Digital Commons Network^™

New Cohort Of Patients With Cednik Syndrome Expands The Phenotypic And Genotypic Spectra, Annelise Y. Mah-Som, Cristina Skrypnyk, Andrea Guerin, Raafat Hammad Seroor Jadah, Vinayak Nivrutti Vardhan, Robert C. Mckinstry, Marwan S. Shinawi

Open Access Publications

No abstract provided.

Noise Exposure Potentiates Exocytosis From Cochlear Inner Hair Cells, Luis E Boero, Shelby Payne, Maria Eugenia Gómez-Casati, Mark A Rutherford, Juan D Goutman

Open Access Publications

Noise-induced hearing loss has gained relevance as one of the most common forms of hearing impairment. The anatomical correlates of hearing loss, principally cell damage and/or death, are relatively well-understood histologically. However, much less is known about the physiological aspects of damaged, surviving cells. Here we addressed the functional consequences of noise exposure on the capacity of inner hair cells (IHCs) to release synaptic vesicles at synapses with spiral ganglion neurons (SGNs). Mice of either sex at postnatal day (P) 15-16 were exposed to 1-12 kHz noise at 120 dB sound pressure level (SPL), for 1 h. Exocytosis was measured …

Trajectory Of Long-Term Outcome In Severe Pediatric Diffuse Axonal Injury: An Exploratory Study, Shih-Shan Lang, Todd Kilbaugh, Stuart Friess, Susan Sotardi, Chong Tae Kim, Vanessa Mazandi, Bingqing Zhang, Phillip B Storm, Gregory G Heuer, Alexander Tucker, Steve B Ampah, Heather Griffis, Ramesh Raghupathi, Jimmy W Huh

Open Access Publications

No abstract provided.

Central Vein Sign: A Diagnostic Biomarker In Multiple Sclerosis (Cavs-Ms) Study Protocol For A Prospective Multicenter Trial, D Ontaneda, S Chahin, Et Al

Open Access Publications

The specificity and implementation of current MRI-based diagnostic criteria for multiple sclerosis (MS) are imperfect. Approximately 1 in 5 of individuals diagnosed with MS are eventually determined not to have the disease, with overreliance on MRI findings a major cause of MS misdiagnosis. The central vein sign (CVS), a proposed MRI biomarker for MS lesions, has been extensively studied in numerous cross sectional studies and may increase diagnostic specificity for MS. CVS has desirable analytical, measurement, and scalability properties. "Central Vein Sign: A Diagnostic Biomarker in Multiple Sclerosis (CAVS-MS)" is an NIH-supported, 2-year, prospective, international, multicenter study conducted by the …

Programmed Cell Death Recruits Macrophages Into The Developing Mouse Cochlea, Vikrant Borse, Tejbeer Kaur, Ashley Hinton, Kevin Ohlemiller, Mark E Warchol

Open Access Publications

Programmed cell death (PCD) plays a critical role in the development and maturation of the cochlea. Significant remodeling occurs among cells of the greater epithelial ridge (GER) of Kölliker's organ, leading to tissue regression and formation of the inner sulcus. In mice, this event normally occurs between postnatal days 5-15 (P5-15) and is regulated by thyroid hormone (T3). During this developmental time period, the cochlea also contains a large population of macrophages. Macrophages are frequently involved in the phagocytic clearance of dead cells, both during development and after injury, but the role of macrophages in the developing cochlea is unknown. …

Follow The Metaplasia: Characteristics And Oncogenic Implications Of Metaplasia's Pattern Of Spread Throughout The Stomach, José B Sáenz

Open Access Publications

The human stomach functions as both a digestive and innate immune organ. Its main product, acid, rapidly breaks down ingested products and equally serves as a highly effective microbial filter. The gastric epithelium has evolved mechanisms to appropriately handle the myriad of injurious substances, both exogenous and endogenous, to maintain the epithelial barrier and restore homeostasis. The most significant chronic insult that the stomach must face is

Bladder Exposure To Gardnerella Activates Host Pathways Necessary For Escherichia Coli Recurrent Uti, Valerie P O'Brien, Amanda L Lewis, Nicole M Gilbert

Open Access Publications

Recurrent urinary tract infections (rUTI) are a costly clinical problem affecting millions of women worldwide each year. The majority of rUTI cases are caused by uropathogenic

Air Pollution Particulate Matter Amplifies White Matter Vascular Pathology And Demyelination Caused By Hypoperfusion, Mikko T Huuskonen, Qinghai Liu, Krista Lamorie-Foote, Kristina Shkirkova, Michelle Connor, Arati Patel, Axel Montagne, Hans Baertsch, Constantinos Sioutas, Todd E Morgan, Caleb E Finch, Berislav V Zlokovic, William J Mack

Open Access Publications

Cerebrovascular pathologies are commonly associated with dementia. Because air pollution increases arterial disease in humans and rodent models, we hypothesized that air pollution would also contribute to brain vascular dysfunction. We examined the effects of exposing mice to nanoparticulate matter (nPM; aerodynamic diameter ≤200 nm) from urban traffic and interactions with cerebral hypoperfusion. C57BL/6 mice were exposed to filtered air or nPM with and without bilateral carotid artery stenosis (BCAS) and analyzed by multiparametric MRI and histochemistry. Exposure to nPM alone did not alter regional cerebral blood flow (CBF) or blood brain barrier (BBB) integrity. However, nPM worsened the white …

Viral Evasion Of Innate Immune Defense: The Case Of Resistance Of Pandemic H1n1 Influenza A Virus To Human Mannose-Binding Proteins, Mitchell R White, Nikolaos M Nikolaidis, Francis Mccormack, Erika C Crouch, Kevan L Hartshorn

Open Access Publications

Mannose-binding lectins effectively inhibit most seasonal strains of influenza A virus and contribute to the innate host defense vs. these viruses. In contrast, pandemic IAV strains are largely resistant to these lectins, likely contributing to increased spread and worse outcomes. In this paper, we evaluated the inhibition of IAV by mannose-binding lectins of human, bacterial, and fungal origin to understand and possibly increase activity vs. the pandemic IAV. A modified version of the human surfactant protein D (SP-D) neck and carbohydrate recognition domain (NCRD) with combinatorial substitutions at the 325 and 343 positions, previously shown to inhibit pandemic H3N2 IAV

Association Of Inventory To Measure And Assess Image Disturbance - Head And Neck Scores With Clinically Meaningful Body Image-Related Distress Among Head And Neck Cancer Survivors, David Macias, Patrik Pipkorn, Et Al

Open Access Publications

No abstract provided.

Paeonol Ameliorates Chronic Itch And Spinal Astrocytic Activation Via Cxcr3 In An Experimental Dry Skin Model In Mice, Wen Wang, Qiaoyun Li, Zhongqiu Zhao, Yutong Liu, Yi Wang, Hui Xiong, Zhinan Mei

Open Access Publications

Paeonol is a bioactive phenol presents mainly in

Shifting Pathways Of Stimulant Use Among Individuals With Opioid Use Disorder: A Retrospective Analysis Of The Last Thirty Years, Matthew S Ellis, Zachary A Kasper, Stephen Scroggins

Open Access Publications

No abstract provided.

Ga4gh: International Policies And Standards For Data Sharing Across Genomic Research And Healthcare, Heidi I. Rehm, Malachi Griffith, Obi L. Griffith, Et Al

Open Access Publications

No abstract provided.

Encephalitic Arboviruses Of Africa: Emergence, Clinical Presentation And Neuropathogenesis, Robyn S Klein

Open Access Publications

Many mosquito-borne viruses (arboviruses) are endemic in Africa, contributing to systemic and neurological infections in various geographical locations on the continent. While most arboviral infections do not lead to neuroinvasive diseases of the central nervous system, neurologic diseases caused by arboviruses include flaccid paralysis, meningitis, encephalitis, myelitis, encephalomyelitis, neuritis, and post-infectious autoimmune or memory disorders. Here we review endemic members of the

Care Gaps And Recommendations In Vestibular Migraine: An Expert Panel Summit, Monica P Mallampalli, Joel A Goebel, Et Al

Open Access Publications

Vestibular migraine (VM) is an increasingly recognized pathology yet remains as an underdiagnosed cause of vestibular disorders. While current diagnostic criteria are codified in the 2012 Barany Society document and included in the third edition of the international classification of headache disorders, the pathophysiology of this disorder is still elusive. The Association for Migraine Disorders hosted a multidisciplinary, international expert workshop in October 2020 and identified seven current care gaps that the scientific community needs to resolve, including a better understanding of the range of symptoms and phenotypes of VM, the lack of a diagnostic marker, a better understanding of …

Academic Performance Of Children With Sickle Cell Disease In The United States: A Meta-Analysis, Andrew M Heitzer, Latacha Hamilton, Claire Stafford, Jeffrey Gossett, Lara Ouellette, Ana Trpchevska, Allison A King, Guolian Kang, Jane S Hankins

Open Access Publications

No abstract provided.

Antibiotic-Driven Intestinal Dysbiosis In Pediatric Short Bowel Syndrome Is Associated With Persistently Altered Microbiome Functions And Gut-Derived Bloodstream Infections, Robert Thänert, Anna Thänert, Jocelyn Ou, Adam Bajinting, Carey-Ann D Burnham, Holly J Engelstad, Maria E Tecos, I Malick Ndao, Carla Hall-Moore, Colleen Rouggly-Nickless, Mike A Carl, Deborah C Rubin, Nicholas O Davidson, Phillip I Tarr, Barbara B Warner, Gautam Dantas, Brad W Warner

Open Access Publications

Surgical removal of the intestine, lifesaving in catastrophic gastrointestinal disorders of infancy, can result in a form of intestinal failure known as short bowel syndrome (SBS). Bloodstream infections (BSIs) are a major challenge in pediatric SBS management. BSIs require frequent antibiotic therapy, with ill-defined consequences for the gut microbiome and childhood health. Here, we combine serial stool collection, shotgun metagenomic sequencing, multivariate statistics and genome-resolved strain-tracking in a cohort of 19 patients with surgically-induced SBS to show that antibiotic-driven intestinal dysbiosis in SBS enriches for persistent intestinal colonization with BSI causative pathogens in SBS. Comparing the gut microbiome composition of …

Association Between Antiviral Prophylaxis And Cytomegalovirus And Epstein-Barr Virus Dnaemia In Pediatric Recipients Of Allogeneic Hematopoietic Stem Cell Transplant, Ndeye Soukeyna Diop, Pascal Roland Enok Bonong, Chantal Buteau, Michel Duval, Jacques Lacroix, Louise Laporte, Marisa Tucci, Nancy Robitaille, Philip C Spinella, Geoffrey Cuvelier, Suzanne M Vercauteren, Victor Lewis, Caroline Alfieri, Helen Trottier

Open Access Publications

BACKGROUND: Epstein-Barr virus (EBV) and cytomegalovirus (CMV) infections can have serious consequences during the period of aplasia and lymphopenia following hematopoietic stem cell transplantation (HSCT). Large pediatric cohort studies examining the effect of antiviral prophylaxis against these viruses are scarce. The present study aimed to analyse the potential effect of antiviral prophylaxis (acyclovir and famciclovir) on active post-transplant EBV and CMV infection in a pediatric cohort of allogeneic HSCT recipients.

METHODS: We used data from the TREASuRE cohort, consisting of 156 patients who had a first allogeneic HSCT, enrolled in four pediatric centers in Canada between July 2013 and March …

Functional Implications Of The Dynamic Regulation Of Epcam During Epithelial-To-Mesenchymal Transition, Taylor C Brown, Narendra V Sankpal, William E Gillanders

Open Access Publications

Epithelial cell adhesion molecule (EpCAM) is a transmembrane glycoprotein expressed in epithelial tissues. EpCAM forms intercellular, homophilic adhesions, modulates epithelial junctional protein complex formation, and promotes epithelial tissue homeostasis. EpCAM is a target of molecular therapies and plays a prominent role in tumor biology. In this review, we focus on the dynamic regulation of EpCAM expression during epithelial-to-mesenchymal transition (EMT) and the functional implications of EpCAM expression on the regulation of EMT. EpCAM is frequently and highly expressed in epithelial cancers, while silenced in mesenchymal cancers. During EMT, EpCAM expression is downregulated by extracellular signal-regulated kinases (ERK) and EMT transcription …

Vaccines For Protecting Infants From Bacterial Causes Of Diarrheal Disease, Richard Walker, Robert W Kaminski, Chad Porter, Robert K M Choy, Jessica A White, James M Fleckenstein, Fred Cassels, Louis Bourgeois

Open Access Publications

The global diarrheal disease burden for

High Optode-Density Wearable Diffuse Optical Probe For Monitoring Paced Breathing Hemodynamics In Breast Tissue, Samuel S. Spink, Fei Teng, Vivian Pera, Hannah M. Peterson, Tim Cormier, Alexis Sauer-Budge, David Chargin, Sam Brookfield, Adam T. Eggebrecht, Naomi Ko, Darren Roblyer

Open Access Publications

No abstract provided.

Flexor Tendon Injury And Repair: The Influence Of Synovial Environment On The Early Healing Response In A Canine Mode, Hua Shen, Susumu Yoneda, Shelly E Sakiyama-Elbert, Qiang Zhang, Stavros Thomopoulos, Richard H Gelberman

Open Access Publications

BACKGROUND: Environmental conditions strongly influence the healing capacity of connective tissues. Well-vascularized extrasynovial tendons typically undergo a robust wound-healing process following transection and repair. In contrast, avascular intrasynovial tendons do not mount an effective repair response. The current study tests the hypothesis that flexor tendons, as a function of their synovial environment, exhibit unique inflammatory, angiogenic, and metabolic responses to injury and repair.

METHODS: Flexor tendons present a distinct opportunity to test the study hypothesis, as they have proximal regions that are extrasynovial and distal regions that are intrasynovial. In an internally controlled study design, the second and fifth forepaw …

Microbial Sharing Between Pediatric Patients And Therapy Dogs During Hospital Animal-Assisted Intervention Programs, Kathryn R Dalton, Kathy Ruble, Laurel E Redding, Daniel O Morris, Noel T Mueller, Roland J Thorpe, Jacqueline Agnew, Karen C Carroll, Paul J Planet, Ronald C Rubenstein, Allen R Chen, Elizabeth A Grice, Meghan F Davis

Open Access Publications

Microbial sharing between humans and animals has been demonstrated in a variety of settings. However, the extent of microbial sharing that occurs within the healthcare setting during animal-assisted intervention programs is unknown. Understanding microbial transmission between patients and therapy dogs can provide important insights into potential health benefits for patients, in addition to addressing concerns regarding potential pathogen transmission that limits program utilization. This study evaluated for potential microbial sharing between pediatric patients and therapy dogs and tested whether patient-dog contact level and a dog decolonization protocol modified this sharing. Patients, therapy dogs, and the hospital environment were sampled before …

Investigation Of Convergent And Divergent Genetic Influences Underlying Schizophrenia And Alcohol Use Disorder, Emma C Johnson, Alexander S Hatoum, Sarah Hartz, Arpana Agrawal, Et Al

Open Access Publications

BACKGROUND: Alcohol use disorder (AUD) and schizophrenia (SCZ) frequently co-occur, and large-scale genome-wide association studies (GWAS) have identified significant genetic correlations between these disorders.

METHODS: We used the largest published GWAS for AUD (total cases = 77 822) and SCZ (total cases = 46 827) to identify genetic variants that influence both disorders (with either the same or opposite direction of effect) and those that are disorder specific.

RESULTS: We identified 55 independent genome-wide significant single nucleotide polymorphisms with the same direction of effect on AUD and SCZ, 8 with robust effects in opposite directions, and 98 with disorder-specific effects. …

Protein Phosphatase 4 Controls Circadian Clock Dynamics By Modulating Clock/Bmal1 Activity, Sabrina Klemz, Thomas Wallach, Sandra Korge, Mechthild Rosing, Roman Klemz, Bert Maier, Nicholas C Fiorenza, Irem Kaymak, Anna K Fritzsche, Erik D Herzog, Ralf Stanewsky, Achim Kramer

Open Access Publications

In all organisms with circadian clocks, post-translational modifications of clock proteins control the dynamics of circadian rhythms, with phosphorylation playing a dominant role. All major clock proteins are highly phosphorylated, and many kinases have been described to be responsible. In contrast, it is largely unclear whether and to what extent their counterparts, the phosphatases, play an equally crucial role. To investigate this, we performed a systematic RNAi screen in human cells and identified protein phosphatase 4 (PPP4) with its regulatory subunit PPP4R2 as critical components of the circadian system in both mammals and

Promoting Coronavirus Disease 2019 (Covid-19) Vaccination Among Healthcare Personnel: A Multifaceted Intervention At A Tertiary-Care Center In Japan, Akane Takamatsu, Hitoshi Honda, Tomoya Kojima, Kengo Murata, Hilary M Babcock

Open Access Publications

OBJECTIVE: The coronavirus disease 2019 (COVID-19) vaccine may hold the key to ending the pandemic, but vaccine hesitancy is hindering the vaccination of healthcare personnel (HCP). We examined their perceptions of the COVID-19 vaccine and implemented an intervention to increase vaccination uptake.

DESIGN: Before-and-after trial.

PARTICIPANTS AND SETTING: Healthcare personnel at a 790-bed tertiary-care center in Tokyo, Japan.

INTERVENTIONS: A prevaccination questionnaire was administered to HCP to examine their perceptions of the COVID-19 vaccine. A multifaceted intervention was then implemented involving (1) distribution of informational leaflets to all HCP, (2) hospital-wide announcements encouraging vaccination, (3) a mandatory lecture, (4) an …

Chronic Nerve Injuries And Delays In Surgical Treatment Negatively Impact Patient-Reported Quality Of Life, John M. Felder, Ivica Ducic

Open Access Publications

No abstract provided.

Effectiveness Of A Vancomycin Dosing Protocol Guided By Area Under The Concentration-Time Curve To Minimal Inhibitory Concentration (Auc/Mic) With Multidisciplinary Team Support To Improve Hospital-Wide Adherence To A Vancomycin Dosing Protocol: A Pilot Study, Panipak Katawethiwong, Anucha Apisarnthanarak, Kittiya Jantarathaneewat, David J Weber, David K Warren, Nuntra Suwantarat

Open Access Publications

BACKGROUND: Limited data are available on the implementation of an area under the concentration-time curve (AUC)-based dosing protocol with multidisciplinary team (MT) support to improve adherence with vancomycin dosing protocol.

OBJECTIVE: To evaluate the effectiveness of an AUC-based dosing protocol with MT support intervention with adherence to a hospital-wide vancomycin dosing protocol at Thammasat University Hospital.

METHOD: We conducted a quasi-experimental study in patients who were prescribed intravenous vancomycin. The study was divided into 2 periods; (1) the preintervention period when the vancomycin dosing protocol was already applied in routine practice and (2) the post-intervention period when the implementation of …

Disentangling The Complexity Of The Rumen Microbial Diversity Through Fractionation Using A Sucrose Density Gradient, Ruth Hernández, Hugo Jimenez, Cesar Vargas-Garcia, Alejandro Caro-Quintero, Alejandro Reyes

Open Access Publications

The ruminal microbial community is an important element in health, nutrition, livestock productivity, and climate impact. Despite the historic and current efforts to characterize this microbial diversity, many of its members remain unidentified, making it challenging to associate microbial groups with functions. Here we present a low-cost methodology for rumen sample treatment that separates the microbial community based on cell size, allowing for the identification of subtle compositional changes. In brief, the sample is centrifuged through a series of sucrose density gradients, and cells migrate to their corresponding density fraction. From each fraction, DNA is extracted and

Structure-Guided Microbial Targeting Of Antistaphylococcal Prodrugs, Justin J. Miller, Ishaan T. Shah, Jayda Hatten, Yasaman Barekatain, Elizabeth A. Mueller, Ahmed M. Moustafa, Rachel L. Edwards, Cynthia S. Dowd, Paul J. Planet, Florian L. Muller, Joseph M. Jez, Audrey R. Odom John

Open Access Publications

Carboxy ester prodrugs are widely employed to increase oral absorption and potency of phosphonate antibiotics. Prodrugging can mask problematic chemical features that prevent cellular uptake and may enable tissue-specific compound delivery. However, many carboxy ester promoieties are rapidly hydrolyzed by serum esterases, limiting their therapeutic potential. While carboxy ester-based prodrug targeting is feasible, it has seen limited use in microbes as microbial esterase-specific promoieties have not been described. Here we identify the bacterial esterases, GloB and FrmB, that activate carboxy ester prodrugs in