T-Bet Expressing B Cells With Distinct Residency And Functional Characteristics Give Rise To Plasma Cells

An increasing body of work shows that T-bet+ B cells play important roles in immune responses to infections a well as in autoimmune diseases. These studies investigate the kinetics, tissue distribution, and functions of T-bet+ B cells in a murine influenza infection model. Both T-bet+ and T-bet- HA-specific B cells emerge early after infection, acquire the memory markers CD73, PD-L2 and CD80, and persist indefinitely with limited interconversion between T-bet+ and T-bet- B cell pools. Moreover, T-bet+ B cells are required for HA stalk specific antibodies and sustained protective HAI titers. T-bet+ HA-specific B cells can be further divided into T-bethigh and T-betlow B cell pools. While T-bethigh, T-betlow, and T-bet- HA-specific B cells are initially found in the spleen, lungs, and draining mediastinal lymph nodes; at later timepoints T-bethigh HA-specific memory B cells are restricted to the spleen, despite the continued presence of T-bet- HA-specific B cells at other anatomical locations. Parabiotic studies show that HA-specific T-bethigh B cells are splenic residents, whereas T-betlow and T-bet- B cells recirculate. T-bethigh B cells give rise to T-betlow B cells but T-betlow B cells do not become T-bethigh. However, T-betlow B cells persist for a minimum of three weeks in the absence of T-bethigh B cells, indicating that they are likely distinct populations. CD138 levels increase with decreasing T-bet expression and T-betlow and T-bethigh B cells downregulate T-bet and give rise to plasma cells. Both B220+ and B220- plasma cells arise from T-bet+ B cells in the spleen and bone marrow. Together, these data suggest that T-bethigh memory B cells are a unique splenic resident population with stem cell like properties that sustains plasma cell numbers and protective antibody titers long term

The Sexual Abuse to Prison Pipeline: The Girls' Story

This report exposes the ways in which we criminalize girls -- especially girls of color -- who have been sexually and physically abused, and it offers policy recommendations to dismantle the abuse to prison pipeline. It illustrates the pipeline with examples, including the detention of girls who are victims of sex trafficking, girls who run away or become truant because of abuse they experience, and girls who cross into juvenile justice from the child welfare system. By illuminating both the problem and potential solutions, we hope to make the first step toward ending the cycle of victimization-to-imprisonment for marginalized girls

Transcatheter Atrial Septal Defect Closure: Preliminary Experience with the Rashkind Occluder Device

Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/72836/1/j.1540-8183.1989.tb00751.x.pd

Metagenomic next-generation sequencing of samples from pediatric febrile illness in Tororo, Uganda.

Febrile illness is a major burden in African children, and non-malarial causes of fever are uncertain. In this retrospective exploratory study, we used metagenomic next-generation sequencing (mNGS) to evaluate serum, nasopharyngeal, and stool specimens from 94 children (aged 2-54 months) with febrile illness admitted to Tororo District Hospital, Uganda. The most common microbes identified were Plasmodium falciparum (51.1% of samples) and parvovirus B19 (4.4%) from serum; human rhinoviruses A and C (40%), respiratory syncytial virus (10%), and human herpesvirus 5 (10%) from nasopharyngeal swabs; and rotavirus A (50% of those with diarrhea) from stool. We also report the near complete genome of a highly divergent orthobunyavirus, tentatively named Nyangole virus, identified from the serum of a child diagnosed with malaria and pneumonia, a Bwamba orthobunyavirus in the nasopharynx of a child with rash and sepsis, and the genomes of two novel human rhinovirus C species. In this retrospective exploratory study, mNGS identified multiple potential pathogens, including 3 new viral species, associated with fever in Ugandan children

Medical and pharmacy students’ perspectives of remote synchronous interprofessional education sessions

Background Interprofessional education (IPE) at university level is an essential component of undergraduate healthcare curricula, as well as being a requirement of many associated regulatory bodies. In this study, the perception of pharmacy and medical students’ of remote IPE was evaluated. Methods A series of IPE sessions took place via Zoom and students’ feedback was collected after each session. Both qualitative and quantitative data were collected and analysed. Results 72% (23/32) of medical students strongly agreed that the sessions had helped to improve their appreciation of the role of pharmacists, whereas 37% (22/59) of pharmacy students strongly agreed, reporting a median response of ‘somewhat agreeing’, that their appreciation of the role of general practitioners had improved. This difference was found to be statistically significant (p = 0.0143). Amongst students who responded, 55% (53/97) identified remote teaching as their preferred mode of delivery for an IPE session. Conclusions The survey demonstrated that the students valued the development of their prescribing skills as well as the ancillary skills gained, such as communication and teamwork. Remote IPE can be a practical means of improving medical and pharmacy students’ understanding of each other’s professional roles, as well as improving the skills required for prescribing

Usefulness of the doppler mean gradient in evaluation of children with aortic valve stenosis and comparison to gradient at catheterization

To assess the usefulness of the Doppler mean gradient as a noninvasive indicator of the need for intervention, 33 children (ages 3 months to 20 years) with valvular aortic stenosis (AS) underwent a 2-dimensional and Doppler echocardiographic examination a median of 1 day before cardiac catheterization. The clinical decision for intervention was based on finding a catheterization peak-to-peak pressure gradient of >75 mm Hg or from 50 to 75 mm Hg in the presence of symptoms or an abnormal exercise treadmill test result. Of the 33 patients, 23 required intervention. The decision for intervention was compared to the Doppler mean gradient, and the Doppler peak and mean gradients were compared to the catheterization peak-to-peak gradient. All 12 patients with a Doppler mean gradient >27 mm Hg had intervention and had a catheterization peak-to-peak gradient of >75 mm Hg. All 3 patients with a Doppler mean gradient From a chi-square table, a Dopppler mean gradient >27 mm Hg predicted the need for intervention with 100% specificity (no false positives) and 52% sensitivity (11 false negatives). if a Doppler mean gradient >24 mm Hg was used to predict intervention, the sensitivity increased to 91% (2 false negatives) but specificity decreased to 70% (3 false positives). To improve the ability to predict the need for intervention in patients with a Doppler mean gradient between 17 and 27 mm Hg, the presence of symptoms or an abnormal exercise treadmill test result was combined with the Doppler mean gradient as criteria for intervention. When the criteria for intervention were a Doppler mean gradient >27 mm Hg or a Doppler mean gradient from 17 to 27 mm Hg in the presence of symptoms or an abnormal exercise test, sensitivity was 96% (1 false negative) and specificity was 80% (2 false positives). Catheterization peak-to-peak gradients correlated well with Doppler mean and peak gradients (r = 0.74 and 0.73, respectively).Thus, the Doppler mean gradient is a useful indicator of the need for intervention in children with AS. A Doppler mean gradient >27 mm Hg indicates the need for intervention with 100% specificity while a Doppler mean gradient < 17 mm Hg predicts mild AS. For patients with Doppler mean gradient between 17 and 27 mm Hg, additional noninvasive data are necessary to determine the need for intervention.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/27748/1/0000140.pd

Additional Common Polymorphisms in the PON Gene Cluster Predict PON1 Activity but Not Vascular Disease

Background. Paraoxonase 1 (PON1) enzymatic activity has been consistently predictive of cardiovascular disease, while the genotypes at the four functional polymorphisms at PON1 have not. The goal of this study was to identify additional variation at the PON gene cluster that improved prediction of PON1 activity and determine if these variants predict carotid artery disease (CAAD). Methods. We considered 1,328 males in a CAAD cohort. 51 tagging single-nucleotide polymorphisms (tag SNPs) across the PON cluster were evaluated to determine their effects on PON1 activity and CAAD status. Results. Six SNPs (four in PON1 and one each in PON2/3) predicted PON1 arylesterase (AREase) activity, in addition to the four previously known functional SNPs. In total, the 10 SNPs explained 30.1% of AREase activity, 5% of which was attributable to the six identified predictive SNPs. We replicate rs854567 prediction of 2.3% of AREase variance, the effects of rs3917510, and a PON3 haplotype that includes rs2375005. While AREase activity strongly predicted CAAD, none of the 10 SNPs predicting AREase predicted CAAD. Conclusions. This study identifies new genetic variants that predict additional PON1 AREase activity. Identification of SNPs associated with PON1 activity is required when evaluating the many phenotypes associated with genetic variation near PON1