29 research outputs found
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Point-of-care testing for <i>Toxoplasma gondii</i> IgG/IgM using <i>Toxoplasma</i> ICT IgG-IgM test with sera from the United States and implications for developing countries
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.</p
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
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
Publisher Correction: Toxoplasma Modulates Signature Pathways of Human Epilepsy, Neurodegeneration & Cancer.
A correction to this article has been published and is linked from the HTML and PDF versions of this paper. The error has been fixed in the paper
Towards social connection for young people with cancer
People with cancer have to contend with a variety of physical, emotional and social difficulties. Young people with cancer are often faced with the additional burden of isolation from their peers and social network. This paper outlines early results from a collaborative project seeking to use emerging technologies to develop and evaluate a peer-based social support system to support social connectivity amongst young people with cancer. We introduce an integrated service named MyTrac, which combines online social network applications and mobile broadband telephony. Seven young people (18-25yo) participated in the three month study. The study encompassed in-depth interview data, questionnaire data and an analysis of system audit logs, which documents participants' use and experience of the system. In this paper we highlight specific communications mediated by MyTrac, showing how they are a reflection of both the individual personalities of participants and a reflection of their cancer journey. We illustrate how these individual identities construct a collaborative identity for MyTrac, one which both encompasses and excludes particular types of interaction. We conclude by articulating some design considerations for social connectivity systems which seek to support young people with cancer
Structural insight into mammalian sialyltransferases
Mammalian cell surfaces are modified by complex arrays of glycoproteins, glycolipids and polysaccharides, many of which terminate in sialic acid and have central roles in essential processes including cell recognition, adhesion and immunogenicity. Sialylation of glycoconjugates is performed by a set of sequencerelated enzymes known as sialyltransferases (STs). Here we present the crystal structure of a mammalian ST, porcine ST3Gal-I, providing a structural basis for understanding the mechanism and specificity of these enzymes and for the design of selective inhibitors.Peer reviewed: YesNRC publication: Ye
Toxoplasma modulates signature pathways of human epilepsy, neurodegeneration & cancer
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
Severe diabetes, age-dependent loss of adipose tissue, and mild growth deficiency in mice lacking Akt2/PKBβ
The serine/threonine kinase Akt/PKB plays key roles in the regulation of cell growth, survival, and metabolism. It remains unclear, however, whether the functions of individual Akt/PKB isoforms are distinct. To investigate the function of Akt2/PKBβ, mice lacking this isoform were generated. Both male and female Akt2/PKBβ-null mice exhibit mild growth deficiency and an age-dependent loss of adipose tissue or lipoatrophy, with all observed adipose depots dramatically reduced by 22 weeks of age. Akt2/PKBβ-deficient mice are insulin resistant with elevated plasma triglycerides. In addition, Akt2/PKBβ-deficient mice exhibit fed and fasting hyperglycemia, hyperinsulinemia, glucose intolerance, and impaired muscle glucose uptake. In males, insulin resistance progresses to a severe form of diabetes accompanied by pancreatic β cell failure. In contrast, female Akt2/PKBβ-deficient mice remain mildly hyperglycemic and hyperinsulinemic until at least one year of age. Thus, Akt2/PKBβ-deficient mice exhibit growth deficiency similar to that reported previously for mice lacking Akt1/PKBα, indicating that both Akt2/PKBβ and Akt1/PKBα participate in the regulation of growth. The marked hyperglycemia and loss of pancreatic β cells and adipose tissue in Akt2/PKBβ-deficient mice suggest that Akt2/PKBβ plays critical roles in glucose metabolism and the development or maintenance of proper adipose tissue and islet mass for which other Akt/PKB isoforms are unable to fully compensate
Review of Literature for Air Medical Evacuation High-Level Containment Transport
Introduction Aeromedical evacuation (AE) is a challenging process, further complicated when a patient has a highly hazardous communicable disease (HHCD). We conducted a review of the literature to evaluate the processes and procedures utilized for safe AE high-level containment transport (AE-HLCT) of patients with HHCDs. Methods A literature search was performed in PubMed/MEDLINE (from 1966 through January 2019). Authors screened abstracts for inclusion criteria and full articles were reviewed if the abstract was deemed to contain information related to the aim. Results Our search criteria yielded 14 publications and were separated based upon publication dates, with the natural break point being the beginning of the 2013-2016 Ebola virus disease epidemic. Best practices and recommendations from identified articles are subdivided into pre-flight preparations, inflight operations, and post-flight procedures. Conclusions Limited peer-reviewed literature exists on AE-HLCT, including important aspects related to healthcare worker fatigue, alertness, shift scheduling, and clinical care performance. This hinders the sharing of best practices to inform evacuations and equip teams for future outbreaks. Despite the successful use of different aircraft and technologies, the unique nature of the mission opens the opportunity for greater coordination and development of consensus standards for AE-HLCT operations
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Novel paradigm enables accurate monthly gestational screening to prevent congenital toxoplasmosis and more
Background: Congenital toxoplasmosis is a treatable, preventable disease, but untreated causes death, prematurity, loss of sight, cognition and motor function, and substantial costs worldwide. Objectives: We asked whether high performance of an Immunochromatographic-test (ICT) could enable accurate, rapid diagnosis/treatment, establishing new, improved care-paradigms at point-of-care and clinical laboratory. Methods: Data were obtained in 12 studies/analyses addressing: 1-feasibility/efficacy; 2-false-positives; 3-acceptability; 4-pink/black-line/all studies; 5-time/cost; 6-Quick-Information/Limit-of-detection; 7, 8-acute;-chronic; 9-epidemiology; 10-ADBio; 11,12-Commentary/Cases/Chronology. Findings: ICT was compared with gold-standard or predicate-tests. Overall, ICT performance for 1093 blood/4967 sera was 99.2%/97.5% sensitive and 99.0%/99.7% specific. However, in clinical trial, FDA-cleared-predicate tests initially caused practical, costly problems due to false-positive-IgM results. For 58 persons, 3/43 seronegative and 2/15 chronically infected persons had false positive IgM predicate tests. This caused substantial anxiety, concerns, and required costly, delayed confirmation in reference centers. Absence of false positive ICT results contributes to solutions: Lyon and Paris France and USA Reference laboratories frequently receive sera with erroneously positive local laboratory IgM results impeding patient care. Therefore, thirty-two such sera referred to Lyon’s Reference laboratory were ICT-tested. We collated these with other earlier/ongoing results: 132 of 137 USA or French persons had false-positive local laboratory IgM results identified correctly as negative by ICT. Five false positive ICT results in Tunisia and Marseille, France, emphasize need to confirm positive ICT results with Sabin-Feldman-Dye-test or western blot. Separate studies demonstrated high performance in detecting acute infections, meeting FDA, CLIA, WHO REASSURED, CEMark criteria and patient and physician satisfaction with monthly-gestational-ICT-screening. Conclusions/significance: This novel paradigm using ICT identifies likely false positives or raises suspicion that a result is truly positive, rapidly needing prompt follow up and treatment. Thus, ICT enables well-accepted gestational screening programs that facilitate rapid treatment saving lives, sight, cognition and motor function. This reduces anxiety, delays, work, and cost at point-of-care and clinical laboratories. Trial registration: NCT04474132, https://clinicaltrials.gov/study/NCT04474132ClinicalTrials.gov</p
ALOX12 In Human Toxoplasmosis.
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