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1.
Open Forum Infect Dis ; 11(7): ofae417, 2024 Jul.
Article in English | MEDLINE | ID: mdl-39050226

ABSTRACT

We evaluated factors associated with the presence of hepatitis A virus antibodies 23 years after initiating vaccination at ages 6-15 months. Among 67 participants, 86% (42/49) of those vaccinated at ages 12-15 months and 61% (11/18) of those vaccinated at 6 months remained seropositive at 23 years. Lack of maternal antibodies at enrollment and higher initial vaccine response were independently associated with higher antibody concentrations at 23 years. Further research is needed to assess the duration of hepatitis A vaccine protection and possible need for a booster dose.

2.
PLoS One ; 16(12): e0260970, 2021.
Article in English | MEDLINE | ID: mdl-34855920

ABSTRACT

BACKGROUND: Direct-acting antiviral (DAA) drugs have been effective in the treatment of chronic hepatitis C virus (HCV) infection. Limited data are available on safety, tolerability, and efficacy in American Indian or Alaska Native people. We aim to evaluate the treatment outcomes of sofosbuvir- based regimens for treatment of HCV in a real life setting in Alaska Native/American Indian (AN/AI) people. METHODS: AN/AI patients within the Alaska Tribal Health System with confirmed positive anti-HCV and HCV RNA, who were 18 years of age and older were included in the study. Pretreatment baseline patient characteristics, treatment efficacy based on sustained virologic response (SVR) 12 weeks after treatment completion, and adverse effects were assessed. The following treatments were given according to the American Association for the Study of Liver Diseases/Infectious Disease Society of America (AASLD/IDSA) HCV Guidance: ledipasvir/sofosbuvir, sofosbuvir plus weight-based ribavirin, and sofosbuvir/velpatasvir. RESULTS: We included 501 patients with a mean age of 54.3 (range 21.3-78.3) in the study. Overall SVR was achieved in 95.2% of patients who received one of the three DAA regimens. For those with cirrhosis, overall SVR was 92.8% and for those with genotype 3 91.1% achieved SVR. The most common symptom experienced during treatment was headache. Joint pain was found to decrease during treatment. One person discontinued sofosbuvir plus ribavirin due to myocardial infarction and one discontinued sofosbuvir/velpatasvir due to urticaria. CONCLUSIONS: In the real-world setting, sofosbuvir-based treatment is safe, effective, and well tolerated in AN/AI patients. Sustained virologic response was high regardless of HCV genotype or cirrhosis status.


Subject(s)
American Indian or Alaska Native/statistics & numerical data , Antiviral Agents/therapeutic use , Benzimidazoles/therapeutic use , Carbamates/therapeutic use , Fluorenes/therapeutic use , Hepacivirus/drug effects , Hepatitis C, Chronic/drug therapy , Heterocyclic Compounds, 4 or More Rings/therapeutic use , Sofosbuvir/therapeutic use , Adult , Aged , Alaska/epidemiology , Drug Combinations , Female , Follow-Up Studies , Hepacivirus/isolation & purification , Hepatitis C, Chronic/epidemiology , Hepatitis C, Chronic/virology , Humans , Male , Middle Aged , Prognosis , Sustained Virologic Response
3.
Clin Infect Dis ; 70(9): 2005-2007, 2020 04 15.
Article in English | MEDLINE | ID: mdl-31504307

ABSTRACT

Most persons with chronic hepatitis C virus (HCV) infection in the United States are undiagnosed or linked to care. We describe a program for the management of Alaska Native patients infection utilizing a computerized registry and statewide liver clinics resulting in higher linkage to care (86%) than national estimates (~25%).


Subject(s)
Hepatitis C, Chronic , Hepatitis C , Alaska/epidemiology , Hepatitis C, Chronic/drug therapy , Hepatitis C, Chronic/epidemiology , Humans , Registries , United States
4.
Open Forum Infect Dis ; 6(6): ofz223, 2019 Jun.
Article in English | MEDLINE | ID: mdl-31249845

ABSTRACT

BACKGROUND: Chronic hepatitis C virus (HCV) infection diminishes immune function through cell exhaustion and repertoire alteration. Direct acting antiviral (DAA)-based therapy can restore immune cell subset function and reduce exhaustion states. However, the extent of immune modulation following DAA-based therapy and the role that clinical and demographic factors play remain unknown. METHODS: We examined natural killer (NK) cell, CD4+, and CD8+ T cell subsets along with activation and exhaustion phenotypes across an observational study of sofosbuvir-based treatment for chronic HCV infection. Additionally, we examined the ability of clinical variables and duration of infection to predict 12 weeks of sustained virologic response (SVR12) immune marker outcomes. RESULTS: We show that sofosbuvir-based therapy restores NK cell subset distributions and reduces chronic activation by SVR12. Likewise, T cell subsets, including HCV-specific CD8+ T cells, show reductions in chronic exhaustion markers by SVR12. Immunosuppressive CD4+ regulatory T cells decrease at 4-weeks treatment and SVR12. We observe the magnitude and direction of change in immune marker values from pretreatment to SVR12 varies greatly among participants. Although we observed associations between the estimated date of infection, HCV diagnosis date, and extent of immune marker outcome at SVR12, our regression analyses did not indicate any factors as strong SVR12 outcome predictors. CONCLUSION: Our study lends further evidence of immune changes following sofosbuvir-based therapy. Further investigation beyond SVR12 and into factors that may predict posttreatment outcome is warranted.

5.
Environ Microbiol ; 19(4): 1518-1535, 2017 04.
Article in English | MEDLINE | ID: mdl-28251799

ABSTRACT

We examined the effect of diet on pre-hibernation fattening and the gut microbiota of captive arctic ground squirrels (Urocitellus parryii). We measured body composition across time and gut microbiota density, diversity and function prior to and after five-weeks on control, high-fat, low-fat (18%, 40% and 10% energy from fat, respectively), or restricted calorie (50% of control) diets. Squirrels fattened at the same rate and to the same degree on all diets. Additionally, we found no differences in gut microbiota diversity or short chain fatty acid production across time or with diet. Analysis of the gut microbial transcriptome indicated differences in community function among diet groups, but not across time, and revealed shifts in the relative contribution of function at a taxonomic level. Our results demonstrate that pre-hibernation fattening of arctic ground squirrels is robust to changes in diet and is accomplished by more than increased food intake. Although our analyses did not uncover a definitive link between host fattening and the gut microbiota, and suggest the squirrels may possess a gut microbial community structure that is unresponsive to dietary changes, studies manipulating diet earlier in the active season may yet uncover a relationship between host diet, fattening and gut microbiota.


Subject(s)
Diet , Gastrointestinal Microbiome , Sciuridae/microbiology , Animals , Eating , Fatty Acids, Volatile/metabolism , Female , Hibernation , Seasons
6.
US Army Med Dep J ; (2-16): 179-81, 2016.
Article in English | MEDLINE | ID: mdl-27215889

ABSTRACT

Effective multilateral military operations such as those conducted by the North Atlantic Treaty Organization (NATO) require close cooperation and standardization between member nations to ensure interoperability. Failure to standardize policies, procedures, and doctrine prior to the commencement of military operations will result in critical interoperability gaps, which jeopardize the health of NATO forces and mission success. To prevent these gaps from occurring, US forces must be actively involved with NATO standardization efforts such as the Committee of the Chiefs of Medical Services to ensure US interests are properly represented when NATO standards are developed and US doctrine and procedures will meet the established NATO requirements.


Subject(s)
Food Supply/standards , International Cooperation/legislation & jurisprudence , Organizational Policy , Water Supply/standards , Humans , Military Medicine/legislation & jurisprudence , Military Medicine/organization & administration , Military Medicine/standards , Military Personnel/education , Program Development , Veterinary Service, Military/standards
7.
Environ Toxicol Chem ; 35(2): 485-93, 2016 Feb.
Article in English | MEDLINE | ID: mdl-26313564

ABSTRACT

High-latitude regions experience unique conditions that affect the degradation rate of agrochemicals in the environment. In the present study, data collected from 2 field sites in Alaska, USA (Palmer and Delta) were used to generate a kinetic model for aminopyralid and clopyralid degradation and to describe the microbial community response to herbicide exposure. Field plots were sprayed with herbicides and sampled over the summer of 2013. Quantification was performed via liquid chromatrography/tandem mass spectrometry, and microbial diversity was assessed via next-generation sequencing of bacterial 16S ribosomal ribonucleic acid (rRNA) genes. Both compounds degraded rapidly via pseudo-first-order degradation kinetics between 0 d and 28 d (t1/2 = 9.1-23.0 d), and then degradation slowed thereafter through 90 d. Aminopyralid concentration was 0.048 µg/g to 0.120 µg/g at 90 d post application, whereas clopyralid degraded rapidly at the Palmer site but was recovered in Delta soil at a concentraction of 0.046 µg/g. Microbial community diversity was moderately impacted by herbicide treatment, with the effect more pronounced at Delta. These data predict reductions in crop yield when sensitive plants (potatoes, tomatoes, marigolds, etc.) are rotated onto treated fields. Agricultural operations in high-latitude regions, both commercial and residential, rely heavily on cultivation of such crops and care must be taken when rotating.


Subject(s)
Biodegradation, Environmental , Carboxylic Acids/metabolism , Carboxylic Acids/toxicity , Herbicides/metabolism , Herbicides/toxicity , Picolinic Acids/metabolism , Picolinic Acids/toxicity , Pyridines/metabolism , Pyridines/toxicity , Soil Microbiology , Soil Pollutants/metabolism , Alaska , Biodiversity , Crops, Agricultural , Kinetics , Pesticide Residues/analysis , Plants , RNA, Ribosomal, 16S/analysis
9.
Appl Environ Microbiol ; 80(18): 5611-22, 2014 Sep.
Article in English | MEDLINE | ID: mdl-25002417

ABSTRACT

We examined the seasonal changes of the cecal microbiota of captive arctic ground squirrels (Urocitellus parryii) by measuring microbial diversity and composition, total bacterial density and viability, and short-chain fatty acid concentrations at four sample periods (summer, torpor, interbout arousal, and posthibernation). Abundance of Firmicutes was lower, whereas abundances of Bacteroidetes, Verrucomicrobia, and Proteobacteria were higher during torpor and interbout arousal than in summer. Bacterial densities and percentages of live bacteria were significantly higher in summer than during torpor and interbout arousal. Likewise, total short-chain fatty acid concentrations were significantly greater during summer than during torpor and interbout arousal. Concentrations of individual short-chain fatty acids varied across sample periods, with butyrate concentrations higher and acetate concentrations lower during summer than at all other sample periods. Characteristics of the gut community posthibernation were more similar to those during torpor and interbout arousal than to those during summer. However, higher abundances of the genera Bacteroides and Akkermansia occurred during posthibernation than during interbout arousal and torpor. Collectively, our results clearly demonstrate that seasonal changes in physiology associated with hibernation and activity affect the gut microbial community in the arctic ground squirrel. Importantly, similarities between the gut microbiota of arctic ground squirrels and thirteen-lined ground squirrels suggest the potential for a core microbiota during hibernation.


Subject(s)
Biota , Cecum/microbiology , Sciuridae/microbiology , Seasons , Animals , Arctic Regions , Bacterial Load , Fatty Acids, Volatile/analysis , Microbial Viability
10.
Appl Environ Microbiol ; 80(14): 4260-8, 2014 Jul.
Article in English | MEDLINE | ID: mdl-24795380

ABSTRACT

Arctic ground squirrels (Urocitellus parryii) are active for a scant 3 to 5 months of the year. During the active season, adult squirrels compete for mates, reproduce, and fatten in preparation for hibernation, while juvenile squirrels, weaned in early July, must grow and acquire sufficient fat to survive their first hibernation season. During hibernation, the gut microbial community is altered in diversity, abundance, and activity. To date, no studies have examined the gut microbiota of hibernators across the truncated active season. We characterized trends in diversity (454 pyrosequencing), density (flow cytometry), viability (flow cytometry), and metabolism (short-chain fatty acid analysis) of the gut microbial community of juvenile arctic ground squirrels across their first active season at weaning and at 4, 6, 8, and 10 weeks postweaning. At 8 weeks postweaning, the mean bacterial density was significantly higher than that at weaning, and the mean percentage of live bacteria was significantly higher than that at either weaning or 4 weeks postweaning. No significant differences in microbial diversity, total short-chain fatty acid concentrations, or molar proportions of individual short-chain fatty acids were observed among sample periods. The level of variability in gut microbial diversity among squirrels was high across the active season but was most similar among littermates, except at weaning, indicating strong maternal or genetic influences across development. Our results indicate that genetic or maternal influences exert profound effects on the gut microbial community of juvenile arctic ground squirrels. We did not find a correlation between host adiposity and gut microbial diversity during prehibernation fattening, likely due to a high level of variability among squirrels.


Subject(s)
Bacteria/isolation & purification , Cecum/microbiology , Gastrointestinal Tract/microbiology , Microbiota , Sciuridae/microbiology , Animals , Bacteria/classification , Bacteria/genetics , Cluster Analysis , DNA, Bacterial/genetics , Fatty Acids, Volatile/analysis , Hibernation , RNA, Ribosomal, 16S/genetics , Reproduction , Seasons , Sequence Analysis, DNA
11.
US Army Med Dep J ; : 86-91, 2013.
Article in English | MEDLINE | ID: mdl-23277450

ABSTRACT

NATO requires all standardization agreements and Al-lied Medical Publications to be reviewed at least once every 3 years to ensure they reflect current technologies and national military policies and procedures. This is particularly applicable with regard to veterinary medi-cine and food and water safety where advances in scientific knowledge and practices may result in documents quickly becoming obsolete. Such is the case with the 8 standardization agreements for which the FWSVS has responsibility; all are currently undergoing major revisions. With each revision, national representatives, including US veterinary and preventive medicine personnel, must review the documents to ensure there are no significant issues which would prevent ratification and implementation. This improves standardization and enhances interoperability between NATO partners to minimize duplication. This is accomplished by leveraging other national military capabilities, while maintaining confidence that the food, water, and veterinary support provided to their Warriors, support personnel, and animals in the field is safe and high in quality. Adherence to such standards is a major factor in maintaining the operational readiness of all alliance armed forces.


Subject(s)
Animal Husbandry/standards , Drinking Water/standards , Food Safety/methods , Veterinary Service, Military/standards , Animal Diseases/prevention & control , Animal Welfare/standards , Animals , Canada , Europe , International Cooperation , United States , Veterinary Drugs/standards
14.
Ecology ; 90(5): 1400-11, 2009 May.
Article in English | MEDLINE | ID: mdl-19537559

ABSTRACT

Recent studies suggest that the growth and fecundity of northern ungulates may be coupled to their summer nutrition. Here, we compare summer dietary nitrogen availability of the five major browse plants (comprising approximately 79% of the diet) of moose (Alces alces) in Denali National Park and Nelchina Basin, Alaska, USA. In recent years the productivity of Denali moose has been significantly higher than that of Nelchina moose, prompting this comparison. We examined the phenological progression of leaf nitrogen concentration, tannin-protein precipitation capacity, and digestible protein over three summers in both regions. We then modeled the potential nutritional consequences for a cow moose consuming representative diets on each range, predicting both net protein intake (NPI) and lean body mass accumulation each year. We found that leaf nitrogen and digestible protein decreased, while tannin-protein precipitation capacity increased throughout the summer for all forages. There was 23% more digestible protein in Denali leaves than Nelchina leaves on average, and this difference was significant in all three years. Tannins accounted for a large (mean = 46%) reduction in protein availability, suggesting a key role of these secondary compounds in the nitrogen balance of moose in these regions. Finally, our NPI model predicted that Denali cows were in positive protein balance 17 days longer than Nelchina cows and accumulated 18 kg more lean body mass over the summer, on average. We conclude that summer dietary nitrogen availability may act as a nutritional constraint on moose and suggest that more emphasis be placed on elucidating its role in population dynamics and conservation of northern ungulates.


Subject(s)
Deer/physiology , Diet/veterinary , Dietary Proteins/metabolism , Nitrogen , Alaska , Animals , Population Growth , Seasons
15.
Anal Biochem ; 340(2): 259-71, 2005 May 15.
Article in English | MEDLINE | ID: mdl-15840499

ABSTRACT

We have developed a high-throughput fluorescence anisotropy screen, using a 384-well format, to identify small molecules that disrupt the DNA binding of B-ZIP proteins. Binding of a B-ZIP dimer to fluorescently labeled DNA can be monitored by fluorescence anisotropy. We screened the National Cancer Institute diversity set of 1990 compounds to identify small molecules that disrupt the B-ZIP|DNA complex of CREB, C/EBPbeta, VBP, and AP-1 (FOS|JUND) bound to their cognate DNA sequence. We identified 21 compounds that inhibited the DNA binding of at least one B-ZIP protein, and 12 representative compounds were grouped depending on whether they displaced ethidium bromide from DNA. Of the 6 compounds that did not displace ethidium bromide, 2 also inhibited B-ZIP binding to DNA in a secondary electrophoretic mobility shift assay screen with some specificity. Thermal stability monitored by circular dichroism spectroscopy demonstrated that both compounds bound the basic region of the B-ZIP motif. NSC13778 preferentially binds C/EBPalpha 1000-fold better than it binds C/EBPbeta. Chimeric proteins combining C/EBPalpha and C/EBPbeta mapped the binding of NSC13778 to three amino acids immediately N terminal of the leucine zipper of C/EBPalpha. These experiments suggest that the DNA binding of B-ZIP transcription factors is a potential target for clinical intervention.


Subject(s)
DNA-Binding Proteins/antagonists & inhibitors , DNA-Binding Proteins/metabolism , DNA/metabolism , Fluorescence Polarization/methods , Transcription Factors/antagonists & inhibitors , Transcription Factors/metabolism , Amino Acid Sequence , Binding Sites , CCAAT-Enhancer-Binding Protein-alpha/chemistry , Circular Dichroism , Dimerization , Drug Evaluation, Preclinical/methods , Ethidium/chemistry , Hot Temperature , Leucine Zippers , Polymerase Chain Reaction , Protein Denaturation , Protein Structure, Tertiary , Thermodynamics
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