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Article: Favipiravir Inhibits Zika Virus (ZIKV) Replication in HeLa Cells by Altering Viral Infectivity.

Franco, Evelyn J / Hanrahan, Kaley C / Brown, Ashley N

2023 Volume 11, Issue 5

Abstract: ... cell lines. HeLa (cervical), SK-N-MC (neuronal), and HUH-7 (liver) cells were infected with ZIKV and exposed ... caused substantial improvements in the viability of infected HeLa cells. Although SK-N-MC and HUH-7 cells ...

Abstract	This study aims to evaluate the antiviral potential of the nucleoside analogue favipiravir (FAV) against ZIKV, an arbovirus for which there are no approved antiviral therapies, in three human-derived cell lines. HeLa (cervical), SK-N-MC (neuronal), and HUH-7 (liver) cells were infected with ZIKV and exposed to different concentrations of FAV. Viral supernatant was sampled daily, and infectious viral burden was quantified by plaque assay. Changes in ZIKV infectivity were quantified by calculating specific infectivity. FAV-related toxicities were also assessed for each cell line in both infected and uninfected cells. Our results demonstrate that FAV activity was most pronounced in HeLa cells, as substantial declines in infectious titers and viral infectivity were observed in this cell type. The decline in infectious virus occurred in an exposure-dependent manner and was more pronounced as FAV exposure times increased. Additionally, toxicity studies showed that FAV was not toxic to any of the three cell lines and, surprisingly, caused substantial improvements in the viability of infected HeLa cells. Although SK-N-MC and HUH-7 cells were susceptible to FAV's anti-ZIKV activity, similar effects on viral infectivity and improvements in cell viability with therapy were not observed. These results indicate that FAV's ability to substantially alter viral infectivity is host cell specific and suggest that the robust antiviral effect observed in HeLa cells is mediated through drug-induced losses of viral infectivity.
Language	English
Publishing date	2023-04-22
Publishing country	Switzerland
Document type	Journal Article
ZDB-ID	2720891-6
ISSN	2076-2607
ISSN	2076-2607
DOI	10.3390/microorganisms11051097
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Article ; Online: Neonatal coagulopathies: A review of established and emerging treatments.

Moiseiwitsch, Nina / Brown, Ashley C

Experimental biology and medicine (Maywood, N.J.)

2021 Volume 246, Issue 12, Page(s) 1447–1457

Abstract: Despite the relative frequency of both bleeding and clotting disorders among patients treated in the neonatal intensive care unit, few clear guidelines exist for treatment of neonatal coagulopathies. The study and treatment of neonatal coagulopathies are ...

Abstract	Despite the relative frequency of both bleeding and clotting disorders among patients treated in the neonatal intensive care unit, few clear guidelines exist for treatment of neonatal coagulopathies. The study and treatment of neonatal coagulopathies are complicated by the distinct hemostatic balance and clotting components present during this developmental stage as well as the relative scarcity of studies specific to this age group. This mini-review examines the current understanding of neonatal hemostatic balance and treatment of neonatal coagulopathies, with particular emphasis on emerging treatment methods and areas in need of further investigative efforts.
MeSH term(s)	Animals ; Blood Coagulation Disorders/etiology ; Blood Coagulation Disorders/therapy ; Hemorrhage/etiology ; Hemorrhage/therapy ; Hemostasis/physiology ; Humans ; Infant, Newborn ; Infant, Newborn, Diseases/etiology ; Infant, Newborn, Diseases/therapy
Language	English
Publishing date	2021-04-15
Publishing country	England
Document type	Journal Article ; Research Support, N.I.H., Extramural ; Research Support, U.S. Gov't, Non-P.H.S. ; Review
ZDB-ID	4015-0
ISSN	1535-3699 ; 1525-1373 ; 0037-9727
ISSN (online)	1535-3699 ; 1525-1373
ISSN	0037-9727
DOI	10.1177/15353702211006046
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Article ; Online: Differences Between Sexual and Nonsexual Homicides of Women in the United States: Findings From the National Violent Death Reporting System.

De Veauuse Brown, Natasha F / Watson, Ashley E N

Journal of interpersonal violence

2022 Volume 37, Issue 23-24, Page(s) NP21975–NP21999

Abstract: Sexual homicide (SH) is the most severe outcome of sexual violence and disproportionately affects women. While SH is rare (<1% in the U.S.) and gravely understudied, it is among the most violent, feared, and well publicized forms of murder. Thus, ... ...

Abstract	Sexual homicide (SH) is the most severe outcome of sexual violence and disproportionately affects women. While SH is rare (<1% in the U.S.) and gravely understudied, it is among the most violent, feared, and well publicized forms of murder. Thus, examining predictors is pertinent to identifying targets for prevention and response efforts. Secondary analysis of 2015-2018 National Violent Death Reporting System data on 6461 female homicide victims age 20-64 was conducted to determine if SH represents a unique killing characterized by specific offender, victim, and incident profiles. Law enforcement and coroner/medical examiner narratives were reviewed to identify cases with sexual elements (
MeSH term(s)	Female ; Male ; Humans ; United States/epidemiology ; Young Adult ; Adult ; Middle Aged ; Homicide ; Violence ; Suicide ; Cause of Death ; Criminals
Language	English
Publishing date	2022-01-06
Publishing country	United States
Document type	Journal Article
ZDB-ID	2028900-5
ISSN	1552-6518 ; 0886-2605
ISSN (online)	1552-6518
ISSN	0886-2605
DOI	10.1177/08862605211064289
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Article ; Online: Evaluating individual biomarkers for predicting health risks in zoo-housed chimpanzees (Pan troglodytes) and bonobos (Pan paniscus).

Edes, Ashley N / Brown, Janine L / Edwards, Katie L

American journal of primatology

2022 Volume 85, Issue 3, Page(s) e23457

Abstract: ... one with all values retained (chimpanzees: n = 148; bonobos: n = 33) and the other from samples ... collected during routine immobilizations only (chimpanzees: n = 95; bonobos: n = 23). Consistent results ...

Abstract	Although biomarkers are often used for predicting morbidity and mortality in humans, similar data are lacking in our closest relatives. This study analyzed 16 biomarkers in zoo-housed chimpanzees and bonobos from serum samples collected during both routine and nonroutine veterinary immobilizations. Generalized linear and generalized linear mixed models were used to determine the efficacy of each biomarker to predict all-cause morbidity, defined as the presence of at least one chronic condition, or cardiac disease as a subset of all-cause morbidity. Cox proportional hazards models were used to examine associations between biomarkers and mortality risk from any cause. Analyses were conducted using two data sets for each species, one with all values retained (chimpanzees: n = 148; bonobos: n = 33) and the other from samples collected during routine immobilizations only (chimpanzees: n = 95; bonobos: n = 23). Consistent results across both data sets in chimpanzees included associations of higher cortisol with all-cause morbidity risk, lower creatinine with cardiac disease risk, and higher creatinine with mortality risk, and in bonobos were increased cardiac disease risk with higher cortisol and lower dehydroepiandrosterone-sulfate, fructosamine, and triglycerides. However, there were some inconsistencies between data sets, such as tumor necrosis factor-α predicting mortality risk positively in chimpanzees when all values were retained, but negatively for routine values only. Despite the close evolutionary relationships between chimpanzees and bonobos, the only result observed in both species was a negative association between albumin and mortality risk in the all values retained data sets. Thus, data suggest some biomarkers may be useful predictors of future health outcomes, although a better understanding of both individual and species variation in biomarkers and their contribution to health risks is needed.
MeSH term(s)	Humans ; Animals ; Pan troglodytes ; Pan paniscus ; Social Behavior ; Creatinine ; Hydrocortisone ; Hominidae ; Biomarkers
Chemical Substances	Creatinine (AYI8EX34EU) ; Hydrocortisone (WI4X0X7BPJ) ; Biomarkers
Language	English
Publishing date	2022-12-20
Publishing country	United States
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	1495834-X
ISSN	1098-2345 ; 0275-2565
ISSN (online)	1098-2345
ISSN	0275-2565
DOI	10.1002/ajp.23457
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Article ; Online: Evidence-based post-ban research to inform effective menthol cigarette bans in the United States and other jurisdictions.

Erinoso, Olufemi / Brown, Jennifer L / Glasser, Allison M / Gravely, Shannon / Fong, Geoffrey T / Chung-Hall, Janet / Kyriakos, Christina N / Liber, Alex C / Craig, Lorraine V / White, Augustus M / Rose, Shyanika W / Smiley, Sabrina L / Zeller, Mitch / Leischow, Scott / Ayo-Yusuf, Olalekan / Cohen, Joanna E / Ashley, David

Nicotine & tobacco research : official journal of the Society for Research on Nicotine and Tobacco

2024

Language	English
Publishing date	2024-04-13
Publishing country	England
Document type	Journal Article
ZDB-ID	1452315-2
ISSN	1469-994X ; 1462-2203
ISSN (online)	1469-994X
ISSN	1462-2203
DOI	10.1093/ntr/ntae082
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Zs.A 5789: Show issues

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Article ; Online: Paediatric group A streptococcal disease in England from October to December, 2022.

Ladhani, Shamez N / Guy, Rebecca / Bhopal, Sunil S / Brown, Colin S / Lamagni, Theresa / Sharp, Ashley

The Lancet. Child & adolescent health

2022 Volume 7, Issue 2, Page(s) e2–e4

MeSH term(s)	Child ; Humans ; England/epidemiology ; Streptococcal Infections/epidemiology ; Streptococcus pyogenes
Language	English
Publishing date	2022-12-22
Publishing country	England
Document type	Letter
ISSN	2352-4650
ISSN (online)	2352-4650
DOI	10.1016/S2352-4642(22)00374-1
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Article: Lower Extremity Total Joint Arthroplasty Has Minimal Effect on Golf Handicap.

Brown, Matthew L / Ashley, Blair S / Copp, Steven N / Ezzet, Kace A

Journal of surgical orthopaedic advances

2021 Volume 29, Issue 4, Page(s) 216–218

Abstract: Although the vast majority of arthroplasty surgeons allow patients to return to participation in golf following total knee arthroplasty (TKA) and total hip arthroplasty (THA), there is relatively little published data regarding how TKA or THA affects a ... ...

Abstract	Although the vast majority of arthroplasty surgeons allow patients to return to participation in golf following total knee arthroplasty (TKA) and total hip arthroplasty (THA), there is relatively little published data regarding how TKA or THA affects a patient's golfing ability. The purpose of this study was to determine how golfers' handicaps change following TKA and THA. We mailed a questionnaire to patients who had underwent primary TKA or THA at our institution and asked whether they played golf and for their golf handicap information network (GHIN) number. We then obtained handicap data for each patient that provided a GHIN number. Handicap increased 0.9 strokes 1 year following THA; however, this difference was not statistically significant (p = 0.20). Handicap increased 0.3 strokes 1 year following TKA; however, this difference was not statistically significant (p = 0.29). Our study demonstrates that despite improved implants, surgical techniques, and rehabilitation protocols that golf handicap does not change significantly following lower extremity total joint arthroplasty (TJA). (Journal of Surgical Orthopaedic Advances 29(4):216-218, 2020).
MeSH term(s)	Arthroplasty, Replacement, Hip ; Arthroplasty, Replacement, Knee ; Golf ; Humans ; Lower Extremity ; Surveys and Questionnaires
Language	English
Publishing date	2021-01-08
Publishing country	United States
Document type	Journal Article
ZDB-ID	2189157-6
ISSN	2158-3811 ; 1548-825X ; 1059-1052
ISSN (online)	2158-3811
ISSN	1548-825X ; 1059-1052
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Zs.A 4751: Show issues

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Article ; Online: Quantifying possible bias in clinical and epidemiological studies with quantitative bias analysis: common approaches and limitations.

Brown, Jeremy P / Hunnicutt, Jacob N / Ali, M Sanni / Bhaskaran, Krishnan / Cole, Ashley / Langan, Sinead M / Nitsch, Dorothea / Rentsch, Christopher T / Galwey, Nicholas W / Wing, Kevin / Douglas, Ian J

BMJ (Clinical research ed.)

2024 Volume 385, Page(s) e076365

MeSH term(s)	Humans ; Bias ; Epidemiologic Studies
Language	English
Publishing date	2024-04-02
Publishing country	England
Document type	Journal Article
ZDB-ID	1362901-3
ISSN	1756-1833 ; 0959-8154 ; 0959-8146 ; 0959-8138 ; 0959-535X ; 1759-2151
ISSN (online)	1756-1833
ISSN	0959-8154 ; 0959-8146 ; 0959-8138 ; 0959-535X ; 1759-2151
DOI	10.1136/bmj-2023-076365
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Article ; Online: COVID-19 patient fibrinogen produces dense clots with altered polymerization kinetics, partially explained by increased sialic acid.

Moiseiwitsch, Nina / Zwennes, Nicole / Szlam, Fania / Sniecinski, Roman / Brown, Ashley

Journal of thrombosis and haemostasis : JTH

2022 Volume 20, Issue 12, Page(s) 2909–2920

Abstract: Background: Thrombogenicity is a known complication of COVID-19, resulting from SARS-CoV-2 infection, with significant effects on morbidity and mortality.: Objective: We aimed to better understand the effects of COVID-19 on fibrinogen and the ... ...

Abstract	Background: Thrombogenicity is a known complication of COVID-19, resulting from SARS-CoV-2 infection, with significant effects on morbidity and mortality. Objective: We aimed to better understand the effects of COVID-19 on fibrinogen and the resulting effects on clot structure, formation, and degradation. Methods: Fibrinogen isolated from COVID-19 patients and uninfected subjects was used to form uniformly concentrated clots (2 mg/ml), which were characterized using confocal microscopy, scanning electron microscopy, atomic force microscopy, and endogenous and exogenous fibrinolysis assays. Neuraminidase digestion and subsequent NANA assay were used to quantify sialic acid residue presence; clots made from the desialylated fibrinogen were then assayed similarly to the original fibrinogen clots. Results: Clots made from purified fibrinogen from COVID-19 patients were shown to be significantly stiffer and denser than clots made using fibrinogen from noninfected subjects. Endogenous and exogenous fibrinolysis assays demonstrated that clot polymerization and degradation dynamics were different for purified fibrinogen from COVID-19 patients compared with fibrinogen from noninfected subjects. Quantification of sialic acid residues via the NANA assay demonstrated that SARS-CoV-2-positive fibrinogen samples contained significantly more sialic acid. Desialylation via neuraminidase digestion resolved differences in clot density. Desialylation did not normalize differences in polymerization, but did affect rate of exogenous fibrinolysis. Discussion: These differences noted in purified SARS-CoV-2-positive clots demonstrate that structural differences in fibrinogen, and not just differences in gross fibrinogen concentration, contribute to clinical differences in thrombotic features associated with COVID-19. These structural differences are at least in part mediated by differential sialylation.
MeSH term(s)	Humans ; Fibrinogen/metabolism ; Fibrin/chemistry ; N-Acetylneuraminic Acid ; COVID-19 ; Polymerization ; Neuraminidase ; SARS-CoV-2 ; Fibrinolysis ; Thrombosis/metabolism ; Hemostatics
Chemical Substances	Fibrinogen (9001-32-5) ; Fibrin (9001-31-4) ; N-Acetylneuraminic Acid (GZP2782OP0) ; Neuraminidase (EC 3.2.1.18) ; Hemostatics
Language	English
Publishing date	2022-10-05
Publishing country	England
Document type	Journal Article ; Research Support, N.I.H., Extramural
ZDB-ID	2112661-6
ISSN	1538-7836 ; 1538-7933
ISSN (online)	1538-7836
ISSN	1538-7933
DOI	10.1111/jth.15882
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Zs.A 5805: Show issues			Location: Je nach Verfügbarkeit (siehe Angabe bei Bestand) bis Jg. 1994: Bestellungen von Artikeln über das Online-Bestellformular Jg. 1995 - 2021: Lesesall (2.OG) ab Jg. 2022: Lesesaal (EG)
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Article: Favipiravir Suppresses Zika Virus (ZIKV) through Activity as a Mutagen.

Franco, Evelyn J / Cella, Eleonora / Tao, Xun / Hanrahan, Kaley C / Azarian, Taj / Brown, Ashley N

Microorganisms

2023 Volume 11, Issue 5

Abstract: ... Zika virus (ZIKV) replication in three human-derived cell lines-HeLa, SK-N-MC, and HUH-7. Our results ...

Abstract	In a companion paper, we demonstrated that the nucleoside analogue favipiravir (FAV) suppressed Zika virus (ZIKV) replication in three human-derived cell lines-HeLa, SK-N-MC, and HUH-7. Our results revealed that FAV's effect was most pronounced in HeLa cells. In this work, we aimed to explain variation in FAV activity, investigating its mechanism of action and characterizing host cell factors relevant to tissue-specific differences in drug effect. Using viral genome sequencing, we show that FAV therapy was associated with an increase in the number of mutations and promoted the production of defective viral particles in all three cell lines. Our findings demonstrate that defective viral particles made up a larger portion of the viral population released from HeLa cells both at increasing FAV concentrations and at increasing exposure times. Taken together, our companion papers show that FAV acts via lethal mutagenesis against ZIKV and highlight the host cell's influence on the activation and antiviral activity of nucleoside analogues. Furthermore, the information gleaned from these companion papers can be applied to gain a more comprehensive understanding of the activity of nucleoside analogues and the impact of host cell factors against other viral infections for which we currently have no approved antiviral therapies.
Language	English
Publishing date	2023-05-19
Publishing country	Switzerland
Document type	Journal Article
ZDB-ID	2720891-6
ISSN	2076-2607
ISSN	2076-2607
DOI	10.3390/microorganisms11051342
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