Integrative neurobiology of metabolic diseases, neuroinflammation, and neurodegeneration

Alzheimer’s disease (AD) is a complex, multifactorial disease with a number of leading mechanisms, including neuroinflammation, processing of amyloid precursor protein (APP) to amyloid β peptide, tau protein hyperphosphorylation, relocalization and deposition. These mechanisms are propagated by obesity, the metabolic syndrome and type-2 diabetes mellitus. Stress, sedentariness, dietary overconsumption of saturated fat and refined sugars, and circadian derangements/disturbed sleep contribute to obesity and related metabolic diseases, but also accelerate age-related damage and senescence that all feed the risk of developing AD too. The complex and interacting mechanisms are not yet completely understood and will require further analysis. Instead of investigating AD as a mono- or oligocausal disease we should address the disease by understanding the multiple underlying mechanisms and how these interact. Future research therefore might concentrate on integrating these by systems biology approaches, but also to regard them from an evolutionary medicine point of view. The current review addresses several of these interacting mechanisms in animal models and compares them with clinical data giving an overview about our current knowledge and puts them into an integrated framework

NIK Stabilization Leads to Increased Bone Resorption in vitro via Cytoskeletal Changes in the Osteoclast

From the Washington University Senior Honors Thesis Abstracts (WUSHTA), Volume 5, Spring 2013. Published by the Office of Undergraduate Research. Joy Zalis Kiefer, Director of Undergraduate Research / Assistant Dean in the College of Arts & Sciences; E. Holly Tasker, Editor; Kristin Sobotka, Undergraduate Research Coordinator. Mentor: Deborah Novac

NIK Stabilization Leads to Increased Bone Resorption In Vitro Via Cytoskeletal Changes in the Osteoclast

Mentor: Deborah Novack From the Washington University Undergraduate Research Digest: WUURD, Volume 8, Issue 2, Spring 2013. Published by the Office of Undergraduate Research, Joy Zalis Kiefer Director of Undergraduate Research and Assistant Dean in the College of Arts & Sciences; Kristin Sobotka, Editor

Isolation and Characterization of Vortex, a Novel Mycobacteriophage

Mentor: Sarah Elgin and Kathy Hafer From the Washington University Undergraduate Research Digest: WUURD, Volume 6, Issue 1, Fall 2010. Published by the Office of Undergraduate Research. Henry Biggs, Director of Undergraduate Research and Associate Dean in the College of Arts & Sciences; Joy Zalis Kiefer, Undergraduate Research Coordinator, Co-editor, and Assistant Dean in the College of Arts & Sciences; Kristin Sobotka, Editor

Moodbook: an application for continuous monitoring of social media usage and mood

The use of mobile phones has transcended its initial use as a communication device to become a medium to fulfilling social needs. While this has been beneficial to some, studies have exposed adverse effects such as depression and social media addiction. Since it is not always clear which category the user belongs, we propose a mobile application that records the social media interaction patterns of a user. The application also captures their mood before and after each social media use, until it can automatically infer the mood of the user through their social media interaction pattern. Consenting users can transmit the data collected on their device to a central location for further analysis by researchers of human behaviour or mobile application developers to provide intervention to users or design guidelines for mobile applications

Moodbook:an application for continuous monitoring of social media usage and mood

\u3cp\u3eThe use of mobile phones has transcended its initial use as a communication device to become a medium to fulfilling social needs. While this has been beneficial to some, studies have exposed adverse effects such as depression and social media addiction. Since it is not always clear which category the user belongs, we propose a mobile application that records the social media interaction patterns of a user. The application also captures their mood before and after each social media use, until it can automatically infer the mood of the user through their social media interaction pattern. Consenting users can transmit the data collected on their device to a central location for further analysis by researchers of human behaviour or mobile application developers to provide intervention to users or design guidelines for mobile applications.\u3c/p\u3

Metal Artifact Reduction MRI of Total Ankle Arthroplasty

Category: Ankle Arthritis Introduction/Purpose: Total ankle arthroplasty (TAA) is an often successful treatment for end-stage ankle arthritis; however, a subset of patient presents with ankle pain following TAA and concern for early failure. Although radiographs are often diagnostic, patients with normal radiographs and continued pain pose a diagnostic challenge. In those patients, magnetic resonance imaging (MRI) may be helpful to evaluate periprosthetic bone and soft tissues. Traditional high-bandwidth (high-BW) metal artifact reduction sequence (MARS) MRI lessens metal artifacts, but image distortions remain with Cobalt-Chromium implants. Slice- Encoding-Metal-Artifact-Correction (SEMAC) is a recently FDA-approved, advanced MARS technique that promises more powerful metal suppression. Therefore, we prospectively tested the hypothesis that SEMAC MARS MRI facilitates better metal reduction and visibility of periprosthetic structures than does traditional MARS MRI in patients with TAA. Methods: In this IRB-approved study, 20 volunteers [10 females/10 males; age, 59 (41-73) years, 15 (3-24) months post- operatively] with TAA were prospectively enrolled. The research protocol consisted of high-BW and SEMAC MARS MRI using a clinical 1.5 Tesla MRI scanner and a dedicated boot-shaped MRI coil. For each technique, intermediate-weighted and fat- suppressed MR images were obtained in axial, sagittal and coronal orientation. Three observes (2 foot/ankle surgeons and 1 musculoskeletal radiologist) evaluated the high-BW and SEMAC MR images in an independent, random and blinded fashion. Equidistance 5-point Likert scales (1=non-diagnostic, 5=very good) were used to grade image quality as well as the quality of metal suppression and visibility of bone-metal interfaces, tendons, ligaments, bone and joints. Differences between the two MARS techniques were assessed with a Kruskall-Wallis test, and interobserver agreement was graded with Intraclass-Correlation- Coefficient (ICC). Bonferroni-corrected p-values ≤ 0.01 were considered significant. Results: All 20 subjects completed the research protocol. There was good agreement between observers (ICC = 0.79; 95% CI, 0.78-0.80). Image quality of high-BW and SEMAC MR images was similar for tissue contrast, fat suppression, and fluid brightness, whereas image sharpness was one interval higher on high-BW images than on SEMAC images (p < 0.01). Metal reduction of TAA components was significantly better (p < 0.01) on SEMAC images (very good) than on high-BW images (poor-to-adequate). At level of the implants, long flexor and peroneal tendons, deep deltoid, syndesmotic and lateral collateral ligaments, and medial and lateral gutters were significantly better seen (p < 0.01) on SEMAC images (good-to-very good) than on high-BW images (poor-to- adequate). Similar visibility (good-to-very good) was found for the remainder of the tendons, ligaments, bones and joints. Conclusion: Based on the results of our study, we accept the hypothesis that SEMAC MARS MRI outperforms traditional high- BW MARS MRI in the degree of metal artifact reduction as well as visibility of bone implant interfaces and periprosthetic tendons and ligaments at level of the joint line. We believe advanced MARS MRI can be a valuable clinical tool to assess osseous integration and soft tissue lesions in patients following TAA

Metal Artifact Reduction MRI for Sagittal Balance Evaluation of Total Ankle Arthroplasty

Category: Ankle Arthritis Introduction/Purpose: Surgical restoration of the anatomical relationship between talus and tibia is considered crucial for longevity of total ankle arthroplasty (TAA). Weight-bearing (WB) radiographs are the current standard for evaluating the sagittal balance alignment, which are, however, prone to rotational misalignment and potentially altered measurements. Metal artifact reduction sequence (MARS) MRI is a cross-sectional technique that minimizes implant-induced artifacts and affords the visualization of bone-implant interfaces and periprosthetic bone without distortions. Although not weight-bearing, MARS MRI offers the ability to align the image plane to the true sagittal axis of the talar implant and anatomically correct measurements. Therefore, the purpose of this study was to compare sagittal balance alignment measurements on MARS MR images and standard WB radiographs in patients with TAA. Methods: In this IRB-approved, prospective study, 23 subjects [10 men/13 women, age 60(41-73) years; 13(3-24) months post- op] underwent MARS MRI and standard lateral WB radiographs. Standardized MARS MR images were obtained in alignment to the sagittal talar component axis and use of a boot-shaped MRI coil. Maximum-intensity-projection MR images that resemble lateral radiographs were created to bring anatomic landmarks, such as lateral talar process, talonavicular joint line, talar implant, tibial shaft, and posterior talus into one single image. Three board-certified foot ankle surgeons performed sagittal balance alignment measurements twice in an independent, random and blinded fashion. The second set of measurements was obtained 1 months after the first assessment. In accordance with published measurements, lateral talar station (LTS), tibial axis-to-talus (T-T) ratio, and normalized tibial axis-to-lateral-process (T-L) distance were measured. Pearson correlation coefficient (r), Concordance-Correlation-Coefficient (CCC) and Intraclass-Correlation-Coefficient (ICC) were used for statistical analysis. Bonferroni-corrected p-values ≤ 0.01 were considered significant. Results: The intra-observer agreement was excellent for radiographic (CCC = 0.93 - 0.97) and MRI (CCC = 0.90 - 0.97) measurements. Inter-observer agreements were good-to-excellent with overall higher agreements for MRI (ICC = 0.76 - 0.93) than for radiography (ICC = 0.58 - 0.95) measurements. There was statistically significant inter-method correlation between radiographic and MRI measurements including LTS (r=0.83, p < 0.001), T-T ratio (r=0.86, p < 0.001) and normalized T-L distance (r=0.72, p < 0.001). The T-T ratios of radiographs and MRI were statistically not different (p=0.36), whereas LTS and normalized T-L distance were significantly lower on MR images when compared with radiographs (p < 0.001). Conclusion: Sagittal balance measurements performed on standardized weight-bearing radiographs and standardized MARS MR images demonstrate substantial correlation and similarity. Given its high inter- and intra-observer agreement, MARS MRI may be helpful for the evaluation of sagittal balance following TAA