Association of Social Determinants of Health With the Likelihood of Treatment With Laser Trabeculoplasty in a US Database.

Prcis: Among 1861 adults with ocular hypertension or mild or moderate primary open angle glaucoma, those with Medicaid or no insurance had a statistically significantly lower likelihood of receiving laser trabeculoplasty compared with those with other insurance.

Purpose: To determine whether social determinants of health are associated with undergoing treatment with laser trabeculoplasty (LTP) among individuals with ocular hypertension (OHT) or mild or moderate primary open angle glaucoma (POAG).

Methods: In this cross-sectional study, we included patients with OHT or mild or moderate POAG from the National Institutes of Health All of Us Research Program, a diverse US nationwide data set.

Hypertension Likely Drives Arteriolar Wall Thickening in Preclinical Diabetic Retinopathy While Diabetes Drives Wall Thickness in Clinical Retinopathy.

Purpose: Both hypertension and diabetes are known to increase the wall-to-lumen ratio (WLR) of retinal arterioles, but the differential effects are unknown. Here, we study the timing and relative impact of hypertension versus diabetes on the WLR in diabetic retinopathy (DR) to address this unresolved question.

Methods: This prospective cross-sectional study compared the retinal arteriolar WLR in 17 healthy eyes, 15 with diabetes but no apparent DR (DM no DR), and 8 with diabetic macular edema (DME) and either nonproliferative or proliferative DR.

A deep population reference panel of tandem repeat variation.

Tandem repeats (TRs) represent one of the largest sources of genetic variation in humans and are implicated in a range of phenotypes. Here we present a deep characterization of TR variation based on high coverage whole genome sequencing from 3550 diverse individuals from the 1000 Genomes Project and H3Africa cohorts. We develop a method, EnsembleTR, to integrate genotypes from four separate methods resulting in high-quality genotypes at more than 1.

A deep population reference panel of tandem repeat variation.

Tandem repeats (TRs) represent one of the largest sources of genetic variation in humans and are implicated in a range of phenotypes. Here we present a deep characterization of TR variation based on high coverage whole genome sequencing from 3,550 diverse individuals from the 1000 Genomes Project and H3Africa cohorts. We develop a method, EnsembleTR, to integrate genotypes from four separate methods resulting in high-quality genotypes at more than 1.

Racial Disparities in Barriers to Care for Patients With Diabetic Retinopathy in a Nationwide Cohort.

Purpose: To ascertain specific barriers of care among patients with diabetic retinopathy (DR) from different racial/ethnic groups.

Methods: In this cross-sectional study, we included adult participants in the National Institutes of Health All of Us Research Program with DR who answered questions in the Healthcare Access & Utilization survey and Social Determinants of Health (SDoH) survey. Logistic regression was used to study the association between barriers to care and race/ethnicity.

The Fovea-Protective Impact of Double-Layer Sign in Eyes With Foveal-Sparing Geographic Atrophy and Age-Related Macular Degeneration.

Purpose: The purpose of this study was to investigate the impact of double-layer sign (DLS) on geographic atrophy (GA) progression in eyes with foveal-sparing GA and age-related macular degeneration (AMD).

Methods: This is a retrospective, consecutive case series of eyes with foveal-sparing GA secondary to AMD with more than 6 months of follow-up. The size of the foveal-sparing area was measured on the fundus autofluorescence images at the first and last visits.

Hemodynamic Effects of Anti-Vascular Endothelial Growth Factor Injections on Optical Coherence Tomography Angiography in Diabetic Macular Edema Eyes.

Purpose: To evaluate retinal hemodynamic responses to anti-vascular endothelial growth factor (VEGF) injection in eyes with diabetic macular edema using optical coherence tomography angiography (OCTA). We performed a comparison of two different thresholding methods to identify the most accurate for studying the vessel density (VD) in diabetic macular edema eyes.

Methods: The study prospectively included 26 eyes of 22 subjects (aged 60.

A CRISPR screen targeting PI3K effectors identifies RASA3 as a negative regulator of LFA-1-mediated adhesion in T cells.

The integrin lymphocyte function-associated antigen 1 (LFA-1) helps to coordinate the migration, adhesion, and activation of T cells through interactions with intercellular adhesion molecule 1 (ICAM-1) and ICAM-2. LFA-1 is activated during the engagement of chemokine receptors and the T cell receptor (TCR) through inside-out signaling, a process that is partially mediated by phosphoinositide 3-kinase (PI3K) and its product phosphatidylinositol 3,4,5-trisphosphate (PIP). To evaluate potential roles of PI3K in LFA-1 activation, we designed a library of CRISPR/single guide RNAs targeting known and potential PIP-binding proteins and screened for effects on the ability of primary mouse T cells to bind to ICAM-1.

Cavβ1 regulates T cell expansion and apoptosis independently of voltage-gated Ca channel function.

TCR stimulation triggers Ca signals that are critical for T cell function and immunity. Several pore-forming α and auxiliary β subunits of voltage-gated Ca channels (VGCC) were reported in T cells, but their mechanism of activation remains elusive and their contribution to Ca signaling in T cells is controversial. We here identify Caβ1, encoded by Cacnb1, as a regulator of T cell function.

In vivo CRISPR screens reveal a HIF-1α-mTOR-network regulates T follicular helper versus Th1 cells.

T follicular helper (Tfh) cells provide signals to initiate and maintain the germinal center (GC) reaction and are crucial for the generation of robust, long-lived antibody responses, but how the GC microenvironment affects Tfh cells is not well understood. Here we develop an in vivo T cell-intrinsic CRISPR-knockout screen to evaluate Tfh and Th1 cells in an acute viral infection model to identify regulators of Tfh cells in their physiological setting. Using a screen of druggable-targets, alongside genetic, transcriptomic and cellular analyses, we identify a function of HIF-1α in suppressing mTORC1-mediated and Myc-related pathways, and provide evidence that VHL-mediated degradation of HIF-1α is required for Tfh development; an expanded in vivo CRISPR screen reveals multiple components of these pathways that regulate Tfh versus Th1 cells, including signaling molecules, cell-cycle regulators, nutrient transporters, metabolic enzymes and autophagy mediators.

Deciphering the genetic architecture and ethnographic distribution of IRD in three ethnic populations by whole genome sequence analysis.

Patients with inherited retinal dystrophies (IRDs) were recruited from two understudied populations: Mexico and Pakistan as well as a third well-studied population of European Americans to define the genetic architecture of IRD by performing whole-genome sequencing (WGS). Whole-genome analysis was performed on 409 individuals from 108 unrelated pedigrees with IRDs. All patients underwent an ophthalmic evaluation to establish the retinal phenotype.

PI3Kδ coordinates transcriptional, chromatin, and metabolic changes to promote effector CD8 T cells at the expense of central memory.

Patients with activated phosphatidylinositol 3-kinase delta (PI3Kδ) syndrome (APDS) present with sinopulmonary infections, lymphadenopathy, and cytomegalvirus (CMV) and/or Epstein-Barr virus (EBV) viremia, yet why patients fail to clear certain chronic viral infections remains incompletely understood. Using patient samples and a mouse model (Pik3cd mice), we demonstrate that, upon activation, Pik3cd CD8 T cells exhibit exaggerated features of effector populations both in vitro and after viral infection that are associated with increased Fas-mediated apoptosis due to sustained FoxO1 phosphorylation and Fasl derepression, enhanced mTORC1 and c-Myc signatures, metabolic perturbations, and an altered chromatin landscape. Conversely, Pik3cd CD8 cells fail to sustain expression of proteins critical for central memory, including TCF1.

Patterns of de novo tandem repeat mutations and their role in autism.

Autism spectrum disorder (ASD) is an early-onset developmental disorder characterized by deficits in communication and social interaction and restrictive or repetitive behaviours. Family studies demonstrate that ASD has a substantial genetic basis with contributions both from inherited and de novo variants. It has been estimated that de novo mutations may contribute to 30% of all simplex cases, in which only a single child is affected per family.

LFA-1 signals to promote actin polymerization and upstream migration in T cells.

T cell entry into inflamed tissue requires firm adhesion, cell spreading, and migration along and through the endothelial wall. These events require the T cell integrins LFA-1 and VLA-4 and their endothelial ligands ICAM-1 and VCAM-1, respectively. T cells migrate against the direction of shear flow on ICAM-1 and with the direction of shear flow on VCAM-1, suggesting that these two ligands trigger distinct cellular responses.

PI3K Orchestrates T Follicular Helper Cell Differentiation in a Context Dependent Manner: Implications for Autoimmunity.

T follicular helper (Tfh) cells are a specialized population of CD4 T cells that provide help to B cells for the formation and maintenance germinal centers, and the production of high affinity class-switched antibodies, long-lived plasma cells, and memory B cells. As such, Tfh cells are essential for the generation of successful long-term humoral immunity and memory responses to vaccination and infection. Conversely, overproduction of Tfh cells has been associated with the generation of autoantibodies and autoimmunity.