Digital Commons Network^™

In Utero And Post-Natal Opioid Exposure Followed By Mild Traumatic Brain Injury Contributes To Cortical Neuroinflammation, Mitochondrial Dysfunction, And Behavioral Deficits In Juvenile Rats, Austin M. Gowen, Jina Yi, Kelly L. Stauch, Luke Miles, Sanjay Srinivasan, Katherine Odegaard, Gurudutt Pendyala, Sowmya V. Yelamanchili

Journal Articles: Anesthesiology

Maternal opioid use poses a significant health concern not just to the expectant mother but also to the fetus. Notably, increasing numbers of children born suffering from neonatal opioid withdrawal syndrome (NOWS) further compounds the crisis. While epidemiological research has shown the heightened risk factors associated with NOWS, little research has investigated what molecular mechanisms underly the vulnerabilities these children carry throughout development and into later life. To understand the implications of in utero and post-natal opioid exposure on the developing brain, we sought to assess the response to one of the most common pediatric injuries: minor traumatic brain injury …

Molecular Signaling Network And Therapeutic Developments In Breast Cancer Brain Metastasis, Mercilena Benjamin, Pushkar Malakar, Rohit Anthony Sinha, Mohd Wasim Nasser, Surinder K. Batra, Jawed A. Siddiqui, Bandana Chakravarti

Journal Articles: Biochemistry & Molecular Biology

Breast cancer (BC) is one of the most frequently diagnosed cancers in women worldwide. It has surpassed lung cancer as the leading cause of cancer-related death. Breast cancer brain metastasis (BCBM) is becoming a major clinical concern that is commonly associated with ER-ve and HER2+ve subtypes of BC patients. Metastatic lesions in the brain originate when the cancer cells detach from a primary breast tumor and establish metastatic lesions and infiltrate near and distant organs via systemic blood circulation by traversing the BBB. The colonization of BC cells in the brain involves a complex interplay in the tumor microenvironment (TME), …

Microrna-1 Attenuates The Growth And Metastasis Of Small Cell Lung Cancer Through Cxcr4/Foxm1/Rrm2 Axis, Parvez Khan, Jawed A. Siddiqui, Prakash Kshirsagar Dr., Ramakanth Chirravuri Venkata, Shailendra K. Maurya, Tamara Mirzapoiazova, Naveenkumar Perumal, Sanjib Chaudhary, Ranjana K. Kanchan, Mahek Fatima, Md Arafat Khan, Asad Ur Rehman, Imayavaramban Lakshmanan, Sidharth Mahapatra, Geoffrey A. Talmon, Prakash Kulkarni, Apar Kishor Ganti, Maneesh Jain, Ravi Salgia, Surinder K. Batra, Mohd W. Nasser

Journal Articles: Biochemistry & Molecular Biology

BACKGROUND: Small cell lung cancer (SCLC) is an aggressive lung cancer subtype that is associated with high recurrence and poor prognosis. Due to lack of potential drug targets, SCLC patients have few therapeutic options. MicroRNAs (miRNAs) provide an interesting repertoire of therapeutic molecules; however, the identification of miRNAs regulating SCLC growth and metastasis and their precise regulatory mechanisms are not well understood.

METHODS: To identify novel miRNAs regulating SCLC, we performed miRNA-sequencing from donor/patient serum samples and analyzed the bulk RNA-sequencing data from the tumors of SCLC patients. Further, we developed a nanotechnology-based, highly sensitive method to detect microRNA-1 (miR-1, …

Specific Targeting And Labeling Of Colonic Polyps In Cpc-Apc Mice With Mucin 5ac Fluorescent Antibodies: A Model For Detection Of Early Colon Cancer, Michael A. Turner, Kristin E. Cox, Shanglei Liu, Nicholas Neel, Siamak Amirfakhri, Hiroto Nishino, Mojgan Hosseini, Joshua A. Alcantara, Amer Ali Abd El-Hafeez, Thinzar M. Lwin, Kavita Mallya, Joseph R. Pisegna, Satish K. Singh, Pradipta Ghosh, Robert M. Hoffman, Surinder K. Batra, Michael Bouvet

Journal Articles: Biochemistry & Molecular Biology

Poor visualization of polyps can limit colorectal cancer screening. Fluorescent antibodies to mucin5AC (MUC5AC), a glycoprotein upregulated in adenomas and colorectal cancer, could improve screening colonoscopy polyp detection rate. Adenomatous polyposis coli flox mice with a Cdx2-Cre transgene (CPC-APC) develop colonic polyps that contain both dysplastic and malignant tissue. Mice received MUC5AC-IR800 or IRdye800 as a control IV and were sacrificed after 48 h for near-infrared imaging of their colons. A polyp-to-background ratio (PBR) was calculated for each polyp by dividing the mean fluorescence intensity of the polyp by the mean fluorescence intensity of the background tissue. The mean 25 …

Roles Unveiled For Membrane-Associated Mucins At The Ocular Surface Using A Muc4 Knockout Mouse Model, Rafael Martinez-Carrasco, Satyanarayan Rachagani, Surinder K. Batra, Pablo Argüeso, M Elizabeth Fini

Journal Articles: Biochemistry & Molecular Biology

Membrane-associated mucins (MAMs) are proposed to play critical roles at the ocular surface; however, in vivo evidence has been lacking. Here we investigate these roles by phenotyping of a Muc4 KO mouse. Histochemical analysis for expression of the beta-galactosidase transgene replacing Muc4 revealed a spiraling ribbon pattern across the corneal epithelium, consistent with centripetal cell migration from the limbus. Depletion of Muc4 compromised transcellular barrier function, as evidenced by an increase in rose bengal staining. In addition, the corneal surface was less smooth, consistent with disruption of tear film stability. While surface cells presented with well-developed microprojections, an increase in …

Chimeric Antibody Targeting Unique Epitope On Onco-Mucin16 Reduces Tumor Burden In Pancreatic And Lung Malignancies, Ashu Shah, Sanjib Chaudhary, Imayavaramban Lakshmanan, Abhijit Aithal, Sophia G. Kisling, Claire Sorrell, Saravanakumar Marimuthu, Shailendra K. Gautam, Sanchita Rauth, Prakash Kshirsagar, Jesse L. Cox, Gopalakrishnan Natarajan, Rakesh Bhatia, Kavita Mallya, Satyanarayana Rachagani, Mohd W. Nasser, Apar Kishor Ganti, Ravi Salgia, Sushil Kumar, Maneesh Jain, Moorthy P. Ponnusamy, Surinder K. Batra

Journal Articles: Biochemistry & Molecular Biology

Aberrantly expressed onco-mucin 16 (MUC16) and its post-cleavage generated surface tethered carboxy-terminal (MUC16-Cter) domain are strongly associated with poor prognosis and lethality of pancreatic (PC) and non-small cell lung cancer (NSCLC). To date, most anti-MUC16 antibodies are directed towards the extracellular domain of MUC16 (CA125), which is usually cleaved and shed in the circulation hence obscuring antibody accessibility to the cancer cells. Herein, we establish the utility of targeting a post-cleavage generated, surface-tethered oncogenic MUC16 carboxy-terminal (MUC16-Cter) domain by using a novel chimeric antibody in human IgG1 format, ch5E6, whose epitope expression directly correlates with disease severity in both cancers. …

Red Cabbage Juice-Mediated Gut Microbiota Modulation Improves Intestinal Epithelial Homeostasis And Ameliorates Colitis, Emily Jean Wilson, Nagabhishek Sirpu Natesh, Parsa Ghadermazi, Ramesh Pothuraju, Dipakkumar R. Prajapati, Sanjit Pandey, Jussuf T. Kaifi, John R. Dodam, Jeffrey N. Bryan, Christian L. Lorson, Aude A. Watrelot, Jason M. Foster, Thomas J. Mansell, Siu Hung Joshua Chan, Surinder K. Batra, Jeyamkondan Subbiah, Satyanarayana Rachagani

Journal Articles: Biochemistry & Molecular Biology

Gut microbiota plays a crucial role in inflammatory bowel diseases (IBD) and can potentially prevent IBD through microbial-derived metabolites, making it a promising therapeutic avenue. Recent evidence suggests that despite an unclear underlying mechanism, red cabbage juice (RCJ) alleviates Dextran Sodium Sulfate (DSS)-induced colitis in mice. Thus, the study aims to unravel the molecular mechanism by which RCJ modulates the gut microbiota to alleviate DSS-induced colitis in mice. Using C57BL/6J mice, we evaluated RCJ's protective role in DSS-induced colitis through two cycles of 3% DSS. Mice were daily gavaged with PBS or RCJ until the endpoint, and gut microbiota composition …

Repeated Social Defeat Stress Induces An Inflammatory Gut Milieu By Altering The Mucosal Barrier Integrity And Gut Microbiota Homeostasis, Santosh K. Yadav, Rizwan Ahmad, Cassandra M. Moshfegh, Jagadesan Sankarasubramanian, Vineet A. Joshi, Safwan K. Elkhatib, Yashpal S. Chhonker, Goeffrey A. Talmon, Chittibabu Guda, Adam Case, Amar B. Singh

Journal Articles: Cellular & Integrative Physiology

Background

Posttraumatic stress disorder (PTSD) is a mental health condition triggered by exposure to traumatic events in an individual’s life. Patients with PTSD are also at a higher risk for comorbidities. However, it is not well understood how PTSD affects human health and/or promotes the risk for comorbidities. Nevertheless, patients with PTSD harbor a proinflammatory milieu and dysbiotic gut microbiota. Gut barrier integrity helps to maintain normal gut homeostasis and its dysregulation promotes gut dysbiosis and inflammation.

Methods

We used a mouse model of repeated social defeat stress (RSDS), a preclinical model of PTSD. Behavioral studies, metagenomics analysis of the …

Commonalities And Differences In Carotid Body Dysfunction In Hypertension And Heart Failure, Igor S. A. Felippe, Rodrigo Del Río, Harold D. Schultz, Benedito H. Machado, Julian F R Paton

Journal Articles: Cellular & Integrative Physiology

Carotid body pathophysiology is associated with many cardiovascular-respiratory-metabolic diseases. This pathophysiology reflects both hyper-sensitivity and hyper-tonicity. From both animal models and human patients, evidence indicates that amelioration of this pathophysiological signalling improves disease states such as a lowering of blood pressure in hypertension, a reduction of breathing disturbances with improved cardiac function in heart failure (HF) and a re-balancing of autonomic activity with lowered sympathetic discharge. Given this, we have reviewed the mechanisms of carotid body hyper-sensitivity and hyper-tonicity across disease models asking whether there is uniqueness related to specific disease states. Our analysis indicates some commonalities and some potential …

Older Adults' Pain Outcomes After Mhealth Interventions: Scoping Review, Marcia Shade, Mariya Kovaleva, Kimberly Harp, Aqueasha Martin-Hammond

Journal Articles: Leon S. McGoogan Health Sciences Library

BACKGROUND: Pain is prevalent and poorly managed in older adults. Although pain self-management strategies are helpful, adoption and access are limited; thus, technology provides an opportunity for intervention delivery. Mobile health (mHealth) is feasible to use in older adults; however, we have yet to understand the effect of mHealth pain self-management interventions on pain outcomes in older adults.

OBJECTIVE: The purpose of this scoping review is to examine the characteristics of mHealth interventions and their efficacy on pain outcomes in older adults with musculoskeletal pain.

METHODS: With the assistance of a medical librarian, keywords and subject headings were generated, including …

Our Avatars, Ourselves, Mala Chatterjee

Faculty Scholarship

On 2013 an episode of the British TV show Black Minvrimagined a harrowing possibility: that technology might allow us to recreate the dead. A young woman named Martha loses her partner in a sudden accident and copes with the loss-or perhaps refuses to cope with itwith the assistance of an unnerving artificial intelligence, trained on her partner's data footprint, that can speak, act, and appear exactly as he did. It's not long before Martha becomes obsessed with the emulation, gathering every remnant of her partner's life to incorporate into the model and spending hours on the phone conversing with his …

The Unfinished Masterpiece: Compulsion And The Evolving Jurisprudence Over Free Speech, Jonathan Turley

Maryland Law Review

No abstract provided.

Original Intent, Racial Equality, And The Conundrums Of “Colorblindness”, Jeffrey D. Hoagland, Vinay Harpalani

Maryland Law Review

No abstract provided.

Public Land Management’S Future Place: Envisioning A Paradigm Shift, Sam Kalen

Maryland Law Review

No abstract provided.

Guilty Minds, Michael Serota

Maryland Law Review

No abstract provided.

Prescribing Exploitation, Charlotte A. Tschider

Maryland Law Review

No abstract provided.

Practicing Queer Legal Theory Critically, Kendall Thomas

Faculty Scholarship

This introduction to the Critical Analysis of Law special issue on queer legal studies excavates three conjugal artifacts: an academic manuscript delineating interracial and same-sex marriages as loci of state surveillance and unfreedom; a TED Talk on same-sex marriage as irrefutably queer; and the United States Supreme Court decision holding same-sex marriage a constitutional right. These artifacts, along with their singular referent (state-sanctioned marriage), point to what is or should be critical about the interdiscipline of queer legal studies: theorization not only of the subjectification of subjects of gender and sexual regulation (spouses, singles, you and me), but also theorization …

Refining Clinician Workflow As A Means To Improving Catheter Quality Measures, Martina Clarke, Jana L. Wardian Phd, Brandon Fleharty, Justin R. Birge

Journal Articles: Hospital Medicine

Objective

This study aimed to improve the quality measure performance for indwelling urinary catheter (IUC) duration, central venous catheter (CVC) duration, and telemetry duration by redesigning clinical decision support (CDS) tools within the documentation process and order workflow.

Methods

The effectiveness of the redesign was evaluated using system standard quality reporting methodology to observe device duration, central-line-associated bloodstream infection (CLABSI) rate, and catheter-associated urinary tract infection (CAUTI) rate preintervention (FY2017) and postintervention (FY2018). Electronic health record (EHR) reporting tools were used to evaluate CDS alert data both preintervention and postintervention.

Results

Total device duration and line days per patient days …

Factors Associated With Prevalent Mycobacterium Tuberculosis Infection And Disease Among Adolescents And Adults Exposed To Rifampin-Resistant Tuberculosis In The Household, Soyeon Kim, Anneke C. Hesseling, Xingye Wu, Michael D. Hughes, N. Sarita Shah, Sanjay Gaikwad, Nishi Kumarasamy, Erika Mitchell, Mey Leon, Pedro Gonzales, Sharlaa Badal-Faesen, Madeleine Lourens, Sandy Nerette, Justin Shenje, Petra De Koker, Supalert Nedsuwan, Lerato Mohapi, Unoda A. Chakalisa, Rosie Mngqbisa, Rodrigo Otávio Da Silva Escada, Samuel Ouma, Barbara Heckman, Linda Naini, Amita Gupta, Susan Swindells, Gavin Churchyard, Actg A5300/Impaact 2003 Phoenix Feasibility Study Team

Journal Articles: Infectious Diseases

BACKGROUND: Understanding factors associated with prevalent Mycobacterium tuberculosis infection and prevalent TB disease in household contacts of patients with drug-resistant tuberculosis (TB) may be useful for TB program staff conducting contact investigations.

METHODS: Using data from a cross-sectional study that enrolled index participants with rifampin-resistant pulmonary TB and their household contacts (HHCs), we evaluated HHCs age ≥15 years for factors associated with two outcomes: Mycobacterium tuberculosis infection and TB disease. Among HHCs who were not already diagnosed with current active TB disease by the TB program, Mycobacterium tuberculosis infection was determined by interferon-gamma release assay (IGRA). TB disease was adjudicated …

An Exploration Of The Link Between Vertebral Endplate Fracture, Velocity, And Health Of The Intervertebral Disc., John Mcmorran

Theses and Dissertations (Comprehensive)

The capacity for fractures to manifest in the growth cartilage of the adolescent human spine is well documented, but much of the knowledge available regarding such fractures remains retrospective and is largely composed of small case series made up of relatively few participants. In-vitro tissue testing has demonstrated that pressurization of the intervertebral disc’s nucleus pulposus significantly contributes to the generation of growth plate fractures. However, a comprehensive biomechanical investigation of the mechanical consequences for the intervertebral disc when exposed to ring apophyseal (growth plate) fractures at different velocities remains to be demonstrated.

The first two experiments of the present …

Specific Performance: On Freedom And Commitment In Contract Law, Hanoch Dagan, Michael A. Heller

Faculty Scholarship

When should specific performance be available for breach of contract? This question — at the core of contract — divides common-law and civil-law jurisdictions and it has bedeviled generations of comparativists, along with legal economists, historians, and philosophers. Yet none of these disciplines has provided a persuasive answer. This Article provides a normatively attractive and conceptually coherent account, one grounded in respect for the autonomy of the promisor’s future self. Properly understood, autonomy explains why expectation damages should be the ordinary remedy for contract breach. This same normative commitment justifies the “uniqueness exception,” where specific performance is typically awarded, and …

Price Gouging In A Pandemic, Christopher Buccafusco, Daniel Hemel, Eric L. Talley

Faculty Scholarship

The COVID-19 pandemic led to acute supply shortages across the country as well as concerns over price increases amid surging demand. In the process, it reawakened a debate about whether and how to regulate “price gouging” — a controversy that continues as inflation has accelerated even as the pandemic abates. Animating this debate is a longstanding conflict between laissez-faire economics, which champions price fluctuations as a means to allocate scarce goods, and perceived norms of consumer fairness, which are thought to cut strongly against sharp price hikes amid shortages.

This Article provides a new, empirically grounded perspective on the price …

Camas, Winter 2023

Camas

Nonfiction:

Degrees of Separation / Sierra Crane Murdoch -- Postmortem from the Hollywood Hills / Lisa Novick

Fiction:

Below / Lars Chinburg -- Heart on Fire / Kevin Chess -- Grace Ambassadors of Wisdom / Jamie Ogden

Poetry:

Liable / Thomas Dunn -- We Used to Talk About the Weather & The Fire / Daniel Callahan -- Body Parts / Donna Stewman -- Like Wildfire / Julie Lunde -- I Will Take You / Anna Winham -- Birds and Saints / Eve Muller -- Living Room / Lauren Tess -- Dream House / Bryce Johle -- Gramma …

Something Smells Fishy: How Lipid Mediators Impact The Maternal-Fetal Interface And Neonatal Development, Maranda Thompson, Arzu Ulu, Maheswari Mukherjee, Ana G. Yuil-Valdes, Melissa K. Thoene, Matthew Van Ormer, Rebecca Slotkowski, Teri Mauch, Ann Anderson-Berry, Corrine K. Hanson, Tara M. Nordgren, Sathish Kumar Natarajan

Journal Articles: Pediatrics

Normal pregnancy relies on inflammation for implantation, placentation, and parturition, but uncontrolled inflammation can lead to poor maternal and infant outcomes. Maternal diet is one modifiable factor that can impact inflammation. Omega-3 and -6 fatty acids obtained through the diet are metabolized into bioactive compounds that effect inflammation. Recent evidence has shown that the downstream products of omega-3 and -6 fatty acids may influence physiology during pregnancy. In this review, the current knowledge relating to omega-3 and omega-6 metabolites during pregnancy will be summarized.

Retinol And Pro-Vitamin A Carotenoid Nutritional Status During Pregnancy Is Associated With Newborn Hearing Screen Results, Rebecca Slotkowski, Matthew Van Ormer, Anum Akbar, Olivia Paetz, Taija Hahka, Maranda Thompson, Alyssa Freeman, Alexandra Hergenrader, Sarah Sweeney, Zeljka Korade, Thiago Genaro-Mattos, Corrine K. Hanson, Ann Anderson-Berry, Melissa K. Thoene

Journal Articles: Pediatrics

The prenatal period is critical for auditory development; thus, prenatal influences on auditory development may significantly impact long-term hearing ability. While previous studies identified a protective effect of carotenoids on adult hearing, the impact of these nutrients on hearing outcomes in neonates is not well understood. The purpose of this study is to investigate the relationship between maternal and umbilical cord plasma retinol and carotenoid concentrations and abnormal newborn hearing screen (NHS) results. Mother-infant dyads (n = 546) were enrolled at delivery. Plasma samples were analyzed using HPLC and LC-MS/MS. NHS results were obtained from medical records. Statistical analysis …

Plasma Retinol Concentrations And Dietary Intakes Of Mother-Infant Sets In Singleton Versus Twin Pregnancy, Anum Akbar, Sarah Duvall, Matthew Van Ormer, Rebecca Slotkowski, Taija Hahka, Thiago Genaro-Mattos, Zeljka Korade, Corrine K. Hanson, Ann Anderson-Berry, Melissa K. Thoene

Journal Articles: Pediatrics

Vitamin A (retinol) is essential for normal fetal development, but the recommendation for maternal dietary intake (Retinol Activity Equivalent, RAE) does not differ for singleton vs. twin pregnancy, despite the limited evaluation of retinol status. Therefore, this study aimed to evaluate plasma retinol concentrations and deficiency status in mother-infant sets from singleton vs. twin pregnancies as well as maternal RAE intake. A total of 21 mother-infant sets were included (14 singleton, 7 twin). The HPLC and LC-MS/HS evaluated the plasma retinol concentration, and data were analyzed using the Mann-Whitney U test. Plasma retinol was significantly lower in twin vs. singleton …

The Relationship Between Nutrition, Gut Dysbiosis, And Pediatric Sickle Cell Pain Outcomes: A Pilot Study, Chinenye R. Dike, Corrine K. Hanson, Dele Davies, Stephen Obaro, Fang Yu, James L. Harper, Helen Grace, Jeffrey Lebensburger, Chittalsinh M. Raulji, Jihyun Ma, Peter Mannon

Journal Articles: Pediatrics

BACKGROUND: Nutritional deficiencies are prevalent in sickle cell disease (SCD) and may be associated with worse pain outcomes. Gut dysbiosis has been reported in patients with SCD and may contribute to both nutritional deficiencies and pain.

OBJECTIVES: We tested the association of nutrition, fat-soluble vitamin (FSV) deficiency, and gut microbiome composition on clinical outcomes in SCD. Second, we measured the association between diet and exocrine pancreatic function on FSV levels.

METHODS: Using case control design, we enrolled children with SCD (n = 24) and matched healthy controls (HC; n = 17, age, sex, race/ethnicity). Descriptive statistics summarized demographic and clinical …

The Pledging World Order, Melissa (M.J.) Durkee

Scholarship@WashULaw

There is an emerging world order characterized by unilateral pledges within a legal or “legal-ish” architecture of commitments. The pledging world order has materialized in the international legal response to climate change and in other diverse sites. It crosses and blurs the public-private divide. It erodes distinctions between multilateralism and localism, law and not-law, and progress and stasis. It is both a symptom of and a contributor to the dismantling of the Westphalian and postwar orders. Its report card is mixed: While pledging can be highly ineffective as a legal technology, the pledging world order may respond to some legitimacy …

Fourth Amendment Notice In The Cloud, Neil M. Richards, Jesse Lieberfeld

Scholarship@WashULaw

The widespread storage of documents through the range of Internet technologies known as “the cloud” offers tremendous convenience but also creates significant risks of exposure to third parties. In particular, law enforcement investigators seeking access to potentially relevant evidence have aggressively and extensively used the Electronic Communications Act of 1986 (“ECPA”) to execute digital searches. But a relatively obscure provision of ECPA, § 2703, allows law enforcement to search a person’s Fourth Amendment “papers” without them ever learning that a warrant has allowed the exposure of their private, sensitive, and possibly incriminating documents. What is more, federal and state law …

A Concrete Proposal For Data Loyalty, Neil M. Richards, Woodrow Hartzog, Jordan Francis

Scholarship@WashULaw

Congress and state legislators are finally experimenting with new privacy frameworks, rights, and duties to move past the thoroughly critiqued “notice and choice” model for data privacy. While many new privacy proposals seek a more fortified version of the fair information practices, some legislators have placed a duty of data loyalty at the heart of their proposed privacy bills. This is important because a duty of data loyalty has the potential to anchor American privacy law in a way analogous to how the European Union approach is grounded in fundamental rights of privacy and data protection.

Unfortunately, there remains some …