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Oxidative Stress And Heme Oxygenase-1 Regulated Human Mesenchymal Stem Cells Differentiation, Luca Vanella, Christopher Sanford Jr., Dong Hyun Kim, Nader G. Abraham, Nabil Ebraheim

Biochemistry and Microbiology

This paper describes the effect of increased expression of HO-1 protein and increased levels of HO activity on differentiation of bone-marrow-derived human MSCs. MSCs are multipotent cells that proliferate and differentiate into many different cell types including adipocytes and osteoblasts. HO, the rate-limiting enzyme in heme catabolism, plays an important role during MSCs differentiation. HO catalyzes the stereospecific degradation of heme to biliverdin, with the concurrent release of iron and carbon monoxide. Upregulation of HO-1 expression and increased HO activity are essential for MSC growth and differentiation to the osteoblast lineage consistent with the role of HO-1 in hematopoietic stem …

Reciprocal Effects Of Oxidative Stress On Heme Oxygenase Expression And Activity Contributes To Reno-Vascular Abnormalities In Ec-Sod Knockout Mice, Tomoko Kawakami, Nitin Puri, Komal Sodhi, Lars Bellner, Toru Takahashi, Kiyoshi Morita, Rita Rezzani, Tim D. Oury, Nader G. Abraham

Biochemistry and Microbiology

Heme oxygenase (HO) system is one of the key regulators of cellular redox homeostasis which responds to oxidative stress (ROS) via HO-1 induction. However, recent reports have suggested an inhibitory effect of ROS on HO activity. In light of these conflicting reports, this study was designed to evaluate effects of chronic oxidative stress on HO system and its role in contributing towards patho-physiological abnormalities observed in extracellular superoxide dismutase (EC-SOD, SOD3) KO animals. Experiments were performed in WT and EC-SOD^(−/−) mice treated with and without HO inducer, cobalt protoporphyrin (CoPP). EC-SOD^(−/−) mice exhibited oxidative stress, renal histopathological abnormalities, …

Defining Bone Health And Fracture Risk In West Virginia: The World Health Organization Frax® Assessment Tool, Franklin D. Shuler Md, Jacob Conjeski Md

Orthopaedics

This article highlights the expanding burden of osteoporosis in West Virginia. WV ranks second nationally in the percentage of its population that is ≥ 65 years of age. Our older population increases the risk of osteoporosis and fracture; the most recent data indicates that 77% of our women age 50 and older have osteoporosis or low bone mass. The lifetime risk of osteoporotic related fracture is alarming and occurs in 50% of females and 25% of males age 50 and older. The risk of osteoporosis related hip fracture in women is equal to the combined risk of breast, uterine or …

Na/K-Atpase Mimetic Pnaktide Peptide Inhibits The Growth Of Human Cancer Cells, Zhichuan Li, Zhongbing Zhang, Joe X. Xie, Xin Li, Jiang Tian, Ting Cai, Hongaun Cui, Hanfei Ding, Joseph I. Shapiro Md, Zijian Xie

Biochemistry and Microbiology

Cells contain a large pool of non-pumping Na/K-ATPase that participates in signal transduction. Here, we show that the expression of α1 Na/K-ATPase is significantly reduced in human prostate carcinoma as well as in several human cancer cell lines. This down-regulation impairs the ability of Na/K-ATPase to regulate Src-related signaling processes. Supplement of pNaKtide, a peptide derived from α1 Na/K-ATPase, reduces activities of Src and Src effectors. Consequently, these treatments stimulate apoptosis and inhibit growth in cultures of human cancer cells. Moreover, administration of pNaKtide inhibits angiogenesis and growth of tumor xenograft. Thus, the new findings demonstrate the in vivo effectiveness …

Standing In The Gap: The Primary Care Physician And Alzheimer’S Disease, Shirley M. Neitch

Internal Medicine

There is a huge volume of information recently published about Alzheimer’s disease, but most of it is not targeted to the average busy primary care physician, even though these PCPs are providing the bulk of care to patients with dementia. This paper is a succinct clinical review of the current state of diagnosis and treatment of Alzheimer’s disease, including citations of resources for physicians and caregivers.

Driving Assessment Results In Patients With A Diagnosis Of Dementia, Shirley M. Neitch, Guillermo Madero, Shawn Maynard

Internal Medicine

Primary care physicians are frequently involved in cases in which they must decide if a patient with dementia should stop driving. The decision is complex, and there are no firm clinical guidelines available. We examined the results of a number of patients who have undergone assessment in our Driving Assessment Clinic, to determine if any of our findings correlated with the diagnosis of dementia. If any associations exist, recommendations may be possible to assist PCPs in making the decision to have patients stop driving, even if full formal testing cannot be done.

The Implications Of Chronic Pain Models For Rehabilitation Of Distal Radius Fracture, Saurabh Mehta, Joy Macdermid, Mary Tremblay

Physical Therapy Faculty Research

Distal radius fracture (DRF) is the most common fracture and usually occurs as a result of a fall. Most patients recover following DRF with minimal residual pain or disability; however, a small subset of patients continue to experience pain and disability even one year after the injury. Currently, there are no practice guidelines for early identification and treatment of patients who are potentially at greater risk of developing these adverse outcomes. As a result, hand therapy management of patients following DRF does not incorporate screening of these at-risk patients. The objective of this paper is to apply constructs from learned …

Dietary Interventions Against Mammary Glands And Prostate Cancers, Juliana Adedayo Akinsete

Theses, Dissertations and Capstones

Dietary components modulate normal cellular functions and, in cancer cells, alter processes that lead to cancer and/or its progression. The change in the patterns of human food production and consumption over time has contributed to increasing risk for diseases including cancer. Omega-3 and omega-6 fatty acids are classes of essential polyunsaturated fatty acids in the human diet and are required for normal growth and development. Omega-3 and omega-6 fats are thought to be required in the ratio of 1:1 to 1:4 on which humans are thought to have evolved. However, the Western diet has greatly shifted from this ratio. The …

Identification Of Genes Involved In Hematopoietic Stem Cell Differentiation And Leukemia Differentiation And Leukemia, Jasjeet Bhullar

Theses, Dissertations and Capstones

Hematopoiesis is maintained by a proper balance between self renewal and multipotent differentiation of the hematopoietic stem cells (HSC). Acute myelogenous leukemia (AML) is characterized by the blockage in the differentiation of HSC, while self renewal and proliferation is preserved. It is important to understand the mechanisms involved in the inhibition of hematopoietic differentiation and maintenance of the HSC state in order to develop better therapies for AML. In these studies I have explored the role of Hsp90, omega-3 fatty acids and YB-1 in hematopoietic differentiation. EML, a hematopoietic precursor cell line, was used as a model for the hematopoietic …

Pitx2 Is Overexpressed In Follicular Cell-Derived Thyroid Cancer And Promotes Thyroid Cancer Proliferation By Regulating Cell Cycle, Yue Huang

Theses, Dissertations and Capstones

Thyroid cancer is the most prevailing malignancy of the endocrine system. Its incidence is rapidly rising at the second fastest rate of all malignancies in the United States, making it a significant health problem. Although the majority of thyroid cancer is slowly-growing and well-differentiated, available treatment options are very limited, and most of them require complete removal of the thyroid gland and surrounding tissues. Patients who have undergone thyroid removal have to take life-long hormone replacement therapy, which is very inconvenient and costly. Therefore, there is an urgent need to develop new treatments for this disease. As a prerequisite for …

Cancer Cachexia And Cardiac Atrophy In The Apcmin/+ Mice Model Of Colon Cancer, Nandini Durga Prasanna Kumar Manne

Theses, Dissertations and Capstones

Cancer cachexia is a muscle wasting condition that occurs in response to a malignant growth in the body. Cachexia is associated with heart failure and is estimated to be the immediate cause of death in about a third of all cancer patients. The purpose of this study was to investigate cardiac atrophy in the APCmin/+ mouse model of colorectal cancer. Compared to age matched C57BL/6 (BL6) mice, APCmin/+ body mass and heart mass were lower at 12 (11.1 Ѡ4.5% and 7.6 Ѡ2.8%, respectively) and 20-weeks (26.1 Ѡ2.5% and 6.0 Ѡ3.8%, respectively) of age (P < 0.05). Immunoblot analysis revealed that these changes in mass were accompanied by increased activation of protein kinase B (Akt Thr 473: 74.4 Ѡ10.9% and 216.0 Ѡ19.6% ; Akt Ser 308: 161.6 Ѡ31.7% and 367.4 Ѡ41.6% at 12- and 20-weeks, respectively, (P < 0.05)), mammalian target of rapamycin (mTOR Ser2448: 23.2 Ѡ13.2% and 44.0 Ѡ16.4% at 12- and 20-weeks, respectively, (P < 0.05)), 5' adenosine monophosphate-activated protein kinase (AMPK: 19.6 Ѡ5.2% and 22.5 Ѡ5.5% at 12- and 20-weeks, respectively, (P < 0.05)) and elevated levels of the autophagy regulator beclin1 (4.7 Ѡ3.3% and 9.5 Ѡ3.0% at 12- and 20-weeks, respectively, (P < 0.05)). No evidence of increased cardiac apoptosis, protein ubiquitination or activation of cardiac caspases or calpains was noted. Taken together, these data suggest that the cardiac atrophy that occurs in the 12- and 20-week old APCmin/+ mouse is relatively modest compared to that seen with other tumor models [1] and is associated with evidence of increased cardiac autophagy.

Predictors Of Postoperative Respiratory Failure In Patients Receiving Anesthesia, Marty Henley

Theses, Dissertations and Capstones

Introduction: Postoperative Respiratory failure has been identified as a prevention quality indicator by The Agency for Health Research and Quality (AHRQ). Postoperative Respiratory Failure is associated with increased length of stay, increased costs and increased morbidity and mortality. Unfortunately, current research is limited regarding scoring methods which are predictive for postoperative respiratory failure. This retrospective case control study was conducted to determine if the various tools of evaluation of risk currently available and to determine if any are predictive of the risk of developing postoperative respiratory failure.

Methodology: The design of this research was a retrospective case control study conducted …

Residency Corner, Tamara Gravano

Physical Therapy Faculty Research

The new Residency Corner will feature articles written by residents that describe topics such as in-depth case analysis, problem solving, and practice as nonphysician primary care providers. Here residents will get to discuss their findings and thought-processes with an audience of their peers--those clinicians and academics interested in the advancement of geriatric health care. Also, for those who may be interested to see what geriatric residency education is really all about, these clinical snapshots can help remove the veil and provide a glimpse into the level of practice our residents are experiencing. Yet, this is only one half of the …

Systematic Review Of Home Physiotherapy After Hip Fracture Surgery, Saurabh Mehta, Jean-Sébastien Roy

Physical Therapy Faculty Research

OBJECTIVE: To compare the benefits of home physiotherapy, institution-based physiotherapy and no physiotherapy following hip fracture surgery.

DESIGN: Systematic review and meta-analysis of randomized controlled trials.

METHODS: Two reviewers independently extracted data from 5 included studies. Standardized mean differences were pooled for health-related quality of life and performance-based outcomes. Review Manager Version 5 was used for data analysis.

RESULTS: Analysis of the 5 included studies indicated that home physiotherapy was better than no physiotherapy and similar to outpatient physiotherapy in improving patient-reported health-related quality of life. Performance-based outcomes were marginally better following outpatient physiotherapy compared with home physiotherapy 3 and …