Digital Commons Network^™

Maternal Hookworm Infection And Its Effects On Maternal Health: A Systematic Review And Meta-Analysis, Tara E Ness, Vedika Agrawal, Kathryn Bedard, Lara Ouellette, Timothy A Erickson, Peter Hotez, Jill E Weatherhead

Library Staff Publications

Hookworm is an intestinal parasite that infects nearly 230 million people, with another 5.1 billion at risk, especially in poverty-stricken tropical and subtropical regions. Pregnancy is an especially vulnerable time for hookworm infection because of its effect on both maternal and subsequently fetal health. A systematic review and meta-analysis was conducted. The meta-analysis was performed on the association between maternal hookworm and maternal anemia, as well as maternal hookworm coinfection with malaria. The prevalence of hookworm ranged from 1% to 78% in pregnant women, whereas malaria prevalence ranged from 11% to 81%. Pregnant women with hookworm infection were more likely …

Maternal Hookworm Infection And Its Effects On Maternal Health: A Systematic Review And Meta-Analysis, Tara E Ness, Vedika Agrawal, Kathryn Bedard, Lara Ouellette, Timothy A Erickson, Peter Hotez, Jill E Weatherhead

Library Staff Publications

Hookworm is an intestinal parasite that infects nearly 230 million people, with another 5.1 billion at risk, especially in poverty-stricken tropical and subtropical regions. Pregnancy is an especially vulnerable time for hookworm infection because of its effect on both maternal and subsequently fetal health. A systematic review and meta-analysis was conducted. The meta-analysis was performed on the association between maternal hookworm and maternal anemia, as well as maternal hookworm coinfection with malaria. The prevalence of hookworm ranged from 1% to 78% in pregnant women, whereas malaria prevalence ranged from 11% to 81%. Pregnant women with hookworm infection were more likely …

Modeling Age-Dependent Developmental Changes In The Expression Of Genes Involved In Citrulline Synthesis Using Pig Enteroids, Mahmoud A Mohammad, Inka C Didelija, Barbara Stoll, Douglas G Burrin, Juan C Marini

Children’s Nutrition Research Center Staff Publications

metabolism of citrulline and arginine are well characterized. Enteroids, a novel ex-vivo model that recreates the three-dimensional structure of the intestinal crypt-villus unit, have shown to replicate molecular and physiological profiles of the intestinal segment from where they originated ("location memory").

Objective: The present study tested the hypothesis that enteroids recapitulate the developmental changes observed in vivo regarding citrulline production in pigs ("developmental memory").

Methods: Preterm (10- and 5-d preterm) and term pigs at birth, together with 7- and 35-d-old pigs were studied. Gene expression was measured in jejunal samples and in enteroids derived from this segment. Whole body citrulline …

The Fgf8 Subfamily (Fgf8, Fgf17 And Fgf18) Is Required For Closure Of The Embryonic Ventral Body Wall, Michael Boylan, Matthew J Anderson, David M Ornitz, Mark Lewandoski

Open Access Publications

The closure of the embryonic ventral body wall in amniotes is an important morphogenetic event and is essential for life. Defects in human ventral wall closure are a major class of birth defect and a significant health burden. Despite this, very little is understood about how the ventral body wall is formed. Here, we show that fibroblast growth factor (FGF) ligands FGF8, FGF17 and FGF18 are essential for this process. Conditional mouse mutants for these genes display subtle migratory defects in the abdominal muscles of the ventral body wall and an enlarged umbilical ring, through which the internal organs are …

Health And Disease Markers Correlate With Gut Microbiome Composition Across Thousands Of People., Ohad Manor, Chengzhen L Dai, Sergey A Kornilov, Brett Smith, Nathan D Price, Jennifer C Lovejoy, Sean M Gibbons, Andrew T Magis

Articles, Abstracts, and Reports

Variation in the human gut microbiome can reflect host lifestyle and behaviors and influence disease biomarker levels in the blood. Understanding the relationships between gut microbes and host phenotypes are critical for understanding wellness and disease. Here, we examine associations between the gut microbiota and ~150 host phenotypic features across ~3,400 individuals. We identify major axes of taxonomic variance in the gut and a putative diversity maximum along the Firmicutes-to-Bacteroidetes axis. Our analyses reveal both known and unknown associations between microbiome composition and host clinical markers and lifestyle factors, including host-microbe associations that are composition-specific. These results suggest potential opportunities …

Splicing Factor Sf3b1 Promotes Endometrial Cancer Progression Via Regulating Ksr2 Rna Maturation, Pooja Popli, Megan M Richters, Sangappa B Chadchan, Tae Hoon Kim, Eric Tycksen, Obi Griffith, Premal H Thaker, Malachi Griffith, Ramakrishna Kommagani

2020-Current year OA Pubs

Although endometrial cancer is the most common cancer of the female reproductive tract, we have little understanding of what controls endometrial cancer beyond the transcriptional effects of steroid hormones such as estrogen. As a result, we have limited therapeutic options for the ~62,000 women diagnosed with endometrial cancer each year in the United States. Here, in an attempt to identify new prognostic and therapeutic targets, we focused on a new area for this cancer-alternative mRNA splicing-and investigated whether splicing factor, SF3B1, plays an important role in endometrial cancer pathogenesis. Using a tissue microarray, we found that human endometrial tumors expressed …

Adaptive Thermogenesis Enhances The Life-Threatening Response To Heat In Mice With An Ryr1 Mutation, Hui J Wang, Chang Seok Lee, Rachel Sue Zhen Yee, Linda Groom, Inbar Friedman, Lyle Babcock, Dimitra K Georgiou, Jin Hong, Amy D Hanna, Joseph Recio, Jong Min Choi, Ting Chang, Nadia H Agha, Jonathan Romero, Poonam Sarkar, Nicol Voermans, M Waleed Gaber, Sung Yun Jung, Matthew L Baker, Robia G Pautler, Robert T Dirksen, Sheila Riazi, Susan L Hamilton

Faculty, Staff and Students Publications

Mutations in the skeletal muscle Ca2+ release channel, the type 1 ryanodine receptor (RYR1), cause malignant hyperthermia susceptibility (MHS) and a life-threatening sensitivity to heat, which is most severe in children. Mice with an MHS-associated mutation in Ryr1 (Y524S, YS) display lethal muscle contractures in response to heat. Here we show that the heat response in the YS mice is exacerbated by brown fat adaptive thermogenesis. In addition, the YS mice have more brown adipose tissue thermogenic capacity than their littermate controls. Blood lactate levels are elevated in both heat-sensitive MHS patients with RYR1 mutations and YS mice due to …

Feasibility And Potential Efficacy Of Commercial Mhealth/Ehealth Tools For Weight Loss In African American Breast Cancer Survivors: Pilot Randomized Controlled Trial, Jeanne M Ferrante, Katie A Devine, Alicja Bator, Ashley Rodgers, Pamela A Ohman-Strickland, Elisa V Bandera, Kevin O Hwang

Faculty, Staff and Student Publications

Weight management after breast cancer (BC) treatment in African American (AA) women is crucial to reduce comorbid conditions and health disparities. We examined feasibility and potential efficacy of commercial eHealth/mHealth tools for weight management in AA BC survivors in New Jersey. Participants (N = 35) were randomized to an intervention (SparkPeople) plus activity tracker, Fitbit Charge (n = 18), or wait-list active control group (Fitbit only, n = 17). Anthropometric, behavioral, and quality of life (QOL) outcomes were collected at baseline, 3, 6, and 12 months. Differences in outcomes were assessed using intent-to-treat analysis. Retention was 97.1%. Both groups lost …

National Nutrition Strategies That Focus On Maternal, Infant, And Young Child Nutrition In Southeast Asia Do Not Consistently Align With Regional And International Recommendations, Tuan T. Nguyen, Ashley Darnell, Amy Weissman, Jennifer Cashin, Mellissa Withers, Roger Mathisen, Karin Lapping, Timothy D. Mastro, Edward A. Frongillo Jr.

Faculty Publications

We examined the consistency of national nutrition strategies and action plans (NNS) focusing on maternal, infant, and young child nutrition in Southeast Asia with regional and international recommendations. Between July and December 2017, we identified and extracted information on context, objectives, interventions, indicators, strategies, and coordination mechanisms from the most recent NNS in nine Southeast Asian countries. All NNS described context, objectives, and the following interventions: antenatal care, micronutrient supplementation during pregnancy, breastfeeding promotion, improved complementary feeding, nutrition in emergencies, and food fortification or dietary diversity. Micronutrient supplementation for young children was included in eight NNS; breastfeeding promotion during pregnancy …

Redefining Cardiac Biomarkers In Predicting Mortality Of Inpatients With Covid-19, Juan-Juan Qin, Xu Cheng, Feng Zhou, Fang Lei, Gauri Akolkar, Jingjing Cai, Xiao-Jing Zhang, Alice Blet, Jing Xie, Peng Zhang, Ye-Mao Liu, Zizhen Huang, Ling-Ping Zhao, Lijin Lin, Meng Xia, Ming-Ming Chen, Xiaohui Song, Liangjie Bai, Ze Chen, Xingyuan Zhang, Da Xiang, Jing Chen, Qingbo Xu, Xin-Liang Ma, Rhian M Touyz, Chen Gao, Haitao Wang, Liming Liu, Weiming Mao, Pengcheng Luo, Youqin Yan, Ping Ye, Manhua Chen, Guohua Chen, Lihua Zhu, Zhi-Gang She, Xiaodong Huang, Yufeng Yuan, Bing-Hong Zhang, Yibin Wang, Peter P Liu, Hongliang Li

Department of Emergency Medicine Faculty Papers

The prognostic power of circulating cardiac biomarkers, their utility, and pattern of release in coronavirus disease 2019 (COVID-19) patients have not been clearly defined. In this multicentered retrospective study, we enrolled 3219 patients with diagnosed COVID-19 admitted to 9 hospitals from December 31, 2019 to March 4, 2020, to estimate the associations and prognostic power of circulating cardiac injury markers with the poor outcomes of COVID-19. In the mixed-effects Cox model, after adjusting for age, sex, and comorbidities, the adjusted hazard ratio of 28-day mortality for hs-cTnI (high-sensitivity cardiac troponin I) was 7.12 ([95% CI, 4.60-11.03] P<0.001), (NT-pro)BNP (N-terminal pro-B-type natriuretic peptide or brain natriuretic peptide) was 5.11 ([95% CI, 3.50-7.47] P<0.001), CK (creatine phosphokinase)-MB was 4.86 ([95% CI, 3.33-7.09] P<0.001), MYO (myoglobin) was 4.50 ([95% CI, 3.18-6.36] P<0.001), and CK was 3.56 ([95% CI, 2.53-5.02] P<0.001). The cutoffs of those cardiac biomarkers for effective prognosis of 28-day mortality of COVID-19 were found to be much lower than for regular heart disease at about 19%-50% of the currently recommended thresholds. Patients with elevated cardiac injury markers above the newly established cutoffs were associated with significantly increased risk of COVID-19 death. In conclusion, cardiac biomarker elevations are significantly associated with 28-day death in patients with COVID-19. The prognostic cutoff values of these biomarkers might be much lower than the current reference standards. These findings can assist in better management of COVID-19 patients to improve outcomes. Importantly, the newly established cutoff levels of COVID-19-associated cardiac biomarkers may serve as useful criteria for the future prospective studies and clinical trials.

Evidence For Craniofacial Enhancer Variation Underlying Nonsyndromic Cleft Lip And Palate, Vershanna E Morris, S Shahrukh Hashmi, Lisha Zhu, Lorena Maili, Christian Urbina, Steven Blackwell, Matthew R Greives, Edward P Buchanan, John B Mulliken, Susan H Blanton, W Jim Zheng, Jacqueline T Hecht, Ariadne Letra

Faculty, Staff and Student Publications

Nonsyndromic cleft lip with or without cleft palate (NSCLP) is a common birth defect for which only ~ 20% of the underlying genetic variation has been identified. Variants in noncoding regions have been increasingly suggested to contribute to the missing heritability. In this study, we investigated whether variation in craniofacial enhancers contributes to NSCLP. Candidate enhancers were identified using VISTA Enhancer Browser and previous publications. Prioritization was based on patterning defects in knockout mice, deletion/duplication of craniofacial genes in animal models and results of whole exome/whole genome sequencing studies. This resulted in 20 craniofacial enhancers to be investigated. Custom amplicon-based …

Neurofibromatosis 1 - Mutant Microglia Exhibit Sexually-Dimorphic Cyclic Amp-Dependent Purinergic Defects, Nirmeen Elmadany, Francesca Logiacco, Alice Buonfiglioli, Verena C Haage, Elizabeth C Wright-Jin, Alexander Schattenberg, Roxane M Papawassiliou, Helmut Kettenmann, Marcus Semtner, David H Gutmann

Open Access Publications

As critical regulators of brain homeostasis, microglia are influenced by numerous factors, including sex and genetic mutations. To study the impact of these factors on microglia biology, we employed genetically engineered mice that model Neurofibromatosis type 1 (NF1), a disorder characterized by clinically relevant sexually dimorphic differences. While microglia phagocytic activity was reduced in both male and female heterozygous Nf1 mutant (Nf1+/-) mice, purinergic control of phagocytosis was only affected in male Nf1+/- mice. ATP-induced P2Y-mediated membrane currents and P2RY12-dependent laser lesion-induced accumulation of microglial processes were also only impaired in male, but not female Nf1+/-, microglia. These defects resulted …

An Autism-Linked Missense Mutation In Shank3 Reveals The Modularity Of Shank3 Function, Li Wang, Kaifang Pang, Kihoon Han, Carolyn J Adamski, Wei Wang, Lingjie He, Jason K Lai, Vitaliy V Bondar, Joseph G Duman, Ronald Richman, Kimberley F Tolias, Patrick Barth, Timothy Palzkill, Zhandong Liu, J Lloyd Holder, Huda Y Zoghbi

Faculty, Staff and Students Publications

Genome sequencing has revealed an increasing number of genetic variations that are associated with neuropsychiatric disorders. Frequently, studies limit their focus to likely gene-disrupting mutations because they are relatively easy to interpret. Missense variants, instead, have often been undervalued. However, some missense variants can be informative for developing a more profound understanding of disease pathogenesis and ultimately targeted therapies. Here we present an example of this by studying a missense variant in a well-known autism spectrum disorder (ASD) causing gene SHANK3. We analyzed Shank3's in vivo phosphorylation profile and identified S685 as one phosphorylation site where one ASD-linked variant has …

Usability Testing Of A Sensor-Controlled Digital Game To Engage Older Adults With Heart Failure In Physical Activity And Weight Monitoring, Kavita Radhakrishnan, Christine Julien, Matthew O'Hair, Thomas Baranowski, Grace Lee, Catherine Allen, Atami Sagna, Edison Thomaz, Miyong Kim

Faculty, Staff and Students Publications

BACKGROUND: Poor self-management of heart failure (HF) has contributed to poor health outcomes. Sensor-controlled digital games (SCDGs) integrates data from behavior-tracking sensors to trigger progress, rewards, content, and positive feedback in a digital game to motivate real-time behaviors.

OBJECTIVES: To assess the usability of an SCDG prototype over a week of game-playing among 10 older adults with HF in their homes.

METHODS: During initial play, participants' SCDG experiences were observed in their homes using a checklist based on the seven-item Serious Game User Evaluator (SeGUE) instrument. After a week of game-playing, participants completed a survey guided by the Intrinsic Motivation …

Trem2 Activation On Microglia Promotes Myelin Debris Clearance And Remyelination In A Model Of Multiple Sclerosis, Francesca Cignarella, Fabia Filipello, Bryan Bollman, Claudia Cantoni, Alberto Locca, Robert Mikesell, Melissa Manis, Adiljan Ibrahim, Li Deng, Bruno A Benitez, Carlos Cruchaga, Danilo Licastro, Kathie Mihindukulasuriya, Oscar Harari, Michael Buckland, David M Holtzman, Arnon Rosenthal, Tina Schwabe, Ilaria Tassi, Laura Piccio

2020-Current year OA Pubs

Multiple sclerosis (MS) is an inflammatory, demyelinating, and neurodegenerative disease of the central nervous system (CNS) triggered by autoimmune mechanisms. Microglia are critical for the clearance of myelin debris in areas of demyelination, a key step to allow remyelination. TREM2 is expressed by microglia and promotes microglial survival, proliferation, and phagocytic activity. Herein we demonstrate that TREM2 was highly expressed on myelin-laden phagocytes in active demyelinating lesions in the CNS of subjects with MS. In gene expression studies, macrophages from subjects with TREM2 genetic deficiency displayed a defect in phagocytic pathways. Treatment with a new TREM2 agonistic antibody promoted the …

Safety And Immunogenicity Of Fc-Eda, A Recombinant Ectodysplasin A1 Replacement Protein, In Human Subjects, Iris Körber, Ophir D Klein, Patrick Morhart, Florian Faschingbauer, Dorothy K Grange, Angus Clarke, Christine Bodemer, Silvia Maitz, Kenneth Huttner, Neil Kirby, Caroline Durand, Holm Schneider

2020-Current year OA Pubs

In X-linked hypohidrotic ectodermal dysplasia, the most frequent ectodermal dysplasia, an inherited deficiency of the signalling protein ectodysplasin A1 (EDA1) impairs the development of the skin and its appendages, various eccrine glands, and dentition. The severe hypohidrosis common to X-linked hypohidrotic ectodermal dysplasia patients may lead to life-threatening hyperthermia, especially during hot weather or febrile illness. Fc-EDA, an EDA1 replacement protein known to prevent the disease in newborn animals, was tested in 2 clinical trials (human adults and neonates) and additionally administered under compassionate use to 3 infants in utero. The data support the safety of Fc-EDA and efficacy if …

Genetic Variant Effects On Gene Expression In Human Pancreatic Islets And Their Implications For T2d., Ana Viñuela, Arushi Varshney, Martijn Van De Bunt, Rashmi B Prasad, Olof Asplund, Amanda Bennett, Michael Boehnke, Andrew A Brown, Michael R Erdos, João Fadista, Ola Hansson, Gad Hatem, Cédric Howald, Apoorva K Iyengar, Paul Johnson, Ulrika Krus, Patrick E Macdonald, Anubha Mahajan, Jocelyn E Manning Fox, Narisu Narisu, Vibe Nylander, Peter Orchard, Nikolay Oskolkov, Nikolaos I Panousis, Anthony Payne, Michael L. Stitzel, Swarooparani Vadlamudi, Ryan Welch, Francis S Collins, Karen L Mohlke, Anna L Gloyn, Laura J Scott, Emmanouil T Dermitzakis, Leif Groop, Stephen C J Parker, Mark I Mccarthy

Faculty Research 2020

Most signals detected by genome-wide association studies map to non-coding sequence and their tissue-specific effects influence transcriptional regulation. However, key tissues and cell-types required for functional inference are absent from large-scale resources. Here we explore the relationship between genetic variants influencing predisposition to type 2 diabetes (T2D) and related glycemic traits, and human pancreatic islet transcription using data from 420 donors. We find: (a) 7741 cis-eQTLs in islets with a replication rate across 44 GTEx tissues between 40% and 73%; (b) marked overlap between islet cis-eQTL signals and active regulatory sequences in islets, with reduced eQTL effect size observed in …

Atrial Myocyte Nlrp3/Camkii Nexus Forms A Substrate For Postoperative Atrial Fibrillation, Jordi Heijman, Azinwi Phina Muna, Tina Veleva, Cristina E Molina, Henry Sutanto, Marcel Tekook, Qiongling Wang, Issam H Abu-Taha, Marcel Gorka, Stephan Künzel, Ali El-Armouche, Hermann Reichenspurner, Markus Kamler, Viacheslav Nikolaev, Ursula Ravens, Na Li, Stanley Nattel, Xander H T Wehrens, Dobromir Dobrev

Faculty, Staff and Students Publications

RATIONALE: Postoperative atrial fibrillation (POAF) is a common and troublesome complication of cardiac surgery. POAF is generally believed to occur when postoperative triggers act on a preexisting vulnerable substrate, but the underlying cellular and molecular mechanisms are largely unknown.

OBJECTIVE: To identify cellular POAF mechanisms in right atrial samples from patients without a history of atrial fibrillation undergoing open-heart surgery.

METHODS AND RESULTS: Multicellular action potentials, membrane ion-currents (perforated patch-clamp), or simultaneous membrane-current (ruptured patch-clamp) and [Ca

CONCLUSIONS: Preexisting Ca

Antibodies To Variable Domain 4 Linear Epitopes Of The Chlamydia Trachomatis Major Outer Membrane Protein Are Not Associated With Chlamydia Resolution Or Reinfection In Women, Amanda L. Collar, Alexandria C. Linville, Susan B. Core, Cosette M. Wheeler, William M. Geisler, David S. Peabody, Bryce Chackerian, Kathryn M. Frietze

Pathology Research and Scholarship

Chlamydia trachomatis is an obligate intracellular bacterium. C. trachomatis infection is the most prevalent bacterial sexually transmitted infection and can lead to pelvic inflammatory disease and infertility in women. There is no licensed vaccine for C. trachomatis prevention, in part due to gaps in our knowledge of C. trachomatis-specific immune responses elicited during human infections. Previous investigations of the antibody response to C. trachomatis have identified immunodominant antigens and antibodies that can neutralize infection in cell culture. However, epitope-specific responses to C. trachomatis are not well characterized, and the impact of these antibodies on infection outcome is unknown. We …

Loss Of Speg Inhibitory Phosphorylation Of Ryanodine Receptor Type-2 Promotes Atrial Fibrillation, Hannah M Campbell, Ann P Quick, Issam Abu-Taha, David Y Chiang, Carlos F Kramm, Tarah A Word, Sören Brandenburg, Mohit Hulsurkar, Katherina M Alsina, Hui-Bin Liu, Brian Martin, Dennis Uhlenkamp, Oliver M Moore, Satadru K Lahiri, Eleonora Corradini, Markus Kamler, Albert J R Heck, Stephan E Lehnart, Dobromir Dobrev, Xander H T Wehrens

Faculty, Staff and Students Publications

BACKGROUND: Enhanced diastolic calcium (Ca

METHODS: Western blotting was performed with right atrial biopsies from patients with paroxysmal AF. SPEG atrial knockout mice were generated using adeno-associated virus 9. In mice, AF inducibility was determined using intracardiac programmed electric stimulation, and diastolic Ca

RESULTS: Western blotting revealed decreased SPEG protein levels in atrial biopsies from patients with paroxysmal AF in comparison with patients in sinus rhythm. SPEG atrial-specific knockout mice exhibited increased susceptibility to pacing-induced AF by programmed electric stimulation and enhanced Ca

CONCLUSIONS: Unlike other kinases (PKA, CaMKII) that increase RyR2 activity, SPEG phosphorylation reduces RyR2-mediated sarcoplasmic reticulum Ca

Swell1 Regulates Skeletal Muscle Cell Size, Intracellular Signaling, Adiposity And Glucose Metabolism, Ashutosh Kumar, Litao Xie, Chau My Ta, Antentor O Hinton, Susheel K Gunasekar, Rachel A Minerath, Karen Shen, Joshua M Maurer, Chad E Grueter, E Dale Abel, Gretchen Meyer, Rajan Sah

2020-Current year OA Pubs

Maintenance of skeletal muscle is beneficial in obesity and Type 2 diabetes. Mechanical stimulation can regulate skeletal muscle differentiation, growth and metabolism; however, the molecular mechanosensor remains unknown. Here, we show that SWELL1 (

Structural Characterization Of A Clinically Described Heparin-Like Substance In Plasma Causing Bleeding, Yanlei Yu, Karen Bruzdoski, Vadim Kostousov, Lisa Hensch, Shiu-Ki Hui, Fakiha Siddiqui, Amber Farooqui, Ahmed Kouta, Fuming Zhang, Jawed Fareed, Jun Teruya, Robert J Linhardt

Faculty, Staff and Students Publications

Heparin-like substances (HLS) have been described in various clinical situations, including in settings of liver disease associated with infection, transplant, and metastasis. HLS are generally attributed to circulating glycosaminoglycans. Initial results for this patient showed coagulopathy due to liver disease without HLS. Two weeks after liver transplantation, a 10 year-old female with liver failure patient began to bleed from catheter insertion sites, mouth, and nares and HLS was suspected. The patient subsequently died and these clinical samples resulted in the isolation of a single heparan sulfate (HS) present at high concentrations in the plasma. Analysis of this HS showed it …

Dual Roles Of Neutrophils In Metastatic Colonization Are Governed By The Host Nk Cell Status., Peishan Li, Mingyang Lu, Jiayuan Shi, Li Hua, Zheng Gong, Qing Li, Leonard D. Shultz, Guangwen Ren

Faculty Research 2020

The role of neutrophils in solid tumor metastasis remains largely controversial. In preclinical models of solid tumors, both pro-metastatic and anti-metastatic effects of neutrophils have been reported. In this study, using mouse models of breast cancer, we demonstrate that the metastasis-modulating effects of neutrophils are dictated by the status of host natural killer (NK) cells. In NK cell-deficient mice, granulocyte colony-stimulating factor-expanded neutrophils show an inhibitory effect on the metastatic colonization of breast tumor cells in the lung. In contrast, in NK cell-competent mice, neutrophils facilitate metastatic colonization in the same tumor models. In an ex vivo neutrophil-NK cell-tumor cell …

Self-Regulation And Emotional Reactivity In Infants With Prenatal Exposure To Opioids And Alcohol, Kathryn G Beauchamp, Jean Lowe, Ronald M Schrader, Shikhar Shrestha, Crystal Aragón, Natalia Moss, Julia M Stephen, Ludmila N Bakhireva

Pediatrics Research and Scholarship

BACKGROUND: Infants with prenatal substance exposure are at increased risk for developmental problems, with self-regulatory challenges being some of the most pronounced. The current study aimed to investigate the extent to which prenatal substance exposure (alcohol, opioids) impacts infant self-regulation during a relational stressor and the association between self-regulation and infant affect.

METHODS: Participants were 100 mother-child dyads recruited prenatally (Mean = 23.8 gestational weeks) and completed the Still Face Paradigm (SFP) when infants were 5 to 8 months of age (Mean = 6.9 months) as part of an ENRICH prospective birth cohort study. Based on prospective repeated assessment of …

Aluminum Reproductive Toxicity: A Summary And Interpretation Of Scientific Reports, Robert A. Yokel

Pharmaceutical Sciences Faculty Publications

Publications addressing aluminum (Al)-induced reproductive toxicity were reviewed. Key details were compiled in summary tables. Approximate systemic Al exposure, a measure of bioavailability, was calculated for each exposure, based on the Al percentage in the dosed Al species, Al bioavailability, and absorption time course reports for the exposure route. This was limited to laboratory animal studies because no controlled-exposure human studies were found. Intended Al exposure was compared to unintended dietary Al exposure. The considerable and variable Al content of laboratory animal diets creates uncertainty about reproductive function in the absence of Al. Aluminum-induced reproductive toxicity in female mice and …

Impact Of Annual And Semi-Annual Mass Drug Administration For Lymphatic Filariasis And Onchocerciasis On Hookworm Infection In Côte D'Ivoire, Agodio Loukouri, Aboulaye Méité, Benjamin G. Koudou, Charles W. Goss, Daphne Lew, Gary J. Weil, Eliezer K. N'Goran, Peter U. Fischer

Open Access Publications

Mass Drug Administration (MDA) programs to eliminate Lymphatic Filariasis (LF) in western Africa use the anthelminthics ivermectin plus albendazole. These drugs have the potential to impact also Soil-Transmitted Helminth (STH) infections, since the drugs have a broad range of anthelminthic activity. Integration of preventive chemotherapy efforts for LF, onchocerciasis and STH is recommended by the World Health Organization (WHO) in order to avoid duplication of MDA and to reduce costs. The objective of the current study was to determine whether five semi-annual rounds of community-wide MDA to eliminate LF and onchocerciasis have a greater impact on STH than three annual …

Masculinized Second-To-Fourth Digit Ratio (2d:4d Ratio) Is Associated With Lower Cortisol Response In Infant Female Rhesus Monkeys (Macaca Mulatta), Elizabeth K. Wood, Parker Jarman, Elysha Cash, Alexander Baxter, John P. Capitanio, James Dee Higley

Faculty Publications

The second-to-fourth digit ratio (2D:4D ratio) is considered a postnatal proxy measure for the degree of prenatal androgen exposure (PAE), which is the primary factor responsible for masculinizing the brain of a developing fetus. Some studies suggest that the organizational effects of PAE may extend to the hypothalamic-pituitary-adrenal (HPA) axis response to stress. This study investigates the relationship between 2D:4D ratio and HPA axis functioning using a rhesus monkey (Macaca mulatta) model. Subjects were N = 268 (180 females, 88 males) rhesus monkey infants (3–4 months of age). Plasma cortisol concentrations were assayed from two blood samples obtained …

Auxora Versus Standard Of Care For The Treatment Of Severe Or Critical Covid-19 Pneumonia: Results From A Randomized Controlled Trial, Joseph B. Miller Md, Charles Bruen, Michael Schnaus, Jeffrey Zhang, Sadia Ali, April Lind, Zachary Stoecker, Kenneth Stauderman, Sudarshan Hebbar

Emergency Medicine Articles

BACKGROUND: Calcium release-activated calcium (CRAC) channel inhibitors stabilize the pulmonary endothelium and block proinflammatory cytokine release, potentially mitigating respiratory complications observed in patients with COVID-19. This study aimed to investigate the safety and efficacy of Auxora, a novel, intravenously administered CRAC channel inhibitor, in adults with severe or critical COVID-19 pneumonia.

METHODS: A randomized, controlled, open-label study of Auxora was conducted in adults with severe or critical COVID-19 pneumonia. Patients were randomized 2:1 to receive three doses of once-daily Auxora versus standard of care (SOC) alone. The primary objective was to assess the safety and tolerability of Auxora. Following FDA …

Comparison Of Repeated Doses Of Ivermectin Versus Ivermectin Plus Albendazole For The Treatment Of Onchocerciasis: A Randomized, Open-Label, Clinical Trial, Linda Batsa Debrah, Kerstin Fischer, Gary Weil, Et Al.

2020-Current year OA Pubs

BACKGROUND: Improved treatment for onchocerciasis is needed to accelerate onchocerciasis elimination in Africa. Aiming to better exploit registered drugs, this study was undertaken to determine whether annual or semiannual treatment with ivermectin (IVM; 200 µg/kg) plus albendazole (ALB; 800 mg single dose) is superior to IVM alone.

METHODS: This trial was performed in Ghana and included 272 participants with microfilariae (MF), who were randomly assigned to 4 treatment arms: (1) IVM annually at 0, 12, and 24 months; (2) IVM semiannually at 0, 6, 12, 18, and 24 months; (3) IVM+ALB annually; or (4) IVM+ALB semiannually. Microfiladermia was determined pretreatment …

Testing The Impact Of A Single Nucleotide Polymorphism In A Plasmodium Berghei Apiap2 Transcription Factor On Experimental Cerebral Malaria In Mice, Munir Akkaya, Abhisheka Bansal, Patrick W Sheehan, Mirna Pena, Clare K Cimperman, Chen Feng Qi, Takele Yazew, Thomas D Otto, Oliver Billker, Louis H Miller, Susan K Pierce

Open Access Publications

Cerebral malaria (CM) is the deadliest form of severe Plasmodium infections. Currently, we have limited understanding of the mechanisms by which Plasmodium parasites induce CM. The mouse model of CM, experimental CM (ECM), induced by infection with the rodent parasite, Plasmodium berghei ANKA (PbANKA) has been extensively used to study the pathophysiology of CM. Recent genomic analyses revealed that the coding regions of PbANKA and the closely related Plasmodium berghei NK65 (PbNK65), that does not cause ECM, differ in only 21 single nucleotide polymorphysims (SNPs). Thus, the SNP-containing genes might contribute to the pathogenesis of ECM. Although the majority of …