Scalable approaches for generating, validating and incorporating data from high-throughput functional assays to improve clinical variant classification.

As the adoption and scope of genetic testing continue to expand, interpreting the clinical significance of DNA sequence variants at scale remains a formidable challenge, with a high proportion classified as variants of uncertain significance (VUSs). Genetic testing laboratories have historically relied, in part, on functional data from academic literature to support variant classification. High-throughput functional assays or multiplex assays of variant effect (MAVEs), designed to assess the effects of DNA variants on protein stability and function, represent an important and increasingly available source of evidence for variant classification, but their potential is just beginning to be realized in clinical lab settings.

Analysis of intraocular lens packaging weight and waste.

Purpose: To analyze waste from intraocular lens (IOL) packaging across a variety of brands.

Setting: Private clinical practice.

Design: Prospective weight and composition analysis of all elements of unopened packages of IOLs sold in the United States-both preloaded and non-preloaded.

Accuracy of the LaserArcs Femtosecond Cataract Surgery Arcuate Incision Nomogram in Patients Undergoing Cataract Surgery and Astigmatism Reduction.

Purpose: The purpose of this study is to evaluate the efficacy and safety of the laserarcs.com nomogram in reducing astigmatism among cataract patients that underwent astigmatism reduction with laser arcuate incisions.

Methods: In this retrospective study, 50 patients who underwent uncomplicated cataract surgery with laser arc incisions for the reduction of astigmatism with a single surgeon between the dates of January 23, 2021 and February 10, 2022 were evaluated in a single eye.

The DEPOT Study (Dry Eye Prescription Options for Therapy): Assessing the Efficacy and Safety of OTX-DED (Dexamethasone Ophthalmic Insert 0.3 mg) for Intracanalicular Use Compared with Loteprednol Suspension for the Treatment of Episodic Dry Eye.

Purpose: To compare OTX-DED, an investigational dexamethasone intracanalicular insert, to loteprednol 0.5% suspension applied QID for 28 days as treatments for acute exacerbations of dry eye disease in terms of patient symptoms, corneal staining, tear breakup time (TBUT), and ocular redness.

Methods: Fifty patients with an acute exacerbation of dry eye with at least grade 1 corneal staining were randomized to receive treatment and were each evaluated in one eye at baseline, two weeks and four weeks with the standard patient evaluation of eye dryness (SPEED) questionnaire, the Oxford Scale for corneal stain, Schulze Scale for ocular redness, and intraocular pressure (IOP).

HspX-mediated protection against tuberculosis depends on its chaperoning of a mycobacterial molecule.

New approaches consisting of 'multistage' vaccines against (TB) are emerging that combine early antigenic proteins with latency-associated antigens. In this study, HspX was tested for its potential to elicit both short- and long-term protective immune responses. HspX is a logical component in vaccine strategies targeting protective immune responses against primary infection, as well as against reactivation of latent infection, because as previously shown, it is produced during latency, and as our studies show, it elicits protection within 30 days of infection.

BCG sub-strains induce variable protection against virulent pulmonary Mycobacterium tuberculosis infection, with the capacity to drive Th2 immunity.

The hallmark of a vaccine is to induce long-term protective immunity against the pathogen. The use of Mycobacterium bovis BCG as a vaccine against tuberculosis has been problematic in that immunity induced by BCG wanes over time and it may be less effective against more virulent strains of Mycobacterium tuberculosis. Thus it is important to determine what factors might be associated with waning or inefficient immunity.

Initiation of acquired immunity in the lungs of mice lacking lymph nodes after infection with aerosolized Mycobacterium tuberculosis.

Recent evidence points to lung draining lymph nodes as the site that initiates the immune response in mice infected with aerosolized Mycobacterium tuberculosis. Here we expanded these studies and showed that infection of mice that lack lymph nodes with aerosolized M. tuberculosis results in a massive mononuclear cell infiltrate in the lungs within 14 days postinfection.

Kinetics of the immune response profile in guinea pigs after vaccination with Mycobacterium bovis BCG and infection with Mycobacterium tuberculosis.

The guinea pig model of tuberculosis is used extensively in assessing novel vaccines, since Mycobacterium bovis BCG vaccination effectively prolongs survival after low-dose aerosol infection with virulent M. tuberculosis. To better understand how BCG extends time to death after pulmonary infection with M.

Protection and polyfunctional T cells induced by Ag85B-TB10.4/IC31 against Mycobacterium tuberculosis is highly dependent on the antigen dose.

Background: Previously we have shown that Ag85B-TB10.4 is a highly efficient vaccine against tuberculosis when delivered in a Th1 inducing adjuvant based on cationic liposomes. Another Th1 inducing adjuvant, which has shown a very promising profile in both preclinical and clinical trials, is IC31.

Mycobacterial infection induces the secretion of high-mobility group box 1 protein.

High-mobility group box protein 1 (HMGB1) is a non-histone nuclear protein that acts as a pro-inflammatory cytokine and is released by monocytes and macrophages. Necrotic cells also release HMGB1 at the site of tissue damage which induces a variety of cellular responses, including the expression of pro-inflammatory mediators. This study investigated the secretion of HMGB1 in mycobacterial infection by macrophages in vitro and in the lungs of infected guinea pigs.