mRNA Vaccine Review against COVID-19 with Potential Applications to Improve Efficacy and Targeting

Coronavirus disease 19 (COVID-19) is a respiratory illness caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). The virus is the cause of the pandemic that has affected over 213 countries and there are over 21 million confirmed cases in the United States. Intense research efforts and funding have been placed into diagnostic, prevention, and treatment options. This review evaluates mRNA vaccines, their advantages, limitations, and current progress towards vaccine production. We included current methods of mRNA vaccine production and introduce potential changes in vaccine delivery methods currently being developed to specifically aid in targeting the coronavirus. We evaluated various routes of administration and their potential to allow vaccines to reach the immune system and induce an immune response to produce antibodies and provide immunity. Safety and efficacy have been evaluated in this review of various mRNA clinical trials that aimed to determine if mRNA vaccines can cause antibody production and the types of adverse events associated with them. Although mRNA vaccines are not perfect in design, the possibilities they offer in advancing vaccine research and fighting other viral infections while improving immunity are worth further research.

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Complementary and Alternative Medicine for Trauma- and Stressor-Related Disorders

10.1093/med/9780190457136.003.0024 ◽

2018 ◽

Author(s):

Gary H. Wynn ◽

David M. Benedek

Keyword(s):

Alternative Medicine ◽

Complementary And Alternative Medicine ◽

Care Delivery ◽

Treatment Options ◽

The United States ◽

Recreational Therapy ◽

Delivery Methods ◽

Animal Therapy ◽

Recent Developments ◽

Complementary And Alternative

The use of complementary and alternative medicine (CAM) throughout the United States and abroad has significantly increased in the past decade. CAM is relevant to trauma and stressor-related disorders given the frequency of use, but there is very limited evidence to support these treatment options. There is also currently no generally accepted list of what treatments constitute CAM, but only a number of generalized definitions that attempt to provide structure to the concept; therefore, a challenge facing providers will be familiarization with the broad range of modalities potentially considered CAM. This chapter uses a clinician focused definition of CAM: dividing CAM in to “complementary”, “alternative”, and “alternative delivery methods”. The first section, on complementary medicine, covers animal therapy, recreational therapy, yoga, creative arts therapy, and meditation. The second, on alternative therapies, describes alternative pharmacology and acupuncture. The last section provides a brief overview recent developments in alternative care delivery methods.

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Current Understanding of Human Enterovirus D68

Viruses ◽

10.3390/v11060490 ◽

2019 ◽

Vol 11 (6) ◽

pp. 490 ◽

Cited By ~ 16

Author(s):

Jing Sun ◽

Xiao-Yi Hu ◽

Xiao-Fang Yu

Keyword(s):

Treatment Options ◽

Antiviral Agents ◽

Respiratory Illness ◽

The United States ◽

Human Enterovirus ◽

Genetic Characteristics ◽

Host Interactions ◽

Acute Flaccid Myelitis ◽

Enterovirus D68 ◽

Neurogenic Disease

Human enterovirus D68 (EV-D68), a member of the species Enterovirus D of the Picornaviridae family, was first isolated in 1962 in the United States. EV-D68 infection was only infrequently reported until an outbreak occurred in 2014 in the US; since then, it has continued to increase worldwide. EV-D68 infection leads to severe respiratory illness and has recently been reported to be linked to the development of the neurogenic disease known as acute flaccid myelitis (AFM), mostly in children, seriously endangering public health. Hitherto, treatment options for EV-D68 infections were limited to supportive care, and as yet there are no approved, specific antiviral drugs or vaccines. Research on EV-D68 has mainly focused on its epidemiology, and its virologic characteristics and pathogenesis still need to be further explored. Here, we provide an overview of current research on EV-D68, including the genotypes and genetic characteristics of recent epidemics, the mechanism of infection and virus–host interactions, and its relationship to acute flaccid myelitis (AFM), in order to broaden our understanding of the biological features of EV-D68 and provide a basis for the development of effective antiviral agents.

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Influenza Virus Infections and Cellular Kinases

Viruses ◽

10.3390/v11020171 ◽

2019 ◽

Vol 11 (2) ◽

pp. 171 ◽

Cited By ~ 18

Author(s):

Robert Meineke ◽

Guus Rimmelzwaan ◽

Husni Elbahesh

Keyword(s):

Influenza Virus ◽

Viral Entry ◽

Influenza A ◽

Viral Infections ◽

Treatment Options ◽

Respiratory Illness ◽

Influenza A Viruses ◽

Host Restriction ◽

Zoonotic Infections

Influenza A viruses (IAVs) are a major cause of respiratory illness and are responsible for yearly epidemics associated with more than 500,000 annual deaths globally. Novel IAVs may cause pandemic outbreaks and zoonotic infections with, for example, highly pathogenic avian influenza virus (HPAIV) of the H5N1 and H7N9 subtypes, which pose a threat to public health. Treatment options are limited and emergence of strains resistant to antiviral drugs jeopardize this even further. Like all viruses, IAVs depend on host factors for every step of the virus replication cycle. Host kinases link multiple signaling pathways in respond to a myriad of stimuli, including viral infections. Their regulation of multiple response networks has justified actively targeting cellular kinases for anti-cancer therapies and immune modulators for decades. There is a growing volume of research highlighting the significant role of cellular kinases in regulating IAV infections. Their functional role is illustrated by the required phosphorylation of several IAV proteins necessary for replication and/or evasion/suppression of the innate immune response. Identified in the majority of host factor screens, functional studies further support the important role of kinases and their potential as host restriction factors. PKC, ERK, PI3K and FAK, to name a few, are kinases that regulate viral entry and replication. Additionally, kinases such as IKK, JNK and p38 MAPK are essential in mediating viral sensor signaling cascades that regulate expression of antiviral chemokines and cytokines. The feasibility of targeting kinases is steadily moving from bench to clinic and already-approved cancer drugs could potentially be repurposed for treatments of severe IAV infections. In this review, we will focus on the contribution of cellular kinases to IAV infections and their value as potential therapeutic targets.

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tiRNAs & tRFs Biogenesis and Regulation of Diseases: A Review

Current Medicinal Chemistry ◽

10.2174/0929867326666190124123831 ◽

2019 ◽

Vol 26 (31) ◽

pp. 5849-5861 ◽

Cited By ~ 3

Author(s):

Pan Jiang ◽

Feng Yan

Keyword(s):

Gene Expression ◽

Protein Synthesis ◽

Metabolic Diseases ◽

Viral Infections ◽

Regulatory Mechanisms ◽

Biological Functions ◽

Reverse Transcriptases ◽

Dna Damage Responses ◽

Potential Applications ◽

Viral Reverse Transcriptases

tiRNAs & tRFs are a class of small molecular noncoding tRNA derived from precise processing of mature or precursor tRNAs. Most tiRNAs & tRFs described originate from nucleus-encoded tRNAs, and only a few tiRNAs and tRFs have been reported. They have been suggested to play important roles in inhibiting protein synthesis, regulating gene expression, priming viral reverse transcriptases, and the modulation of DNA damage responses. However, the regulatory mechanisms and potential function of tiRNAs & tRFs remain poorly understood. This review aims to describe tiRNAs & tRFs, including their structure, biological functions and subcellular localization. The regulatory roles of tiRNAs & tRFs in translation, neurodegeneration, metabolic diseases, viral infections, and carcinogenesis are also discussed in detail. Finally, the potential applications of these noncoding tRNAs as biomarkers and gene regulators in different diseases is also highlighted.

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Systematic Government Access to Private-Sector Data in the United States I

10.1093/oso/9780190685515.003.0008 ◽

2017 ◽

Author(s):

Stephanie K. Pell

Keyword(s):

Private Sector ◽

Public Information ◽

The United States ◽

Third Party ◽

Threat Detection ◽

Detection And Identification ◽

Potential Applications ◽

September 11 Attacks ◽

Access To Data ◽

Sector Data

After the September 11 attacks, law enforcement's mission expanded to include, at times even prioritize, the general “prevention, deterrence and disruption” of terrorist attacks, which presumed a new emphasis upon threat detection and identification by analyzing patterns in larger, less specific bodies of information. Indeed, the unprecedented level of “third-party” possession of information inevitably makes the private sector the most reliable and comprehensive source of information available to law enforcement and intelligence agencies alike. This chapter explores the potential applications of systematic government access to data held by third-party private-sector intermediaries that would not be considered public information sources but, rather, data generated based on the role these intermediaries play in facilitating economic and business transactions (including personal business, such as buying groceries or staying at a hotel on vacation).

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Serum Biomarkers for the Prediction of Hepatocellular Carcinoma

Cancers ◽

10.3390/cancers13071681 ◽

2021 ◽

Vol 13 (7) ◽

pp. 1681

Author(s):

José Debes ◽

Pablo Romagnoli ◽

Jhon Prieto ◽

Marco Arrese ◽

Angelo Mattos ◽

...

Keyword(s):

Hepatocellular Carcinoma ◽

Viral Infections ◽

Treatment Options ◽

Serum Biomarkers ◽

Variable Degree ◽

Protein Markers ◽

Cytokines And Chemokines ◽

Micro Rnas ◽

Recent Developments ◽

Metabolic Conditions

Hepatocellular carcinoma (HCC) is a leading cause of global cancer death. Major etiologies of HCC relate to chronic viral infections as well as metabolic conditions. The survival rate of people with HCC is very low and has been attributed to late diagnosis with limited treatment options. Combining ultrasound and the biomarker alpha-fetoprotein (AFP) is currently one of the most widely used screening combinations for HCC. However, the clinical utility of AFP is controversial, and the frequency and operator-dependence of ultrasound lead to a variable degree of sensitivity and specificity across the globe. In this review, we summarize recent developments in the search for non-invasive serum biomarkers for early detection of HCC to improve prognosis and outcome for patients. We focus on tumor-associated protein markers, immune mediators (cytokines and chemokines), and micro-RNAs in serum or circulating extracellular vesicles and examine their potential for clinical application.

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Influenza vaccine effectiveness against hospitalization in the United States, 2019-2020

The Journal of Infectious Diseases ◽

10.1093/infdis/jiaa800 ◽

2020 ◽

Author(s):

Mark W Tenforde ◽

H Keipp Talbot ◽

Christopher H Trabue ◽

Manjusha Gaglani ◽

Tresa M McNeal ◽

...

Keyword(s):

United States ◽

Influenza Vaccine ◽

Influenza Vaccination ◽

Respiratory Illness ◽

The United States ◽

Vaccine Effectiveness ◽

Influenza Viruses ◽

Current Season ◽

Hospital Resources ◽

Negative Controls

Abstract Background Influenza causes significant morbidity and mortality and stresses hospital resources during periods of increased circulation. We evaluated the effectiveness of the 2019-2020 influenza vaccine against influenza-associated hospitalizations in the United States. Methods We included adults hospitalized with acute respiratory illness at 14 hospitals and tested for influenza viruses by reserve transcription polymerase chain reaction. Vaccine effectiveness (VE) was estimated by comparing the odds of current-season influenza vaccination in test-positive influenza cases versus test-negative controls, adjusting for confounders. VE was stratified by age and major circulating influenza types along with A(H1N1)pdm09 genetic subgroups. Results 3116 participants were included, including 18% (553) influenza-positive cases. Median age was 63 years. Sixty-seven percent (2079) received vaccination. Overall adjusted VE against influenza viruses was 41% (95% confidence interval [CI]: 27-52). VE against A(H1N1)pdm09 viruses was 40% (95% CI: 24-53) and 33% against B viruses (95% CI: 0-56). Of the two major A(H1N1)pdm09 subgroups (representing 90% of sequenced H1N1 viruses), VE against one group (5A+187A,189E) was 59% (95% CI: 34-75) whereas no significant VE was observed against the other group (5A+156K) [-1%, 95% CI: -61-37]. Conclusions In a primarily older population, influenza vaccination was associated with a 41% reduction in risk of hospitalized influenza illness.

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Immunometabolic Status of COVID-19 Cancer Patients

Physiological Reviews ◽

10.1152/physrev.00018.2020 ◽

2020 ◽

Vol 100 (4) ◽

pp. 1839-1850

Author(s):

A. Sica ◽

M. P. Colombo ◽

A. Trama ◽

L. Horn ◽

M. C. Garassino ◽

...

Keyword(s):

Cancer Patients ◽

Cancer Progression ◽

Macrophage Activation ◽

Viral Infections ◽

Immune Cell ◽

Case Series ◽

The United States ◽

Alternative Activation ◽

Nad Metabolism ◽

Increased Risk

Cancer patients appear to be more likely to be diagnosed with coronavirus disease 2019 (COVID-19). This is supported by the understanding of immunometabolic pathways that intersect patients with infection and cancer. However, data derived by case series and retrospective studies do not offer a coherent interpretation, since data from China suggest an increased risk of COVID-19, while data from the United States and Italy show a prevalence of COVID-19 in cancer patients comparable with the general population. Noteworthy, cancer and COVID-19 exploit distinct patterns of macrophage activation that promote disease progression in the most severe forms. In particular, the alternative activation of M2-polarized macrophages plays a crucial role in cancer progression. In contrast, the macrophage-activation syndrome appears as the source of M1-related cytokine storm in severe COVID-19 disease, thus indicating macrophages as a source of distinct inflammatory states in the two diseases, nonetheless as a common therapeutic target. New evidence indicates that NAMPT/NAD metabolism can direct both innate immune cell effector functions and the homeostatic robustness, in both cancer and infection. Moreover, a bidirectional relationship exists between the metabolism of NAD and the protective role that angiotensin converting enzyme 2, the COVID-19 receptor, can play against hyperinflammation. Within this immunometabolic framework, the review considers possible interference mechanisms that viral infections and tumors elicit on therapies and provides an overview for the management of patients with cancer affected by COVID-19, particularly for the balance of risk and benefit when planning normally routine cancer treatments and follow-up appointments.

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The Public’s Perception of Interventions for Migraine Headache Disorders: A Crowdsourcing Population-Based Study

Aesthetic Surgery Journal Open Forum ◽

10.1093/asjof/ojz007 ◽

2019 ◽

Vol 1 (2) ◽

Cited By ~ 5

Author(s):

Orr Shauly ◽

Daniel J Gould ◽

Ketan M Patel

Keyword(s):

Migraine Headache ◽

Treatment Options ◽

The United States ◽

Cost Of Care ◽

Adverse Outcomes ◽

Amazon Mechanical Turk ◽

Cross Sectional ◽

Economic Productivity ◽

Migraine Headaches ◽

Patient Reported

Abstract Background Migraine disorders are a leading cause of morbidity and decreased economic productivity in the United States among both men and women. As such, it is important to consider patient opinions, and have an accurate representation of the burden and sentiment toward currently available interventions among those suffering from migraines. Objectives The aim of the study was to assess patient options regarding adverse outcomes of the various treatment options available for migraine headaches. Methods A prospective cross-sectional study of volunteers recruited through an internet crowdsourcing service, Amazon Mechanical Turk©, was conducted. Surveys were administered to collect patient-reported opinions regarding adverse outcomes of both surgical and nonsurgical treatment options for migraine headaches. Results The prevalence of migraine headache across all study participants was 15.6% and varied slightly across participant demographics. Individuals ages 35–44 (2.73 migraines per month) experienced the fewest migraine and with the lowest severity. Those individuals ages 45+ experienced the most severe headaches (Visual Analog Scale = 44.23 mm). Additionally, the greatest migraine frequency and severity existed among those households with yearly income of $75,000–$100,000. The lowest injection therapy utility scores were obtained for adverse outcomes of hematoma (47.60 mm) and vertigo (54.40 mm). Conclusions Migraine headaches remains a significant problem among the US population, with an overall prevalence of 15.6% (approximately 50 million Americans). Additionally, physicians interesting in offering minimally invasive or surgical treatment for migraine headaches should focus on mitigating patient fears regarding clinical outcomes and cost of care.

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