropping a 10 kg weight one time from 1 m directly above the knee in extension.

Mcl-1 protects prostate cancer cells from cell death mediated by chemotherapy-induced DNA damage.

The anti-apoptotic protein Mcl-1 is highly expressed in castration-resistant prostate cancer (CRPC), resulting in resistance to apoptosis and association with poor prognosis. Although predominantly localized in the cytoplasm, there is evidence that Mcl-1 exhibits nuclear localization where it is thought to protect against DNA damage-induced cell death. The role of Mcl-1 in mediating resistance to chemotherapy-induced DNA damage in prostate cancer (PCa) is not known.

Acute-on-Chronic Kidney Injury in Thyroid Hormone Withdrawal: A Case with Possible Implications for Radioactive Iodine Planning.

The association between renal dysfunction and hypothyroidism is of increasing clinical importance as thyroid hormone replacement may attenuate decline in renal function and improve cardiovascular outcomes in patients with chronic kidney disease (CKD). Although multiple mechanisms for the induction of renal insufficiency in hypothyroidism have been described, the renal impact of short-term, acute hypothyroidism is unknown, which has possible implications for thyroid cancer patients preparing to receive radioactive iodine (RAI). A 56-year-old gentleman with history of unilateral renal agenesis and CKD stage III presented with intermediate-risk papillary thyroid cancer.

TAp63γ and ΔNp63β promote osteoblastic differentiation of human mesenchymal stem cells: regulation by vitamin D3 Metabolites.

The transcription factor p63 is required for skeletal formation, and is important for the regulation of 1α,25(OH)2D3 receptor (VDR) in human mesenchymal stem cells (hMSC). Herein we report that TAp63γ and ΔNp63β appear to be an integral part of the osteoblastic differentiation of hMSC and are differentially regulated by the vitamin D3 metabolites 1α,25(OH)2D3 and 24R,25(OH)2D3. We compared the endogenous expression of p63 isoforms (TA- and ΔNp63) and splice variants (p63α, -β, -γ), in naive hMSC and during osteoblastic differentiation of hMSC.

Study design and baseline characteristics of participants in the Vitamin D in Vulnerable Adults at the VA (the VIVA Study).

Hypovitaminosis D has been associated with age-related physical decline and an increased risk for falls. The objective of this study is to test whether supplementation with 4000IU of vitamin D(3) (vitD(3)) for 9 months will improve, or slow down the decline of the ability to perform physical tests which have been associated with the preservation of independence in sedentary older men. We describe the study design and the baseline characteristics of the 314 men screened in the VIVA-VA Study (Vitamin D In Vulnerable Adults in the VA), a 2-year, single-site, double-blind, placebo-controlled, randomized clinical trial that enrolled sedentary male veterans ages 65 to 95.

MutT Homolog 1 (MTH1) maintains multiple KRAS-driven pro-malignant pathways.

Oncogenic RAS promotes production of reactive oxygen species (ROS), which mediate pro-malignant signaling but can also trigger DNA damage-induced tumor suppression. Thus RAS-driven tumor cells require redox-protective mechanisms to mitigate the damaging aspects of ROS. Here, we show that MutT Homolog 1 (MTH1), the mammalian 8-oxodGTPase that sanitizes oxidative damage in the nucleotide pool, is important for maintaining several KRAS-driven pro-malignant traits in a nonsmall cell lung carcinoma (NSCLC) model.

Innate immune responses to HIV infection in the central nervous system.

Human immunodeficiency virus (HIV) invades the brain early during infection and generates a chronic inflammatory microenvironment that can eventually result in neurological disease, even in the absence of significant viral replication. Thus, HIV-1 infection of the brain has been characterized both as a neuroimmunological and neurodegenerative disorder. While the brain and central nervous system (CNS) have historically been regarded as immune privileged or immunologically quiescent, newer concepts of CNS immunity suggest an important if not defining role for innate immune responses generated by glial cells.

Phytoestrogens in the prevention of postmenopausal bone loss.

Postmenopausal osteoporosis is a condition associated with low bone mass resulting from the increased bone resorption that occurs following a decline in estrogen levels. Phytoestrogens are plant-derived compounds that have affinity to the estrogen receptor and are able to act as either estrogen agonists or antagonists. Because of their structural similarity to 17-beta-estradiol, they have been studied extensively for their role in the prevention of postmenopausal bone loss.

ABT-737, a small molecule Bcl-2/Bcl-xL antagonist, increases antimitotic-mediated apoptosis in human prostate cancer cells.

Castration-resistant prostate cancer (CRPC) expresses high levels of the anti-apoptotic proteins Bcl-2, Bcl-xL and Mcl-1, resulting in resistance to apoptosis and association with poor prognosis. Docetaxel, an antimitotic drug that is the first-line treatment strategy for CRPC, is known to provide a small survival benefit. However, docetaxel chemotherapy alone is not enough to counteract the high levels of Bcl-2/Bcl-xL/Mcl-1 present in CRPC.

Apolipoprotein E-dependent differences in innate immune responses of maturing human neuroepithelial progenitor cells exposed to HIV-1.

HIV enters the brain early during infection and induces a chronic inflammatory state that can result in neurological abnormalities in a subset of infected individuals. To investigate the effects of HIV exposure on neurogenesis and neuronal survival in the brain, we have used a model system consisting of human neuroepithelial progenitor (NEP) cells that undergo directed differentiation into astrocytes and neurons in vitro. Changes in gene expression in NEP cultures as a result of HIV exposure were investigated using gene expression microarrays with the Illumina HT-12 V4_0_R1 platform array.

Betulinic acid selectively increases protein degradation and enhances prostate cancer-specific apoptosis: possible role for inhibition of deubiquitinase activity.

Inhibition of the ubiquitin-proteasome system (UPS) of protein degradation is a valid anti-cancer strategy and has led to the approval of bortezomib for the treatment of multiple myeloma. However, the alternative approach of enhancing the degradation of oncoproteins that are frequently overexpressed in cancers is less developed. Betulinic acid (BA) is a plant-derived small molecule that can increase apoptosis specifically in cancer but not in normal cells, making it an attractive anti-cancer agent.

Phytoestrogens for menopausal bone loss and climacteric symptoms.

Women have always looked for non-hormonal options to alleviate menopausal vasomotor symptoms and prevent menopausal bone loss. The use of complementary and alternative medicine for these purposes has particularly increased after the publication of the Women's Health Initiative's results suggesting that there might be more risks than benefits with hormone replacement. Phytoestrogens are plant-derived estrogens that, although less potent than estradiol, bind to the estrogen receptor and can function as estrogen agonists or antagonists.

Simulating geriatric home safety assessments in a three-dimensional virtual world.

Virtual worlds could offer inexpensive and safe three-dimensional environments in which medical trainees can learn to identify home safety hazards. Our aim was to evaluate the feasibility, usability, and acceptability of virtual worlds for geriatric home safety assessments and to correlate performance efficiency in hazard identification with spatial ability, self-efficacy, cognitive load, and presence. In this study, 30 medical trainees found the home safety simulation easy to use, and their self-efficacy was improved.

Differences in vitamin D3 dosing regimens in a geriatric community-dwelling population.

Objective: The adequate dose of vitamin D supplementation for community-dwelling elderly people has not been thoroughly investigated. This study aims to determine the efficacy of a low-dose and a higher dose of vitamin D3 in maintaining 25-hydroxyvitamin D [25(OH)D] levels at or above 30 ng/mL.

Methods: This was a single site, double-blind, randomized exploratory clinical trial that enrolled adults 65 years of age and older.

Ergogenic dietary aids for the elderly.

Ergogenic dietary aids might be useful adjunctive therapy to enhance the effects of exercise in the elderly, who lose physical function with age. Many such aids have been tested in athletes and untrained younger persons in laboratory and athletic performance settings, with positive results, although not all studies have demonstrated benefit. Some substances have been tested in the elderly, including creatine, caffeine, β-hydroxy-β-methylbutyrate, ubiquinone, and carnitine.

Rac1b regulates NT3-stimulated Mek-Erk signaling, directing marrow-isolated adult multilineage inducible (MIAMI) cells toward an early neuronal phenotype.

Due to the limitations of neural stem cells to repair neuronal damage in the human brain, alternative approaches of repair using autologous adult stem cells have been examined for direct cell-replacement, or paracrine mediated neuroprotective effects. Human bone marrow-derived stromal cells (hMSCs) are a heterogeneous adult stem cell population with diverse immunomodulatory properties and the potential to differentiate into cells characteristic of all three germ layers. hMSCs are a renewable source of progenitor cells suitable for cell-based tissue repair.

Development and pilot testing of a self-management internet-based program for older adults with overactive bladder.

Objectives: To implement and pilot test our Self-Management Internet-Based Program for Older Adults with Overactive Bladder (OAB-SMIP) in a group of older adults with overactive bladder (OAB) to determine its usability and outcomes, including knowledge, self-efficacy, perception of bladder condition, and health-related quality of life.

Methods: In a single-group study design with pre- and post-tests, we recruited 25 men and women age 55 or older with symptoms of OAB. The OAB-SMIP intervention consisted of 3 multimedia e-learning tutorials, social networking features, and other online resources delivered over 6 weeks.

Telehealth-assisted care coordination of older veterans with type 2 diabetes lowers coronary heart disease risk despite clinical inertia.

Background: The purpose of this study was to determine the impact of a telehealth care coordination (T-Care) program on coronary heart disease (CHD) risk in older adults with type 2 diabetes (T2D).

Methods: Forty-one patients with T2D, 68.7 (±8.

The script concordance test as a measure of clinical reasoning skills in geriatric urinary incontinence.

Objectives: To validate the use of a script concordance test (SCT), a tool to assess clinical reasoning in contexts of uncertainty, which are common in clinical geriatrics practice, on geriatric urinary incontinence (UI) to discriminate levels of expertise in this content area.

Design: A reference panel (15 geriatricians) and 12 respondents (10 senior geriatrics fellows and 2 interns) completed an online 100-item SCT test covering major topics in UI. The test was then optimized by discarding items with negative item-total correlation; the remaining 70 questions covered all major topics in UI.

A review of selected longitudinal studies on aging: past findings and future directions.

A review of the 51 longitudinal aging studies currently in the National Institute on Aging Database of Longitudinal Studies was conducted to identify major information gaps and areas for future research. Database information, which included posted study summaries, study details from principal investigators or directors of these projects, and more than 300 recent publications based on the studies, were reviewed to identify significant findings of each study. This review summarizes the main findings and identifies the need for future work within six broad study topics: cognitive function, socioeconomic status, health and physical performance, morbidity and mortality predictors, healthcare costs, and genetics.

Medical student perspectives on geriatrics and geriatric education.

Objective: To ascertain medical students' perspectives on geriatrics.

Design: Interpretative phenomenological analysis.

Setting: An allopathic, Liaison Committee on Medical Education-accredited, former Donald W.

Prevention of urinary tract infections in persons with spinal cord injury in home health care.

More than 250,000 persons in the United States live with spinal cord injury (SCI), and 10,000 to 12,000 new injuries occur each year. Of these spinal cord injured persons, 53% have tetraplegia, 46% have paraplegia, and less than 1% experience complete neurologic recovery. About 48% have complete injuries (i.