Medical Pathology Commons^™

Comparison Of Varying Tissue Freezing Methods On Murine Colonic Tissue, James Hughes

Biomedical Engineering Undergraduate Honors Theses

Histology often requires a tissue specimen to be embedded so that it may be sectioned, stained, and mounted on a microscope slide for viewing. One common method of tissue embedding for rapid histology is freezing, since freezing allows tissue to be stored without the need for fixing. Frozen tissue is often embedded in a medium such as Optimal Cutting Temperature (OCT) compound so that it can be sectioned using a cryostat. However, factors such as ice-crystal formation during the freezing process can cause damage to the tissue. As such, the protocol used to freeze the tissue can affect the quality …

Spinal Cord Trauma: An Overview Of Normal Structure And Function, Primary And Secondary Mechanisms Of Injury, And Emerging Treatment Modalities, Daniel Morin

Senior Honors Theses

The structures of the spinal cord and vertebral column are designed to provide flexibility, while still providing ample protection for the spinal cord deep within. While it does offer remarkable protection against most routine trauma, the spinal cord is still vulnerable to high-force etiologies of trauma and may become damaged as a result. These events are referred to as primary injury. Following the initial injury, the body’s own physiological responses cause a cascade of deleterious effects, known as secondary injury. Secondary injury is a major therapeutic target in mitigating the effects of spinal cord injury (SCI), and much research is …

Otologic Blast Injuries, Michelle Singer

Dissertations, Theses, and Capstone Projects

The otologic system functions as a highly sensitive pressure transducer. Because of this, the ear is the most commonly affected organ in primary blast injury. Frequently encountered symptoms include hearing loss, tinnitus, and tympanic membrane perforations. The ear is repeatedly overlooked during triage and easily forgotten in subjects with multiple injuries after major catastrophic events such as explosions. This systematic review provides an overview of the most common otologic injuries observed after blast exposure in a variety of settings and populations. An analysis of 35 studies and an additional 23 reviews was performed in attempt to uncover patterns of otologic …

Credibility, Replicability, And Reproducibility In Simulation For Biomedicine And Clinical Applications In Neuroscience., Lealem Mulugeta, Andrew Drach, Ahmet Erdemir, C A Hunt, Marc Horner, Joy P. Ku, Jerry G Myers, Rajanikanth Vadigepalli, William W. Lytton

Department of Pathology, Anatomy, and Cell Biology Faculty Papers

Modeling and simulation in computational neuroscience is currently a research enterprise to better understand neural systems. It is not yet directly applicable to the problems of patients with brain disease. To be used for clinical applications, there must not only be considerable progress in the field but also a concerted effort to use best practices in order to demonstrate model credibility to regulatory bodies, to clinics and hospitals, to doctors, and to patients. In doing this for neuroscience, we can learn lessons from long-standing practices in other areas of simulation (aircraft, computer chips), from software engineering, and from other biomedical …

Extending The Phenotypic Spectrum Of Sengers Syndrome: Congenital Lactic Acidosis With Synthetic Liver Dysfunction., David B Beck, Kristina Cusmano-Ozog, Nickie Andescavage, Eyby Leon

Pathology Faculty Publications

Sengers syndrome is a rare autosomal recessive mitochondrial disease characterized by lactic acidosis, hypertrophic cardiomyopathy and bilateral cataracts. We present here a case of neonatal demise, within the first day of life, who initially presented with severe lactic acidosis, with evidence of both chorioamnionitis and cardiogenic shock. Initial metabolic labs demonstrated a severe lactic acidosis prompting genetic testing which revealed a homozygous pathogenic variant for Sengers syndrome in

Puma Amplifies Necroptosis Signaling By Activating Cytosolic Dna Sensors., Dongshi Chen, Jingshan Tong, Liheng Yang, Liang Wei, Donna B. Stolz, Jian Yu, Jianke Zhang, Lin Zhang

Department of Microbiology and Immunology Faculty Papers

Necroptosis, a form of regulated necrotic cell death, is governed by RIP1/RIP3-mediated activation of MLKL. However, the signaling process leading to necroptotic death remains to be elucidated. In this study, we found that PUMA, a proapoptotic BH3-only Bcl-2 family member, is transcriptionally activated in an RIP3/MLKL-dependent manner following induction of necroptosis. The induction of PUMA, which is mediated by autocrine TNF-α and enhanced NF-κB activity, contributes to necroptotic death in RIP3-expressing cells with caspases inhibited. On induction, PUMA promotes the cytosolic release of mitochondrial DNA and activation of the DNA sensors DAI/Zbp1 and STING, leading to enhanced RIP3 and MLKL …

Vte Prevention: A Risk Assessment Tool, Mary Gilkey

Scholars Week

VTEs are a leading cause of hospital deaths and cost healthcare systems billions. A risk assessment tool that correctly identifies at risk patients and provides appropriate prophylactic measures can decrease the rate of hospital acquired VTE.

The Lifecycle Of An Evidence-Based Laboratory Practice Guideline: Origin, Update, Affirmation, And Impact!, Raouf Nakhleh, Patrick L Fitzgibbons, Jan A Nowak, Robert M Najarian, David F Keren, Terence J Colgan, Carol Colasacco, Lisa A Fatheree

Articles, Abstracts, and Reports

No abstract provided.

Hutchinson-Gilford Progeria Syndrome Vascular Pathology: A Focused Review, Danielle M. Eschedor

Senior Honors Theses

Hutchinson-Gilford Progeria is an accelerated aging disorder caused by a de novo point mutation in the LMNA gene which codes for an intermediate filament of the nuclear lamina called lamin A. The point mutation at c.1824C>T causes a 50-amino-acid deletion that removes the binding site for Zmpste24, a metalloprotease responsible for defarnesylating prelamin A and producing mature lamin A. Without the ability to be defarnesylated, the mutated protein, called progerin, is more lipophilic and has a myriad of cytotoxic effects. As cardiovascular disease is the most common cause of death in HGPS patients, it is important for both healthcare …

A Closer Look At The Global Management Of Spina Bifida: The Implementation Of Endoscopic Third Ventriculostomy In The Treatment Of Spina Bifida-Related Hydrocephalus In Africa, Caryssa Burckart

Senior Honors Theses

Spina bifida, specifically myelomeningocele, is a debilitating neural tube defect that affects patients and families throughout the world. Traditional management and treatment methods are described, followed by an explanation of why this is often inadequate in providing care for those in impoverished areas of the world, including many regions of Africa. Endoscopic third ventriculostomy is proposed as a promising alternative to traditional methods for treating hydrocephalus, an often associated condition, and the implementation of this treatment method in Africa is explored. In order to relieve Africa of the burden of spina bifida-related hydrocephalus and improve global management of spina bifida, …

Does Sex Of The Patient Play A Role In Survival For Msi Colorectal Cancer?, Adrian Tulin, Iulian Slavu, Raluca Tulin, Lucian Alecu, Radu C. Jecan, Cristina Orlov, Cristian I. Iaciu, Dana L. Stanculeanu, Razvan Hainarosie, Silviu Pituru, Anca Pantea Stoian, Cornelia Nitipir

Journal of Mind and Medical Sciences

Microsatellite instability (MSI) is a feature of colorectal tumors that develops as a result of inactivation of the DNA mismatch repair system. It is found in about 15% of all colorectal cancers and is an important prognostic molecular marker when assessing patients with colorectal cancer. It can influence prognosis and treatment decisions in both the advanced and early stages. Although in early stages this marker suggests a favorable prognosis and presents an important argument against adjuvant treatment in stage II disease, in metastatic stages it no longer associated with such an optimistic outcome. The present trial is a prospective, single-center …

The Psychosocial Impact Of Vaginal Delivery And Cesarean Section In Primiparous Women, Ples Liana, Romina M. Sima, Delia Carp, Camelia Alexandroaia, Denisa O. Balalau, Anca D. Stanescu, Octavian G. Olaru

Journal of Mind and Medical Sciences

The aim of this study was to identify how the method of delivery and birth experience interfere with maternal psychological status early after puerperium. We conducted a prospective study on 148 women after puerperium from November 2017 to January 2018 in Bucur Maternity Hospital. Women that delivered vaginally mobilized in the first 6 hours in 73.7% of the cases, but for cesarean section after 12- 24 hours in 43.6% of the cases. Women described good support from the obstetrician in 58.1% of the cases. 90.5% of the women reported that the method of delivery did not have an impact on …

Self-Directed Learning Modules Enhance Mastery Of Diagnostic Imaging In Dissection-Based Anatomy Course For Physician Assistant Students, Guiyan Zhang, Bruce Fenderson, Xuan Zuo

Department of Pathology, Anatomy, and Cell Biology Posters

Abstract

The virtues of using computer-based learning modules as an alternative to traditional didactic lectures were tested in a human anatomy course for Physician Assistant (PA) students. Self-directed learning modules on diagnostic imaging were created using ArticulateTM software and provided online as homework assignments for PA students taking a human anatomy lecture and dissection laboratory course. These interactive self-learning modules replaced the content of traditional didactic lectures on the same topics that had been given in previous years. For the PA class of 2016 (n=103), diagnostic imaging was taught via traditional lectures, whereas for the PA class of 2017 (n=100), …

Maternal Psychological Distress And Cortsiol, Jenna Schroeder

Grace Peterson Nursing Research Colloquium

Abstract

Background: Previous studies have reported associations between prenatal maternal distress and negative health outcomes for the unborn. There are gaps within this body of knowledge and inconsistencies in the research which make the relevant relationships unclear. If changes in maternal cortisol cause alterations in fetal development, it is important to gain an adequate understanding of how, and if, maternal psychological distress predicts maternal cortisol levels. This study is an integrative literature review that looks at the research investigating a connection between maternal psychological distress and maternal cortisol levels during pregnancy. Lazarus and Folkman’s (1984) Transactional Model of Stress and …

Head Injury Risk And Car Seat Use For Children In Collisions, Peyton A. Schroeder, M.J. Skhurm, D. Fraser, K. Mcclafferty

Western Research Forum

Background: Motor vehicle collisions (MVCs) are the leading cause of death for people under the age of 17 years. Almost 80% of rear seat motor vehicle passengers are children. Previous studies have shown that a large fraction of injuries to children in MVCs involved the head and chest. In this study, the hypothesis that children under the age of eight using a forward-facing child restraint system (FFCRS) will have more severe head injuries than children using any other type of restraints in an MVC was tested.

Methods: Several datasets obtained from Transport Canada and Level 1 Pediatric Trauma Centre emergency …

P16-Ki67-Hmb45 Immunohistochemical Profiling May Help Discriminate Between Spitzoid Melanoma And Atypical Spitz Nevi, Robert E. Garola, Vivekanand Singh

Posters

Background

When Spitz nevi have increased vertical thickness (>1.5 MM), show ulceration and deep seated mitosis, the differential diagnostic considerations of atypical Spitz nevus (ASN) or a Spitzoid melanoma (SM) enter into consideration. While expert consultation from a dermatopathologist is most often sought to resolve the differential diagnosis, it could be expensive and time consuming. Recently, the use of molecular genetic testing has also been advocated in the work group up of atypical melanocytic proliferations. On the contrary, immunohistochemistry is a more routinely used technique in most pathology centers may be more simple to apply. A single immunohistochemical marker …

A Comparison Of Oral And Intravenous Mouse Models Of Listeriosis, Michelle G. Pitts, Sarah E. F. D'Orazio

Microbiology, Immunology, and Molecular Genetics Faculty Publications

Listeria monocytogenes is one of several enteric microbes that is acquired orally, invades the gastric mucosa, and then disseminates to peripheral tissues to cause systemic disease in humans. Intravenous (i.v.) inoculation of mice with L. monocytogenes has been the most widely-used small animal model of listeriosis over the past few decades. The infection is highly reproducible and has been invaluable in deciphering mechanisms of adaptive immunity in vivo, particularly CD8+ T cell responses to intracellular pathogens. However, the i.v. model completely bypasses the gut phase of the infection. Recent advances in generating both humanized mice and murinized bacteria, as well …

Endoscopic Full-Thickness Resection Of A Gastric Subepithelial Tumor, Bhavtosh Dedania, Tejal Mistry, Jamie Buryanek, Shashideep Singhal

Faculty, Staff and Student Publications

No abstract provided.

An Aged Canid With Behavioral Deficits Exhibits Blood And Cerebrospinal Fluid Amyloid Beta Oligomers, Clare Rusbridge, Francisco J. Salguero, Monique Antoinette David, Kiterie M. E. Faller, Jose T. Bras, Rita J. Guerreiro, Angela C. Richard-Londt, Duncan Grainger, Elizabeth Head, Sebastian G. P. Brandner, Brian Summers, John Hardy, Mourad Tayebi

Pharmacology and Nutritional Sciences Faculty Publications

Many of the molecular and pathological features associated with human Alzheimer disease (AD) are mirrored in the naturally occurring age-associated neuropathology in the canine species. In aged dogs with declining learned behavior and memory the severity of cognitive dysfunction parallels the progressive build up and location of Aβ in the brain. The main aim of this work was to study the biological behavior of soluble oligomers isolated from an aged dog with cognitive dysfunction through investigating their interaction with a human cell line and synthetic Aβ peptides. We report that soluble oligomers were specifically detected in the dog's blood and …

Ssaw: A New Sequence Similarity Analysis Method Based On The Stationary Discrete Wavelet Transform, Jie Lin, Donald Adjeroh, Bing-Hua Jiang, Yue Jiang

Faculty & Staff Scholarship

Background: Alignment-free sequence similarity analysis methods often lead to significant savings in computational time over alignment-based counterparts.

Results: Anewalignment-freesequencesimilarityanalysismethod,calledSSAWisproposed.SSAWstandsfor Sequence Similarity Analysis using the Stationary Discrete Wavelet Transform (SDWT). It extracts k-mers from a sequence, then maps each k-mer to a complex number field. Then, the series of complex numbers formed are transformed into feature vectors using the stationary discrete wavelet transform. After these steps, the original sequence is turned into a feature vector with numeric values, which can then be used for clustering and/or classification.

Conclusions: Usingtwodifferenttypesofapplications,namely,clusteringandclassification,wecomparedSSAW against the the-state-of-the-art alignment free sequence analysis methods. SSAW demonstrates competitive or …

A Functional Signature Ontology (Fusion) Screen Detects An Ampk Inhibitor With Selective Toxicity Toward Human Colon Tumor Cells, Binita Das, Beth K. Neilsen, Kurt W. Fisher, Drew Gehring, Youcai Hu, Deanna J. Volle, Hyun Seok Kim, Jamie L. Mccall, David L. Kelly, John B. Macmillian, Michael A. White, Robert E. Lewis

Faculty & Staff Scholarship

AMPK is a serine threonine kinase composed of a heterotrimer of a catalytic, kinase-containing α and regulatory β and γ subunits. Here we show that individual AMPK subunit expression and requirement for survival varies across colon cancer cell lines. While AMPKα1 expression is relatively consistent across colon cancer cell lines, AMPKα1 depletion does not induce cell death. Conversely, AMPKα2 is expressed at variable levels in colon cancer cells. In high expressing SW480 and moderate expressing HCT116 colon cancer cells, siRNA-mediated depletion induces cell death. These data suggest that AMPK kinase inhibition may be a useful component of future therapeutic strategies. …

A Tangled Web: Origins Of Reproductive Parasitism, Joseph J. Gillespie, Timothy P. Driscoll, Victoria I. Verhoeve, Mohammed Sayeedur Rahman, Kevin R. Macaluso

Faculty & Staff Scholarship

While typically a flea parasite and opportunistic human pathogen, the presence of Rickettsia felis (strain LSU-Lb) in the non-blood- feeding, parthenogenetically reproducing booklouse, Liposcelis bostrychophila, provides a system to ascertain factors governing not only host transitions but also obligate reproductive parasitism (RP). Analysis of plasmid pLbAR, unique to R. felis str. LSU-Lb, revealed a toxin–antitoxin module with similar features to prophage-encoded toxin–antitoxin modules utilized by parasitic Wolbachia strains to induce another form of RP, cytoplasmic incompatibility, in their arthropod hosts. Curiously, multiple deubiquitinase and nuclease domains of the large (3,841 aa) pLbAR toxin, as well the entire antitoxin, facilitated the …

Altered Ratio Of T Follicular Helper Cells To T Follicular Regulatory Cells Correlates With Autoreactive Antibody Response In Simian Immunodeficiency Virus–Infected Rhesus Macaques, Wenjin Fan, Andrew James Demers, Yanmin Wan, Qingsheng Li

Nebraska Center for Virology: Faculty Publications

Individuals with chronic HIV-1 infection have an increased prevalence of autoreactive Abs. Many of the isolated HIV broadly neutralizing Abs from these individuals are also autoreactive. However, the underlying mechanism(s) that produce these autoreactive broadly neutralizing Abs remains largely unknown. The highly regulated coordination among B cells, T follicular helper (T_FH) cells, and T follicular regulatory (T_FR) cells in germinal centers (GCs) of peripheral lymphatic tissues (LTs) is essential for defense against pathogens while also restricting autoreactive responses. We hypothesized that an altered ratio of T_FH/T_FR cells in the GC contributes to the …

Mucosal Antibody Responses To Vaccines Targeting Siv Protease Cleavage Sites Or Fulllength Gag And Env Proteins In Mauritian Cynomolgus Macaques, Hongzhao Li, Yan Hai, So-Yon Lim, Nikki Toledo, Jose Crecente-Campo, Dane Schalk, Lin Li, Robert W. Omange, Tamara G. Dacoba, Lewis R. Liu, Mohammad Abul Kashem, Yanmin Wan, Binhua Liang, Qingsheng Li, Eva Rakasz, Nancy Schultz-Darken, Maria J. Alonso, Francis A. Plummer, James B. Whitney, Ma Luo

Nebraska Center for Virology: Faculty Publications

HIV mutates rapidly and infects CD4⁺ T cells, especially when they are activated. A vaccine targeting conserved, essential viral elements while limiting CD4⁺ T cell activation could be effective. Learning from natural immunity observed in a group of highly HIV-1 exposed seronegative Kenyan female sex workers, we are testing a novel candidate HIV vaccine targeting the 12 viral protease cleavage sites (PCSs) (the PCS vaccine), in comparison with a vaccine targeting full-length Gag and Env (the Gag/Env vaccine) in a Mauritian cynomolgus macaque/SIV model. In this study we evaluated these vaccines for induction of mucosal antibodies to SIV …

The Pathology Workforce And Clinical Licensure, Robin Lorenz, Donald S. Karcher, Michael Gautreaux, Melvin Limson, Dani Zander

Pathology Faculty Publications

There has been a recent recognition of the need to prepare PhD-trained scientists for increasingly diverse careers in academia, industry, and health care. The PhD Data Task Force was formed to better understand the current state of PhD scientists in the clinical laboratory workforce and collect up-to-date information on the training and certification of these laboratorians. In this report, we summarize the findings of the PhD Data Task Force and discuss the relevance of the data collected to the future supply of and demand for PhD clinical laboratory scientists. It is clear that there are multiple career opportunities for PhD …

Pd-L1 Checkpoint Inhibition And Anti-Ctla-4 Whole Tumor Cell Vaccination Counter Adaptive Immune Resistance: A Mouse Neuroblastoma Model That Mimics Human Disease., Priya Srinivasan, Xiaofang Wu, Mousumi Basu, Christopher Rossi, Anthony D Sandler

Pathology Faculty Publications

BACKGROUND: Adaptive immune resistance induces an immunosuppressive tumor environment that enables immune evasion. This phenomenon results in tumor escape with progression and metastasis. Programmed cell death-ligand 1 (PD-L1) expressed on tumors is thought to inhibit tumor-infiltrating lymphocytes (TILs) through programmed cell death 1 (PD1), enabling adaptive immune resistance. This study investigates the role of PD-L1 in both mouse and human neuroblastoma immunity. The consequence of PD-L1 inhibition is characterized in the context of an established whole tumor cell vaccine.

METHODS AND FINDINGS: A mouse model of neuroblastoma was investigated using an Id2 knockdown whole cell vaccine in combination with checkpoint …

Sivcpz Closely Related To The Ancestral Hiv-1 Is Less Or Non-Pathogenic To Humans In A Hu-Blt Mouse Model, Zhe Yuan, Guobin Kang, Lance Daharsh, Wenjin Fan, Qingsheng Li

Nebraska Center for Virology: Faculty Publications

The HIV-1 pandemic is a consequence of the cross-species transmission of simian immunodeficiency virus in wild chimpanzees (SIVcpz) to humans. Our previous study demonstrated SIVcpz strains that are closely related to the ancestral viruses of HIV-1 groups M (SIVcpzMB897) and N (SIVcpzEK505) and two SIVcpz lineages that are not associated with any known HIV-1 infections in humans (SIVcpzMT145 and SIVcpzBF1167), all can readily infect and robustly replicate in the humanized-BLT mouse model of humans. However, the comparative pathogenicity of different SIVcpz strains remains unknown. Herein, we compared the pathogenicity of the above four SIVcpz strains with HIV-1 using humanized-BLT mice. …

Identification Of Unequally Represented Founder Viruses Among Tissues In Very Early Siv Rectal Transmission, Jian Chen, Yanqin Ren, Lance Daharsh, Lu Liu, Guobin Kang, Qingsheng Li, Qiang Wei, Yanmin Wu, Jianqing Xu

Nebraska Center for Virology: Faculty Publications

Characterizing the transmitted/founder (T/F) viruses of multi-variant SIV infection may shed new light on the understanding of mucosal transmission.We intrarectally inoculated six Chinese rhesus macaques with a single high dose of SIVmac251 (3.1 × 10⁴ TCID₅₀) and obtained 985 full-length env sequences from multiple tissues at 6 and 10 days post-infection by single genome amplification (SGA). All 6 monkeys were infected with a range of 2 to 8 T/F viruses and the dominant variants from the inoculum were still dominant in different tissues from each monkey. Interestingly, our data showed that a cluster of rare T/F viruses …

Analytical Performance Of A Low‐Cost Multiplex Polymerase Chain Reaction Human Papillomavirus Genotyping Assay For Use In Sub‐Saharan Africa, Kandali Samwel, Crispin Kahesa, Julius Mwaiselage, Daniela Gonzalez, John T. West, Charles Wood, Joel Palefsky, Peter C. Angeletti

Nebraska Center for Virology: Faculty Publications

We have tested a multiplex polymerase chain reaction (PCR) human papillomavirus (HPV) genotyping assay to fill the need for rapid and low‐cost HPV detection in Sub‐ Saharan Africa. This method allows high throughput genotyping and simultaneous detection of 14 high‐risk and two low‐risk HPV types, by PCR amplification of HPV DNAs in a single reaction tube. In this study, we describe stepwise experiments to validate the multiplex HPV PCR assay for determination of HPV genotypes from 104 cervical brush samples from Tanzanian women. Assay performance was evaluated by determination of intra‐laboratory reproducibility, sensitivity, and specificity. Further performance was assessed by …

Discovery Of A Non-Nucleoside Rna Polymerase Inhibitor For Blocking Zika Virus Replication Through In Silico Screening, Aryamav Pattnaik, Nicholas Palermo, Bikash R. Sahoo, Zhe Yuan, Duoyi Hu, Arun S. Annamalai, Hiep L. X. Vu, Ignacio Correas, Pavan Kumar Prathipati, Christopher J. Destache, Qingsheng Li, Fernando A. Osorio, Asit K. Pattnaik, Shi-Hua Xiang

Nebraska Center for Virology: Faculty Publications

Zika virus (ZIKV), an emerging arbovirus, has become a major human health concern globally due to its association with congenital abnormalities and neurological diseases. Licensed vaccines or antivirals against ZIKV are currently unavailable. Here, by employing a structure-based approach targeting the ZIKV RNA-dependent RNA polymerase (RdRp), we conducted in silico screening of a library of 100,000 small molecules and tested the top ten lead compounds for their ability to inhibit the virus replication in cell-based in vitro assays. One compound, 3-chloro-N-[({4-[4-(2-thienylcarbonyl)-1-piperazinyl]phenyl}amino)carbonothioyl]-1-benzothiophene-2-carboxamide (TPB), potently inhibited ZIKV replication at submicromolar concentrations. Molecular docking analysis suggests that …