23 research outputs found

    Point-of-Care Testing for Toxoplasma Gondii IgG/IgM Using Toxoplasma ICT IgG-IgM Test with Sera from the United States and Implications for Developing Countries

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    Background Congenital toxoplasmosis is a serious but preventable and treatable disease. Gestational screening facilitates early detection and treatment of primary acquisition. Thus, fetal infection can be promptly diagnosed and treated and outcomes can be improved. Methods We tested 180 sera with the Toxoplasma ICT IgG-IgM point-of-care (POC) test. Sera were from 116 chronically infected persons (48 serotype II; 14 serotype I-III; 25 serotype I-IIIa; 28 serotype Atypical, haplogroup 12; 1 not typed). These represent strains of parasites infecting mothers of congenitally infected children in the U.S. 51 seronegative samples and 13 samples from recently infected persons known to be IgG/IgM positive within the prior 2.7 months also were tested. Interpretation was confirmed by two blinded observers. A comparison of costs for POC vs. commercial laboratory testing methods was performed. Results We found that this new Toxoplasma ICT IgG-IgM POC test was highly sensitive (100%) and specific (100%) for distinguishing IgG/IgM-positive from negative sera. Use of such reliable POC tests can be cost-saving and benefit patients. Conclusions Our work demonstrates that the Toxoplasma ICT IgG-IgM test can function reliably as a point-of-care test to diagnose Toxoplasma gondii infection in the U.S. This provides an opportunity to improve maternal-fetal care by using approaches, diagnostic tools, and medicines already available. This infection has serious, lifelong consequences for infected persons and their families. From the present study, it appears a simple, low-cost POC test is now available to help prevent morbidity/disability, decrease cost, and make gestational screening feasible. It also offers new options for improved prenatal care in low- and middle-income countries

    Health Informatics Journal

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    The use of Cox regression and genetic algorithm (CoRGA) for identifying risk factors for mortality in older peopl

    A retrospective survey of childhood glaucoma prevalence according to Childhood Glaucoma Research Network classification

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    Purpose: To evaluate the Childhood Glaucoma Research Network (CGRN) classification system and describe the prevalence of each subtype according to this classification. Materials and Methods: Retrospectively, the medical records of 205 consecutive childhood glaucoma and glaucoma suspect patients at an urban tertiary care center were reviewed. The initial diagnosis and new diagnosis according to CGRN classification were recorded. Results: All patients fit one of the seven categories of the new classification. Seventy-one percent of diagnoses were changed upon reclassification. Twenty-three percent of patients had primary glaucoma (juvenile open-angle glaucoma and primary congenital glaucoma [PCG]); 36% had secondary glaucoma (glaucoma associated with nonacquired ocular anomalies; glaucoma associated with nonacquired systemic disease or syndrome; glaucoma associated with acquired condition; and glaucoma following cataract surgery); and 39% were glaucoma suspect. Of the patients diagnosed with glaucoma, PCG was the most common diagnosis, seen in 32% of patients. Conclusion: The CGRN classification provides a useful method of classifying childhood glaucoma

    The use of Cox regression and genetic algorithm (CoRGA) for identifying risk factors for mortality in older people

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    The increase in the proportion and number of older people in developed countries has resulted in research investigating risk factors for adverse health outcomes, including mortality. However, research has been limited by the range of risk factors included in regression models. This is partly because traditional statistical methods and software packages allow a restricted number of variables and combinations of variables. This article describes ongoing research to overcome these limitations through the CoRGA program, which combines Cox regression with a genetic algorithm for the variable selection process. CoRGA was used to try and identify the best combination of risk factors for 4-year all-cause mortality. The combination of 10 risk factors identified by CoRGA included both known and new risk factors for mortality in older people. Further research is seeking to develop the program further and to identify further risk factors for all-cause mortality in older people

    Chorioretinal lesions in mothers of children with congenital toxoplasmosis in the National Collaborative Chicago-based, Congenital Toxoplasmosis Study

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    Aims: To determine whether mothers of children with congenital toxoplasmosis have chorioretinal lesions consistent with toxoplasmosis.Methods: Prospective cohort study. Ophthalmologists in our study have examined 173 children with congenital toxoplasmosis in a hospital outpatient setting. These children were referred to us by their primary care physicians. One hundred and thirty mothers of these children had retina examinations of both eyes at least once. Main outcome measure was lesion(s) consistent with ocular toxoplasmosis.Results: Of 130 mothers examined between 1991-2005, 10 (7.7%, 95% Confidence Interval 3.8%, 13.7%) had chorioretinal lesions which likely represent resolved toxoplasmic chorioretinitis. Most of these were small peripheral chorioretinal lesions. None reactivated between 1991-2005.Conclusions: Chorioretinal lesions consistent with quiescent ocular toxoplasmosis occur in mothers of children with congenital toxoplasmosis in the United States

    Toxoplasma modulates signature pathways of human epilepsy, neurodegeneration & cancer

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    One third of humans are infected lifelong with the brain-dwelling, protozoan parasite, Toxoplasma gondii. Approximately fifteen million of these have congenital toxoplasmosis. Although neurobehavioral disease is associated with seropositivity, causality is unproven. To better understand what this parasite does to human brains, we performed a comprehensive systems analysis of the infected brain: We identified susceptibility genes for congenital toxoplasmosis in our cohort of infected humans and found these genes are expressed in human brain. Transcriptomic and quantitative proteomic analyses of infected human, primary, neuronal stem and monocytic cells revealed effects on neurodevelopment and plasticity in neural, immune, and endocrine networks. These findings were supported by identification of protein and miRNA biomarkers in sera of ill children reflecting brain damage and T. gondii infection. These data were deconvoluted using three systems biology approaches: "Orbital-deconvolution" elucidated upstream, regulatory pathways interconnecting human susceptibility genes, biomarkers, proteomes, and transcriptomes. "Cluster-deconvolution" revealed visual protein-protein interaction clusters involved in processes affecting brain functions and circuitry, including lipid metabolism, leukocyte migration and olfaction. Finally, "disease-deconvolution" identified associations between the parasite-brain interactions and epilepsy, movement disorders, Alzheimer's disease, and cancer. This "reconstruction-deconvolution" logic provides templates of progenitor cells' potentiating effects, and components affecting human brain parasitism and diseases

    ALOX12 In Human Toxoplasmosis.

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    International audience: ALOX12 is a gene encoding arachidonate 12-lipoxygenase (12-LOX), a member of a non-heme lipoxygenase family of dioxygenases. ALOX12 catalyzes the addition of oxygen onto arachidonic acid producing 12-hydroperoxyeicosatetraenoic acid, 12-HPETE, which can be reduced to eicosanoid, 12-HETE. 12-HETE acts in diverse cellular processes including catecholamine synthesis, vasoconstriction, neuronal function and inflammation. Consistent with effects on these fundamental mechanisms, allelic variants of ALOX12 are associated with diseases including schizophrenia, atherosclerosis and cancers without definition of mechanisms. Toxoplasma gondii is an apicomplexan parasite that causes morbidity and mortality and stimulates an innate and adaptive immune inflammatory reaction. Recently, it has been shown that a gene region known as Toxo1 is critical for susceptibility or resistance to T. gondii infection in rats. An orthologous gene region with ALOX12 centromeric is also present in humans. Herein, we report that the human ALOX12 gene has susceptibility alleles for human congenital toxoplasmosis (rs6502997 [P<0.000309], rs312462 [P<0.028499], rs6502998 [P<0.029794], rs434473 [P<0.038516]). A human monocytic cell line was genetically engineered using lentivirus RNA interference to knockdown ALOX12. In ALOX12 knockdown cells, ALOX12 RNA expression decreased and ALOX12 substrate, arachidonic acid, increased. ALOX12 knockdown attenuated progression of T. gondii infection and resulted in greater parasite burden, but decreased consequent late cell death of the human monocytic cell line. These findings suggest that, ALOX12 influences host responses to T. gondii infection in human cells. ALOX12 has been shown in other studies to be important in numerous diseases. Herein, we now demonstrate the critical role ALOX12 plays in T. gondii infection in humans
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