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1.
Sci Rep ; 14(1): 14373, 2024 06 22.
Article in English | MEDLINE | ID: mdl-38909151

ABSTRACT

Continued spread of chronic wasting disease (CWD) through wild cervid herds negatively impacts populations, erodes wildlife conservation, drains resource dollars, and challenges wildlife management agencies. Risk factors for CWD have been investigated at state scales, but a regional model to predict locations of new infections can guide increasingly efficient surveillance efforts. We predicted CWD incidence by county using CWD surveillance data depicting white-tailed deer (Odocoileus virginianus) in 16 eastern and midwestern US states. We predicted the binary outcome of CWD-status using four machine learning models, utilized five-fold cross-validation and grid search to pinpoint the best model, then compared model predictions against the subsequent year of surveillance data. Cross validation revealed that the Light Boosting Gradient model was the most reliable predictor given the regional data. The predictive model could be helpful for surveillance planning. Predictions of false positives emphasize areas that warrant targeted CWD surveillance because of similar conditions with counties known to harbor CWD. However, disagreements in positives and negatives between the CWD Prediction Web App predictions and the on-the-ground surveillance data one year later underscore the need for state wildlife agency professionals to use a layered modeling approach to ensure robust surveillance planning. The CWD Prediction Web App is at https://cwd-predict.streamlit.app/ .


Subject(s)
Deer , Machine Learning , Wasting Disease, Chronic , Animals , Wasting Disease, Chronic/epidemiology , Wasting Disease, Chronic/diagnosis , Animals, Wild , United States/epidemiology , Incidence
2.
J Wildl Dis ; 58(3): 664-669, 2022 07 01.
Article in English | MEDLINE | ID: mdl-35436343

ABSTRACT

The white-tailed deer (Odocoileus virginianus) is a popular game species in North America and often lives in close proximity to humans and domestic animals. Deer with neurologic signs are of high interest to the general public and wildlife managers because of disease and safety concerns. Our aim was to describe diagnostic findings from free-ranging white-tailed deer diagnosed with rabies from across the eastern US from 2000 to 2021, with emphasis on gross lesions in the skin and soft tissue overlying the skull. We reviewed diagnostic reports of white-tailed deer cases submitted to the Southeastern Cooperative Wildlife Disease Study for those diagnosed with rabies from 2000 to 2021. Rabies virus infection was confirmed by immunohistochemistry or fluorescent antibody test of brain, or both. Nine adult deer from five states were diagnosed with rabies, including seven (78%) females and two (22%) males. Three (33%) deer were found dead, and six (67%) were humanely dispatched for abnormal behavior. Six deer heads were examined grossly and had lesions, including forehead or periorbital alopecia, cutaneous erythema, abrasions and ulcers, and subcutaneous edema. Histologic examination was performed for eight of nine cases, all of which had intraneuronal eosinophilic inclusion (Negri) bodies in cerebrum, cerebellum, or both. Most (6/8; 75%) had perivascular lymphoplasmacytic encephalitis. Rabies should be considered a differential diagnosis in deer with this pattern of head lesions, suggestive of head rubbing or head pressing.


Subject(s)
Deer , Rabies , Animals , Animals, Wild , Brain/pathology , Female , Humans , Male , Rabies/epidemiology , Rabies/veterinary
3.
J Biol Chem ; 298(4): 101834, 2022 04.
Article in English | MEDLINE | ID: mdl-35304100

ABSTRACT

Chronic wasting disease (CWD) is an invariably fatal prion disease affecting cervid species worldwide. Prions can manifest as distinct strains that can influence disease pathology and transmission. CWD is profoundly lymphotropic, and most infected cervids likely shed peripheral prions replicated in lymphoid organs. However, CWD is a neurodegenerative disease, and most research on prion strains has focused on neurogenic prions. Thus, a knowledge gap exists comparing neurogenic prions to lymphogenic prions. In this study, we compared prions from the obex and lymph nodes of naturally exposed white-tailed deer to identify potential biochemical strain differences. Here, we report biochemical evidence of strain differences between the brain and lymph node from these animals. Conformational stability assays, glycoform ratio analyses, and immunoreactivity scanning across the structured domain of the prion protein that refolds into the amyloid aggregate of the infectious prion reveal significantly more structural and glycoform variation in lymphogenic prions than neurogenic prions. Surprisingly, we observed greater biochemical differences among neurogenic prions than lymphogenic prions across individuals. We propose that the lymphoreticular system propagates a diverse array of prions from which the brain selects a more restricted pool of prions that may be quite different than those from another individual of the same species. Future work should examine the biological and zoonotic impact of these biochemical differences and examine more cervids from multiple locations to determine if these differences are conserved across species and locations.


Subject(s)
Deer , Prions , Wasting Disease, Chronic , Animals , Prions/chemistry , Prions/metabolism , Wasting Disease, Chronic/physiopathology
4.
5.
Evol Appl ; 14(6): 1673-1689, 2021 Jun.
Article in English | MEDLINE | ID: mdl-34178112

ABSTRACT

Approximately 100 years ago, unregulated harvest nearly eliminated white-tailed deer (Odocoileus virginianus) from eastern North America, which subsequently served to catalyze wildlife management as a national priority. An extensive stock-replenishment effort soon followed, with deer broadly translocated among states as a means of re-establishment. However, an unintended consequence was that natural patterns of gene flow became obscured and pretranslocation signatures of population structure were replaced. We applied cutting-edge molecular and biogeographic tools to disentangle genetic signatures of historical management from those reflecting spatially heterogeneous dispersal by evaluating 35,099 single nucleotide polymorphisms (SNPs) derived via reduced-representation genomic sequencing from 1143 deer sampled statewide in Arkansas. We then employed Simpson's diversity index to summarize ancestry assignments and visualize spatial genetic transitions. Using sub-sampled transects across these transitions, we tested clinal patterns across loci against theoretical expectations of their response under scenarios of re-colonization and restricted dispersal. Two salient results emerged: (A) Genetic signatures from historic translocations are demonstrably apparent; and (B) Geographic filters (major rivers; urban centers; highways) now act as inflection points for the distribution of this contemporary ancestry. These results yielded a statewide assessment of contemporary population structure in deer as driven by historic translocations as well as ongoing processes. In addition, the analytical framework employed herein to effectively decipher extant/historic drivers of deer distribution in Arkansas is also applicable for other biodiversity elements with similarly complex demographic histories.

6.
Prion ; 14(1): 238-248, 2020 12.
Article in English | MEDLINE | ID: mdl-33078661

ABSTRACT

Chronic-wasting disease (CWD) is a prion-derived fatal neurodegenerative disease that has affected wild cervid populations on a global scale. Susceptibility has been linked unambiguously to several amino acid variants within the prion protein gene (PRNP). Quantifying their distribution across landscapes can provide critical information for agencies attempting to adaptively manage CWD. Here we attempt to further define management implications of PRNP polymorphism by quantifying the contemporary geographic distribution (i.e., phylogeography) of PRNP variants in hunter-harvested white-tailed deer (WTD; Odocoileus virginianus, N = 1433) distributed across Arkansas (USA), including a focal spot for CWD since detection of the disease in February 2016. Of these, PRNP variants associated with the well-characterized 96S non-synonymous substitution showed a significant increase in relative frequency among older CWD-positive cohorts. We interpreted this pattern as reflective of a longer life expectancy for 96S genotypes in a CWD-endemic region, suggesting either decreased probabilities of infection or reduced disease progression. Other variants showing statistical signatures of potential increased susceptibility, however, seemingly reflect an artefact of population structure. We also showed marked heterogeneity across the landscape in the prevalence of 'reduced susceptibility' genotypes. This may indicate, in turn, that differences in disease susceptibility among WTD in Arkansas are an innate, population-level characteristic that is detectable through phylogeographic analysis.


Subject(s)
Aging/genetics , Aging/pathology , Deer/genetics , Polymorphism, Genetic , Prion Proteins/genetics , Animals , Female , Gene Frequency/genetics , Geography , Haplotypes/genetics , Odds Ratio
7.
Infect Dis Obstet Gynecol ; 2020: 8890619, 2020.
Article in English | MEDLINE | ID: mdl-33082702

ABSTRACT

Preterm birth is a major public health problem, occurring in more than half a million births per year in the United States. A number of maternal conditions have been recognized as risk factors for preterm birth, but for the majority of cases, the etiology is not completely understood. Chlamydia trachomatis is one of the most prevalent sexually transmitted infections in the world. However, its role in adverse pregnancy outcome in women is still debated. In order to determine if genitourinary tract infection with C. trachomatis during pregnancy was associated with preterm birth, we conducted a case-control study on women who delivered at Boston Medical Center, an urban "safety-net" hospital that serves a socioeconomically disadvantaged and racially diverse population. Women with known risk factors for preterm birth or immune suppression were excluded. Variables collected on enrolled subjects included demographics; diagnosis of C. trachomatis during or prior to pregnancy; tobacco, alcohol, and illicit substance use; gestational age; and birthweight and gender of the newborn. We also collected urine for chlamydia testing at the time of delivery and placental biopsies for nucleic acid amplification and histological studies. A total of 305 subjects were enrolled: 100 who delivered preterm and 205 who delivered full term. Among those subjects, we identified 19 cases of pregnancy-associated C. trachomatis infection: 6/100 preterm and 13/205 full term, a difference which was not statistically significant. Only two cases of untreated chlamydia infection were identified postpartum, and both occurred in women who delivered at term. We conclude that genitourinary tract infection with C. trachomatis during pregnancy, when appropriately treated, is not associated with preterm birth.


Subject(s)
Chlamydia Infections/drug therapy , Chlamydia trachomatis/isolation & purification , Pregnancy Complications, Infectious/drug therapy , Premature Birth/epidemiology , Adolescent , Adult , Case-Control Studies , Chlamydia Infections/diagnosis , Chlamydia Infections/epidemiology , Chlamydia trachomatis/genetics , DNA, Bacterial/genetics , Female , Hospitals, Urban , Humans , Maternal Age , Placenta/microbiology , Pregnancy , Pregnancy Complications, Infectious/diagnosis , Pregnancy Complications, Infectious/epidemiology , Risk Factors , Safety-net Providers , Urine/microbiology , Young Adult
8.
Emerg Infect Dis ; 23(12): 1958-1965, 2017 12.
Article in English | MEDLINE | ID: mdl-28841405

ABSTRACT

Wellfleet Bay virus (WFBV), a novel orthomyxovirus in the genus Quaranjavirus, was first isolated in 2006 from carcasses of common eider (Somateria mollissima) during a mortality event in Wellfleet Bay (Barnstable County, Massachusetts, USA) and has since been repeatedly isolated during recurrent mortality events in this location. Hepatic, pancreatic, splenic, and intestinal necrosis was observed in dead eiders. We inoculated 6-week-old common eider ducklings with WFBV in an attempt to recreate the naturally occurring disease. Approximately 25% of inoculated eiders had onset of clinical disease and required euthanasia; an additional 18.75% were adversely affected based on net weight loss during the trial. Control ducklings did not become infected and did not have clinical disease. Infected ducklings with clinical disease had pathologic lesions consistent with those observed during natural mortality events. WFBV was reisolated from 37.5% of the inoculated ducklings. Ducklings surviving to 5 days postinoculation developed serum antibody titers to WFBV.


Subject(s)
Antibodies, Viral/biosynthesis , Bird Diseases/virology , Ducks/virology , Necrosis/veterinary , Orthomyxoviridae Infections/veterinary , Orthomyxoviridae/physiology , Animals , Bays , Bird Diseases/immunology , Bird Diseases/pathology , Disease Models, Animal , Ducks/immunology , Intestines/immunology , Intestines/pathology , Intestines/virology , Liver/immunology , Liver/pathology , Liver/virology , Massachusetts , Necrosis/immunology , Necrosis/pathology , Necrosis/virology , Orthomyxoviridae/pathogenicity , Orthomyxoviridae Infections/immunology , Orthomyxoviridae Infections/pathology , Orthomyxoviridae Infections/virology , Pancreas/immunology , Pancreas/pathology , Pancreas/virology , Spleen/immunology , Spleen/pathology , Spleen/virology , Weight Loss
9.
J Wildl Dis ; 53(4): 875-879, 2017 10.
Article in English | MEDLINE | ID: mdl-28640712

ABSTRACT

Wellfleet Bay virus (WFBV) is a recently described orthomyxovirus isolated from the tissues of Common Eiders (Somateria mollissima) collected during recurrent mortality events on Cape Cod, Massachusetts, US. Coastal Massachusetts is the only location where disease or mortality associated with this virus has been detected in wild birds, and a previous seroprevalence study found a significantly higher frequency of viral exposure in eiders from this location than from other areas sampled in North America. This suggests that coastal Massachusetts is an epicenter of WFBV exposure, but the reason for this is unknown. Opportunistic sampling of sympatric species and testing of banked serum was used to investigate potential host range and spatiotemporal patterns of WFBV exposure. Antibodies were detected in Herring Gulls (Larus argentatus), Ring-billed Gulls (Larus delawarensis), a White-winged Scoter (Melanitta fusca), and a Black Scoter (Melanitta nigra). These findings demonstrate the likely occurrence of fall/winter transmission, expand our understanding of the host range of the virus, and provide further insight into the epidemiology of WFBV in the northeastern US.


Subject(s)
Anseriformes , Bird Diseases/virology , Charadriiformes , Orthomyxoviridae Infections/veterinary , Orthomyxoviridae/immunology , Animals , Antibodies, Viral/blood , Bird Diseases/epidemiology , Bird Diseases/immunology , Massachusetts/epidemiology , New Jersey/epidemiology , Orthomyxoviridae Infections/epidemiology , Orthomyxoviridae Infections/immunology
10.
J Wildl Dis ; 53(1): 81-90, 2017 01.
Article in English | MEDLINE | ID: mdl-27763829

ABSTRACT

Between 1998 and 2014, recurrent mortality events were reported in the Dresser's subspecies of the Common Eider ( Somateria mollissima dresseri) on Cape Cod, Massachusetts, US near Wellfleet Harbor. The early die-offs were attributed to parasitism and emaciation, but beginning in 2006 a suite of distinct lesions was observed concomitant with the isolation of a previously unknown RNA virus. This novel pathogen was identified as an orthomyxovirus in the genus Quaranjavirus and was named Wellfleet Bay virus (WFBV). To assess evidence of exposure to this virus in Common Eiders, we conducted a longitudinal study of the prevalence of WFBV antibodies at multiple locations from 2004-14; we collected 2,258 serum samples from six locations and analyzed each using a microneutralization assay. Results corroborate the emergence of WFBV in 2006 based on the first detection of antibodies in that year. Significantly higher prevalence was detected in Common Eiders sampled in Massachusetts compared to those in Maine, Nova Scotia, and Québec. For birds breeding and wintering in Massachusetss, viral exposure varied by age, sex, and season of sampling, and prevalence by season and sex were highly interrelated with greater numbers of antibody-positive males in the autumn and females in the spring. No evidence of viral exposure was detected in the Northern subspecies ( Somateria mollissima borealis). Among the locations sampled, Massachusetts appears to be the epicenter of Common Eider exposure to WFBV. Further research is warranted to understand the factors controlling the epidemiology of WFBV in Massachussetts, including those that may be limiting geographic expansion of this virus.


Subject(s)
Ducks/virology , RNA Viruses/isolation & purification , Animals , Bays , Female , Longitudinal Studies , Maine , Male , Prevalence , Quebec , RNA Viruses/pathogenicity
11.
Am J Kidney Dis ; 67(5): 775-8, 2016 May.
Article in English | MEDLINE | ID: mdl-26744127

ABSTRACT

There is little information about pregnancy outcomes in patients with active membranous nephropathy (MN), especially those with circulating autoantibodies to M-type phospholipase A2receptor (PLA2R), the major autoantigen in primary MN. We present what we believe to be the first known case of successful pregnancy in a 39-year-old woman with PLA2R-associated MN. In the year prior to pregnancy, the patient developed anasarca, hypoalbuminemia (albumin, 1.3-2.2g/dL), and proteinuria (protein excretion, 29.2 g/d). Kidney biopsy revealed MN with staining for PLA2R, and the patient was seropositive for anti-PLA2R autoantibodies. She did not respond to conservative therapy and was treated with intravenous rituximab (2 doses of 1 g each). Several weeks after presentation, she was found to be 6 weeks pregnant and was closely followed up without further immunosuppressive treatment. Proteinuria remained with protein excretion in the 8- to 12-g/d range. Circulating anti-PLA2R levels declined but were still detectable. At 38 weeks, a healthy baby girl was born, without proteinuria at birth or at her subsequent 6-month postnatal visit. At the time of delivery, the mother still had detectable circulating anti-PLA2R of immunoglobulin G1 (IgG1), IgG3, and IgG4 subclasses, although at low titers. Only trace amounts of IgG4 anti-PLA2R were found in cord blood. Potential reasons for the discrepancy between anti-PLA2R levels in the maternal and fetal circulation are discussed.


Subject(s)
Autoantibodies/immunology , Glomerulonephritis, Membranous/immunology , Pregnancy Complications/immunology , Receptors, Phospholipase A2/immunology , Adult , Female , Glomerulonephritis, Membranous/drug therapy , Humans , Immunosuppressive Agents/therapeutic use , Pregnancy , Rituximab/therapeutic use
12.
PLoS One ; 10(12): e0144524, 2015.
Article in English | MEDLINE | ID: mdl-26677841

ABSTRACT

Wild waterfowl are primary reservoirs of avian influenza viruses (AIV). However the role of sea ducks in the ecology of avian influenza, and how that role differs from freshwater ducks, has not been examined. We obtained and analyzed sera from North Atlantic sea ducks and determined the seroprevalence in those populations. We also tested swab samples from North Atlantic sea ducks for the presence of AIV. We found relatively high serological prevalence (61%) in these sea duck populations but low virus prevalence (0.3%). Using these data we estimated that an antibody half-life of 141 weeks (3.2 years) would be required to attain these prevalences. These findings are much different than what is known in freshwater waterfowl and have implications for surveillance efforts, AIV in marine environments, and the roles of sea ducks and other long-lived waterfowl in avian influenza ecology.


Subject(s)
Ducks/virology , Ecology , Influenza in Birds/epidemiology , Animals , Atlantic Ocean
13.
Conn Med ; 79(6): 357-60, 2015.
Article in English | MEDLINE | ID: mdl-26263717

ABSTRACT

To increase opportunities for Obstetrics and Gynecology(Ob/Gyn) residents to present their research, an Annual State of Connecticut Ob/Gyn Resident Research Day (RRD) was created. At the first annual RRD, 33 residents, representing five of six Connecticut Ob/Gyn residency programs, presented 39 poster and eight oral presentations. RRD evaluators rated the overall symposium and the quality of resident oral and poster presentations as either "excellent" or "above average." Residency program directors reported that the symposium was "very helpful" for evidencing resident scholarship as required by the Accreditation Council for Graduate Medical Education (ACGME). Surveyed residents reported that the symposium promoted their research and was a valuable investment of their time. An annual specialty-specific, statewide RRD was created, experienced good participation, and was well evaluated. The annual, statewide Ob/Gyn RRD may serve as a model for development of other specialty-specific, statewide RRD events.


Subject(s)
Biomedical Research , Gynecology/education , Internship and Residency , Obstetrics/education , Biomedical Research/education , Congresses as Topic , Connecticut , Humans , Surveys and Questionnaires
14.
J Pediatr Hematol Oncol ; 37(6): 443-8, 2015 Aug.
Article in English | MEDLINE | ID: mdl-26115508

ABSTRACT

Utilizing a multiparametric flow cytometry protocol, we assessed various cell types implicated in tumor angiogenesis that were found circulating in the peripheral blood of children with sarcomas (cases) based on their cell surface antigen expression. Circulating endothelial cells (CECs), endothelial colony-forming cells (ECFCs), and the ratio of 2 distinct populations of circulating hematopoietic stem and progenitor cells (CHSPCs), the proangiogenic CHSPCs (pCHSPCs) and nonangiogenic CHSPCs (nCHSPCs) were enumerated. Multiparametric flow cytometry was analyzed in cases at baseline and at 4 additional timepoints until the end of treatment and levels compared with each other and with healthy controls. At all timepoints, cases had significantly lower levels of CECs, but elevated ECFCs and a pCHSPC:nCHSPC ratio compared with controls (all P-values <0.05). There was no significant difference in any of the cell types analyzed based on tumor histology, stage (localized vs. metastatic), or tumor size. After treatment, only the CECs among the complete responders were significantly lower at end of therapy (P<0.01) compared with nonresponders, whereas the ECFCs among all cases significantly increased (P<0.05) compared with baseline. No decline in the pCHSPC:nCHSPC ratio was observed despite tumor response. On the basis of these results, a validation of CECs as prognostic biomarker is now warranted.


Subject(s)
Endothelial Cells/pathology , Hematopoietic Stem Cells/pathology , Neoplastic Cells, Circulating/pathology , Sarcoma/pathology , Adolescent , Adult , Case-Control Studies , Child , Child, Preschool , Combined Modality Therapy , Female , Follow-Up Studies , Humans , Infant , Longitudinal Studies , Male , Neoplasm Staging , Pilot Projects , Prognosis , Sarcoma/therapy , Young Adult
15.
Conserv Physiol ; 3(1): cov028, 2015.
Article in English | MEDLINE | ID: mdl-27293713

ABSTRACT

Most Arctic marine birds are migratory, wintering south of the limit of annual pack ice and returning north each year for the physiologically stressful breeding season. The Arctic environment is changing rapidly due to global warming and anthropogenic activities, which may influence the timing of breeding in relation to arrival times following migration, as well as providing additional stressors (e.g. disturbance from ships) to which birds may respond. During stressful parts of their annual cycle, such as breeding, birds may reallocate resources so that they have increased heterophil-to-lymphocyte ratios in their white blood cell (leucocyte) profiles. We analysed leucocyte profiles of nine species of marine birds to establish reference ranges for these species in advance of future Arctic change. Leucocyte profiles tended to cluster among taxonomic groups across studies, suggesting that reference values for a particular group can be established, and within species there was evidence that birds from colonies that had to migrate farther had higher heterophil-to-lymphocyte ratios during incubation than those that did not have to travel as far, particularly for species with high wing loading.

16.
J Virol ; 89(2): 1389-403, 2015 Jan 15.
Article in English | MEDLINE | ID: mdl-25392223

ABSTRACT

UNLABELLED: Since 1998, cyclic mortality events in common eiders (Somateria mollissima), numbering in the hundreds to thousands of dead birds, have been documented along the coast of Cape Cod, MA, USA. Although longitudinal disease investigations have uncovered potential contributing factors responsible for these outbreaks, detecting a primary etiological agent has proven enigmatic. Here, we identify a novel orthomyxovirus, tentatively named Wellfleet Bay virus (WFBV), as a potential causative agent of these outbreaks. Genomic analysis of WFBV revealed that it is most closely related to members of the Quaranjavirus genus within the family Orthomyxoviridae. Similar to other members of the genus, WFBV contains an alphabaculovirus gp64-like glycoprotein that was demonstrated to have fusion activity; this also tentatively suggests that ticks (and/or insects) may vector the virus in nature. However, in addition to the six RNA segments encoding the prototypical structural proteins identified in other quaranjaviruses, a previously unknown RNA segment (segment 7) encoding a novel protein designated VP7 was discovered in WFBV. Although WFBV shows low to moderate levels of sequence similarity to Quaranfil virus and Johnston Atoll virus, the original members of the Quaranjavirus genus, additional antigenic and genetic analyses demonstrated that it is closely related to the recently identified Cygnet River virus (CyRV) from South Australia, suggesting that WFBV and CyRV may be geographic variants of the same virus. Although the identification of WFBV in part may resolve the enigma of these mass mortality events, the details of the ecology and epidemiology of the virus remain to be determined. IMPORTANCE: The emergence or reemergence of viral pathogens resulting in large-scale outbreaks of disease in humans and/or animals is one of the most important challenges facing biomedicine. For example, understanding how orthomyxoviruses such as novel influenza A virus reassortants and/or mutants emerge to cause epidemic or pandemic disease is at the forefront of current global health concerns. Here, we describe the emergence of a novel orthomyxovirus, Wellfleet Bay virus (WFBV), which has been associated with cyclic large-scale bird die-offs in the northeastern United States. This initial characterization study provides a foundation for further research into the evolution, epidemiology, and ecology of newly emerging orthomyxoviruses, such as WFBV, and their potential impacts on animal and/or human health.


Subject(s)
Bird Diseases/epidemiology , Bird Diseases/mortality , Disease Outbreaks , Orthomyxoviridae Infections/epidemiology , Orthomyxoviridae Infections/mortality , Orthomyxoviridae/isolation & purification , Animals , Anseriformes , Bird Diseases/pathology , Bird Diseases/virology , Cluster Analysis , Female , Male , Models, Molecular , Molecular Sequence Data , New England/epidemiology , Orthomyxoviridae/classification , Orthomyxoviridae/genetics , Orthomyxoviridae Infections/pathology , Orthomyxoviridae Infections/virology , Phylogeny , Protein Conformation , RNA, Viral/genetics , Sequence Analysis, DNA , Viral Proteins/chemistry , Viral Proteins/genetics
17.
Pediatr Blood Cancer ; 61(10): 1754-60, 2014 Oct.
Article in English | MEDLINE | ID: mdl-24976003

ABSTRACT

BACKGROUND: This Phase 2 study tested the tolerability and efficacy of bortezomib combined with reinduction chemotherapy for pediatric patients with relapsed, refractory or secondary acute myeloid leukemia (AML). Correlative studies measured putative AML leukemia initiating cells (AML-LIC) before and after treatment. PROCEDURE: Patients with <400 mg/m(2) prior anthracycline received bortezomib combined with idarubicin (12 mg/m(2) days 1-3) and low-dose cytarabine (100 mg/m(2) days 1-7) (Arm A). Patients with ≥400 mg/m(2) prior anthracycline received bortezomib with etoposide (100 mg/m(2) on days 1-5) and high-dose cytarabine (1 g/m(2) every 12 hours for 10 doses) (Arm B). RESULTS: Forty-six patients were treated with 58 bortezomib-containing cycles. The dose finding phase of Arm B established the recommended Phase 2 dose of bortezomib at 1.3 mg/m(2) on days 1, 4, and 8 with Arm B chemotherapy. Both arms were closed after failure to meet predetermined efficacy thresholds during the first stage of the two-stage design. The complete response (CR + CRp) rates were 29% for Arm A and 43% for Arm B. Counting additional CRi responses (CR with incomplete neutrophil recovery), the overall CR rates were 57% for Arm A and 48% for Arm B. The 2-year overall survival (OS) was 39 ± 15%. Correlative studies showed that LIC depletion after the first cycle was associated with clinical response. CONCLUSION: Bortezomib is tolerable when added to chemotherapy regimens for relapsed pediatric AML, but the regimens did not exceed preset minimum response criteria to allow continued accrual. This study also suggests that AML-LIC depletion has prognostic value.


Subject(s)
Antineoplastic Combined Chemotherapy Protocols/therapeutic use , Leukemia, Myeloid, Acute/drug therapy , Adolescent , Animals , Boronic Acids/administration & dosage , Boronic Acids/adverse effects , Bortezomib , Child , Child, Preschool , Cytarabine/administration & dosage , Cytarabine/adverse effects , Dose-Response Relationship, Drug , Etoposide/administration & dosage , Etoposide/adverse effects , Female , Humans , Idarubicin/administration & dosage , Idarubicin/adverse effects , Infant , Kaplan-Meier Estimate , Leukemia, Myeloid, Acute/mortality , Male , Neoplasm Recurrence, Local/drug therapy , Pyrazines/administration & dosage , Pyrazines/adverse effects , Rabbits , Salvage Therapy/methods , Treatment Outcome , Young Adult
18.
J Parasitol ; 99(6): 1133-6, 2013 Dec.
Article in English | MEDLINE | ID: mdl-23641900

ABSTRACT

Avian hemosporidian parasites are a genetically diverse group of parasites with a near cosmopolitan distribution. Over the past 2 decades, several PCR protocols have been designed to detect these parasites. The majority of these protocols amplify part of or the entire mitochondrial cytochrome b gene. However, many of these protocols co-amplify 2 genera (Haemoproteus and Plasmodium), making it impossible to determine which genus is amplified without post-PCR analysis. A uniform database (MalAvi), containing sequences amplified with the primers HAEMF and HAEMR2, has been developed to increase comparability across studies. We analyzed sequences from the MalAvi database and new sequences and found that digestion with EcoRV could be used to distinguish Haemoproteus from the majority of Plasmodium sequences. In addition, we tested 220 wild birds from Costa Rica and the United States for avian hemosporidians and assessed the ability of EcoRV to distinguish these 2 genera. Thirty-six positive samples were sequenced to confirm the restriction profiles, and we also analyzed 63 new hemosporidian sequences from ongoing studies in the United States for the restriction site. Among these new samples, all of the 85 Haemoproteus (subgenus Parahaemoproteus) and 14 Plasmodium were distinguishable. Overall, 887 of 898 (98.8%) sequences from our studies and the MalAvi database were assigned to the correct genus. Of these samples, all Haemoproteus samples were correctly identified and all but 11 Plasmodium samples were correctly identified by the EcoRV assay. Overall, this restriction enzyme protocol is able to quickly and efficiently classify these 2 genera of avian malarial parasites and would be useful for researchers interested in identifying parasites to genus-level, studies focused on sequence analysis of only a single genus, or for detecting co-infections that would need cloning prior to sequence analysis.


Subject(s)
Bird Diseases/diagnosis , Genome, Mitochondrial , Haemosporida/isolation & purification , Plasmodium/isolation & purification , Protozoan Infections, Animal/diagnosis , Restriction Mapping/standards , Animals , Anseriformes/parasitology , Bird Diseases/parasitology , Birds , Costa Rica , Cytochromes c/genetics , Cytochromes c/metabolism , Databases, Nucleic Acid , Deoxyribonucleases, Type II Site-Specific , Diagnosis, Differential , Haemosporida/genetics , Malaria, Avian/diagnosis , Malaria, Avian/parasitology , Passeriformes/parasitology , Plasmodium/genetics , Polymerase Chain Reaction , Polymorphism, Restriction Fragment Length , Protozoan Infections, Animal/parasitology , United States
19.
Conserv Biol ; 26(5): 862-72, 2012 Oct.
Article in English | MEDLINE | ID: mdl-22889077

ABSTRACT

Riparian and quaking aspen (Populus tremuloides) woodlands are centers of avian abundance and diversity in the western United States, but they have been affected adversely by land use practices, particularly livestock grazing. In 1990, cattle were removed from a 112,500-ha national wildlife refuge in southeastern Oregon. Thereafter, we monitored changes in vegetation and bird abundance in years 1-3 (phase 1) and 10-12 (phase 2) in 17 riparian and 9 snow-pocket aspen plots. On each 1.5-ha plot, we sampled vegetation in 6 transects. Three times during each breeding season, observers recorded all birds 50 m to each side of the plot's 150-m centerline for 25 minutes. We analyzed data with multivariate analysis of variance and paired t tests with p values adjusted for multiple comparisons. In both periods, riparian and snow-pocket aspen produced extensive regeneration of new shoots (stems/ha and 7079 stems/ha, respectively). By phase 2, a 64% increase in medium-diameter trees in riparian stands indicated successful recruitment into the overstory, but this pattern was not seen in snow-pocket stands, where the density of trees was over 2 times greater. By phase 2 in riparian and snow-pocket stands, native forb cover had increased by 68% and 57%, respectively, mesic shrub cover had increased by 29% and 58%, and sagebrush cover had decreased by 24% and 31%. Total avian abundance increased by 33% and 39% in riparian and snow-pocket aspen, respectively, ground or understory nesters increased by 133% and 67% and overstory nesters increased by 34% and 33%. Similarly, ground or understory foragers increased by 25% and 32%, aerial foragers by 55% and 57%, and overstory foragers by 66% and 43%. We interpreted the substantial regeneration of aspen shoots, increased densities of riparian forbs and shrubs, and increased avian abundances as a multitrophic-level response to the total removal of livestock and as substantial movement toward recovery of biological integrity.


Subject(s)
Biota , Birds/physiology , Conservation of Natural Resources , Ecosystem , Plants , Animal Husbandry , Animals , Cattle , Oregon , Population Density , Seasons , Time Factors , Trees
20.
Int J Cardiol ; 145(2): 267-270, 2010 Nov 19.
Article in English | MEDLINE | ID: mdl-19854523

ABSTRACT

AIMS: Comparison of supervised home-based exercise program as adjunctive therapy, with comprehensive disease management alone, on symptoms and quality of life in congestive heart failure patients. METHODS: 8 women and 11 men were enrolled in a randomized trial. The mean subject age was 69 (±4.44) in the controls and 70 (±4.05) in the intervention group. Baseline and 3, 6, and 12-month evaluations consisted of the Chronic Heart Failure Questionnaire (CHFQ), measuring perceived functional capacity (perceived symptoms of dyspnea, fatigue, and emotional function) and the Yale Physical Activity Survey (YPAS). A stress test was given at baseline and 12 months. RESULTS AND CONCLUSIONS: The home-based exercise intervention caused a significant change in perceived fatigue between study groups (p=0.015), after 6 months of study participation, with the control group feeling less fatigued than the intervention group. After 12 months of participation, there were no significant differences in perceived functional capacity. Home-based exercise was well tolerated and favorably evaluated. This pilot study demonstrates the feasibility of studying home-based exercise in patients with moderate congestive heart failure. Larger and longer studies will be required to determine treatment effects.


Subject(s)
Exercise Therapy/methods , Exercise/physiology , Heart Failure/therapy , Home Care Services , Aged , Exercise/psychology , Exercise Therapy/psychology , Feasibility Studies , Female , Heart Failure/physiopathology , Heart Failure/psychology , Humans , Male , Pilot Projects , Treatment Outcome
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