Identifying antinuclear antibody positive individuals at risk for developing systemic autoimmune disease: development and validation of a real-time risk model.

Objective: Positive antinuclear antibodies (ANAs) cause diagnostic dilemmas for clinicians. Currently, no tools exist to help clinicians interpret the significance of a positive ANA in individuals without diagnosed autoimmune diseases. We developed and validated a risk model to predict risk of developing autoimmune disease in positive ANA individuals. Methods: Using a de-identified electronic health record (EHR), we randomly chart reviewed 2,000 positive ANA individuals to determine if a systemic autoimmune disease was diagnosed by a rheumatologist. A priori, we considered demographics, billing codes for autoimmune disease-related symptoms, and laboratory values as variables for the risk model. We performed logistic regression and machine learning models using training and validation samples. Results: We assembled training (n = 1030) and validation (n = 449) sets. Positive ANA individuals who were younger, female, had a higher titer ANA, higher platelet count, disease-specific autoantibodies, and more billing codes related to symptoms of autoimmune diseases were all more likely to develop autoimmune diseases. The most important variables included having a disease-specific autoantibody, number of billing codes for autoimmune disease-related symptoms, and platelet count. In the logistic regression model, AUC was 0.83 (95% CI 0.79-0.86) in the training set and 0.75 (95% CI 0.68-0.81) in the validation set. Conclusion: We developed and validated a risk model that predicts risk for developing systemic autoimmune diseases and can be deployed easily within the EHR. The model can risk stratify positive ANA individuals to ensure high-risk individuals receive urgent rheumatology referrals while reassuring low-risk individuals and reducing unnecessary referrals.

Resilin Distribution and Abundance in Apis mellifera across Biological Age Classes and Castes.

The presence of resilin, an elastomeric protein, in insect vein joints provides the flexible, passive deformations that are crucial to flapping flight. This study investigated the resilin gene expression and autofluorescence dynamics among Apis mellifera (honey bee) worker age classes and drone honey bees. Resilin gene expression was determined via ddPCR on whole honey bees and resilin autofluorescence was measured in the 1m-cu, 2m-cu, Cu-V, and Cu2-V joints on the forewing and the Cu-V joint of the hindwing. Resilin gene expression varied significantly with age, with resilin activity being highest in the pupae. Autofluorescence of the 1m-cu and the Cu-V joints on the ventral forewing and the Cu-V joint on the ventral hindwing varied significantly between age classes on the left and right sides of the wing, with the newly emerged honey bees having the highest level of resilin autofluorescence compared to all other groups. The results of this study suggest that resilin gene expression and deposition on the wing is age-dependent and may inform us more about the physiology of aging in honey bees.

Metformin Attenuates Inflammatory Responses and Enhances Antibody Production in an Acute Pneumonia Model of Streptococcus pneumoniae.

Metformin may potentially reverse various age-related conditions; however, it is unclear whether metformin can also mitigate or delay the deterioration of immunological resilience that occurs in the context of infections that are commonly observed in older persons. We examined whether metformin promotes the preservation of immunological resilience in an acute S. pneumoniae (SPN) infection challenge in young adult mice. Mice were fed metformin (MET-alone) or standard chow (controls-alone) for 10 weeks prior to receiving intratracheal inoculation of SPN. A subset of each diet group received pneumococcal conjugate vaccine at week 6 (MET + PCV and control + PCV). Compared to controls-alone, MET-alone had significantly less infection-associated morbidity and attenuated inflammatory responses during acute SPN infection. Metformin lowered the expression of genes in the lungs related to inflammation as well as shorter lifespan in humans. This was accompanied by significantly lower levels of pro-inflammatory cytokines (e.g., IL6). MET + PCV vs. control + PCV manifested enhanced SPN anticapsular IgM and IgG levels. The levels of SPN IgM production negatively correlated with expression levels of genes linked to intestinal epithelial structure among MET + PCV vs. control + PCV groups. Correspondingly, the gut microbial composition of metformin-fed mice had a significantly higher abundance in the Verrucomicrobia, Akkermansia muciniphila, a species previously associated with beneficial effects on intestinal integrity and longevity. Together, these findings indicate metformin's immunoprotective potential to protect against infection-associated declines in immunologic resilience.

Land Use Influences the Composition and Antimicrobial Effects of Propolis.

Honey bee propolis is a complex, resinous mixture created by bees using plant sources such as leaves, flowers, and bud exudates. This study characterized how cropland surrounding apiaries affects the chemical composition and antimicrobial effects of propolis. The chemical composition and compound abundance of the propolis samples were analyzed using Gas Chromatography-Mass Spectrometry (GC-MS) and the antimicrobial effects were analyzed using the 50% minimum inhibitory concentration (MIC50) assay against four relevant bee pathogens, Serratia marcescens, Paenibacillus larvae, Lysinibacillus sphaericus, and Klebsiella pneumoniae. Propolis composition varied significantly with apiary, and cropland coverage predicted mean sum abundance of compounds. The apiary with the highest cropland coverage exhibited significantly higher MIC50 values for S. marcescens and K. pneumoniae compared to other apiaries. These results demonstrate that agricultural land use surrounding honey bee apiaries decreases the chemical quality and antimicrobial effects of propolis, which may have implications for the impacts of land use on hive immunity to potential pathogens.

Clinical Leaflet Thrombosis in Transcatheter and Surgical Bioprosthetic Aortic Valves by Four-Dimensional Computed Tomography.

BACKGROUND: The incidence of leaflet thrombosis after transcatheter aortic valve replacement (TAVR) with active surveillance by four-dimensional computed tomography (4DCT) ranges from 7% to 14%. The incidence of leaflet thrombosis when 4DCT is performed for clinical and echocardiographic indications is unknown. METHODS: All patients with prior TAVR or surgical aortic valve replacement (SAVR) who underwent evaluation between October 2015 and January 2017 at our institution and had clinical or echocardiographic indications of leaflet thrombosis were evaluated by 4DCT. Indications for 4DCT by echocardiography included (1) interval increase in mean gradient of 10 mm Hg or more, (2) interval decrease in ejection fraction of 10% or more, (3) thrombus seen on transthoracic echocardiography, (4) persistent or increasing paravalvular leak, or (5) valve dehiscence or thickened leaflets seen on transthoracic echocardiography. Clinical indicators were (1) stroke, (2) transient ischemic attack, or (3) new or worsening heart failure. RESULTS: During the study period, 612 patients underwent TAVR, and 101 patients (55 TAVR; 46 SAVR) met the criteria for 4DCT imaging. Leaflet thrombosis was seen in 17 of 55 TAVR patients (30.9%) and 15 of 46 SAVR patients (32.6%). Follow-up imaging with 4DCT after treatment with anticoagulation showed improvement or resolution in thrombus burden and leaflet excursion in all TAVR patients and in two-thirds of SAVR patients. CONCLUSIONS: One-third of patients with clinical or echocardiographic indications suggestive of leaflet thrombosis were found to have evidence of leaflet thrombosis using 4DCT. This allowed tailored anticoagulation therapy with resolution of the thrombus in most patients and avoiding unnecessary anticoagulation in the remaining two-thirds of patients.

Genetic and Environmental Contributions of Negative Valence Systems to Internalizing Pathways.

The genetic and environmental contributions of negative valence systems (NVS) to internalizing pathways study (also referred to as the Adolescent and Young Adult Twin Study) was designed to examine varying constructs of the NVS as they relate to the development of internalizing disorders from a genetically informed perspective. The goal of this study was to evaluate genetic and environmental contributions to potential psychiatric endophenotypes that contribute to internalizing psychopathology by studying adolescent and young adult twins longitudinally over a 2-year period. This report details the sample characteristics, study design, and methodology of this study. The first wave of data collection (i.e., time 1) is complete; the 2-year follow-up (i.e., time 2) is currently underway. A total of 430 twin pairs (N = 860 individual twins; 166 monozygotic pairs; 57.2% female) and 422 parents or legal guardians participated at time 1. Twin participants completed self-report surveys and participated in experimental paradigms to assess processes within the NVS. Additionally, parents completed surveys to report on themselves and their twin children. Findings from this study will help clarify the genetic and environmental influences of the NVS and their association with internalizing risk. The goal of this line of research is to develop methods for early internalizing disorder risk detection.

A study on blood product usage and wastage at the public hospital, Guyana.

BACKGROUND: Blood is a valuable resource and blood wastage in a low socio economic country could impose a very serious impact on healthcare. This study therefore analyzes the usage and wastage of blood and blood products at the Georgetown Public Hospital Cooperation (GPHC), Guyana. METHODS: A retrospective study was conducted on the data retrieved from laboratory blood banking information system on usage and wastage of blood products during the years 2012-2014 at the public hospital. The data were analyzed in MS Excel and SPSS 20.0. RESULTS: A total of 16,426 units of blood were issued from National Blood Transfusion Services. During the study period the most frequently requested blood component was packed cells followed by fresh frozen plasma (FFP), platelet, cryoprecipitate (CRYO) and whole blood respectively. Data indicated that 4167 units (25 %) of blood were wasted due to various reasons at GPHC. CONCLUSIONS: There is a need for intervention through raising awareness among medical staff in reducing blood wastage.