Papers by Robert Ricketson
Journal of the Oklahoma State Medical Association, 2022
On January 10, 2020, our global scientific and medical communities were set on fire with the iden... more On January 10, 2020, our global scientific and medical communities were set on fire with the identification of a novel Betacoronavirus, SARS-CoV-2, initially isolated from a patient hospitalized with severe respiratory disease on December 26, 2019, in Wuhan, Hubei province, China. This article compares the recent lineages with our collective experiences since the first case was recorded in March of 2020 in Oklahoma, USA. The mutation frequencies in the entire proteome expressed by the virus with emphasis on transmission and the contribution of each viral peptide to COVID-19 are discussed. Lastly, this article presents unique binding considerations in the Delta and Omicron variants that require further study. Methods Daily and cumulative case and death counts were obtained from the CDC and OSDH from January 2020 through December 2021. Surface glycoprotein amino acid sequence data from Oklahoma was mined from the NCBI SARS-CoV-2 Data Hub and individually annotated as to PANGO lineage, collection date, and accession number. Unassigned PANGO lineages were subsequently identified though complete genome submission via the online Pangolin COVID-19 Lineage Assigner. Mutation frequencies of each viral peptide were recorded and analyzed in MS Excel. Comparative surface glycoprotein structures from each VOC bound to hACE2 were generated de novo using Modeller in UCSF Chimera. Results A total of 8,260 surface glycoprotein amino acid sequences from Oklahoma with 139 assigned PANGO lineages were utilized in this analysis. Factors affecting persistent transmission were identified including nonsynonymous mutations in the receptor binding domain, waning immunity, and multiple societal factors surrounding misinformation leading to continued vaccine hesitancy. Conclusions We must continue to reassess and identify global and community resources towards reducing transmission in this pandemic. If not, more variants of unpredictable consequences will undoubtedly arise. In the words of William Foege, "If a house is on fire, no one wastes time putting water on nearby houses just in case the fire spreads. They rush to pour water where it will do the most good — on the burning house.”
Additional file 2. Datasheet. The excel datasheet used in this study.
Journal of trace elements in medicine and biology : organ of the Society for Minerals and Trace Elements (GMS), 2018
FDA regulations require safety testing of constituent ingredients in drugs (21 CFR 610.15). With ... more FDA regulations require safety testing of constituent ingredients in drugs (21 CFR 610.15). With the exception of extraneous proteins, no component safety testing is required for vaccines or vaccine schedules. The dosing of aluminum in vaccines is based on the production of antibody titers, not safety science. Here we estimate a Pediatric Dose Limit that considers body weight. We identify several serious historical missteps in past analyses of provisional safe levels of aluminum in vaccines, and provide updates relevant to infant aluminum exposure in the pediatric schedule considering pediatric body weight. When aluminum doses are estimated from Federal Regulatory Code given body weight, exposure from the current vaccine schedule are found to exceed our estimate of a weight-corrected Pediatric Dose Limit. Our calculations show that the levels of aluminum suggested by the currently used limits place infants at risk of acute, repeated, and possibly chronic exposures of toxic levels of...
ABSTRACT The Ebolavirus outbreak of 2014 in West Africa is unprecedented. As of the most recent s... more ABSTRACT The Ebolavirus outbreak of 2014 in West Africa is unprecedented. As of the most recent situation report from the World Health Organization on November 11, 2014, there have been 14,098 suspected, probable and confirmed cases with 5160 deaths reported globally in this Public Health Emergency of International Concern. 5 cases outside the continent of Africa have been reported. Entry and exit screening for EVD (Ebola Virus Disease) of individuals originating from known outbreak regions currently include the presence of fever or additional symptoms consistent with EVD. Despite these efforts, the rate of transmission [R(t)] remains at 1.4 to 1.7, transnational cases are increasing, and a resurgence of the outbreak in Mali has recently been reported. This perspective article discusses the pitfalls associated with the determination of fever in the screening process as well as the difficulties with individual, subjective self-reporting of symptoms. Keywords EVD Screening Ebolavirus ...
Spine, 1996
The study compared the presence of the high-intensity zone on magnetic resonance imaging with the... more The study compared the presence of the high-intensity zone on magnetic resonance imaging with the results of awake discography. To see if there was a correlation between the results of awake discography and the presence of a high-intensity zone on magnetic resonance imaging. The evaluation of discogenic pain has proved to be somewhat elusive. Recent studies have indicated the high-intensity zone as being highly sensitive in the diagnosis of the painful discogenic segment. The present study was designed to investigate whether the presence of a high-intensity zone is associated with a concordant pain response on awake discography. Magnetic resonance images were obtained in 29 patients with low back pain with and without radiculopathy. Consecutive patients were considered for surgical intervention after falling to respond to conservative treatment. The presence of a high-intensity zone was specifically looked for within the posterior anulus. Each patient subsequently underwent awake discography with computed tomography. Computed tomography was classified according to the Dallas Discogram Scale and the presence of a concordant pain response. Chi-square analysis was used to calculate the presence of a high-intensity zone versus disc disruption and the correlation of high-intensity zone and concordant pain response. There was no statistically significant correlation between the presence of a high-intensity zone and a concordant pain response at any level. The high-intensity zone was, however, never seen in a morphologically normal disc. Although the high-intensity zone is present within the posterior anulus of some abnormal discs, it is not necessarily associated with a concordant pain response.
The Zaire ebolavirus is one of the most virulent of human viral pathogens with a reported CFR of ... more The Zaire ebolavirus is one of the most virulent of human viral pathogens with a reported CFR of 90% resulting from complete disruption of the host immune response. Despite the relatively minor genetic differences between the species of the genera Ebolavirus, the case fatality rate (CFR) is significantly different. The Zaire Ebolavirus (EBOV) historically is the most lethal, with its sporadic outbreaks resulting in a CFR ranging from 60% (Minkébé, Gabon 1994) to 90% (Kéllé, Congo 2003). This is in sharp contrast to Reston ebolavirus (RESTV) which, despite its genetic similarity to EBOV and serologic evidence of human transmission, has yet to result in even minor symptoms of the disease. The viral protein, VP35, has been shown to be a multifunctional virulence factor by antagonizing anti-viral signalling pathways via its interferon inhibitory domain (IID). However, it is unlikely the VP35 pathways could fully account for the observed differential virulence between the species. Viral ...
Pathologies associated with Zika virus infection include partial progressive paralysis (Guillan B... more Pathologies associated with Zika virus infection include partial progressive paralysis (Guillan Barre Syndrome) and microcephaly in Brazil and Panama. We identified an 85 nucleotide stem loop structure in the 3' end of Zika virus sfRNA (position (343-428) with the canonical structural and sequence characteristics of a miRNA. In comparison, the West Nile Virus has been previously demonstrated to contain a miRNA in its 3’ untranslated (UTR) sfRNA region. The West Nile Virus miRNA, KUN-mir-1, was found to be 81 nucleotides in length (492-573) and 58% conserved overall as to the corresponding Zika virus stem loop nucleotide sequence. The majority on the sequence homology was in the terminal loop (78%). The 40 nucleotide (nt) 3p arm demonstrated 60% homology, decreasing at the distal segment. The 5p arm demonstrates on 42% sequence homology. The Zika virus stem loop in this study was identified to contain a hairpin structure in the 3’ end of the Zika virus sfRNA 3’ UTR segment predic...
The incidence of various ocular, CNS, and musculoskeletal complaints in the convalescent period f... more The incidence of various ocular, CNS, and musculoskeletal complaints in the convalescent period following recovery from Ebola Virus Disease (PEVDS) has become an intense area of interest in the aftermath of the recent West Africa outbreak 2014-2015. A review of past outbreaks involving EBOV, SUDV, TAFV, and BDBV revealed similar, but poorly documented symptoms in the convalescent period. Additionally, viable virus has been identified in the recovery phase in sperm and ocular fluid up to 9 months after recovery with no evidence of viremia. A prior study by Yang in 2000 demonstrated the mucin-like domain was responsible for the vascular permeability and inflammation seen in EVD with Zaire ebolavirus infections but not in Reston ebolavirus infections. To study the mucin-like domain further, a comparative multi-sequence amino acid analysis of the poorly conserved MLD was performed and all 16 B-cell epitopes previously identified comparing all virulent species of Ebolavirus against RESTV...
Studies have found convincing evidence of association of ZIKV with Guillan-Barre Syndrome (GBS), ... more Studies have found convincing evidence of association of ZIKV with Guillan-Barre Syndrome (GBS), a small preliminary report suggests association with microcephaly in one location. We have previously found a plausible cause (molecular mimicry to Polio Virus Receptors A, B and C). We also found plausible evidence of pathways from ZIKV infection to microcephaly though P53-BAX-mitochondrial mediated apoptosis via the ZIKV capsid protein and the Helicase domain within the NS3 protein. A study of ZIKV infection in neural precursor cells found that infection hampered growth rates (Tang et al., 2016). To date, no specific mechanism of gestational microcephaly has been demonstrated. Here, we expand the l ist of plausible mechanisms of microcephaly in ZIKV. In fact, ZIKV appears to be a potential “perfect storm” candidate for microcephaly. We conclude with open questions and future directions.
When the dorsal root ganglion is irritated by any of a variety of mechanisms, pain is referred to... more When the dorsal root ganglion is irritated by any of a variety of mechanisms, pain is referred to the various structures innervated by that root. In many circumstances, this pain is specific and may be used as a diagnostic aid. Unfortunately, emphasis is placed on defining a dermatomal distribution; the existence of a myotomal or sclerotomal origin of referred pain is often overlooked. This review presents the embryologic, anatomic, and neurophysiologic etiology of referred pain from the lumbar spine.
BMC Public Health
Background This study aimed to assess the extent of knowledge and understanding of rabies disease... more Background This study aimed to assess the extent of knowledge and understanding of rabies disease in rural and urban communities of Pakistan. It also identified malpractices after suspected dog bite that might pose a risk for humans contracting rabies. Methods A cross-sectional study was conducted (n = 1466) on people having different age groups and educational levels in four different geographic regions of Punjab and Khyber Pakhtunkhwa provinces in Pakistan. Knowledge, attitude, and practices of people were assessed using a structured questionnaire. We used a bivariate and multivariate analysis to study the association between rabies related mortalities in near or extended family members and different risk behaviors. Results Our results demonstrate that the majority of the juvenile population (less than 18 years of age) were not aware of the clinical signs of rabies in animals. 75% of the total respondents were not vaccinated against rabies, 60% did not seek a doctor’s advice after...
When the dorsal root ganglion is irritated by any of a variety of mechanisms, pain is referred to... more When the dorsal root ganglion is irritated by any of a variety of mechanisms, pain is referred to the various structures innervated by that root. In many circumstances, this pain is specific and may be used as a diagnostic aid. Unfortunately, emphasis is placed on defining a dermatomal distribution; the existence of a myotomal or sclerotomal origin of referred pain is often overlooked. This review presents the embryologic, anatomic, and neurophysiologic etiology of referred pain from the lumbar spine. Low back pain is one of the most common presentations to the orthopedic surgeon, affecting nearly 85% of the population during their lifetime. It is frequently accompanied by radiation and/or dysesthesias down the length of one or both of the lower extremities in either a dermatomal, 1, 2 or somatotopic (sclerotomal 3,7 or myotomal 8) sensory pattern. Additionally, moderate to acutely tender distal motor points have been described in disk pathology. 8, 9 " Referred pain " is defined as pain that is felt in a region other than its source of origin. 10 For example, pain from myocardial ischemia is commonly referred to the left arm, that from splenic abnormalities to the left shoulder, and that from an' acutely inflamed appendix to the umbilicus 11. As with visceral structures, when a spinal nerve root ganglion is irritated pain, is referred to the various structures innervated by that root. In many circumstances, this pain is specific and may be used as a diagnostic tool. Unfortunately, emphasis is placed on defining a dermatomal distribution, and little emphasis is attributed to the existence of the myotome or sclerotome. The purpose of this review is to recapitulate the embryologic basis for referred pain patterns, with specific regard to their dermatomal, myotomal, and sclerotomal origin. In addition, we present the current understanding of the neurophysiologic and anatomic basis of referred pain of lumbosacral origin. EMBRYOLOGIC DEVELOPMENT Very early in embryologic development, there is an intimate segmental relationship established between each nerve and its corresponding dermatomal, myotomal, and sclerotomal components. A brief review of this process provides clinically important clues to why affliction of one structure can manifest itself in other segmentally related structures. The musculoskeletal system is derived from the embryonic mesoderm, which subsequently differentiates into three parts: the paraxial, intermediate, and lateral mesoderm. The paraxial mesoderm is the major thrust of this review. MESODERM INDUCTION Mesoderm induction is initiated before the zygotic genome is transcriptionally active and the extra-embryonic proteins needed to initiate induction are most likely oocytic in origin 10,11. In the vertebrate, the formation of both the mesoderm and endoderm appears to require requires signaling by nodal protein-related ligands from the TGFβ superfamily 1,2,3. The exact signaling mechanism in humans is not known. However, Ogawa et al (2007) reported TGFβ regulates multiple effectors of embryonic stem cell pluripotency and differentiation5. Lee et al., (2011) demonstrated high-level Nodal signaling with Activin, also a member of the TGFβ superfamily 9 , and induced differentiation toward mesoendoderm formation 6. The effect of tobacco smoke on mesoderm development was recently studied by Liszewski, et al 4 .
A Mood Disorder covers a broad spectrum of affective disorders in the Diagnostic and Statistical ... more A Mood Disorder covers a broad spectrum of affective disorders in the Diagnostic and Statistical Manual of Mental Disorders (DSM IV TR) classification system in ICD 10 where a disturbance in the person's affect, or mood, is thought to be the main underlying feature. These diagnoses include the Depressive Disorders, Bipolar Disorders, Substance-Induced Mood Disorders, and Mood Disorders due to a General Medical Condition.
Pain is a subjective component and as defined by the International Association of Pain is, "Pain is an unpleasant sensory and emotional experience associated with actual or potential tissue damage, or described in terms of such damage.”The concurrent interrelationship of chronic pain and the prevalence of mood disorders in our society with or without substance abuse today has demonstrable impact in our overall wellness and health.
Our retrospective literature review has disclosed an association of pain and depression as high as 46%, a 51% incidence of chronic pain in bipolar disorders, and the association of anxiety effecting the severity of pain in patients with depression.
The evaluation of discogenic pain has proved to be somewhat elusive. Recent studies have indicate... more The evaluation of discogenic pain has proved to be somewhat elusive. Recent studies have indicated the high-intensity zone as being highly sensitive in the diagnosis of the painful discogenic segment. The present study was designed to investigate whether the presence of a high-intensity zone is associated with a concordant pain response on awake discography.
Our study found there was no statistically significant correlation between the presence of a high-intensity zone and a concordant pain response at any level. The high-intensity zone was, however, never seen in a morphologically normal disc.
Conclusions: Although the high-intensity zone is present within the posterior annulus of some abnormal discs, it is not necessarily associated with a concordant pain response.
Ebolavirus is one of the most virulent of human viral pathogens, killing 25-90% of patients withi... more Ebolavirus is one of the most virulent of human viral pathogens, killing 25-90% of patients within 6-16 days (EBOV and SUDV) resulting from complete disruption of the host immune response. Despite the relatively minor genetic differences between the species, the case fatality rate (CFR) is significantly different. The Zaire Ebolavirus (EBOV) historically is the most lethal, with its sporadic outbreaks resulting in a CFR ranging from 60% (Minkébé, Gabon 1994, Gueckedou 2014) to 90% (Kéllé, Congo 2003). This is in sharp contrast to Reston ebolavirus (RESTV) which, despite its translational similarity to EBOV and serologic evidence of human transmission, has yet to result in even minor symptoms of the disease. The viral protein, VP35, has been shown to be a multifunctional virulence factor by antagonizing anti-viral signalling pathways via its interferon inhibitory domain (IID). However, it is unlikely the VP35 pathways could fully account for the observed differential virulence between the species. Viral encoded miRNAs have already been identified in many species and shown to modulate the expression and antiviral function of interferons (IFNs). This is the first paper to summarize the computational identification of a likely miRNA, termed the Pandora Element, within the intergenic, untranslated region of the Zaire ebolavirus nucleoprotein gene that appears to target multiple human transcripts.
The Ebolavirus outbreak of 2014 in West Africa is unprecedented. As of the situation report from ... more The Ebolavirus outbreak of 2014 in West Africa is unprecedented. As of the situation report from the World Health Organization (WHO) dated November 11, 2014 there were 16,899 suspected, probable, and confirmed cases along with 5987 deaths reported globally in this Public Health
Emergency of International Concern. Five cases outside the continent of Africa have been reported.
Entry and exit screening for EVD (Ebola Virus Disease) of individuals originating from known outbreak regions currently include the presence of fever or additional symptoms consistent with EVD. Despite these efforts, the rate of transmission [R (t)] remains at 1.4 to 1.7, transnational
cases are increasing, and a resurgence of the outbreak in Mali has recently been reported.
This perspective article discusses the pitfalls associated with the determination of fever in the screening process as well as the difficulties with individual, subjective self-reporting of symptoms, and denial of disease as a risk not previously reported in screening for fever in
infectious disease outbreaks. Additional bioinformatics data is presented with focus upon the poorly conserved mucin-like domain of the Zaire ebolavirus glycoprotein with comparison between the current Zaire
ebolavirus strain Guekedou (2014), and the Zaire ebolavirus, strain Mayinga (1976). The specific dynamics are illustrated by a multiple sequence alignment and de novo modelling of the Ebolavirus, strain Guekedou (August 2014) C-terminus MLD and GP2 translated proteins.
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Papers by Robert Ricketson
Pain is a subjective component and as defined by the International Association of Pain is, "Pain is an unpleasant sensory and emotional experience associated with actual or potential tissue damage, or described in terms of such damage.”The concurrent interrelationship of chronic pain and the prevalence of mood disorders in our society with or without substance abuse today has demonstrable impact in our overall wellness and health.
Our retrospective literature review has disclosed an association of pain and depression as high as 46%, a 51% incidence of chronic pain in bipolar disorders, and the association of anxiety effecting the severity of pain in patients with depression.
Our study found there was no statistically significant correlation between the presence of a high-intensity zone and a concordant pain response at any level. The high-intensity zone was, however, never seen in a morphologically normal disc.
Conclusions: Although the high-intensity zone is present within the posterior annulus of some abnormal discs, it is not necessarily associated with a concordant pain response.
Emergency of International Concern. Five cases outside the continent of Africa have been reported.
Entry and exit screening for EVD (Ebola Virus Disease) of individuals originating from known outbreak regions currently include the presence of fever or additional symptoms consistent with EVD. Despite these efforts, the rate of transmission [R (t)] remains at 1.4 to 1.7, transnational
cases are increasing, and a resurgence of the outbreak in Mali has recently been reported.
This perspective article discusses the pitfalls associated with the determination of fever in the screening process as well as the difficulties with individual, subjective self-reporting of symptoms, and denial of disease as a risk not previously reported in screening for fever in
infectious disease outbreaks. Additional bioinformatics data is presented with focus upon the poorly conserved mucin-like domain of the Zaire ebolavirus glycoprotein with comparison between the current Zaire
ebolavirus strain Guekedou (2014), and the Zaire ebolavirus, strain Mayinga (1976). The specific dynamics are illustrated by a multiple sequence alignment and de novo modelling of the Ebolavirus, strain Guekedou (August 2014) C-terminus MLD and GP2 translated proteins.
Pain is a subjective component and as defined by the International Association of Pain is, "Pain is an unpleasant sensory and emotional experience associated with actual or potential tissue damage, or described in terms of such damage.”The concurrent interrelationship of chronic pain and the prevalence of mood disorders in our society with or without substance abuse today has demonstrable impact in our overall wellness and health.
Our retrospective literature review has disclosed an association of pain and depression as high as 46%, a 51% incidence of chronic pain in bipolar disorders, and the association of anxiety effecting the severity of pain in patients with depression.
Our study found there was no statistically significant correlation between the presence of a high-intensity zone and a concordant pain response at any level. The high-intensity zone was, however, never seen in a morphologically normal disc.
Conclusions: Although the high-intensity zone is present within the posterior annulus of some abnormal discs, it is not necessarily associated with a concordant pain response.
Emergency of International Concern. Five cases outside the continent of Africa have been reported.
Entry and exit screening for EVD (Ebola Virus Disease) of individuals originating from known outbreak regions currently include the presence of fever or additional symptoms consistent with EVD. Despite these efforts, the rate of transmission [R (t)] remains at 1.4 to 1.7, transnational
cases are increasing, and a resurgence of the outbreak in Mali has recently been reported.
This perspective article discusses the pitfalls associated with the determination of fever in the screening process as well as the difficulties with individual, subjective self-reporting of symptoms, and denial of disease as a risk not previously reported in screening for fever in
infectious disease outbreaks. Additional bioinformatics data is presented with focus upon the poorly conserved mucin-like domain of the Zaire ebolavirus glycoprotein with comparison between the current Zaire
ebolavirus strain Guekedou (2014), and the Zaire ebolavirus, strain Mayinga (1976). The specific dynamics are illustrated by a multiple sequence alignment and de novo modelling of the Ebolavirus, strain Guekedou (August 2014) C-terminus MLD and GP2 translated proteins.
Transposable elements (TEs) are mobile genetic elements that must gain unfettered access to host DNA in order to integrate into a new site. Transposable element encoded proteins are often found to interact with host proteins and to alter host processes. NeSL-1, a non-LTR retrotransposon originally discovered in Caenorhabditis elegans, is one of a diverse set of transposable elements that have been reported to have independently acquired the catalytic core of a ubiquitin-like protease (ULP), although none of the acquisitions have been examined for retention of its ability to recognize SUMO or to cleave isopeptide bonds.
Using NeSL-1 elements mined from several worm genome projects, the conservation of the NeSL-1 encoded ULP was examined with respect to the previously recorded motifs known in cellular ULPs to interact with SUMO and its homologues [16]. In addition, 3D models of NeSL-1 ULP complexed to species-specific Caenorhabditis SUMO-1 were generated. The models indicate that the NeSL-1 ULP has likely retained the ability to recognize SUMO and to cleave SUMO from tagged proteins. Lastly, the NeSL-1 ULP domain from C. elegans was cloned and biochemically tested for desumoylation activity.