5-HTP inhibits eosinophilia via intracellular endothelial 5-HTRs; SNPs in 5-HTRs associate with asthmatic lung function.

Background: Previous research showed that 5-hydroxytryptophan (5HTP), a metabolic precursor of serotonin, reduces allergic lung inflammation by inhibiting eosinophil migration across endothelial monolayers.

Objective: It is unknown if serotonin receptors are involved in mediating this 5HTP function or if serotonin receptor (HTR) single nucleotide polymorphisms (SNPs) associate with lung function in humans.

Methods: Serotonin receptor subtypes were assessed by qPCR, western blot, confocal microscopy, pharmacological inhibitors and siRNA knockdown.

Current state and future perspectives in the diagnosis of eyelid margin disease: clinical review.

The eyelid margin is vital to ocular surface integrity. Much peer-reviewed literature has been established in eyelid margin inflammation, better known as blepharitis. The purpose was to review and understand the impact of eyelid margin disease.

Eyelid margin disease (blepharitis and meibomian gland dysfunction): clinical review of evidence-based and emerging treatments.

Blepharitis is a common ophthalmic condition with multiple etiologies and no definitive, universal treatment. The treatment modalities for managing lid margin diseases vary depending on the disease's cause, location, and severity. For anterior blepharitis, management options include eyelid hygiene with warm compresses, eyelid scrubs, baby shampoo, and over-the-counter eyelid cleansers.

Novel insights into the whole-blood DNA methylome of asthma in ethnically diverse children and youth.

Background: The epigenetic mechanisms of asthma remain largely understudied in African Americans and Hispanics/Latinos, two populations disproportionately affected by asthma. We aimed to identify markers, regions and processes with differential patterns of DNA methylation (DNAm) in whole blood by asthma status in ethnically diverse children and youth, and to assess their functional consequences.

Methods: DNAm levels were profiled with the Infinium MethylationEPIC or HumanMethylation450 BeadChip arrays among 1226 African Americans or Hispanics/Latinos and assessed for differential methylation per asthma status at the CpG and region (differentially methylated region (DMR)) level.

Epigenomic response to albuterol treatment in asthma-relevant airway epithelial cells.

Background: Albuterol is the first-line asthma medication used in diverse populations. Although DNA methylation (DNAm) is an epigenetic mechanism involved in asthma and bronchodilator drug response (BDR), no study has assessed whether albuterol could induce changes in the airway epithelial methylome. We aimed to characterize albuterol-induced DNAm changes in airway epithelial cells, and assess potential functional consequences and the influence of genetic variation and asthma-related clinical variables.

More than bad luck: Cancer and aging are linked to replication-driven changes to the epigenome.

Aging is a leading risk factor for cancer. While it is proposed that age-related accumulation of somatic mutations drives this relationship, it is likely not the full story. We show that aging and cancer share a common epigenetic replication signature, which we modeled using DNA methylation from extensively passaged immortalized human cells in vitro and tested on clinical tissues.

Metformin reduces SARS-CoV-2 in a Phase 3 Randomized Placebo Controlled Clinical Trial.

Current antiviral treatment options for SARS-CoV-2 infections are not available globally, cannot be used with many medications, and are limited to virus-specific targets. Biophysical modeling of SARS-CoV-2 replication predicted that protein translation is an especially attractive target for antiviral therapy. Literature review identified metformin, widely known as a treatment for diabetes, as a potential suppressor of protein translation via targeting of the host mTor pathway.

Outpatient treatment of COVID-19 and incidence of post-COVID-19 condition over 10 months (COVID-OUT): a multicentre, randomised, quadruple-blind, parallel-group, phase 3 trial.

Background: Post-COVID-19 condition (also known as long COVID) is an emerging chronic illness potentially affecting millions of people. We aimed to evaluate whether outpatient COVID-19 treatment with metformin, ivermectin, or fluvoxamine soon after SARS-CoV-2 infection could reduce the risk of long COVID.

Methods: We conducted a decentralised, randomised, quadruple-blind, parallel-group, phase 3 trial (COVID-OUT) at six sites in the USA.

Health inequities in SARS-CoV-2 infection, seroprevalence, and COVID-19 vaccination: Results from the East Bay COVID-19 study.

Comprehensive data on transmission mitigation behaviors and both SARS-CoV-2 infection and serostatus are needed from large, community-based cohorts to identify COVID-19 risk factors and the impact of public health measures. We conducted a longitudinal, population-based study in the East Bay Area of Northern California. From July 2020-March 2021, approximately 5,500 adults were recruited and followed over three data collection rounds to investigate the association between geographic and demographic characteristics and transmission mitigation behavior with SARS-CoV-2 prevalence.

Practical management of ocular surface disease in patients with atopic dermatitis, with a focus on conjunctivitis: A review.

Atopic dermatitis (AD) is a chronic inflammatory skin disease that can significantly decrease quality of life. AD is commonly associated with comorbidities including ocular surface disease (OSD). Conjunctivitis is the most common OSD associated with AD and can increase in incidence with use of monoclonal antibody biologics that target the type 2 inflammatory pathway.

Multi-omic approach associates blood methylome with bronchodilator drug response in pediatric asthma.

Background: Albuterol is the drug most widely used as asthma treatment among African Americans despite having a lower bronchodilator drug response (BDR) than other populations. Although BDR is affected by gene and environmental factors, the influence of DNA methylation is unknown.

Objective: This study aimed to identify epigenetic markers in whole blood associated with BDR, study their functional consequences by multi-omic integration, and assess their clinical applicability in admixed populations with a high asthma burden.

Admixture mapping of severe asthma exacerbations in Hispanic/Latino children and youth.

Background: In the USA, genetically admixed populations have the highest asthma prevalence and severe asthma exacerbations rates. This could be explained not only by environmental factors but also by genetic variants that exert ethnic-specific effects. However, no admixture mapping has been performed for severe asthma exacerbations.

Epigenome-wide association study of lung function in Latino children and youth with asthma.

Introduction: DNA methylation studies have associated methylation levels at different CpG sites or genomic regions with lung function. Moreover, genetic ancestry has been associated with lung function in Latinos. However, no epigenome-wide association study (EWAS) of lung function has been performed in this population.

The genome of the zebra mussel, Dreissena polymorpha: a resource for comparative genomics, invasion genetics, and biocontrol.

The zebra mussel, Dreissena polymorpha, continues to spread from its native range in Eurasia to Europe and North America, causing billions of dollars in damage and dramatically altering invaded aquatic ecosystems. Despite these impacts, there are few genomic resources for Dreissena or related bivalves. Although the D.

The corneal endothelium: clinical review of endothelial cell health and function.

The endothelial cell is a critical structure within the cornea and is responsible for maintaining corneal clarity through its pump function. Endothelial cells are lost over time naturally but can be injured medically, surgically, or as a part of various dystrophies. Monitoring of endothelial cells can be performed clinically or more formally with specular microscopy.

Epithelium-on Corneal Collagen Cross-Linking with Hypotonic Riboflavin Solution in Progressive Keratoconus.

Introduction: Epithelium-off cross-linking (epi-off CXL) has long been established as the gold standard treatment for progressive keratoconus. Several protocols for epithelium-on (epi-on) CXL have been proposed to help reduce post-operative pain and facilitate visual recovery, but there is no epi-on treatment approach that is currently approved in the United States. The hydrophilic and macromolecular characteristics of conventional epi-off riboflavin formulations may create clinical challenges for absorption through an intact epithelium.

Saliva Testing Is Accurate for Early-Stage and Presymptomatic COVID-19.

Although nasopharyngeal samples have been considered the gold standard for COVID-19 testing, variability in viral load across different anatomical sites could cause nasopharyngeal samples to be less sensitive than saliva or nasal samples in certain cases. Self-collected samples have logistical advantages over nasopharyngeal samples, making them amenable to population-scale screening. To evaluate sampling alternatives for population screening, we collected nasopharyngeal, saliva, and nasal samples from two cohorts with varied levels and types of symptoms.

A multi-center phase II randomized clinical trial of losartan on symptomatic outpatients with COVID-19.

Background: The SARS-CoV-2 virus enters cells via Angiotensin-converting enzyme 2 (ACE2), disrupting the renin-angiotensin-aldosterone axis, potentially contributing to lung injury. Treatment with angiotensin receptor blockers (ARBs), such as losartan, may mitigate these effects, though induction of ACE2 could increase viral entry, replication, and worsen disease.

Methods: This study represents a placebo-controlled blinded randomized clinical trial (RCT) to test the efficacy of losartan on outpatients with COVID-19 across three hospital systems with numerous community sites in Minnesota, U.

Neither Donor nor Recipient Mitochondrial Haplotypes Are Associated with Unrelated Donor Transplant Outcomes: A Validation Study from the CIBMTR.

Graft-versus-host-disease (GVHD) is a multistep process that involves T-cell recognition and priming toward alloantigen, expansion, acquisition of effector function, and repeated tissue injury, resulting in clinical manifestations of the disease. All of these processes have considerable metabolic demands and understanding the key role of mitochondria in cellular metabolism as it relates to GVHD has increased significantly. Mitochondrial DNA (mtDNA) haplotypes have been linked to functional differences in vitro, suggesting they have functional differences at an organismal level.

KPI-121 1% for pain and inflammation in ocular surgery.

Pain and inflammation are common experiences following ocular surgery and, if uncontrolled, can compromise patients' vision, functioning and quality of life. Corticosteroid drugs are available to manage inflammation and discomfort but have limitations in penetrating the ocular mucus barrier to reach the target ocular tissues. KPI-121 1% (INVELTYS) is a novel formulation of loteprednol etabonate that employs innovative proprietary technology to deliver nanoparticle-sized mucus-penetrating particles to the cornea.

Dissecting and tuning primer editing by proofreading polymerases.

Proofreading polymerases have 3' to 5' exonuclease activity that allows the excision and correction of mis-incorporated bases during DNA replication. In a previous study, we demonstrated that in addition to correcting substitution errors and lowering the error rate of DNA amplification, proofreading polymerases can also edit PCR primers to match template sequences. Primer editing is a feature that can be advantageous in certain experimental contexts, such as amplicon-based microbiome profiling.

Prediction of False-Positive Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) Molecular Results in a High-Throughput Open-Platform System.

Widespread high-throughput testing for identification of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection by RT-PCR has been a foundation in the response to the coronavirus disease 2019 (COVID-19) pandemic. Quality assurance metrics for these RT-PCR tests are still evolving as testing is widely implemented. As testing increases, it is important to understand performance characteristics and the errors associated with these tests.