Chagas Disease Diagnostic Practices at Four Major Hospital Systems in California and Texas.

BACKGROUND: Chagas disease (CD) is a parasitic disease that affects ∼300 000 people living in the United States. CD leads to cardiac and/or gastrointestinal disease in up to 30% of untreated people. However, end-organ damage can be prevented with early diagnosis and antiparasitic therapy. METHODS: We reviewed electronic health records of patients who underwent testing for CD at four hospital systems in California and Texas between 2016 and 2020. Descriptive analyses were performed as a needs assessment for improving CD diagnosis. RESULTS: In total, 470 patients were tested for CD. Cardiac indications made up more than half (60%) of all testing, and the most frequently cited cardiac condition was heart failure. Fewer than 1% of tests were ordered by obstetric and gynecologic services. Fewer than half (47%) of patients had confirmatory testing performed at the Centers for Disease Control and Prevention. DISCUSSION: Four major hospitals systems in California and Texas demonstrated low overall rates of CD diagnostic testing, testing primarily among older patients with end-organ damage, and incomplete confirmatory testing. This suggests missed opportunities to diagnose CD in at-risk individuals early in the course of infection when antiparasitic treatment can reduce the risk of disease progression and prevent vertical transmission.

Balanced, Orientation-Dependent Dichoptic Masking in Cortex of Visually Normal Humans Measured Using Electroencephalography (EEG).

In the human visual system, cerebral cortex combines left- and right-eye retinal inputs, enabling single, comfortable binocular vision. In visual cortex, the signals from each eye inhibit one another (interocular suppression). While this mechanism may be disrupted by e.g. traumatic brain injury, clinical assessments of interocular suppression are subjective, qualitative, and lack reliability. EEG is a potentially useful clinical tool for objective, quantitative assessment of binocular vision. In a cohort of normal participants, we measured occipital, visual evoked potentials (VEPs) in response to dichoptically-presented vertical and/or horizontal sine-wave gratings. Response amplitudes to orthogonal gratings were greater than that of parallel gratings, which were in turn greater than that of monocular gratings. Our results indicate that interocular suppression is (normally) balanced, orientation-tuned, and that suppression per se is reduced for orthogonal gratings. This objective measure of suppression may have application in clinical settings.

Towards the Classification of Error-Related Potentials using Riemannian Geometry.

The error-related potential (ErrP) is an event-related potential (ERP) evoked by an experimental participant's recognition of an error during task performance. ErrPs, originally described by cognitive psychologists, have been adopted for use in brain-computer interfaces (BCIs) for the detection and correction of errors, and the online refinement of decoding algorithms. Riemannian geometry-based feature extraction and classification is a new approach to BCI which shows good performance in a range of experimental paradigms, but has yet to be applied to the classification of ErrPs. Here, we describe an experiment that elicited ErrPs in seven normal participants performing a visual discrimination task. Audio feedback was provided on each trial. We used multi-channel electroencephalogram (EEG) recordings to classify ErrPs (success/failure), comparing a Riemannian geometry-based method to a traditional approach that computes time-point features. Overall, the Riemannian approach outperformed the traditional approach (78.2% versus 75.9% accuracy, p <0.05); this difference was statistically significant (p <0.05) in three of seven participants. These results indicate that the Riemannian approach better captured the features from feedback-elicited ErrPs, and may have application in BCI for error detection and correction.

Auranofin Resistance in Toxoplasma gondii Decreases the Accumulation of Reactive Oxygen Species but Does Not Target Parasite Thioredoxin Reductase.

Auranofin, a reprofiled FDA-approved drug originally designed to treat rheumatoid arthritis, has emerged as a promising anti-parasitic drug. It induces the accumulation of reactive oxygen species (ROS) in parasites, including Toxoplasma gondii. We generated auranofin resistant T. gondii lines through chemical mutagenesis to identify the molecular target of this drug. Resistant clones were confirmed with a competition assay using wild-type T. gondii expressing yellow fluorescence protein (YFP) as a reference strain. The predicted auranofin target, thioredoxin reductase, was not mutated in any of our resistant lines. Subsequent whole genomic sequencing analysis (WGS) did not reveal a consensus resistance locus, although many have point mutations in genes encoding redox-relevant proteins such as superoxide dismutase (TgSOD2) and ribonucleotide reductase. We investigated the SOD2 L201P mutation and found that it was not sufficient to confer resistance when introduced into wild-type parasites. Resistant clones accumulated less ROS than their wild type counterparts. Our results demonstrate that resistance to auranofin in T. gondii enhances its ability to abate oxidative stress through diverse mechanisms. This evidence supports a hypothesized mechanism of auranofin anti-parasitic activity as disruption of redox homeostasis.

Treatment for seasonal allergic rhinitis by Chinese herbal medicine: a randomized placebo controlled trial.

CONTEXT: Chinese herbal medicine (CHM) is widely used to treat seasonal allergic rhinitis (SAR), however, evidence of efficacy is lacking. OBJECTIVE: To evaluate the efficacy of a Chinese herbal formulation for the treatment of SAR. DESIGN: Randomized, double blind, placebo controlled trial. SETTING: RMIT Chinese Medicine Clinic. PATIENTS: 55 patients with seasonal allergic rhinitis (active 28, placebo 27). INTERVENTIONS: CHM extract capsule (containing 18 herbs) or placebo, given daily for 8 weeks. MAIN OUTCOME MEASURES: The primary measure of efficacy were changes in severity of nasal and non-nasal symptoms using a Five Point Scale (FPS) measured by both patients and the practitioner. The secondary measure was the change in score for the domains measured in the Rhinoconjunctivitis and Rhinitis Quality of Life Questionnaire (RQLQ) assessed by patients. RESULTS: Forty-nine patients completed the study (active 24, placebo 25). After eight weeks, the severity of nasal symptoms and non-nasal symptoms were significantly less in the active treatment group than in the control group, both for measurements made by patients and those by the practitioner. Comparison of active and placebo treatment groups RQLQ scores also indicated significant beneficial effects of treatment (end point Section 1: P < 0.05; Section 2: P < 0.01). Intention-to-treat analyses of categorical items showed moderate to marked improvement rates were 60.7% and 29.6% for active and placebo respectively. Eleven patients reported mild adverse events including 1 withdrawn from the trial. CONCLUSIONS: This CHM formulation appears to offer symptomatic relief and improvement of quality of life for some patients with seasonal allergic rhinitis.

Regulator of G protein signaling Z1 (RGSZ1) interacts with Galpha i subunits and regulates Galpha i-mediated cell signaling.

Regulator of G protein signaling (RGS) proteins constitute a family of over 20 proteins that negatively regulate heterotrimeric G protein-coupled receptor signaling pathways by enhancing endogenous GTPase activities of G protein alpha subunits. RGSZ1, one of the RGS proteins specifically localized to the brain, has been cloned previously and described as a selective GTPase accelerating protein for Galpha(z) subunit. Here, we employed several methods to provide new evidence that RGSZ1 interacts not only with Galpha(z,) but also with Galpha(i), as supported by in vitro binding assays and functional studies. Using glutathione S-transferase fusion protein pull-down assays, glutathione S-transferase-RGSZ1 protein was shown to bind (35)S-labeled Galpha(i1) protein in an AlF(4)(-)dependent manner. The interaction between RGSZ1 and Galpha(i) was confirmed further by co-immunoprecipitation studies and yeast two-hybrid experiments using a quantitative luciferase reporter gene. Extending these observations to functional studies, RGSZ1 accelerated endogenous GTPase activity of Galpha(i1) in single-turnover GTPase assays. Human RGSZ1 functionally regulated GPA1 (a yeast Galpha(i)-like protein)-mediated yeast pheromone response when expressed in a SST2 (yeast RGS protein) knockout strain. In PC12 cells, transfected RGSZ1 blocked mitogen-activated protein kinase activity induced by UK14304, an alpha(2)-adrenergic receptor agonist. Furthermore, RGSZ1 attenuated D2 dopamine receptor agonist-induced serum response element reporter gene activity in Chinese hamster ovary cells. In summary, these data suggest that RGSZ1 serves as a GTPase accelerating protein for Galpha(i) and regulates Galpha(i)-mediated signaling, thus expanding the potential role of RGSZ1 in G protein-mediated cellular activities.