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Article ; Online: Patent Ductus Arteriosus in Preterm Infants and Innovative Cardiac Interventions.

Bloom, David L / Glatz, Andrew C

NeoReviews

2023 Volume 24, Issue 8, Page(s) e479–e491

Abstract: Management of patent ductus arteriosus (PDA) in preterm infants has long been a challenging and controversial topic for neonatologists and cardiologists. Until recently, surgical ligation was the only available therapeutic option that could definitively ... ...

Abstract	Management of patent ductus arteriosus (PDA) in preterm infants has long been a challenging and controversial topic for neonatologists and cardiologists. Until recently, surgical ligation was the only available therapeutic option that could definitively close a PDA. A lack of proven benefit and concern for patient morbidity have led to a decrease in the number of surgical ligation procedures in the United States per year. There has been significant growth in the field of interventional cardiology in terms of technique and device availability for the purpose of PDA occlusion. Recent studies have demonstrated that transcatheter (TC) PDA closure is feasible and safe in patients weighing as low as 700 g. This review will describe the current strategy for the identification of a hemodynamically significant PDA, as well as the controversy that exists among medical, surgical, and conservative management strategies, and will specifically focus on the innovative TC techniques and devices available for preterm infants. We will also discuss the importance of large randomized trials to evaluate TC PDA closure compared with conservative medical management.
Language	English
Publishing date	2023-07-31
Publishing country	United States
Document type	Journal Article
ISSN	1526-9906
ISSN (online)	1526-9906
DOI	10.1542/neo.24-8-e479
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Article ; Online: HSV-1 LAT Promoter Deletion Viruses Exhibit Strain-Specific and LAT-Dependent Epigenetic Regulation of Latent Viral Genomes in Human Neurons.

Grams, Tristan R / Edwards, Terri G / Bloom, David C

Journal of virology

2023 Volume 97, Issue 2, Page(s) e0193522

Abstract: Herpes simplex virus 1 (HSV-1) establishes latency in neurons and expresses long noncoding RNAs termed the latency-associated transcripts (LATs). Two previous studies using HSV-1 recombinants containing deletions in the LAT promoter revealed opposing ... ...

Abstract	Herpes simplex virus 1 (HSV-1) establishes latency in neurons and expresses long noncoding RNAs termed the latency-associated transcripts (LATs). Two previous studies using HSV-1 recombinants containing deletions in the LAT promoter revealed opposing effects of the promoter deletion regarding the heterochromatinization of latent viral genomes in mice ganglia. Confounding variables in these studies include viral strains utilized (17
MeSH term(s)	Animals ; Humans ; Mice ; Epigenesis, Genetic ; Genome, Viral ; Herpes Simplex ; Herpesvirus 1, Human/physiology ; Neurons/virology ; Promoter Regions, Genetic ; Virus Activation/genetics ; Virus Latency/genetics
Chemical Substances	latency associated transcript, herpes simplex virus-1
Language	English
Publishing date	2023-02-01
Publishing country	United States
Document type	Journal Article ; Research Support, N.I.H., Extramural
ZDB-ID	80174-4
ISSN	1098-5514 ; 0022-538X
ISSN (online)	1098-5514
ISSN	0022-538X
DOI	10.1128/jvi.01935-22
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Article ; Online: A viral lncRNA tethers HSV-1 genomes at the nuclear periphery to establish viral latency.

Grams, Tristan R / Edwards, Terri G / Bloom, David C

Journal of virology

2023 Volume 97, Issue 12, Page(s) e0143823

Abstract: Importance: Herpes simplex virus 1 (HSV-1) establishes lifelong latency in neuronal cells. Following a stressor, the virus reactivates from latency, virus is shed at the periphery and recurrent disease can occur. During latency, the viral lncRNA termed ... ...

Abstract	Importance: Herpes simplex virus 1 (HSV-1) establishes lifelong latency in neuronal cells. Following a stressor, the virus reactivates from latency, virus is shed at the periphery and recurrent disease can occur. During latency, the viral lncRNA termed the latency-associated transcript (LAT) is known to accumulate to high abundance. The LAT is known to impact many aspects of latency though the molecular events involved are not well understood. Here, we utilized a human neuronal cell line model of HSV latency and reactivation (LUHMES) to identify the molecular-binding partners of the LAT during latency. We found that the LAT binds to both the cellular protein, TMEM43, and HSV-1 genomes in LUHMES cells. Additionally, we find that knockdown of TMEM43 prior to infection results in a decreased ability of HSV-1 to establish latency. This work highlights a potential mechanism for how the LAT facilitates the establishment of HSV-1 latency in human neurons.
MeSH term(s)	Humans ; Cell Line ; Herpes Simplex/genetics ; Herpes Simplex/metabolism ; Herpes Simplex/virology ; Herpesvirus 1, Human/genetics ; RNA, Long Noncoding/genetics ; Virus Activation/genetics ; Virus Latency/genetics ; Cell Nucleus/metabolism ; Cell Nucleus/virology ; Neurons/metabolism ; Neurons/virology ; Membrane Proteins/deficiency ; Membrane Proteins/metabolism ; Genome, Viral/genetics
Chemical Substances	RNA, Long Noncoding ; latency associated transcript, herpes simplex virus-1 ; TMEM43 protein, human ; Membrane Proteins
Language	English
Publishing date	2023-11-22
Publishing country	United States
Document type	Journal Article
ZDB-ID	80174-4
ISSN	1098-5514 ; 0022-538X
ISSN (online)	1098-5514
ISSN	0022-538X
DOI	10.1128/jvi.01438-23
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Article ; Online: Lifecycle model-based evaluation of infant 4CMenB vaccination in the UK.

Sevilla, J P / Tortorice, Daniel / Kantor, David / Regan, John / Meszaros, Kinga H / Beck, Ekkehard C / Begum, Najida / Bloom, David E

The European journal of health economics : HEPAC : health economics in prevention and care

2024

Abstract: Objectives: Invasive meningococcal disease, an uncommon but severe disease, imposes catastrophic health and economic burdens. Cost-utility analysis (CUA) assumes separability in lifetime health and economic variables and cannot capture the full value of ...

Abstract	Objectives: Invasive meningococcal disease, an uncommon but severe disease, imposes catastrophic health and economic burdens. Cost-utility analysis (CUA) assumes separability in lifetime health and economic variables and cannot capture the full value of preventing such burdens. We overcome these limitations with a retrospective societal perspective cost-benefit analysis (CBA) of meningococcal serogroup B vaccination (4CMenB) of one infant cohort in the United Kingdom using a health-augmented lifecycle model (HALM) incorporating health's interactions with consumption, earnings, non-market time and financial risk. Methods: We used a static Markov model of vaccination's health impact and an HALM to estimate the private willingness to pay (PWTP) for the intrinsic and instrumental value of health under perfect capital markets, financial risk protection in the absence of insurance against permanent disability, parental spillovers, and acute phase disability. We estimated social WTP (SWTP) incorporating social severity preferences. We estimated rates of return that inform health payer reimbursement decisions, finance ministry budgeting decisions, and legislature taxation decisions. An expert Advisory Board investigated the validity of applying the HALM to infant 4CMenB. Results: The PWTP for a 2 + 1 vaccination schedule is £395, comprising £166 of disability insurance value, £79 of positive parental spillover value, £28 in the value of averting acute phase disability, and £122 in residual intrinsic and instrumental value of health. SWTP is £969. Conclusions: HALM-based CBA provides an empirically richer, more utility-theoretically grounded approach to vaccine evaluation than CUA, demonstrating good value for money for legislatures (based on private values) and for all decision-makers (based on social values).
Language	English
Publishing date	2024-01-05
Publishing country	Germany
Document type	Journal Article
ZDB-ID	2045253-6
ISSN	1618-7601 ; 1618-7598
ISSN (online)	1618-7601
ISSN	1618-7598
DOI	10.1007/s10198-023-01654-y
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Article ; Online: Alphaherpesvirus Latency: A Dynamic State of Transcription and Reactivation.

Bloom, David C

Advances in virus research

2016 Volume 94, Page(s) 53–80

Abstract: Alphaherpesviruses infect a variety of species from sea turtles to man and can cause significant disease in mammals including humans and livestock. These viruses are characterized by a lytic and latent state in nerve ganglia, with the ability to ... ...

Abstract	Alphaherpesviruses infect a variety of species from sea turtles to man and can cause significant disease in mammals including humans and livestock. These viruses are characterized by a lytic and latent state in nerve ganglia, with the ability to establish a lifelong latent infection that is interrupted by periodic reactivation. Previously, it was accepted that latency was a dominant state and that only during relatively infrequent reactivation episodes did latent genomes within ganglia become transcriptionally active. Here, we review recent data, focusing mainly on Herpes Simplex Virus type 1 which indicate that the latent state is more dynamic than recently appreciated.
MeSH term(s)	Animals ; Cell Culture Techniques ; Disease Models, Animal ; Ganglia/virology ; Herpesviridae Infections/virology ; Herpesvirus 1, Human/genetics ; Herpesvirus 1, Human/physiology ; Humans ; Transcription, Genetic ; Virus Activation ; Virus Latency
Language	English
Publishing date	2016
Publishing country	United States
Document type	Journal Article ; Review
ZDB-ID	195-8
ISSN	1557-8399 ; 0065-3527
ISSN (online)	1557-8399
ISSN	0065-3527
DOI	10.1016/bs.aivir.2015.10.001
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Article ; Online: Contributions of Ccr4 and Gcn2 to the Translational Response of

Knowles, Corey M / Goich, David / Bloom, Amanda L M / Kalem, Murat C / Panepinto, John C

mBio

2023 Volume 14, Issue 2, Page(s) e0019623

Abstract: In response to the host environment, the human pathogen Cryptococcus neoformans must rapidly reprogram its translatome from one which promotes growth to one which is responsive to host stress. In this study, we investigate the two events which comprise ... ...

Abstract	In response to the host environment, the human pathogen Cryptococcus neoformans must rapidly reprogram its translatome from one which promotes growth to one which is responsive to host stress. In this study, we investigate the two events which comprise translatome reprogramming: the removal of abundant, pro-growth mRNAs from the translating pool, and the regulated entry of stress-responsive mRNAs into the translating pool. Removal of pro-growth mRNAs from the translating pool is controlled primarily by two regulatory mechanisms, repression of translation initiation via Gcn2, and decay mediated by Ccr4. We determined that translatome reprogramming in response to oxidative stress requires both Gcn2 and Ccr4, whereas the response to temperature requires only Ccr4. Additionally, we assessed ribosome collision in response to host-relevant stress and found that collided ribosomes accumulated during temperature stress but not during oxidative stress. The phosphorylation of eIF2α that occurred as a result of translational stress led us to investigate the induction of the integrated stress response (ISR). We found that eIF2α phosphorylation varied in response to the type and magnitude of stress, yet all tested conditions induced translation of the ISR transcription factor Gcn4. However, Gcn4 translation did not necessarily result in canonical Gcn4-dependent transcription. Finally, we define the ISR regulon in response to oxidative stress. In conclusion, this study begins to reveal the translational regulation in response to host-relevant stressors in an environmental fungus which is capable of adapting to the environment inside the human host.
MeSH term(s)	Humans ; Cryptococcus neoformans/metabolism ; Ribosomes/metabolism ; Phosphorylation ; Oxidative Stress ; Cryptococcosis/microbiology ; Transcription Factors/metabolism ; Saccharomyces cerevisiae/genetics ; Protein Biosynthesis ; Receptors, CCR4/genetics ; Receptors, CCR4/metabolism ; Ribonucleases/genetics ; Saccharomyces cerevisiae Proteins/genetics ; Protein Serine-Threonine Kinases/genetics
Chemical Substances	Transcription Factors ; CCR4 protein, human ; Receptors, CCR4 ; CCR4 protein, S cerevisiae (EC 3.1.-) ; Ribonucleases (EC 3.1.-) ; Saccharomyces cerevisiae Proteins ; GCN2 protein, S cerevisiae (EC 2.7.11.1) ; Protein Serine-Threonine Kinases (EC 2.7.11.1)
Language	English
Publishing date	2023-04-05
Publishing country	United States
Document type	Journal Article ; Research Support, N.I.H., Extramural
ZDB-ID	2557172-2
ISSN	2150-7511 ; 2161-2129
ISSN (online)	2150-7511
ISSN	2161-2129
DOI	10.1128/mbio.00196-23
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Article ; Online: Lund Human Mesencephalic (LUHMES) Neuronal Cell Line Supports Herpes Simplex Virus 1 Latency

Edwards, Terri G / Bloom, David C

Journal of virology

2019 Volume 93, Issue 6

Abstract: Lund human mesencephalic (LUHMES) cells are human embryonic neuronal precursor cells that can be maintained as proliferating cells due to the expression of a tetracycline-regulatable (Tet-off) v- ...

Abstract	Lund human mesencephalic (LUHMES) cells are human embryonic neuronal precursor cells that can be maintained as proliferating cells due to the expression of a tetracycline-regulatable (Tet-off) v-
MeSH term(s)	Cell Line ; Ganglia, Spinal/virology ; Gene Expression Regulation, Viral/physiology ; Herpes Simplex/virology ; Herpesvirus 1, Human/physiology ; Humans ; Neurons/virology ; Transcription, Genetic/physiology ; Virus Activation/physiology ; Virus Latency/physiology ; Virus Replication/physiology
Language	English
Publishing date	2019-03-05
Publishing country	United States
Document type	Journal Article ; Research Support, N.I.H., Extramural
ZDB-ID	80174-4
ISSN	1098-5514 ; 0022-538X
ISSN (online)	1098-5514
ISSN	0022-538X
DOI	10.1128/JVI.02210-18
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ab Jg. 2022: Lesesaal (EG)

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Article ; Online: Signaling Pathway Reporter Screen with SARS-CoV-2 Proteins Identifies nsp5 as a Repressor of p53 Activity.

Kumar, Abhishek / Grams, Tristan R / Bloom, David C / Toth, Zsolt

Viruses

2022 Volume 14, Issue 5

Abstract: ... signaling pathways, namely, Wnt, p53, TGFβ, c-Myc, Hypoxia, Hippo, AP-1, Notch, Oct4/Sox2, and NF-κB, using ...

Abstract	The dysregulation of host signaling pathways plays a critical role in severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection and viral pathogenesis. While a number of viral proteins that can block type I IFN signaling have been identified, a comprehensive analysis of SARS-CoV-2 proteins in the regulation of other signaling pathways that can be critical for viral infection and its pathophysiology is still lacking. Here, we screened the effect of 21 SARS-CoV-2 proteins on 10 different host signaling pathways, namely, Wnt, p53, TGFβ, c-Myc, Hypoxia, Hippo, AP-1, Notch, Oct4/Sox2, and NF-κB, using a luciferase reporter assay. As a result, we identified several SARS-CoV-2 proteins that could act as activators or inhibitors for distinct signaling pathways in the context of overexpression in HEK293T cells. We also provided evidence for p53 being an intrinsic host restriction factor of SARS-CoV-2. We found that the overexpression of p53 is capable of reducing virus production, while the main viral protease nsp5 can repress the transcriptional activity of p53, which depends on the protease function of nsp5. Taken together, our results provide a foundation for future studies, which can explore how the dysregulation of specific signaling pathways by SARS-CoV-2 proteins can control viral infection and pathogenesis.
MeSH term(s)	COVID-19 ; Coronavirus 3C Proteases/metabolism ; HEK293 Cells ; Humans ; SARS-CoV-2 ; Signal Transduction ; Tumor Suppressor Protein p53/metabolism
Chemical Substances	Tumor Suppressor Protein p53 ; 3C-like proteinase, SARS-CoV-2 (EC 3.4.22.-) ; Coronavirus 3C Proteases (EC 3.4.22.28)
Language	English
Publishing date	2022-05-13
Publishing country	Switzerland
Document type	Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't
ZDB-ID	2516098-9
ISSN	1999-4915 ; 1999-4915
ISSN (online)	1999-4915
ISSN	1999-4915
DOI	10.3390/v14051039
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Article ; Online: Author Correction: Modeling the potential health impact of prospective Strep A vaccines.

Giannini, Fiona / Cannon, Jeffrey W / Cadarette, Daniel / Bloom, David E / Moore, Hannah C / Carapetis, Jonathan / Abbas, Kaja

NPJ vaccines

2023 Volume 8, Issue 1, Page(s) 104

Language	English
Publishing date	2023-07-15
Publishing country	England
Document type	Published Erratum
ISSN	2059-0105
ISSN (online)	2059-0105
DOI	10.1038/s41541-023-00704-z
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Article ; Online: Use of a mixed reality system for navigational mapping during cardiac electrophysiological testing does not prolong case duration: A subanalysis from the Cardiac Augmented REality study.

Bloom, David / Catherall, David / Miller, Nathan / Southworth, Michael K / Glatz, Andrew C / Silva, Jonathan R / Avari Silva, Jennifer N

Cardiovascular digital health journal

2023 Volume 4, Issue 4, Page(s) 111–117

Abstract: Background: CommandEP™ is a mixed reality (MXR) system for cardiac electrophysiological (EP) procedures that provides a real-time 3-dimensional digital image of cardiac geometry and catheter locations. In a previous study, physicians using the system ... ...

Abstract	Background: CommandEP™ is a mixed reality (MXR) system for cardiac electrophysiological (EP) procedures that provides a real-time 3-dimensional digital image of cardiac geometry and catheter locations. In a previous study, physicians using the system demonstrated improved navigational accuracy. This study investigated the impact of the CommandEP system on EP procedural times compared to the standard-of-care electroanatomic mapping system (EAMS) display. Objective: The purpose of this retrospective case-controlled analysis was to evaluate the impact of a novel MXR interface on EP procedural times compared to a case-matched cohort. Methods: Cases from the Cardiac Augmented REality (CARE) study were matched for diagnosis and weight using a contemporary cohort. Procedural time was compared from the roll-in and full implementation cohort. During routine EP procedures, operators performed tasks during the postablation waiting phase, including creation of cardiac geometry and 5-point navigation under 2 conditions: (1) EAMS first; and (2) CommandEP. Results: From a total of 16 CARE study patients, the 10 full implementation patients were matched to a cohort of 20 control patients (2 controls:1 CARE, matched according to pathology and age/weight). No statistical difference in total case times between CARE study patients vs control group (118 ± 29 minutes vs 97 ± 20 minutes; Conclusion: MXR did not prolong overall procedural time compared to a matched cohort. There was no prolongation in study task completion time. Future studies with experienced CommandEP users directly assessing procedural time and task completion time in a randomized study population would be of interest.
Language	English
Publishing date	2023-06-14
Publishing country	United States
Document type	Journal Article
ISSN	2666-6936
ISSN (online)	2666-6936
DOI	10.1016/j.cvdhj.2023.06.003
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