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Real-World Evaluation Of The Impact Of Implementation Of The Virtuo Blood Culture System In A Tertiary Care Hospital, Miguel A Chavez, Satish Munigala, Carey-Ann D Burnham, Melanie L Yarbrough, David K Warren Sep 2021

Real-World Evaluation Of The Impact Of Implementation Of The Virtuo Blood Culture System In A Tertiary Care Hospital, Miguel A Chavez, Satish Munigala, Carey-Ann D Burnham, Melanie L Yarbrough, David K Warren

Open Access Publications

The bioMérieux BacT/Alert Virtuo blood culture system used in combination with resin-containing media may enhance the growth of microorganisms. Our objective was to assess the impact of transitioning to the Virtuo system in comparison to the VersaTREK blood culture system at a tertiary care medical center. We retrospectively reviewed all blood cultures performed at a 1,250-bed academic medical center between January and December 2018 (VersaTREK) and January and December 2019 (Virtuo). Blood culture positivity rates and contamination rates were compared before and after Virtuo implementation. Of 101,438 blood cultures performed during the study period, 48,839 (48.1%) were processed preimplementation and …


Clinicians' Perspectives On The Functions Of Communication In Pediatric Oncology, Bryan A. Sisk, Ginny L. Schulz, Erica C. Kaye, Justin N. Baker, Jennifer W. Mack, James M. Dubois Sep 2021

Clinicians' Perspectives On The Functions Of Communication In Pediatric Oncology, Bryan A. Sisk, Ginny L. Schulz, Erica C. Kaye, Justin N. Baker, Jennifer W. Mack, James M. Dubois

Open Access Publications

No abstract provided.


Autologous And Allogeneic Hematopoietic Cell Transplantation For Diffuse Large B-Cell Lymphoma–Type Richter Syndrome, Alex F. Herrera, Shalini Shenoy, Et Al Sep 2021

Autologous And Allogeneic Hematopoietic Cell Transplantation For Diffuse Large B-Cell Lymphoma–Type Richter Syndrome, Alex F. Herrera, Shalini Shenoy, Et Al

Open Access Publications

No abstract provided.


Falls: A Marker Of Preclinical Alzheimer Disease: A Cohort Study Protocol, Rebecca M Bollinger, Audrey Keleman, Regina Thompson, Elizabeth Westerhaus, Anne M Fagan, Tammie Ls Benzinger, Suzanne E Schindler, Chengjie Xiong, David Balota, John C Morris, Beau M Ances, Susan L Stark Sep 2021

Falls: A Marker Of Preclinical Alzheimer Disease: A Cohort Study Protocol, Rebecca M Bollinger, Audrey Keleman, Regina Thompson, Elizabeth Westerhaus, Anne M Fagan, Tammie Ls Benzinger, Suzanne E Schindler, Chengjie Xiong, David Balota, John C Morris, Beau M Ances, Susan L Stark

Open Access Publications

INTRODUCTION: Progression to symptomatic Alzheimer disease (AD) occurs slowly over a series of preclinical stages. Declining functional mobility may be an early indicator of loss of brain network integration and may lead to an increased risk of experiencing falls. It is unknown whether measures of functional mobility and falls are preclinical markers of AD. The purpose of this study is to examine (1) the relationship between falls and functional mobility with AD biomarkers to determine when falls occur within the temporal progression to symptomatic Alzheimer disease, and (2) the attentional compared with perceptual/motor systems that underlie falls and functional mobility …


Intestinal Antiviral Signaling Is Controlled By Autophagy Gene Epg5 Independent Of The Microbiota, Sanghyun Lee, Gowri Kalugotla, Harshad Ingle, Rachel Rodgers, Yating Wang, Yuhao Li, Nicolette R Borella, Hongju Deng, Lindsay Droit, Ryan Hill, Stefan T Peterson, Chandni Desai, Dylan Lawrence, Megan T Baldridge, Et Al Sep 2021

Intestinal Antiviral Signaling Is Controlled By Autophagy Gene Epg5 Independent Of The Microbiota, Sanghyun Lee, Gowri Kalugotla, Harshad Ingle, Rachel Rodgers, Yating Wang, Yuhao Li, Nicolette R Borella, Hongju Deng, Lindsay Droit, Ryan Hill, Stefan T Peterson, Chandni Desai, Dylan Lawrence, Megan T Baldridge, Et Al

Open Access Publications

Mutations in the macroautophagy/autophagy gene


Neuropathic Pain: Biomolecular Intervention And Imaging Via Targeting Microglia Activation, Aijun Ji, Jinbin Xu Sep 2021

Neuropathic Pain: Biomolecular Intervention And Imaging Via Targeting Microglia Activation, Aijun Ji, Jinbin Xu

Open Access Publications

Many diseases, including cancer, can lead to neuropathic pain (NP). NP is one of the accompanying symptoms of suffering in many conditions and the life quality of NP patient is seriously affected. Due to complex causes, the effects of clinical treatments have been very unsatisfactory. Many experts have found that neuron-microglia interaction plays an essential role in NP occurrence and development. Therefore, the activation of microglia, related inflammatory mediators and molecular and cellular signaling pathways have become the focus of NP research. With the help of modern functional imaging technology, advanced pre-and clinical studies have been carried out and NP …


Signaling Through Retinoic Acid Receptors Is Essential For Mammalian Uterine Receptivity And Decidualization, Yan Yin, Meade E. Haller, Sangappa B. Chadchan, Ramakrishna Kommagani, Liang Ma Sep 2021

Signaling Through Retinoic Acid Receptors Is Essential For Mammalian Uterine Receptivity And Decidualization, Yan Yin, Meade E. Haller, Sangappa B. Chadchan, Ramakrishna Kommagani, Liang Ma

Open Access Publications

Retinoic acid (RA) signaling has long been speculated to regulate embryo implantation, because many enzymes and proteins responsible for maintaining RA homeostasis and transducing RA signals are tightly regulated in the endometrium during this critical period. However, due to a lack of genetic data, it was unclear whether RA signaling is truly required for implantation and which specific RA signaling cascades are at play. Herein we utilize a genetic murine model that expresses a dominant-negative form of RA receptor (RAR) specifically in female reproductive organs to show that functional RA signaling is fundamental to female fertility, particularly implantation and decidualization. …


Racial Disparities In Modifiable Risk Factors And Statin Usage In Black Patients With Familial Hypercholesterolemia, Anandita Agarwala, Nathan Bekele, Elena Deych, Michael W Rich, Aliza Hussain, Laney K Jones, Amy C Sturm, Karen Aspry, Elizabeth Nowak, Zahid Ahmad, Christie M Ballantyne, Anne C Goldberg Sep 2021

Racial Disparities In Modifiable Risk Factors And Statin Usage In Black Patients With Familial Hypercholesterolemia, Anandita Agarwala, Nathan Bekele, Elena Deych, Michael W Rich, Aliza Hussain, Laney K Jones, Amy C Sturm, Karen Aspry, Elizabeth Nowak, Zahid Ahmad, Christie M Ballantyne, Anne C Goldberg

Open Access Publications

Background Black men and women are at higher risk for, and suffer greater morbidity and mortality from, atherosclerotic cardiovascular disease (ASCVD) compared with adults of European Ancestry (EA). Black patients with familial hypercholesterolemia are at particularly high risk for ASCVD complications because of lifelong exposure to elevated levels of low-density-lipoprotein cholesterol. Methods and Results This retrospective study analyzed ASCVD prevalence and risk factors in 808 adults with heterozygous familial hypercholesterolemia from 5 US-based lipid clinics, and compared findings in Black versus EA patients. Multivariate logistic regression models were used to determine the strongest predictors of ASCVD as a function of …


Brain White Matter Structure And Amyloid Deposition In Black And White Older Adults: The Aric-Pet Study, Keenan A Walker, Noah Silverstein, Yun Zhou, Timothy M Hughes, Clifford R Jack, David S Knopman, A Richey Sharrett, Dean F Wong, Thomas H Mosley, Rebecca F Gottesman Sep 2021

Brain White Matter Structure And Amyloid Deposition In Black And White Older Adults: The Aric-Pet Study, Keenan A Walker, Noah Silverstein, Yun Zhou, Timothy M Hughes, Clifford R Jack, David S Knopman, A Richey Sharrett, Dean F Wong, Thomas H Mosley, Rebecca F Gottesman

Open Access Publications

Background White matter abnormalities are a common feature of aging and Alzheimer disease, and tend to be more severe among Black individuals. However, the extent to which white matter abnormalities relate to amyloid deposition, a marker of Alzheimer pathology, remains unclear. This cross-sectional study examined the association of white matter abnormalities with cortical amyloid in a community sample of older adults without dementia and examined the moderating effect of race. Methods and Results Participants from the ARIC-PET (Atherosclerosis Risk in Communities-Positron Emission Tomography) study underwent brain magnetic resonance imaging, which quantified white matter hyperintensity volume and microstructural integrity using diffusion …


Social Determinants Of Health Discussed With Mothers During Personal Visits Before And During The Covid-19 Pandemic, Rachel G Tabak, Cynthia D Schwarz, Allison Kemner, Shelly Johnston, Adriana Aramburu, Debra Haire-Joshu Sep 2021

Social Determinants Of Health Discussed With Mothers During Personal Visits Before And During The Covid-19 Pandemic, Rachel G Tabak, Cynthia D Schwarz, Allison Kemner, Shelly Johnston, Adriana Aramburu, Debra Haire-Joshu

Open Access Publications

No abstract provided.


Hsp90 Inhibitors Reduce Cholesterol Storage In Niemann-Pick Type C1 Mutant Fibroblasts, Nina H Pipalia, Syed Z Saad, Kanagaraj Subramanian, Abigail Cross, Aisha Al-Motawa, Kunal Garg, Brian S J Blagg, Len Neckers, Paul Helquist, Olaf Wiest, Daniel S Ory, Frederick R Maxfield Sep 2021

Hsp90 Inhibitors Reduce Cholesterol Storage In Niemann-Pick Type C1 Mutant Fibroblasts, Nina H Pipalia, Syed Z Saad, Kanagaraj Subramanian, Abigail Cross, Aisha Al-Motawa, Kunal Garg, Brian S J Blagg, Len Neckers, Paul Helquist, Olaf Wiest, Daniel S Ory, Frederick R Maxfield

Open Access Publications

Niemann Pick type C1 (NPC1) disease is a lysosomal lipid storage disorder caused by mutations of the NPC1 gene. More than 300 disease-associated mutations are reported in patients, resulting in abnormal accumulation of unesterified cholesterol, glycosphingolipids and other lipids in late endosomes and lysosomes (LE/Ly) of many cell types. Previously, we showed that treatment of many different NPC1 mutant fibroblasts with histone deacetylase inhibitors resulted in reduction of cholesterol storage, and we found that this was associated with enhanced exit of the NPC1 protein from the endoplasmic reticulum and delivery to LE/Ly. This suggested that histone deacetylase inhibitors may work …


Protection Levels Of N95-Level Respirator Substitutes Proposed During The Covid-19 Pandemic: Safety Concerns And Quantitative Evaluation Procedures, David Ballard, Alex Scott, Broc Burke, Jason Morris, Connie Gan, Jesse Hu, Udayabhanu Jammalamadaka, Sena Sayood, Stephen Liang, Bruno Maranhao, J. Tyler Bertroche, Nirah Shomer, Pamela Woodard, Kathleen Meacham, Et Al Sep 2021

Protection Levels Of N95-Level Respirator Substitutes Proposed During The Covid-19 Pandemic: Safety Concerns And Quantitative Evaluation Procedures, David Ballard, Alex Scott, Broc Burke, Jason Morris, Connie Gan, Jesse Hu, Udayabhanu Jammalamadaka, Sena Sayood, Stephen Liang, Bruno Maranhao, J. Tyler Bertroche, Nirah Shomer, Pamela Woodard, Kathleen Meacham, Et Al

Open Access Publications

OBJECTIVE: The COVID-19 pandemic has precipitated widespread shortages of filtering facepiece respirators (FFRs) and the creation and sharing of proposed substitutes (novel designs, repurposed materials) with limited testing against regulatory standards. We aimed to categorically test the efficacy and fit of potential N95 respirator substitutes using protocols that can be replicated in university laboratories.

SETTING: Academic medical centre with occupational health-supervised fit testing along with laboratory studies.

PARTICIPANTS: Seven adult volunteers who passed quantitative fit testing for small-sized (n=2) and regular-sized (n=5) commercial N95 respirators.

METHODS: Five open-source potential N95 respirator substitutes were evaluated and compared with commercial National Institute …


Loss Of Synergistic Transcriptional Feedback Loops Drives Diverse B-Cell Cancers, Jared M Andrews, Sarah C Pyfrom, Jennifer A Schmidt, Olivia I Koues, Rodney A Kowalewski, Nicholas R Grams, Jessica J Sun, Leigh R Berman, Eric J Duncavage, Yi-Shan Lee, Amanda F Cashen, Eugene M Oltz, Jacqueline E Payton Sep 2021

Loss Of Synergistic Transcriptional Feedback Loops Drives Diverse B-Cell Cancers, Jared M Andrews, Sarah C Pyfrom, Jennifer A Schmidt, Olivia I Koues, Rodney A Kowalewski, Nicholas R Grams, Jessica J Sun, Leigh R Berman, Eric J Duncavage, Yi-Shan Lee, Amanda F Cashen, Eugene M Oltz, Jacqueline E Payton

Open Access Publications

BACKGROUND: The most common B-cell cancers, chronic lymphocytic leukemia/lymphoma (CLL), follicular and diffuse large B-cell (FL, DLBCL) lymphomas, have distinct clinical courses, yet overlapping "cell-of-origin". Dynamic changes to the epigenome are essential regulators of B-cell differentiation. Therefore, we reasoned that these distinct cancers may be driven by shared mechanisms of disruption in transcriptional circuitry.

METHODS: We compared purified malignant B-cells from 52 patients with normal B-cell subsets (germinal center centrocytes and centroblasts, naïve and memory B-cells) from 36 donor tonsils using >325 high-resolution molecular profiling assays for histone modifications, open chromatin (ChIP-, FAIRE-seq), transcriptome (RNA-seq), transcription factor (TF) binding, and …


Phagocytes Produce Prostaglandin E2 In Response To Cytosolic Listeria Monocytogenes, Courtney E. Mcdougal, Zachary T. Morrow, Tighe Christopher, Seonyoung Kim, Drake Carter, David M. Stevenson, Daniel Amador-Noguez, Mark J. Miller, John-Demian Sauer Sep 2021

Phagocytes Produce Prostaglandin E2 In Response To Cytosolic Listeria Monocytogenes, Courtney E. Mcdougal, Zachary T. Morrow, Tighe Christopher, Seonyoung Kim, Drake Carter, David M. Stevenson, Daniel Amador-Noguez, Mark J. Miller, John-Demian Sauer

Open Access Publications

Listeria monocytogenes is an intracellular bacterium that elicits robust CD8+ T-cell responses. Despite the ongoing development of L. monocytogenes-based platforms as cancer vaccines, our understanding of how L. monocytogenes drives robust CD8+ T-cell responses remains incomplete. One overarching hypothesis is that activation of cytosolic innate pathways is critical for immunity, as strains of L. monocytogenes that are unable to access the cytosol fail to elicit robust CD8+ T-cell responses and in fact inhibit optimal T-cell priming. Counterintuitively, however, activation of known cytosolic pathways, such as the inflammasome and type I IFN, lead to impaired immunity. Conversely, production of prostaglandin E2 …


Endothelial Fgf Signaling Is Protective In Hypoxia-Induced Pulmonary Hypertension, Kel Vin Woo, Isabel Y Shen, Carla J Weinheimer, Attila Kovacs, Jessica Nigro, Chieh-Yu Lin, Murali Chakinala, Derek E Byers, David M Ornitz Sep 2021

Endothelial Fgf Signaling Is Protective In Hypoxia-Induced Pulmonary Hypertension, Kel Vin Woo, Isabel Y Shen, Carla J Weinheimer, Attila Kovacs, Jessica Nigro, Chieh-Yu Lin, Murali Chakinala, Derek E Byers, David M Ornitz

Open Access Publications

Hypoxia-induced pulmonary hypertension (PH) is one of the most common and deadliest forms of PH. Fibroblast growth factor receptors 1 and 2 (FGFR1/2) are elevated in patients with PH and in mice exposed to chronic hypoxia. Endothelial FGFR1/2 signaling is important for the adaptive response to several injury types and we hypothesized that endothelial FGFR1/2 signaling would protect against hypoxia-induced PH. Mice lacking endothelial FGFR1/2, mice with activated endothelial FGFR signaling, and human pulmonary artery endothelial cells (HPAECs) were challenged with hypoxia. We assessed the effect of FGFR activation and inhibition on right ventricular pressure, vascular remodeling, and endothelial-mesenchymal transition …


Adrenal Vein Sampling For Acth-Producing Pheochromocytomas, Nicholas Leader, Alexander Ushinsky, Christopher D Malone Sep 2021

Adrenal Vein Sampling For Acth-Producing Pheochromocytomas, Nicholas Leader, Alexander Ushinsky, Christopher D Malone

Open Access Publications

Adrenocorticotropic hormone (ACTH)-producing pheochromocytoma can cause a variety of clinical manifestations of excess catecholamine and corticosteroid. Anatomic localization of this source of ectopic ACTH is critical to facilitate unilateral adrenalectomy and prevent adrenal insufficiency due to bilateral adrenalectomy. Although nuclear scintigraphy remains the diagnostic gold standard, recent radiotracer supply shortages have necessitated alternative diagnostic paradigms to localize adrenal pheochromocytomas. We present a case where adrenal vein sampling (AVS) was utilized to lateralize an adrenal pheochromocytoma and discuss the approach and nuance as it differs from routine AVS for hyperaldosteronism or hypercortisolism.


A Comparison Of Machine Learning Classifiers For Pediatric Epilepsy Using Resting-State Functional Mri Latency Data, Ryan D Nguyen, Matthew D Smyth, Liang Zhu, Ludovic P Pao, Shannon K Swisher, Emmett H Kennady, Anish Mitra, Rajan P Patel, Jeremy E Lankford, Gretchen Von Allmen, Michael W Watkins, Michael E Funke, Manish N Shah Sep 2021

A Comparison Of Machine Learning Classifiers For Pediatric Epilepsy Using Resting-State Functional Mri Latency Data, Ryan D Nguyen, Matthew D Smyth, Liang Zhu, Ludovic P Pao, Shannon K Swisher, Emmett H Kennady, Anish Mitra, Rajan P Patel, Jeremy E Lankford, Gretchen Von Allmen, Michael W Watkins, Michael E Funke, Manish N Shah

Open Access Publications

Epilepsy affects 1 in 150 children under the age of 10 and is the most common chronic pediatric neurological condition; poor seizure control can irreversibly disrupt normal brain development. The present study compared the ability of different machine learning algorithms trained with resting-state functional MRI (rfMRI) latency data to detect epilepsy. Preoperative rfMRI and anatomical MRI scans were obtained for 63 patients with epilepsy and 259 healthy controls. The normal distribution of latency z-scores from the epilepsy and healthy control cohorts were analyzed for overlap in 36 seed regions. In these seed regions, overlap between the study cohorts ranged from …


Memory-Like Differentiation Enhances Nk Cell Responses To Melanoma, Nancy D Marin, Bradley A Krasnick, Michelle Becker-Hapak, Leah Conant, Simon P Goedegebuure, Melissa M Berrien-Elliott, Keenan J Robbins, Jennifer A Foltz, Mark Foster, Pamela Wong, Celia C Cubitt, Jennifer Tran, Christopher B Wetzel, Miriam Jacobs, Alice Y Zhou, David Russler-Germain, Lynne Marsala, Timothy Schappe, Ryan C Fields, Todd A Fehniger Sep 2021

Memory-Like Differentiation Enhances Nk Cell Responses To Melanoma, Nancy D Marin, Bradley A Krasnick, Michelle Becker-Hapak, Leah Conant, Simon P Goedegebuure, Melissa M Berrien-Elliott, Keenan J Robbins, Jennifer A Foltz, Mark Foster, Pamela Wong, Celia C Cubitt, Jennifer Tran, Christopher B Wetzel, Miriam Jacobs, Alice Y Zhou, David Russler-Germain, Lynne Marsala, Timothy Schappe, Ryan C Fields, Todd A Fehniger

Open Access Publications

PURPOSE: Treatment of advanced melanoma is a clinical challenge. Natural killer (NK) cells are a promising cellular therapy for T cell-refractory cancers, but are frequently deficient or dysfunctional in patients with melanoma. Thus, new strategies are needed to enhance NK-cell antitumor responses. Cytokine-induced memory-like (ML) differentiation overcomes many barriers in the NK-cell therapeutics field, resulting in potent cytotoxicity and enhanced cytokine production against blood cancer targets. However, the preclinical activity of ML NK against solid tumors remains largely undefined.

EXPERIMENTAL DESIGN: Phenotypic and functional alterations of blood and advanced melanoma infiltrating NK cells were evaluated using mass cytometry. ML NK …


Alterations Of The Gut Mycobiome In Patients With Ms, Saumya Shah, Alberto Locca, Claudia Cantoni, Laura Ghezzi, Emily Evans, Robert Mikesell, Kathleen Obert, Amber Salter, Anne H Cross, Phillip I Tarr, Laura Piccio, Et Al Sep 2021

Alterations Of The Gut Mycobiome In Patients With Ms, Saumya Shah, Alberto Locca, Claudia Cantoni, Laura Ghezzi, Emily Evans, Robert Mikesell, Kathleen Obert, Amber Salter, Anne H Cross, Phillip I Tarr, Laura Piccio, Et Al

Open Access Publications

BACKGROUND: The mycobiome is the fungal component of the gut microbiome and is implicated in several autoimmune diseases. However, its role in MS has not been studied.

METHODS: In this case-control observational study, we performed ITS sequencing and characterised the gut mycobiome in people with MS (pwMS) and healthy controls at baseline and after six months.

FINDINGS: The mycobiome had significantly higher alpha diversity and inter-subject variation in pwMS than controls. Saccharomyces and Aspergillus were over-represented in pwMS. Saccharomyces was positively correlated with circulating basophils and negatively correlated with regulatory B cells, while Aspergillus was positively correlated with activated CD16 …


Cryptorchidism As An Obscure Cause Of Adhesive Small Bowel Obstruction In An Adult, A Case Report, Savni Satoskar, Sarang Kashyap, Joshua Ziehm, Francisco Benavides, Avian Chang, Vinay Singhal Sep 2021

Cryptorchidism As An Obscure Cause Of Adhesive Small Bowel Obstruction In An Adult, A Case Report, Savni Satoskar, Sarang Kashyap, Joshua Ziehm, Francisco Benavides, Avian Chang, Vinay Singhal

Open Access Publications

INTRODUCTION AND IMPORTANCE: Cryptorchidism is seen in 3% of fullterm neonates. Rarely, it may cause small bowel obstruction. Knowledge of this presentation of cryptorchidism is essential to treat bowel obstruction arising due to cryptorchidism before the patient suffers complications.

CASE PRESENTATION: We present a case of a patient who underwent exploratory laparotomy for small bowel obstruction that did not resolve with conservative management. At laparotomy, on initial exploration, this patient had adhesive bands causing the small bowel obstruction. On further exploration, the bands were found to arise from a cryptorchid testis.

CLINICAL DISCUSSION: Cryptorchidism is a common finding among newborns …


Hypoglycemia Secondary To Insulinoma Masking The Onset Of Type 1 Diabetes In An Adolescent, Sriya Subramani, Andrew M Bellizzi, Nicholas Borcherding, Simon C Kao, Joseph Dillon, James Howe, Andrew W Norris, Michael J Tansey, Catherina T Pinnaro Sep 2021

Hypoglycemia Secondary To Insulinoma Masking The Onset Of Type 1 Diabetes In An Adolescent, Sriya Subramani, Andrew M Bellizzi, Nicholas Borcherding, Simon C Kao, Joseph Dillon, James Howe, Andrew W Norris, Michael J Tansey, Catherina T Pinnaro

Open Access Publications

Type 1 diabetes and insulinoma can co-occur in pediatric patients and may present with episodes of hypo- and hyperglycemia, significant glycemic variability, and weight gain. Surgical resection leads to development of fulminant diabetes.


A Phase 1/2 Open Label Nonrandomized Clinical Trial Of Intravenous 2-Hydroxypropyl-Β-Cyclodextrin For Acute Liver Disease In Infants With Niemann-Pick C1, Margaret Reynolds, Laura A Linneman, Sofia Luna, Barbara B Warner, Yumirle P Turmelle, Sakil S Kulkarni, Xuntian Jiang, Geetika Khanna, Marwan Shinawi, Forbes D Porter, Daniel S Ory, F. Sessions Cole, Patricia I Dickson Sep 2021

A Phase 1/2 Open Label Nonrandomized Clinical Trial Of Intravenous 2-Hydroxypropyl-Β-Cyclodextrin For Acute Liver Disease In Infants With Niemann-Pick C1, Margaret Reynolds, Laura A Linneman, Sofia Luna, Barbara B Warner, Yumirle P Turmelle, Sakil S Kulkarni, Xuntian Jiang, Geetika Khanna, Marwan Shinawi, Forbes D Porter, Daniel S Ory, F. Sessions Cole, Patricia I Dickson

Open Access Publications

Introduction: Niemann-Pick C (NPC) is an autosomal recessive disease due to defective NPC1 or NPC2 proteins resulting in

Methods: Infants received intravenous 2HPBCD twice a week for 6 weeks, followed by monthly infusion for 6-months. Primary outcome measure was reduction of plasma (3β,5α,6β-trihydroxy-cholan-24-oyl) glycine (TCG), a bile acid generated from cholesterol sequestered in lysosome.

Results: Three participants completed this protocol. A fourth patient received intravenous 2HPBCD under an emergency investigational new drug study but later expired from her underlying condition. The three protocol patients are living and have improved liver enzymes and TCG. No patient has experienced a drug-related adverse …


Mapt R406w Increases Tau T217 Phosphorylation In Absence Of Amyloid Pathology, Chihiro Sato, Nipun Mallipeddi, Nupur Ghoshal, Brenton A Wright, Gregory S Day, Albert A Davis, Albert H Kim, Gregory J Zipfel, Randall J Bateman, Audrey Gabelle, Nicolas R Barthélemy Sep 2021

Mapt R406w Increases Tau T217 Phosphorylation In Absence Of Amyloid Pathology, Chihiro Sato, Nipun Mallipeddi, Nupur Ghoshal, Brenton A Wright, Gregory S Day, Albert A Davis, Albert H Kim, Gregory J Zipfel, Randall J Bateman, Audrey Gabelle, Nicolas R Barthélemy

Open Access Publications

OBJECTIVE: Tau hyperphosphorylation at threonine 217 (pT217) in cerebrospinal fluid (CSF) has recently been linked to early amyloidosis and could serve as a highly sensitive biomarker for Alzheimer's disease (AD). However, it remains unclear whether other tauopathies induce pT217 modifications. To determine if pT217 modification is specific to AD, CSF pT217 was measured in AD and other tauopathies.

METHODS: Using immunoprecipitation and mass spectrometry methods, we compared CSF T217 phosphorylation occupancy (pT217/T217) and amyloid-beta (Aβ) 42/40 ratio in cognitively normal individuals and those with symptomatic AD, progressive supranuclear palsy, corticobasal syndrome, and sporadic and familial frontotemporal dementia.

RESULTS: Individuals with …


Interplay Of Trypanosome Lytic Factor And Innate Immune Cells In The Resolution Of Cutaneous Leishmania Infection, Jyoti Pant, Marie Samanovic, Maria T. Nelson, Mert K. Keceli, Joseph Verdi, Stephen M. Beverley, Jayne Raper Sep 2021

Interplay Of Trypanosome Lytic Factor And Innate Immune Cells In The Resolution Of Cutaneous Leishmania Infection, Jyoti Pant, Marie Samanovic, Maria T. Nelson, Mert K. Keceli, Joseph Verdi, Stephen M. Beverley, Jayne Raper

Open Access Publications

Trypanosome Lytic Factor (TLF) is a primate-specific high-density lipoprotein (HDL) complex that, through the cation channel-forming protein apolipoprotein L-1 (APOL1), provides innate immunity to select kinetoplastid parasites. The immunoprotective effects of TLF have been extensively investigated in the context of its interaction with the extracellular protozoan Trypanosoma brucei brucei, to which it confers sterile immunity. We previously showed that TLF could act against an intracellular pathogen Leishmania, and here we dissected the role of TLF and its synergy with host-immune cells. Leishmania major is transmitted by Phlebotomine sand flies, which deposit the parasite intradermally into mammalian hosts, where neutrophils are …


A Novel Intervention Combining Supplementary Food And Infection Control Measures To Improve Birth Outcomes In Undernourished Pregnant Women In Sierra Leone: A Randomized, Controlled Clinical Effectiveness Trial, David Taylor Hendrixson, Kristie Smith, Patrick Lasowski, Meghan Callaghan-Gillespie, Jacklyn Weber, Peggy Papathakis, Per Ole Iversen, Aminata Shamit Koroma, Mark J. Manary Sep 2021

A Novel Intervention Combining Supplementary Food And Infection Control Measures To Improve Birth Outcomes In Undernourished Pregnant Women In Sierra Leone: A Randomized, Controlled Clinical Effectiveness Trial, David Taylor Hendrixson, Kristie Smith, Patrick Lasowski, Meghan Callaghan-Gillespie, Jacklyn Weber, Peggy Papathakis, Per Ole Iversen, Aminata Shamit Koroma, Mark J. Manary

Open Access Publications

BACKGROUND: Innovations for undernourished pregnant women that improve newborn survival and anthropometry are needed to achieve the Sustainable Development Goals 1 and 3. This study tested the hypothesis that a combination of a nutritious supplementary food and several proven chemotherapeutic interventions to control common infections would increase newborn weight and length in undernourished pregnant women.

METHODS AND FINDINGS: This was a prospective, randomized, controlled clinical effectiveness trial of a ready-to-use supplementary food (RUSF) plus anti-infective therapies compared to standard therapy in undernourished pregnant women in rural Sierra Leone. Women with a mid-upper arm circumference (MUAC) ≤23.0 cm presenting for antenatal …


Future Directions For Hiv Service Delivery Research: Research Gaps Identified Through Who Guideline Development, Nathan Ford, Ingrid Eshun-Wilson, Wole Ameyan, Morkor Newman, Lara Vojnov, Meg Doherty, Elvin Geng Sep 2021

Future Directions For Hiv Service Delivery Research: Research Gaps Identified Through Who Guideline Development, Nathan Ford, Ingrid Eshun-Wilson, Wole Ameyan, Morkor Newman, Lara Vojnov, Meg Doherty, Elvin Geng

Open Access Publications

Nathan Ford and co-authors discuss the systematic identification of research gaps in improving HIV service delivery.


Reactive Arthritis Post-Sars-Cov-2, Faizal Ouedraogo, Rachita Navara, Rusha Thapa, Kunj G. Patel Sep 2021

Reactive Arthritis Post-Sars-Cov-2, Faizal Ouedraogo, Rachita Navara, Rusha Thapa, Kunj G. Patel

Open Access Publications

Reactive arthritis (ReA) following bacterial infection from the urogenital and gastrointestinal tract is widely described but is not typical post-viral infections. This report presents the second case of ReA after severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection in the United States. A 45-year-old black male with chronic low back pain was hospitalized for 45 days with coronavirus disease 2019 (COVID-19), complicated due to the development of multiorgan failure managed with intubation, extracorporeal membrane oxygenation, and hemodialysis. He was subsequently discharged to an acute rehabilitation facility where he complained of new-onset pain in his shoulders, left elbow, and left knee …


Evaluation Of Admission Chest X-Ray Findings In Patients With Respiratory Infection During The Covid-19 Pandemic, Dimitrios Velissaris, Maria Lagadinou, Themistoklis Paraskevas, Eleousa Oikonomou, Vasileios Karamouzos, Fotios Sampsonas, Markos Marangos, Menelaos Karanikolas Sep 2021

Evaluation Of Admission Chest X-Ray Findings In Patients With Respiratory Infection During The Covid-19 Pandemic, Dimitrios Velissaris, Maria Lagadinou, Themistoklis Paraskevas, Eleousa Oikonomou, Vasileios Karamouzos, Fotios Sampsonas, Markos Marangos, Menelaos Karanikolas

Open Access Publications

AIMS: To evaluate the prevalence of X-ray findings in hospitalized patients requiring hospitalization with suspected Coronavirus disease 2019 (COVID-19) infection and potential differences in the laboratory values and clinical outcomes related to the presence of abnormal chest X-ray (CXR) findings.

METHODS:

RESULTS:

CONCLUSION: CXR is a routine examination in all patients with symptoms of lower respiratory tract disease and its findings relate to in-hospital mortality and PaO


Covid-19 In Patients With Neuromyelitis Optica Spectrum Disorders And Myelin Oligodendrocyte Glycoprotein Antibody Disease In North America: From The Covims Registry, Scott D Newsome, Anne H Cross, Robert J Fox, June Halper, Pamela Kanellis, Bruce Bebo, David Li, Gary R Cutter, Kottil W Rammohan, Amber Salter Sep 2021

Covid-19 In Patients With Neuromyelitis Optica Spectrum Disorders And Myelin Oligodendrocyte Glycoprotein Antibody Disease In North America: From The Covims Registry, Scott D Newsome, Anne H Cross, Robert J Fox, June Halper, Pamela Kanellis, Bruce Bebo, David Li, Gary R Cutter, Kottil W Rammohan, Amber Salter

Open Access Publications

BACKGROUND AND OBJECTIVE: To describe the impact of coronavirus disease 2019 (COVID-19) on people with neuromyelitis optica spectrum disorders (NMOSD) and myelin oligodendrocyte glycoprotein antibody disease (MOGAD).

METHODS: The COVID-19 Infections in Multiple Sclerosis (MS) and Related Diseases (COViMS) Registry collected data on North American patients with MS and related diseases with laboratory-positive or highly suspected SARS-CoV-2 infection. Deidentified data were entered into a web-based registry by health care providers. Data were analyzed using

RESULTS: As of June 7, 2021, 77 patients with NMOSD and 20 patients with MOGAD were reported in the COViMS Registry. Most patients with NMOSD were …


Impact Of Nerve Surgery On Opioid And Medication Use In Patients With Chronic Nerve Injuries, John M Felder, Ivica Ducic Sep 2021

Impact Of Nerve Surgery On Opioid And Medication Use In Patients With Chronic Nerve Injuries, John M Felder, Ivica Ducic

Open Access Publications

Introduction: Limited information is available regarding the ability of nerve surgery to affect medication use patterns in patients with chronic pain or neuropathy due to nerve injury.

Methods: A retrospective survey was distributed to all operative patients (N = 767) from a single nerve surgeon's practice between 2014 and 2020. Data collected included demographics, specifics of the injury and symptoms, medication and opioid use before surgery, and medication/opioid use following surgery.

Results: Out of the 767 patients, 209 (27.2%) completed the survey. Average age was 48.8 (SD = 19.1) years; 68.9% female and 31.1% male. More than 50% of the …