Paramedic Education and Training for the Management of Patients Presenting with Low-Acuity Clinical Conditions: A Scoping Review.

Ambulance services around the world are increasingly attending to calls for non-emergency conditions. These lower-acuity conditions do not always require patients to be transported to the emergency department. Consequently, over the past two decades, ambulance services have implemented strategies to support paramedics in diverting non-urgent patients to alternative care pathways. However, assessing and managing low-acuity conditions can be challenging for paramedics, especially when education and training has traditionally focussed on emergency care. This scoping review explores the education and training provided to paramedics on low-acuity clinical conditions and the use of alternative care pathways. The Preferred Reporting Items for Systematic Reviews and Meta-Analyses extension for Scoping Reviews was applied. The databases searched included Scopus, CINAHL, Embase, Emcare, and MEDLINE (PubMed). The search identified one-hundred sixty-six records, with a total of nine articles reviewed after the removal of duplicates and the screening process. The articles were diverse, with education and training ranging from university degrees for extended care practitioners to short in-service-based training for a suite of protocols or assessment tools. However, the literature addressing education and training on low-acuity conditions and alternative care pathways is limited, with the type and length of education programs appearing to influence practice. There is a need for further research to establish a low acuity education model.

RANGE EXPANSION OF GREEN TREEFROGS (HYLA CINEREA) IN SOUTHERN ILLINOIS: NO EVIDENCE OF PARASITE RELEASE.

For several decades, green treefrogs (Hyla cinerea) have been undergoing rapid range expansion northward and eastward in Illinois, Indiana, and Kentucky. While range expansion of green treefrogs in these states may be linked to climate change, a recent study suggested this expansion could be facilitated by parasites, given that expanded range populations of green treefrogs from Kentucky and Indiana exhibited significant decreases in helminth species diversity compared to those examined from historical locations of Kentucky. Because rapid range expansion may lead to hosts escaping their parasites (= parasite release), a reprieve from parasitic infection could allocate additional resources to growth and reproduction and thus facilitate the expansion. The present study compares patterns of helminth diversity for green treefrogs from historical and 2 types (early and late expansion) of expanded range locations of southern Illinois to test whether these range-expansion populations are also experiencing a reduction in parasitism due to parasite release. The results of this study did not find significant differences in helminth diversity when helminth communities of green treefrogs from their historical and expanded ranges were compared. These results appear to downplay the putative role of parasite release in the northward range expansion of H. cinerea in Illinois. Studies are underway to determine whether local factors, including abiotic conditions and amphibian host diversity, play a more prominent role in influencing helminth diversity of green treefrogs.

Paramedic Education to Support the Use of Low-Acuity Care Pathways: A Scoping Review Protocol.

Ambulance services worldwide have transformed over time into health care services that not only attend to life-threatening emergencies, but are also increasingly being utilised for patients with low-acuity or non-urgent illness and injury. As a result, there has been a need to adapt and include mechanisms to assist paramedics in the assessment and management of such patients, including alternative pathways of care. However, it has been identified that education and training for paramedics in the care of low-acuity patients is limited. This study aims to identify potential gaps in the literature and inform further research, paramedic education and training, patient care guidelines, and policy. A scoping review will be conducted utilising the Joanna Briggs Institutes methodology. A range of relevant electronic databases will be searched along with the grey literature, using search terms related to paramedic education for low-acuity patient care pathways. The search results will be screened by two authors and presented in the PRISMA-ScR format, with articles presented in tabular format and analysed thematically. The results of this scoping review will inform further research exploring paramedic education, clinical guidelines, policy and experiences in the management of low-acuity patients.

Altruism in Paramedicine: A Scoping Review.

While altruism has been studied in healthcare professions such as nursing and medicine, the exploration of the characteristics of altruism, as related to paramedicine and emergency care in Australia, is limited. This scoping review explores altruism in paramedicine from the perspective of the paramedic as practitioner, learner, and educator as seen through the lens of the paramedic and the patient. Also discussed is the positive impact of altruism on the patient experience of care. A scoping review was used to assess the availability of data related to altruism in paramedicine. The Preferred Reporting Items for Systematic Reviews and Meta-Analyses extension for Scoping Reviews was used to guide the process. Search categories were orientated around the subject (altruism) and discipline (paramedicine). A total of 27 articles are included in this scoping review. Initial searching identified 742 articles; after duplicate removal, 396 articles were screened with 346 excluded. Fifty articles were full-text reviewed and 23 excluded. The final 27 were extracted following full-text screening. None of the articles are specific to altruism in paramedicine. The data related to the practice of altruism in paramedicine are extremely limited. The preponderance of data arise from Europe and North America which, due to crewing and service differences, may impact the practice of altruism in different regions. Recent changes to the scope of paramedic practice, workload, education, and case acuity may influence behaviour regarding altruism, compassion, caring, and associated caring behaviours. The practice and education of paramedics including altruism, compassion, caring and caring behaviours in the Australasian setting warrants further research.

HELMINTH DIVERSITY OF GREEN TREEFROGS (HYLA CINEREA) IN THEIR EXPANDED GEOGRAPHICAL RANGE.

There has been a growing interest in characterizing the parasite faunas of species populations as they expand their geographical ranges as a result of climate change. Expanded-range populations often exhibit lower parasite diversity than historical-range populations, and reduced parasitism may, in part, be attributable to expanded-range populations escaping their native range parasites. The present study compares the helminth faunas of green treefrogs (Hyla cinerea) from 4 historical and 4 expanded-range populations to determine whether these latter populations have undergone parasite escape. Results of this study found relatively high degrees of similarity in species composition among helminth assemblages within historical or within range-expansion locations, with marked differences in the composition of helminth faunas between historical and expanded-range populations of these frogs. Because green treefrogs from expanded-range locations exhibited significant decreases in helminth species diversity compared with those from historical sites, they appear to be escaping levels of parasitism typically experienced by these frogs in their native range. Most notably, there was a decrease in the abundance of helminths with direct life cycles and the absence of trematode assemblages with indirect life cycles among expanded-range populations of H. cinerea. The low prevalence of trematode assemblages among historical populations of green treefrogs could limit these parasites' ability to be introduced and propagated in expanded-range locations. However, the lack of trematode assemblages among populations of H. cinerea in its expanded range may also be due to the absence or limited availability of other aquatic hosts that are required to complete the life cycles of these parasites. The reduction in helminth diversity among expanded-range populations of green treefrogs lends some credence to the notion that individuals at the front of a range expansion often invest less energy in reproduction and in doing so allocate more energy to dispersal and other life-history traits, including resistance to parasites. There may, however, be other explanations for differences in parasite species diversity between historical and expanded-range populations of H. cinerea. Because many of the helminths reported from this study are host generalists of amphibians whose recruitment and transmission among intermediate and paratenic hosts are known to be constrained by water and/or soil moisture conditions, we cannot ignore the role of both local amphibian diversity and local abiotic factors in influencing helminth diversity between the 2 population types of green treefrogs. These latter factors would decrease the role of parasite escape or energy trade-offs in driving helminth diversity among populations of H. cinerea and instead would suggest that local conditions play a more prominent role in structuring their helminth communities.

Host Diversity Affects Parasite Diversity: A Case Study Involving Unionicola spp. Inhabiting Freshwater Mussels.

Water mites of the genus Unionicola are common parasites of freshwater mussels, living on the gills or mantle of their hosts and using these tissues as sites of oviposition. Although surveys of this mite fauna among North American unionid mussels indicate that these mites represent highly diverse assemblages, we know very little regarding the determinants of Unionicola species diversity among their molluscan hosts. The present study addresses the relationship between host diversity and mite diversity for Unionicola assemblages associated with unionid mussels of North America. The results of this study found a significantly positive relationship between host species richness and mite species richness, adding to a growing body of evidence that host diversity is an important determinant of parasite diversity. In recent years, molecular sequence data have discovered cryptic biodiversity among unionid mussels, yielding revisions in the nomenclature and systematic taxonomy of the group. DNA sequence variation has also revealed cryptic species complexes among Unionicola mites. Collectively, these findings suggest that the results of the present study may be underestimating species richness among mites and their host mussels. Unfortunately, human perturbations are known to have caused high recent rates of extinction in the mussel and mite faunas of North America and could play a major role in influencing patterns of species richness for this host-parasite system moving forward.

A Comparison of Helminth Faunas of Cope's Gray ( Hyla chrysoscelis ) and Green ( Hyla cinerea ) Treefrogs in Areas of Recent Niche Overlap.

This study compares the helminth faunas between Cope's gray treefrogs ( Hyla chrysoscelis ) and green treefrogs ( Hyla cinerea ), in areas where they have recently overlapped due to range expansion by H. cinerea , to determine whether or not 2 species of frogs with a high degree of similarity in many of their life history traits also exhibit similarities in the composition of their helminth assemblages. Results of this study did not find significant differences in helminth species diversity when sympatric and allopatric populations of the same species of frog were compared. There was, however, a significant difference in helminth diversity among sympatric populations of H. chrysoscelis and H. cinerea , and this difference was in large part attributable to the significantly higher abundance of the gastrointestinal nematode Cosmocercoides variabilis among H. chrysoscelis . Additional studies will be required to determine whether the observed patterns are due to differences in arrival time, perch locations within the chorus, or parasite-mediated competition.

Patterns of species richness among assemblages of Unionicola spp. (Acari: Unionicolidae) inhabiting freshwater mussels (Bivalvia: Unionoida) of North America.

Water mites of Unionicola species are common symbionts of freshwater mussels, living on the gills or mantle and foot of their hosts and using these tissues as sites of oviposition. Although surveys of the mite fauna among North American mussels suggest that these mites represent highly diverse assemblages, there are currently no quantitative data characterizing Unionicola species diversity among their molluscan hosts. The present study addresses patterns of species richness of Unionicola assemblages from freshwater mussels, including the relationship between richness and host specificity among these mites. Results from this study indicate that mite species richness increased significantly with an increase in the number of host individuals sampled. When corrected for sampling effort, there was a positive relationship between host size and mite species richness. Results from this study also reveal a significant relationship between mite species richness and the geographical distribution of host mussels. Overall, the patterns of species richness observed for this study are consistent with those examining the richness of parasitic helminth communities. Because the phylogenetic history of host taxa can have a significant influence on patterns of parasite species richness, studies that correct for the phylogenetic history among host mussels will be required to better understand the role that evolutionary processes have in determining Unionicola species richness. The present study did not indicate a significant relationship between species richness and host specificity and, in not doing so, suggests that the dispersal ability of mites may also play a role in influencing Unionicola species richness. The host recognition behavior and swimming abilities for a larger sample of mites will be required to substantiate this hypothesis.

Integration of cell phone imaging with microchip ELISA to detect ovarian cancer HE4 biomarker in urine at the point-of-care.

Ovarian cancer is asymptomatic in the early stages and most patients present with advanced levels of disease. The lack of cost-effective methods that can achieve frequent, simple and non-invasive testing hinders early detection and causes high mortality in ovarian cancer patients. Here, we report a simple and inexpensive microchip ELISA-based detection module that employs a portable detection system, i.e., a cell phone/charge-coupled device (CCD) to quantify an ovarian cancer biomarker, HE4, in urine. Integration of a mobile application with a cell phone enabled immediate processing of microchip ELISA results, which eliminated the need for a bulky, expensive spectrophotometer. The HE4 level detected by a cell phone or a lensless CCD system was significantly elevated in urine samples from cancer patients (n = 19) than healthy controls (n = 20) (p < 0.001). Receiver operating characteristic (ROC) analyses showed that the microchip ELISA coupled with a cell phone running an automated analysis mobile application had a sensitivity of 89.5% at a specificity of 90%. Under the same specificity, the microchip ELISA coupled with a CCD had a sensitivity of 84.2%. In conclusion, integration of microchip ELISA with cell phone/CCD-based colorimetric measurement technology can be used to detect HE4 biomarker at the point-of-care (POC), paving the way to create bedside technologies for diagnostics and treatment monitoring.

Immediate effects of quantified hamstring stretching: hold-relax proprioceptive neuromuscular facilitation versus static stretching.

PURPOSE: To compare the immediate effects of a hold-relax proprioceptive neuromuscular facilitation stretching (HR-PNF) versus static stretch (SS) on hamstring flexibility in healthy, asymptomatic subjects. SUBJECTS: Thirty subjects (13 female; mean age 25.7 ± 3.0, range 22-37) without excessive hamstring muscle flexibility were randomly assigned to one of two stretch groups: HR-PNF or SS. METHODS: The left leg was treated as a control and did not receive any intervention. The right leg was measured for ROM pre- and post-stretch interventions, with subjects receiving randomly assigned interventions one week apart. Data were analyzed with a 3 (intervention: HR-PNF, SS, control) × 2 (time: pre and post) factorial ANOVA with repeated measures and appropriate post-hoc analyses. RESULTS: A significant interaction was observed between intervention and time for hamstring extensibility, F(2,58) = 25.229, p < .0005. Main effect of intervention for the tested leg was not significant, p = .782 indicating that there was no difference between the two stretch conditions. However, main effect for time was significant (p < .0005), suggesting that hamstring extensibility (for both stretching conditions) after intervention was greater than before. CONCLUSION: No significant differences were found when comparing the effectiveness of HR-PNF and SS techniques. Both stretching methods resulted in significant immediate increases in hamstring length.

Ginkgo may prevent genetic-associated ovarian cancer risk: multiple biomarkers and anticancer pathways induced by ginkgolide B in BRCA1-mutant ovarian epithelial cells.

Women carrying BRCA1 mutations have a higher risk of developing ovarian cancers. Options to reduce this risk are largely limited to prophylactic surgery, which leads to a decrease in the quality of life and permanently damages fertility. There is a obvious and an urgent need to identify a noninvasive approach to effectively prevent the ovarian cancer risk, specifically for those women of reproductive age. Our previous studies showed that the use of the herbal remedy Ginkgo biloba may reduce the risk for nonmucinous ovarian cancer. Here, we explored whether Ginkgo biloba might also be an effective agent to reduce BRCA1-associated ovarian cancer (always serous-type) risk. A human ovarian surface epithelial cell line-636 was developed from a BRCA1-mutant carrier. Cells were treated with ginkgolide B (GB) or dimethyl sulfoxide, and protein lysates from the cells were applied to antibody microarrays to determine upregulated or downregulated protein expression patterns. Anticancer activities and the associated networking pathways with the altered proteins were analyzed by using the Pathway Studio software. After GB treatment, 28 proteins were shown to be consistently upregulated (1.5-15.5-fold), and 22 proteins were downregulated (1.5-28.3-fold). Bioinformatics software analysis indicated that multiple mechanisms and signal pathways are involved in anticancer activities in BRCA1-mutant cells induced by GB treatment. These pathways include cell proliferation, tumor suppression, and DNA damage repair. Our study suggested that GB found in the herbal Ginkgo biloba may have cancer-preventive activities in BRCA1-mutant ovarian epithelial cells.

Paramedic preceptor: work readiness in graduate paramedics.

BACKGROUND: The paramedic profession is growing within Australia, and is undergoing change both in the nature of its roles in health care and in the nature of the education systems that produce paramedic graduates. CONTEXT: Within Australia there are two educational models for paramedic education: the post-employment vocational model and the pre-employment university model. With the progressive phasing out of the vocational model and the rising number of paramedic students there is increasing demand on paramedic preceptors. This increase in demand raises questions about the education of paramedics to perform the teaching role and their work readiness. INNOVATION: This article explores issues associated with the work readiness of paramedic graduates from the perspective of the preceptor role. Links are drawn to the industry competency standards for paramedic graduates. IMPLICATIONS: This article identifies the need for further research into the role of the paramedic preceptor and the work readiness of paramedic graduates to undertake this role.

Mitochondrial genome sequence of Unionicola parkeri (Acari: Trombidiformes: Unionicolidae): molecular synapomorphies between closely-related Unionicola gill mites.

The mitochondrial genome of Unionicola parkeri is a 14,734 bp circular DNA molecule. The sequence and annotation revealed a unique gene order, related to but distinct from the gene order in the closely related species U. foili. Mitochondrial tRNA sequences annotated in this genome predict non-canonical secondary structures for these molecules. The continuing patterns of unique gene orders and unusual tRNA structures in the Trombidiformes in general and Unionicola in particular support the use of phylogenetic approaches that use these types of molecular features as shared, derived character states. Further progress in using these molecular character states to reconstruct phylogeny will depend on careful annotation, especially of tRNA genes.

Activated networking of platelet activating factor receptor and FAK/STAT1 induces malignant potential in BRCA1-mutant at-risk ovarian epithelium.

OBJECTIVES: It is essential to understand the molecular basis of ovarian cancer etiology and tumor development to provide more effective preventive and therapeutic approaches to reduce mortality. Particularly, the molecular targets and pathways involved in early malignant transformation are still not clear. Pro-inflammatory lipids and pathways have been reported to play significant roles in ovarian cancer progression and metastasis. The major objective of this study was to explore and determine whether platelet activating factor (PAF) and receptor associated networking pathways might significantly induce malignant potential in BRCA1-mutant at-risk epithelial cells. METHODS: BRCA1-mutant ovarian epithelial cell lines including (HOSE-636, HOSE-642), BRCA1-mutant ovarian cancer cell (UWB1.289), wild type normal ovarian epithelial cell (HOSE-E6E7) and cancerous cell line (OVCA429), and the non-malignant BRCA1-mutant distal fallopian tube (fimbria) tissue specimens were used in this study. Mutation analysis, kinase microarray, western blot, immune staining, co-immune precipitation, cell cycle, apoptosis, proliferation and bioinformatic pathway analysis were applied. RESULTS: We found that PAF, as a potent pro-inflammatory mediator, induced significant anti-apoptotic effect in BRCA1-mutant ovarian surface epithelial cells, but not in wild type HOSE cells. With kinase microarray technology and the specific immune approaches, we found that phosphor-STAT1 was activated by 100 nM PAF treatment only in BRCA1-mutant associated at-risk ovarian epithelial cells and ovarian cancer cells, but not in BRCA1-wild type normal (HOSE-E6E7) or malignant (OVCA429) ovarian epithelial cells. Co-immune precipitation revealed that elevated PAFR expression is associated with protein-protein interactions of PAFR-FAK and FAK-STAT1 in BRCA1-mutant ovarian epithelial cells, but not in the wild-type control cells. CONCLUSION: Previous studies showed that potent inflammatory lipid mediators such as PAF and its receptor (PAFR) significantly contribute to cancer progression and metastasis. Our findings suggest that these potent inflammatory lipids and receptor pathways are significantly involved in the early malignant transformation through PAFR-FAK-STAT1 networking and to block apoptosis pathway in BRCA1 dysfunctional at-risk ovarian epithelium.

Mitochondrial genome sequence of Unionicola foili (Acari: Unionicolidae): a unique gene order with implications for phylogenetic inference.

The mitochondrial genome of Unionicola foili is circular, 14,738 bp in length, and contains several notable features. The sequence and annotation revealed a unique gene order, continuing a pattern of highly rearranged mitochondrial genomes in the Trombidiformes. U. foili mitochondrial tRNA sequences predict non-canonical secondary structures for these molecules, and our annotation suggests an in-frame fusion between the nad4L and nad5 genes in this genome. The unique gene order and unusual tRNA structures could serve as idiosyncratic characters and have the potential to be phylogenetically informative.

Activation of platelet-activating factor receptor and pleiotropic effects on tyrosine phospho-EGFR/Src/FAK/paxillin in ovarian cancer.

Among the proinflammatory mediators, platelet-activating factor (PAF, 1-O-alkyl-2-acetyl-sn-glycero-3-phosphorylcholine) is a major primary and secondary messenger involved in intracellular and extracellular communication. Evidence suggests that PAF plays a significant role in oncogenic transformation, tumor growth, angiogenesis, and metastasis. However, PAF, with its receptor (PAFR) and their downstream signaling targets, has not been thoroughly studied in cancer. Here, we characterized the PAFR expression pattern in 4 normal human ovarian surface epithelial (HOSE) cell lines, 13 ovarian cancer cell lines, paraffin blocks (n = 84), and tissue microarrays (n = 230) from patients with ovarian cancer. Overexpression of PAFR was found in most nonmucinous types of ovarian cancer but not in HOSE and mucinous cancer cells. Correspondingly, PAF significantly induced cell proliferation and invasion only in PAFR-positive cells (i.e., OVCA429 and OVCA432), but not in PAFR-negative ovarian cells (HOSE and mucinous RMUG-L). The dependency of cell proliferation and invasion on PAFR was further confirmed using PAFR-specific small interfering RNA gene silencing probes, antibodies against PAFR and PAFR antagonist, ginkgolide B. Using quantitative multiplex phospho-antibody array technology, we found that tyrosine phosphorylation of EGFR/Src/FAK/paxillin was coordinately activated by PAF treatment, which was correlated with the activation of phosphatidylinositol 3-kinase and cyclin D1 as markers for cell proliferation, as well as matrix metalloproteinase 2 and 9 for invasion. Specific tyrosine Src inhibitor (PP2) reversibly blocked PAF-activated cancer cell proliferation and invasion. We suggest that PAFR is an essential upstream target of Src and other signal pathways to control the PAF-mediated cancer progression.

Resolution enhancement by homonuclear J-decoupling: application to three-dimensional solid-state magic angle spinning NMR spectroscopy.

We describe a simple protocol to achieve homonuclear J-decoupling in the indirect dimensions of multidimensional experiments, and to enhance spectral resolution of the backbone Calpha carbons in the 3D NCACX experiment. In the proposed protocol, the refocusing of the Calpha-CO homonuclear J-couplings is achieved by applying an off-resonance selective pi pulse to the CO spectral region in the middle of Calpha chemical shift evolution. As is commonly used in solution NMR, a compensatory echo period is used to refocus the unwanted chemical shift evolution of Calpha spins, which takes place during the off-resonance selective pulse. The experiments were carried out on the beta1 immunoglobulin binding domain of protein G (GB1). In GB1, such implementation results in significantly reduced line widths, and leads to an overall sensitivity enhancement.

Ginkgo biloba and ovarian cancer prevention: epidemiological and biological evidence.

There is considerable interest in herbal therapies for cancer prevention but often with little scientific evidence to support their use. In this study, we examined epidemiological data regarding effects of commonly used herbal supplements on risk for ovarian cancer and sought supporting biological evidence. 4.2% of 721 controls compared to 1.6% of 668 cases regularly used Ginkgo biloba for an estimated relative risk (and 95% confidence interval) of 0.41 (0.20,0.84) (p=0.01); and the effect was most apparent in women with non-mucinous types of ovarian cancer, RR=0.33 (0.15,0.74) (p=0.007). In vitro experiments with normal and ovarian cancer cells showed that Ginkgo extract and its components, quercetin and ginkgolide A and B, have significant anti-proliferative effects ( approximately 40%) in serous ovarian cancer cells, but little effect in mucinous (RMUG-L) cells. For the ginkgolides, the inhibitory effect appeared to be cell cycle blockage at G0/G1 to S phase. This combined epidemiological and biological data provide supportive evidence for further studies of the chemopreventive or therapeutic effects of Ginkgo and ginkgolides on ovarian cancer.

Host specificity among Unionicola spp. (Acari: Unionicolidae) parasitizing freshwater mussels.

Water mites of Unionicola spp. are common parasites of freshwater mussels as adults, living on the gills, or mantle and foot of their hosts and using these tissues as sites of oviposition. The present study addresses specialization among North American Unionicola mussel-mites using 2 measures of host specificity: (1) the number of host species used by a species of mite; and (2) a measure that considers the taxonomic distinctness of the hosts utilized by mites, weighted for their prevalence in the different hosts. Results of this study indicate the Unionicola spp. mussel-mites are highly host specific, with most species occurring in association with 1 or 2 species of hosts. If 2 or more host species are utilized, they are typically members of the same genus. These data are consistent with studies examining the dispersal abilities and host recognition behavior for members of the group. When the average values of host specificity for Unionicola subgenera were mapped on a phylogenetic tree for these taxa, a clade comprised of gill mites appeared to be more host specific than a clade consisting of mantle mites. There were, however, no apparent patterns of host specificity within each of the clades. Differences in specificity between the 2 lineages may reflect either a long evolutionary history that gill mites have had with host mussels or the intense competition among gill mites for oviposition sites within unionid mussels, leading to increased host specialization.

Proteomic-based discovery and characterization of glycosylated eosinophil-derived neurotoxin and COOH-terminal osteopontin fragments for ovarian cancer in urine.

PURPOSE: The objective was to identify and characterize low molecular weight proteins/peptides in urine and their posttranslational modifications that might be used as a screening tool for ovarian cancer. EXPERIMENTAL DESIGN: Urine samples collected preoperatively from postmenopausal women with ovarian cancer and benign conditions and from nonsurgical controls were analyzed by surface-enhanced laser desorption/ionization mass spectrometry and two-dimensional gel electrophoresis. Selected proteins from mass profiles were purified by chromatography and followed by liquid chromatography-tandem mass spectrometry sequence analysis. Specific antibodies were generated for further characterization, including immunoprecipitation and glycosylation. Quantitative and semiquantitative ELISAs were developed for preliminary validation in patients of 128 ovarian cancer, 52 benign conditions, 44 other cancers, and 188 healthy controls. RESULTS: A protein (m/z approximately 17,400) with higher peak intensities in cancer patients than in benign conditions and controls was identified and subsequently defined as eosinophil-derived neurotoxin (EDN). A glycosylated form of EDN was specifically elevated in ovarian cancer patients. A cluster of COOH-terminal osteopontin was identified from two-dimensional gels of urine from cancer patients. Modified forms EDN and osteopontin fragments were elevated in early-stage ovarian cancers and a combination of both resulted to 93% specificity and 72% sensitivity. CONCLUSIONS: Specific elevated posttranslationally modified urinary EDN and osteopontin COOH-terminal fragments in ovarian cancer might lead to potential noninvasive screening tests for early diagnosis. Urine with less complexity than serum and relatively high thermodynamic stability of peptides or metabolites is a promising study medium for discovery of the novel biomarkers which may present in many non-urinary tract neoplastic diseases.