scholarly journals Estimating relative CWD susceptibility and disease progression in farmed whitetail deer with rare PRNP alleles

2019 ◽  
Author(s):  
NJ Haley ◽  
K Merrett ◽  
A Buros Stein ◽  
D Simpson ◽  
A Carlton ◽  
...  
Keyword(s):  
Past Research ◽  
The United States ◽  
Disease Stage ◽  
Relative Fitness ◽  
Wasting Disease ◽  
Prnp Genotype ◽  
High Prevalence ◽  
Incubation Periods ◽  
Free Ranging ◽  
Kinetics Of

AbstractChronic wasting disease is a prion disease affecting both free-ranging and farmed cervids in North America and Scandinavia. A range of cervid species have been found to be susceptible, each with variations in the gene for the normal prion protein, PRNP, reportedly influencing both disease susceptibility and progression in the respective hosts. Despite the finding of several different PRNP alleles in whitetail deer, the majority of past research has focused on two of the more common alleles identified – the 96G and 96S alleles. In the present study, we evaluate both infection status and disease stage in nearly 2100 farmed deer depopulated in the United States and Canada, including 714 CWD-positive deer and correlate our findings with PRNP genotype, including the more rare 95H, 116G, and 226K alleles. We found significant differences in either likelihood of being found infected or disease stage (and in many cases both) at the time of depopulation in all genotypes present, relative to the most common 96GG genotype. Despite high prevalence in many of the herds examined, infection was not found in several of the reported genotypes. These findings suggest that additional research is necessary to more properly define the role that these genotypes may play in managing CWD in both farmed and free-ranging whitetail deer, with consideration for factors including relative fitness levels, incubation periods, and the kinetics of shedding in animals with these rare genotypes.

scholarly journals Low frequency of PrP genotype 225SF among free-ranging mule deer (Odocoileus hemionus) with chronic wasting disease

2005 ◽  
Vol 86 (8) ◽  
pp. 2127-2134 ◽  
Author(s):  
Jean E. Jewell ◽  
Mary M. Conner ◽  
Lisa L. Wolfe ◽  
Michael W. Miller ◽  
Elizabeth S. Williams
Keyword(s):  
Dna Sequences ◽  
Chronic Wasting Disease ◽  
Mule Deer ◽  
Low Frequency ◽  
Odocoileus Hemionus ◽  
Infection Status ◽  
Wasting Disease ◽  
Incubation Periods ◽  
Free Ranging ◽  
Prp Gene

The prion protein (PrP) gene was characterized in 1482 free-ranging mule deer (Odocoileus hemionus) from Wyoming and Colorado. Using DNA sequences from 363 deer, dimorphisms at codons 20 (aspartate/glycine) and 225 [serine (S)/phenylalanine (F)] were found; silent changes occurred at codons 131 (tyrosine) and 247 (isoleucine). The remaining samples were surveyed for codon 225 genotype and all were characterized for chronic wasting disease (CWD) infection status. A total of 112 deer with the genotype 225SF or FF were found, of which one was CWD-positive; 1370 were 225SS, with 289 positive for CWD. Among CWD-negative deer, the frequency of 225SF/FF genotypes was 9·3 % but among CWD-positive deer it was only 0·3 %. For all samples combined, CWD status was not independent of codon 225 genotype (P<0·0001). The odds that a deer of the 225SS genotype was CWD-infected were 30 times greater (95 % confidence intervals=4–213) than for a 225SF deer. The proportion of 225SF animals in sampled subpopulations varied from 0 to 18 %; the CWD prevalence varied from 0 to 25 %. However, no relationship was observed between genotype frequency and CWD prevalence in different areas. The PrP sequences of experimentally infected mule deer were analysed from pre-existing projects and 10 animals were found with 225SF genotypes, all of which were positive for CWD. Data available from some of these animals suggest that the 225SF genotype could be associated with longer incubation periods in CWD infection compared with the 225SS genotype.

Detection by real-time quaking-induced conversion (RT-QuIC), ELISA, and IHC of chronic wasting disease prion in lymph nodes from Pennsylvania white-tailed deer with specific PRNP genotypes

2021 ◽  
pp. 104063872110214
Author(s):  
Deepanker Tewari ◽  
David Steward ◽  
Melinda Fasnacht ◽  
Julia Livengood
Keyword(s):  
Real Time ◽  
Disease Susceptibility ◽  
Chronic Wasting Disease ◽  
Low Frequency ◽  
The United States ◽  
Detection Methods ◽  
Spongiform Encephalopathy ◽  
Wasting Disease ◽  
Diagnostic Laboratory ◽  
Highly Sensitive

Chronic wasting disease (CWD) is a prion-mediated, transmissible disease of cervids, including deer ( Odocoileus spp.), which is characterized by spongiform encephalopathy and death of the prion-infected animals. Official surveillance in the United States using immunohistochemistry (IHC) and ELISA entails the laborious collection of lymphoid and/or brainstem tissue after death. New, highly sensitive prion detection methods, such as real-time quaking-induced conversion (RT-QuIC), have shown promise in detecting abnormal prions from both antemortem and postmortem specimens. We compared RT-QuIC with ELISA and IHC for CWD detection utilizing deer retropharyngeal lymph node (RLN) tissues in a diagnostic laboratory setting. The RLNs were collected postmortem from hunter-harvested animals. RT-QuIC showed 100% sensitivity and specificity for 50 deer RLN (35 positive by both IHC and ELISA, 15 negative) included in our study. All deer were also genotyped for PRNP polymorphism. Most deer were homozygous at codons 95, 96, 116, and 226 (QQ/GG/AA/QQ genotype, with frequency 0.86), which are the codons implicated in disease susceptibility. Heterozygosity was noticed in Pennsylvania deer, albeit at a very low frequency, for codons 95GS (0.06) and 96QH (0.08), but deer with these genotypes were still found to be CWD prion-infected.

scholarly journals An Exploratory Qualitative Study of Patient and Caregiver Perspectives of Ambulatory Kidney Palliative Care

2021 ◽  
pp. 104990912098612
Author(s):  
Alycia A. Bristol ◽  
Sobaata Chaudhry ◽  
Dana Assis ◽  
Rebecca Wright ◽  
Derek Moriyama ◽  
...  
Keyword(s):  
Palliative Care ◽  
Kidney Disease ◽  
Chronic Kidney Disease Stage ◽  
Stage Iv ◽  
The United States ◽  
Qualitative Description ◽  
Disease Stage ◽  
Structured Interviews ◽  
Care Clinic ◽  
Clinical Model

Objectives: The ideal clinical model to deliver palliative care to patients with advanced kidney disease is currently unknown. Internationally, ambulatory kidney palliative care clinics have emerged with positive outcomes, yet there is limited data from the United States (US). In this exploratory study we report perceptions of a US-based ambulatory kidney palliative care clinic from the perspective of patient and caregiver attendees. The objective of this study was to inform further improvement of our clinical program. Methods: Semi-structured interviews were conducted to elicit the patient and caregiver experience. Eleven interviews (8 patients with chronic kidney disease stage IV or V and 3 caregivers) were analyzed using qualitative description design. Results: We identified 2 themes: “Communication addressing the emotional and physical aspects of disease” and “Filling gaps in care”; Subthemes include perceived value in symptom management, assistance with coping with disease, engagement in advance care planning, program satisfaction and patient activation. Significance of Results: Qualitative analysis showed that attendees of an ambulatory kidney palliative care clinic found the clinic enhanced the management of their kidney disease and provided services that filled current gaps in their care. Shared experiences highlight the significant challenges of life with kidney disease and the possible benefits of palliative care for this population. Further study to determine the optimal model of care for kidney palliative care is needed. Inclusion of the patient and caregiver perspective will be essential in this development.

scholarly journals Trends in Esophageal Cancer Mortality and Stage at Diagnosis by Race and Ethnicity in the United States

2021 ◽  
Author(s):  
Edgar Corona ◽  
Liu Yang ◽  
Eric Esrailian ◽  
Kevin A. Ghassemi ◽  
Jeffrey L. Conklin ◽  
...  
Keyword(s):  
United States ◽  
Esophageal Cancer ◽  
Race And Ethnicity ◽  
The United States ◽  
Disease Stage ◽  
Stage Migration ◽  
Stage At Diagnosis ◽  
Annual Percent Change ◽  
Seer Data ◽  
Race Ethnicity

Abstract Introduction Esophageal cancer (EC) is an aggressive malignancy with poor prognosis. Mortality and disease stage at diagnosis are important indicators of improvements in cancer prevention and control. We examined United States trends in esophageal adenocarcinoma (EAC) and esophageal squamous cell carcinoma (ESCC) mortality and stage at diagnosis by race and ethnicity. Methods We used Surveillance, Epidemiology, and End Results (SEER) data to identify individuals with histologically confirmed EAC and ESCC between 1 January 1992 and 31 December 2016. For both EAC and ESCC, we calculated age-adjusted mortality and the proportion presenting at each stage by race/ethnicity, sex, and year. We then calculated the annual percent change (APC) in each indicator by race/ethnicity and examined changes over time. Results The study included 19,257 EAC cases and 15,162 ESCC cases. EAC mortality increased significantly overall and in non-Hispanic Whites from 1993 to 2012 and from 1993 to 2010, respectively. EAC mortality continued to rise among non-Hispanic Blacks (NHB) (APC = 1.60, p = 0.01). NHB experienced the fastest decline in ESCC mortality (APC = − 4.53, p < 0.001) yet maintained the highest mortality at the end of the study period. Proportions of late stage disease increased overall by 18.5 and 24.5 percentage points for EAC and ESCC respectively; trends varied by race/ethnicity. Conclusion We found notable differences in trends in EAC and ESCC mortality and stage at diagnosis by race/ethnicity. Stage migration resulting from improvements in diagnosis and treatment may partially explain recent trends in disease stage at diagnosis. Future efforts should identify factors driving current esophageal cancer disparities.

scholarly journals Susceptibility of Sixteen Citrus Genotypes to ‘Candidatus Liberibacter asiaticus’

Plant Disease ◽  
2016 ◽  
Vol 100 (6) ◽  
pp. 1080-1086 ◽  
Author(s):  
Greg McCollum ◽  
Mark Hilf ◽  
Mike Irey ◽  
Weiqi Luo ◽  
Tim Gottwald
Keyword(s):  
The United States ◽  
Insect Vector ◽  
Candidatus Liberibacter Asiaticus ◽  
Citrus Germplasm ◽  
Citrus Production ◽  
Candidatus Liberibacter ◽  
Liberibacter Asiaticus ◽  
Florida Citrus ◽  
Citrus Macrophylla ◽  
Free Ranging

Huanglongbing (HLB) disease is the most serious threat to citrus production worldwide and, in the last decade, has devastated the Florida citrus industry. In the United States, HLB is associated with the phloem-limited α-proteobacterium ‘Candidatus Liberibacter asiaticus’ and its insect vector, the Asian citrus psyllid (ACP; Diaphorina citri). Significant effort is being put forth to develop novel citrus germplasm that has a lower propensity to succumb to HLB than do currently available varieties. Effective methods of screening citrus germplasm for susceptibility to HLB are essential. In this study, we exposed small, grafted trees of 16 citrus types to free-ranging ACP vectors and ‘Ca. L. asiaticus’ inoculum in the greenhouse. During 45 weeks of exposure to ACP, the cumulative incidence of ‘Ca. L. asiaticus’ infection was 70%. Trees of Citrus macrophylla and C. medica were most susceptible to ‘Ca. L. asiaticus’, with 100% infection by the end of the test period in three trials, while the complex genetic hybrids ‘US 1-4-59’ and ‘Fallglo’ consistently were least susceptible, with approximately 30% infection. Results obtained in this greenhouse experiment showed good agreement with trends observed in the orchard, supporting the validity of our approach for screening citrus germplasm for susceptibility to HLB.

scholarly journals Chimeric elk/mouse prion proteins in transgenic mice

2013 ◽  
Vol 94 (2) ◽  
pp. 443-452 ◽  
Author(s):  
Gültekin Tamgüney ◽  
Kurt Giles ◽  
Abby Oehler ◽  
Natrina L. Johnson ◽  
Stephen J. DeArmond ◽  
...  
Keyword(s):  
Neurodegenerative Disorder ◽  
Prion Proteins ◽  
Second Line ◽  
Mouse Line ◽  
Wasting Disease ◽  
C Terminus ◽  
Incubation Periods ◽  
N Terminus ◽  
Mouse Lines

Chronic wasting disease (CWD) of deer and elk is a highly communicable neurodegenerative disorder caused by prions. Investigations of CWD are hampered by slow bioassays in transgenic (Tg) mice. Towards the development of Tg mice that will be more susceptible to CWD prions, we created a series of chimeric elk/mouse transgenes that encode the N terminus of elk PrP (ElkPrP) up to residue Y168 and the C terminus of mouse PrP (MoPrP) beyond residue 169 (mouse numbering), designated Elk3M(SNIVVK). Between codons 169 and 219, six residues distinguish ElkPrP from MoPrP: N169S, T173N, V183I, I202V, I214V and R219K. Using chimeric elk/mouse PrP constructs, we generated 12 Tg mouse lines and determined incubation times after intracerebral inoculation with the mouse-passaged RML scrapie or Elk1P CWD prions. Unexpectedly, one Tg mouse line expressing Elk3M(SNIVVK) exhibited incubation times of <70 days when inoculated with RML prions; a second line had incubation times of <90 days. In contrast, mice expressing full-length ElkPrP had incubation periods of >250 days for RML prions. Tg(Elk3M,SNIVVK) mice were less susceptible to CWD prions than Tg(ElkPrP) mice. Changing three C-terminal mouse residues (202, 214 and 219) to those of elk doubled the incubation time for mouse RML prions and rendered the mice resistant to Elk1P CWD prions. Mutating an additional two residues from mouse to elk at codons 169 and 173 increased the incubation times for mouse prions to >300 days, but made the mice susceptible to CWD prions. Our findings highlight the role of C-terminal residues in PrP that control the susceptibility and replication of prions.

Abstract P211: Single High Na + Ingestion Leads To An Increase In Oxidative Stress And Triggers Inflammation.

Hypertension ◽  
2021 ◽  
Vol 78 (Suppl_1) ◽  
Author(s):  
Ginette Bordcoch ◽  
Ivan Tavera Busso ◽  
Juan Masjoan Juncos ◽  
Luis I Juncos
Keyword(s):  
Oxidative Stress ◽  
The United States ◽  
Male Rats ◽  
Control Group ◽  
Aortic Tissue ◽  
Tissue Samples ◽  
Extracellular Signal ◽  
High Prevalence ◽  
Markers Of Oxidative Stress ◽  
The Difference

Hypertension has been linked to a progressive increased in oxidative stress and inflammation. The high prevalence of hypertension poses a great risk to public health as 108 million adults in the United States have the condition. For that reason, a better understanding of the link between a high Na+ intake and the development of hypertension is of crucial importance. We hypothesize that a single ingestion of a high Na+ solution leads to increased oxidative stress and triggers an inflammatory response. Wistar 200-250 g male rats had gastric infusions through the esophagus. Groups were infused with 8 mL liquid Vaseline (Control), 8 mL of NaCl 0.684 M (4% m/v), and 8 mL of NaCl 1.368 M (8% m/v). After infusion, blood was collected at different time points during the first hour. Tissue samples were obtained from the aorta, heart, and kidney. Electron Microscopy (EM) was performed on all tissues, which were also analyzed for molecular markers of oxidative stress: Superoxide Dismutase (SOD) and Malondialdehyde (MDA), and an inflammation marker: Extracellular Signal-Regulated Kinase (ERK). At 2 and a half minutes, serum Na+ concentration was unchanged in the control group compared to an increase observed in animals receiving 4% and 8% Na+ with concentrations of 135±1.4 mEq/L, 141±2.0 mEq/L, and 140±1.2 mEq/L respectively. At the 1-hour time point after infusion, the difference was further increased in the 8% group with serum concentrations of 135±1.8 mEq/L, 140±1.5 mEq/L, and 152±1mEq/L respectively (p<0.05). There was an increase in oxidative stress in the aorta from values of 36.22±4.64 mU/mg SOD and 0.131±0.013 pg/mL MDA in the control group, to 47.11±4.89 mU/mg SOD and 0.291±0.022 pg/mL MDA in the 8% group (p<0.05 in both cases). The same was observed in the heart, where values were: 174.6125.26 mU/mg SOD, 0.026±0.007 pg/mL MDA in controls, and 259.22±21.98 mU/mg SOD, 0.215±0.073 pg/mL MDA in 8% group (p<0.05 both cases). Increased ERK in aortic tissue, values of 0.29±0.03 pg/mL in controls, 2.68±0.18 pg/mL in 4% group and 3.97±0.68pg/mL in 8% group (p<0.05) suggest increased inflammation. We conclude that the elevation in serum Na+ concentration that follows Na+ ingestion leads to increased oxidative stress and inflammation.

Postherpetic Neuralgia: A Patient’s and a Physician’s Perspective

2016 ◽  
Author(s):  
James H. Diaz
Keyword(s):  
Neuropathic Pain ◽  
Herpes Zoster ◽  
Postherpetic Neuralgia ◽  
Clinical Manifestations ◽  
The United States ◽  
Evidence Based ◽  
Pain Medicine ◽  
High Prevalence ◽  
Antiviral Medications ◽  
Physician’S Perspective

Herpes zoster can plague anyone who has had varicella or has received the varicella or chickenpox vaccine. The incidence of herpes zoster increases with age and rises exponentially after 60 years of age. Postherpetic neuralgia (PHN) may occur after herpes zoster at any age but typically occurs after 50 years of age, with over 40% of persons over 60 years of age suffering from PHN after a shingles attack. Up to 1 million new cases of herpes zoster and 200,000 new cases of PHN may now be anticipated in the United States every year, with the incidence rate increasing as the population grows and ages with prolonged life expectancies. Although new antiviral medications will improve and shorten the course of herpes zoster, they do not guarantee the prevention of PHN. Given the high prevalence of PHN in an aging population and the availability of primary prevention by vaccination, the objectives of this review are to describe the epidemiology, pathophysiology, and clinical manifestations of zoster and PHN and to recommend a combination of strategies for the clinical management and prevention of PHN. This review contains 6 figures, 4 tables and 13 references Key words: evidence-based pain medicine, herpes zoster, neuropathic pain, postherpetic neuralgia

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