Novel application of behavioral assays allows dissociation of joint pathology from systemic extra-articular alterations induced by inflammatory arthritis

Introduction: Although rheumatoid arthritis (RA) is a disease of articular joints, patients often suffer from co-morbid neuropsychiatric changes, such as anxiety, that may reflect links between heightened systemic inflammation and abnormal regulation of the hypothalamic-pituitary-adrenal (HPA) axis. Here, we apply behavioral neuroscience methods to assess the impact of antigen-induced arthritis (AIA) on behavioral performance in wild type (WT) and interleukin-10 deficient (Il10-/-) mice. Our aim was to identify limb-specific motor impairments, as well as neuropsychological responses to inflammatory arthritis. Methods: Behavioral testing was performed longitudinally in WT and Il10-/- mice before and after the induction of arthritic joint pathology. Footprint analysis, beam walking and open field assessment determined a range of motor, exploratory and anxiety-related parameters. Specific gene changes in HPA axis tissues were analyzed using qPCR. Results: Behavioral assessment revealed transient motor and exploratory impairments in mice receiving AIA, coinciding with joint swelling. Hind limb coordination deficits were independent of joint pathology. Behavioral impairments returned to baseline by 10 days post-AIA in WT mice. Il10-/- mice demonstrated comparable levels of swelling and joint pathology as WT mice up to 15 days post-AIA, but systemic differences were evident in mRNA expression in HPA axis tissues from Il10-/- mice post-AIA. Interestingly, the behavioral profile of Il10-/- mice revealed a significantly longer time post-AIA for activity and anxiety-related behaviors to recover. Conclusions: The novel application of sensitive behavioral tasks has enabled dissociation between behaviors that occur due to transient joint-specific pathology and those generated by more subtle systemic alterations that manifest post-AIA

Upregulation of CD36, a Fatty Acid Translocase, Promotes Colorectal Cancer Metastasis by Increasing MMP28 and Decreasing E-Cadherin Expression

Altered fatty acid metabolism continues to be an attractive target for therapeutic intervention in cancer. We previously found that colorectal cancer (CRC) cells with a higher metastatic potential express a higher level of fatty acid translocase (CD36). However, the role of CD36 in CRC metastasis has not been studied. Here, we demonstrate that high expression of CD36 promotes invasion of CRC cells. Consistently, CD36 promoted lung metastasis in the tail vein model and GI metastasis in the cecum injection model. RNA-Seq analysis of CRC cells with altered expression of CD36 revealed an association between high expression of CD36 and upregulation of MMP28, a novel member of the metallopeptidase family of proteins. Using shRNA-mediated knockdown and overexpression of CD36, we confirmed that CD36 regulates MMP28 expression in CRC cells. siRNA-mediated knockdown of MMP28 decreases invasion of CRC cells, suggesting that MMP28 regulates the metastatic properties of cells downstream of CD36. Importantly, high expression of MMP28 leads to a significant decrease in active E-cadherin and an increase in the products of E-cadherin cleavage, CTF1 and CTF2. In summary, upregulation of CD36 expression promotes the metastatic properties of CRC via upregulation of MMP28 and an increase in E-cadherin cleavage, suggesting that targeting the CD36–MMP28 axis may be an effective therapeutic strategy for CRC metastasis

Chancellor\u27s Citations for Extraordinary Campus Leadership and Service (2014)

The Chancellor’s Citations for Extraordinary Campus Leadership and Service recognize graduating students who are extraordinary campus leaders for their significant service to others

Moebius Syndrome Awareness Day 2016 at Oregon State University

Moebius Syndrome is a congenital neurological disorder that results in weakness or paralysis of the sixth and seventh cranial nerves, resulting in inability to form facial expression. The current study examined the relationship between orientation of describing Moebius Syndrome and the participant ratings of pictures of individuals with Moebius Syndrome of friendliness and capability. The medical model is a description of Moebius Syndrome focusing on symptoms and treatment. The social model is a description focusing on how Moebius affects patient’s lives and social relationships. Participants were then asked to rate pictures of people with Moebius Syndrome in terms of friendliness and capability on a five-point scale. It was hypothesized that participants chosen to participate in the social model would rate the pictures higher on both dimensions than participants in the medical model. Participants were invited to create a sign with what others should know about Moebius Syndrome. These signs were then analyzed for content using Linguistic Inquiry and Word Count (LIWC) software. Signs were separated into medical and social model and compared across five categories. It was hypothesized that signs created after the social model would reflect a higher percentage of social words, whereas medical signs would reflect more medical terms. It was found that there was no significant difference between social and medical model groups in how participants rated pictures in terms of both variables. Participants were asked to rate their knowledge of Moebius Syndrome before and after the intervention on a five-point scale. It was found that knowledge about the condition significantly increased during the course of the intervention. Signs created after partaking in the social model of disability scored significantly higher in the “social” category. Signs created after hearing the medical model of disability resulted in significantly higher in the “medical” and “body” categories. Regardless of model received, participants felt social understanding was significantly more important than finding treatments and cures. The results of this study indicate that informing participants of Moebius Syndrome results in an increase of knowledge. This would indicate that the intervention was successful, regardless of the insignificance between groups on progression of knowledge. Overall, knowledge intervention in a population of college students, faculty and community members results in increased knowledge and positive ratings of capability and friendliness

Epidemiology of Injuries at a Tertiary Care Center in Malawi

Injury surveillance is an ongoing process required for primary, secondary, and tertiary injury prevention. In Malawi, hospital-based injury data are not available

Design and development of trash trap of stream for mini hydro

The river became increasingly contaminated over the years and in the wake of rapid development in the town. The purpose of this paper is to invent and provide a trash collector for mini hydro that is readily removable so that the trashes collected can be easily disposed of. Design of the trash trap should be compatible with existing stream structures. Trash trap must prevent any trash and debris from passing through the mini hydro. Fieldwork was done at the stream river to investigate the surrounding and stream structure. The data collected were mass of trash collected with diverter and without diverter. A total of 10.0 kg of trashes were collected. The efficiency of the trash trap was calculated by the proportion of the average mass of diverted trashes by the total mass of trapped trashes. The targeted efficiency for this trash trap project is 70.0%. Based on the data collected, the efficiency of this trash trap is 84.12%. The targeted efficiency was achieved and design improvement of this trash trap will be discussed at the recommendation. In conclusion, the trash trap had been proven as a potential solution for the mini hydro machine problem, diverts and prevents most of the trashes from entering the mini hydro and blocked the turbine from rotating

Clotrimazole Preferentially Inhibits Human Breast Cancer Cell Proliferation, Viability and Glycolysis

BACKGROUND: Clotrimazole is an azole derivative with promising anti-cancer effects. This drug interferes with the activity of glycolytic enzymes altering their cellular distribution and inhibiting their activities. The aim of the present study was to analyze the effects of clotrimazole on the growth pattern of breast cancer cells correlating with their metabolic profiles. METHODOLOGY/PRINCIPAL FINDINGS: Three cell lines derived from human breast tissue (MCF10A, MCF-7 and MDA-MB-231) that present increasingly aggressive profiles were used. Clotrimazole induces a dose-dependent decrease in glucose uptake in all three cell lines, with K(i) values of 114.3±11.7, 77.1±7.8 and 37.8±4.2 µM for MCF10A, MCF-7 and MDA-MB-231, respectively. Furthermore, the drug also decreases intracellular ATP content and inhibits the major glycolytic enzymes, hexokinase, phosphofructokinase-1 and pyruvate kinase, especially in the highly metastatic cell line, MDA-MB-231. In this last cell lineage, clotrimazole attenuates the robust migratory response, an effect that is progressively attenuated in MCF-7 and MCF10A, respectively. Moreover, clotrimazole reduces the viability of breast cancer cells, which is more pronounced on MDA-MB-231. CONCLUSIONS/SIGNIFICANCE: Clotrimazole presents deleterious effects on two human breast cancer cell lines metabolism, growth and migration, where the most aggressive cell line is more affected by the drug. Moreover, clotrimazole presents little or no effect on a non-tumor human breast cell line. These results suggest, at least for these three cell lines studied, that the more aggressive the cell is the more effective clotrimazole is

Assessment of Cardiac, Vascular, and Pulmonary Pathobiology In Vivo During Acute COVID-19.

Background Acute COVID-19-related myocardial, pulmonary, and vascular pathology and how these relate to each other remain unclear. To our knowledge, no studies have used complementary imaging techniques, including molecular imaging, to elucidate this. We used multimodality imaging and biochemical sampling in vivo to identify the pathobiology of acute COVID-19. Specifically, we investigated the presence of myocardial inflammation and its association with coronary artery disease, systemic vasculitis, and pneumonitis. Methods and Results Consecutive patients presenting with acute COVID-19 were prospectively recruited during hospital admission in this cross-sectional study. Imaging involved computed tomography coronary angiography (identified coronary disease), cardiac 2-deoxy-2-[fluorine-18]fluoro-D-glucose positron emission tomography/computed tomography (identified vascular, cardiac, and pulmonary inflammatory cell infiltration), and cardiac magnetic resonance (identified myocardial disease) alongside biomarker sampling. Of 33 patients (median age 51 years, 94% men), 24 (73%) had respiratory symptoms, with the remainder having nonspecific viral symptoms. A total of 9 patients (35%, n=9/25) had cardiac magnetic resonance-defined myocarditis. Of these patients, 53% (n=5/8) had myocardial inflammatory cell infiltration. A total of 2 patients (5%) had elevated troponin levels. Cardiac troponin concentrations were not significantly higher in patients with and without myocarditis (8.4 ng/L [interquartile range, IQR: 4.0-55.3] versus 3.5 ng/L [IQR: 2.5-5.5]; P=0.07) or myocardial cell infiltration (4.4 ng/L [IQR: 3.4-8.3] versus 3.5 ng/L [IQR: 2.8-7.2]; P=0.89). No patients had obstructive coronary artery disease or vasculitis. Pulmonary inflammation and consolidation (percentage of total lung volume) was 17% (IQR: 5%-31%) and 11% (IQR: 7%-18%), respectively. Neither were associated with the presence of myocarditis. Conclusions Myocarditis was present in a third patients with acute COVID-19, and the majority had inflammatory cell infiltration. Pneumonitis was ubiquitous, but this inflammation was not associated with myocarditis. The mechanism of cardiac pathology is nonischemic and not attributable to a vasculitic process. Registration URL: https://www.isrctn.com; Unique identifier: ISRCTN12154994