Medicine and Health Sciences Commons^™

Breakthroughs In Hormonal Male Contraception, Alexander Patton, Seth Vann

Physician Assistant Capstones, 2020-current

Objective: Assess the efficacy of a nestorone plus testosterone gel at suppressing progestin levels and spermatogenesis.

Design: Systematic literature review.

Methods: Searches were done in PubMed and Dartmouth library using the terms nestorone, randomized control trial, human, and male. Limits used while searching included published in the last 10 years, randomized control trials, and English.

Results: Using the search criteria the following three studies were found that met the inclusion/exclusion criteria of this study: Ilani et al, Zitzmann et al, and Anawalt et al. All three studies were found on PubMed and reference the Ilani et al study.

Conclusion: Nestorone …

Ifit3 (Interferon Induced Protein With Tetratricopeptide Repeats 3) Modulates Stat1 Expression In Small Extracellular Vesicles., Nicole M Naranjo, Israa Salem, Maisha A Harris, Lucia R Languino

Department of Pharmacology, Physiology, and Cancer Biology Faculty Papers

We have previously shown that the αvβ6 integrin plays a key role in promoting prostate cancer (PrCa) and it can be transferred to recipient cells via small extracellular vesicles (sEVs). Furthermore, we have reported in a proteomic analysis that αvβ6 integrin down-regulation increases the expression of IFIT3 (interferon induced protein with tetratricopeptide repeats 3) in PrCa cells and their derived sEVs. IFIT3 is a protein well known for being an antiviral effector, but recently its role in cancer has also been elucidated. To study the relationship between IFIT3 and STAT1 (signal transducer and activator of transcription 1), an upstream regulator …

Effects Of The Tailored Activity Program (Tap) On Dementia-Related Symptoms, Health Events And Caregiver Wellbeing: A Randomized Controlled Trial, Laura N Gitlin, Katherine Marx, Catherine V. Piersol, Nancy A Hodgson, Jin Huang, David L Roth, Constantine Lyketsos

Department of Occupational Therapy Faculty Papers

BACKGROUND: People living with dementia (PLWD) and caregivers are adversely impacted by lack of meaningful activity leading to worse symptoms and impaired quality-of-life. There is a critical need to develop effective and well-tolerated treatments that mitigate clinical symptoms, engage PLWD and support caregiver wellbeing. We tested whether, compared to attention control, the Tailored Activity Program (TAP) reduced clinical symptoms and health-related events, and improved caregiver wellbeing, and if TAP activities were well-tolerated.

METHODS: We conducted a single-blind randomized controlled trial among 250 dyads recruited from Baltimore-Washington DC (2012-2016) with a dementia diagnosis and clinically significant agitation/aggression. Dyads were randomized to …

Long-Term Survival Of Older Patients Hospitalized For Covid-19. Do Clinical Characteristics Upon Admission Matter?, Michał Chojnicki, Agnieszka Neumann-Podczaska, Mikołaj Seostianin, Zofia Tomczak, Hamza Tariq, Jerzy Chudek, Sławomir Tobis, Iwona Mozer-Lisewska, Aleksandra Suwalska, Andrzej Tykarski, Piotr Merks, Sylwia Kropińska, Małgorzata Sobieszczańska, Frank Romanelli, Katarzyna Wieczorowska-Tobis

Pharmacy Practice and Science Faculty Publications

Older adults are particularly susceptible to COVID-19 in terms of both disease severity and risk of death. To compare clinical differences between older COVID-19 hospitalized survivors and non-survivors, we investigated variables influencing mortality in all older adults with COVID-19 hospitalized in Poznań, Poland, through the end of June 2020 (n = 322). In-hospital, post-discharge, and overall 180-day mortality were analyzed. Functional capacity prior to COVID-19 diagnosis was also documented. The mean age of subjects was 77.5 ± 10.0 years; among them, 191 were females. Ninety-five (29.5%) died during their hospitalization and an additional 30 (9.3%) during the post-discharge period …

Chloride Sensing By Wnk1 Regulates Nlrp3 Inflammasome Activation And Pyroptosis., Lindsey Mayes-Hopfinger, Aura Enache, Jian Xie, Chou-Long Huang, Robert Köchl, Victor L.J. Tybulewicz, Teresa Fernandes-Alnemri, Emad S. Alnemri

Department of Biochemistry and Molecular Biology Faculty Papers

The NLRP3 inflammasome mediates the production of proinflammatory cytokines and initiates inflammatory cell death. Although NLRP3 is essential for innate immunity, aberrant NLRP3 inflammasome activation contributes to a wide variety of inflammatory diseases. Understanding the pathways that control NLRP3 activation will help develop strategies to treat these diseases. Here we identify WNK1 as a negative regulator of the NLRP3 inflammasome. Macrophages deficient in WNK1 protein or kinase activity have increased NLRP3 activation and pyroptosis compared with control macrophages. Mice with conditional knockout of WNK1 in macrophages have increased IL-1β production in response to NLRP3 stimulation compared with control mice. Mechanistically, …

Rnase Κ Promotes Robust Pirna Production By Generating 2',3'-Cyclic Phosphate-Containing Precursors, Megumi Shigematsu, Takuya Kawamura, Keisuke Morichika, Natsuko Izumi, Takashi Kiuchi, Shozo Honda, Venetia Pliatsika, Ryuma Matsubara, Isidore Rigoutsos, Susumu Katsuma, Yukihide Tomari, Yohei Kirino

Computational Medicine Center Faculty Papers

In animal germlines, PIWI proteins and the associated PIWI-interacting RNAs (piRNAs) protect genome integrity by silencing transposons. Here we report the extensive sequence and quantitative correlations between 2′,3′-cyclic phosphate-containing RNAs (cP-RNAs), identified using cP-RNA-seq, and piRNAs in the Bombyx germ cell line and mouse testes. The cP-RNAs containing 5′-phosphate (P-cP-RNAs) identified by P-cP-RNA-seq harbor highly consistent 5′-end positions as the piRNAs and are loaded onto PIWI protein, suggesting their direct utilization as piRNA precursors. We identified Bombyx RNase Kappa (BmRNase κ) as a mitochondria-associated endoribonuclease which produces cP-RNAs during piRNA biogenesis. BmRNase κ-depletion elevated transposon levels and disrupted a piRNA-mediated …

Reduced Mitochondrial Dna And Oxphos Protein Content In Skeletal Muscle Of Children With Cerebral Palsy, Ferdinand Von Walden, Ivan J. Vechetti Jr., Davis A. Englund, Vandré C. Figueiredo, Rodrigo Fernandez-Gonzalo, Kevin A. Murach, Jessica Pingel, John J. Mccarthy, Per Stål, Eva Pontén

Physiology Faculty Publications

AIM: To provide a detailed gene and protein expression analysis related to mitochondrial biogenesis and assess mitochondrial content in skeletal muscle of children with cerebral palsy (CP).

METHOD: Biceps brachii muscle samples were collected from 19 children with CP (mean [SD] age 15y 4mo [2y 6mo], range 9-18y, 16 males, three females) and 10 typically developing comparison children (mean [SD] age 15y [4y], range 7-21y, eight males, two females). Gene expression (quantitative reverse transcription polymerase chain reaction [PCR]), mitochondrial DNA (mtDNA) to genomic DNA ratio (quantitative PCR), and protein abundance (western blotting) were analyzed. Microarray data sets (CP/aging/bed rest) were …

Candida Cell-Surface-Specific Monoclonal Antibodies Protect Mice Against Candida Auris Invasive Infection, Jonothan Rosario-Colon, Karen Eberle, Abby Adams, Evan Courville, Hong Xin

School of Graduate Studies Faculty Publications

Candida auris is a multidrug-resistant fungal pathogen that can cause disseminated bloodstream infections with up to 60% mortality in susceptible populations. Of the three major classes of antifungal drugs, most C. auris isolates show high resistance to azoles and polyenes, with some clinical isolates showing resistance to all three drug classes. We reported in this study a novel approach to treating C. auris disseminated infections through passive transfer of monoclonal antibodies (mAbs) targeting cell surface antigens with high homology in medically important Candida species. Using an established A/J mouse model of disseminated infection that mimics human candidiasis, we showed that …

Long-Term Impacts Of Acute Stressor Exposure On Locus Coeruleus Function And Anxiety-Like Behavior In Rats, Olga Borodovitsyna

Graduate School of Biomedical Sciences Theses and Dissertations

Stress is a physiological state characterized by behavioral arousal that occurs during exposure to harmful or threatening stimuli, and usually facilitates an adaptive behavioral response. The persistence of stress sometimes causes it to become maladaptive, potentially contributing to disease development, including physiological complications with altered neuroendocrine signaling and impaired function of organ systems, and psychological conditions including depression and anxiety. Anxiety disorders in particular are associated with a history of stress and are the most common class of mental disorders, with a lifetime prevalence of 33.7% in the general population. The locus coeruleus (LC) is a major node in the …

Severe Acute Respiratory Syndrome Coronavirus 2-Induced Acute Aortic Occlusion: A Case Report, Artem Minalyan, Franklin L. Thelmo, Vincent Chan, Stephanie Tzarnas, Faizan Ahmed

Department of Medicine Faculty Papers

Background: Severe acute respiratory syndrome coronavirus 2 infection can lead to a constellation of viral and immune symptoms called coronavirus disease 2019. Emerging literature increasingly supports the premise that severe acute respiratory syndrome coronavirus 2 promotes a prothrombotic milieu. However, to date there have been no reports of acute aortic occlusion, itself a rare phenomenon. We report a case of fatal acute aortic occlusion in a patient with coronavirus disease 2019.

Case report: A 59-year-old Caucasian male with past medical history of peripheral vascular disease presented to the emergency department for evaluation of shortness of breath, fevers, and dry cough. …

Point-Of-Care Lung Ultrasound For Covid-19: Findings And Prognostic Implications From 105 Consecutive Patients, Kosuke Yasukawa, Taro Minami, David R Boulware, Ayako Shimada, Ernest A Fischer

Department of Pharmacology and Experimental Therapeutics Faculty Papers

Background: The prognostic value of point-of-care lung ultrasound has not been evaluated in a large cohort of patients with COVID-19 admitted to general medicine ward in the United States. The aim of this study was to describe lung ultrasound findings and their prognostic value in patients with COVID-19 admitted to internal medicine ward.

Method: This prospective observational study consecutively enrolled 105 hospitalized participants with COVID-19 at 2 tertiary care centers. Ultrasound was performed in 12 lung zones within 24 hours of admission. Findings were assessed relative to 4 outcomes: intensive care unit (ICU) need, need for intensive respiratory support, length …

Impaired Eif5a Function Causes A Mendelian Disorder That Is Partially Rescued In Model Systems By Spermidine., Víctor Faundes, Martin D. Jennings, Siobhan Crilly, Sarah Legraie, Sarah E. Withers, Sara Cuvertino, Sally J. Davies, Andrew G L Douglas, Andrew E. Fry, Victoria Harrison, Jeanne Amiel, Daphné Lehalle, William G. Newman, Patricia Newkirk, Judith Ranells, Miranda Splitt, Laura A. Cross, Carol J. Saunders, Bonnie Sullivan, Jorge L. Granadillo, Christopher T. Gordon, Paul R. Kasher, Graham D. Pavitt, Siddharth Banka

Manuscripts, Articles, Book Chapters and Other Papers

The structure of proline prevents it from adopting an optimal position for rapid protein synthesis. Poly-proline-tract (PPT) associated ribosomal stalling is resolved by highly conserved eIF5A, the only protein to contain the amino acid hypusine. We show that de novo heterozygous EIF5A variants cause a disorder characterized by variable combinations of developmental delay, microcephaly, micrognathia and dysmorphism. Yeast growth assays, polysome profiling, total/hypusinated eIF5A levels and PPT-reporters studies reveal that the variants impair eIF5A function, reduce eIF5A-ribosome interactions and impair the synthesis of PPT-containing proteins. Supplementation with 1 mM spermidine partially corrects the yeast growth defects, improves the polysome profiles …