Impact of Duration of Exposure to Intraretinal Fluid on Visual Outcomes in Neovascular Age-Related Macular Degeneration.

Objective: To evaluate the impact of total duration of intraretinal fluid (IRF) exposure on visual acuity and vision-related quality of life in patients with neovascular age-related macular degeneration (nAMD).

Design: A post hoc analysis of integrated data from the VIEW 1 and VIEW 2 trials.

Participants: Patients with nAMD.

Absolute and relative intensities of solo, free-form dancing in adults: A pilot study.

Objectives: Engaging in dance of various styles confers health benefits among adults; however, additional studies on free-form dancing are needed to quantify its intensity and advance research on dance and health. This study characterized the absolute and relative physical activity (PA) intensities of solo, free-form dancing at self-determined moderate and vigorous intensities in adults.

Method: Participants (N = 48) ages 18 to 83 years old, with 0 to 56 years of dance training experience, engaged in 5-minute free-form dance bouts at respectively self-determined moderate and vigorous intensities, both with and without music.

TmeA promotes pedestal formation through N-WASP and TOCA-1 interactions.

() is the causative agent of several human diseases, including the sexually transmitted infection chlamydia and eye infection trachoma. As an obligate intracellular bacterial pathogen, invasion is essential for establishing infection and subsequent pathogenesis. To facilitate invasion, secretes effector proteins through its type III secretion system (T3SS).

The Distinct Roles of NEIL1 and XPA in Limiting Aflatoxin B1-Induced Mutagenesis in Mice.

Dietary exposure to aflatoxin B1 (AFB1) is a risk factor for the development of hepatocellular carcinomas. Following metabolic activation, AFB1 reacts with guanines to form covalent DNA adducts, which induce high-frequency G > T transversions. The molecular signature associated with these mutational events aligns with the single-base substitution signature 24 (SBS24) in the Catalog of Somatic Mutations in Cancer database.

Obeticholic acid's effect on HDL function in MASH varies by diabetic status.

Inflammation and oxidative stress are the key factors in the pathogenesis of both metabolic dysfunction-associated steatohepatitis (MASH) and atherosclerosis. Obeticholic acid (OCA), a farnesoid X receptor (FXR) agonist, improves hepatic inflammation and fibrosis in patients with MASH. However, it also reduces HDL cholesterol, suggesting that OCA may increase cardiovascular disease (CVD) risk in patients with MASH.

Interactions of pixantrone with apurinic/apyrimidinic sites in DNA.

Pixantrone and mitoxantrone are structurally related anticancer drugs which have been shown to generate covalent conjugates at apurinic/apyrimidinic (AP) sites in DNA. Mitoxantrone binding to AP sites induces DNA strand cleavage and inhibits the endonuclease activity of human AP endonuclease 1 (APE1). Here, pixantrone was demonstrated to have similar properties, but relative to mitoxantrone, it was significantly less potent in both DNA incision and APE1 inhibition.

Liver tissue lipids in metabolic dysfunction-associated steatotic liver disease with diabetes and obesity.

Background: Diabetes and obesity are associated with altered lipid metabolism and hepatic steatosis. Studies suggest that increases in lipid accumulation in these patients with metabolic dysfunction-associated steatotic liver disease (MASLD) are not uniform for all lipid components. This study evaluates this variation.

Functional characterization of single nucleotide polymorphic variants of DNA repair enzyme NEIL1 in South Asian populations.

The base excision repair (BER) pathway is a precise and versatile mechanism of DNA repair that is initiated by DNA glycosylases. Endonuclease VIII-like 1 (NEIL1) is a bifunctional glycosylase/abasic site (AP) lyase that excises a damaged base and subsequently cleaves the phosphodiester backbone. NEIL1 is able to recognize and hydrolyze a broad range of oxidatively-induced base lesions and substituted ring-fragmented guanines, including aflatoxin-induced 8,9-dihydro-8-(2,6-diamino-4-oxo-3,4-dihydropyrimid-5-yl-formamido)-9-hydroxyaflatoxin B (AFB-FapyGua).

Frequencies and spectra of aflatoxin B-induced mutations in liver genomes of NEIL1-deficient mice as revealed by duplex sequencing.

Increased risk for the development of hepatocellular carcinoma (HCC) is driven by a number of etiological factors including hepatitis viral infection and dietary exposures to foods contaminated with aflatoxin-producing molds. Intracellular metabolic activation of aflatoxin B (AFB) to a reactive epoxide generates highly mutagenic AFB-Fapy-dG adducts. Previously, we demonstrated that repair of AFB-Fapy-dG adducts can be initiated by the DNA glycosylase NEIL1 and that male mice were significantly more susceptible to AFB-induced HCC relative to wild-type mice.

Presenilin-1 mutation position influences amyloidosis, small vessel disease, and dementia with disease stage.

Introduction: Amyloidosis, including cerebral amyloid angiopathy, and markers of small vessel disease (SVD) vary across dominantly inherited Alzheimer's disease (DIAD) presenilin-1 (PSEN1) mutation carriers. We investigated how mutation position relative to codon 200 (pre-/postcodon 200) influences these pathologic features and dementia at different stages.

Methods: Individuals from families with known PSEN1 mutations (n = 393) underwent neuroimaging and clinical assessments.

Investigating White Matter Neuroinflammation in Alzheimer Disease Using Diffusion-Based Neuroinflammation Imaging.

Background And Objectives: Alzheimer disease (AD) is primarily associated with accumulations of amyloid plaques and tau tangles in gray matter, however, it is now acknowledged that neuroinflammation, particularly in white matter (WM), significantly contributes to the development and progression of AD. This study aims to investigate WM neuroinflammation in the continuum of AD and its association with AD pathologies and cognition using diffusion-based neuroinflammation imaging (NII).

Methods: This is a cross-sectional, single-center, retrospective evaluation conducted on an observational study of 310 older research participants who were enrolled in the Knight Alzheimer's Disease Research Center cohort.

A Case of Sustained Viral Shedding of Mpox With Ocular Involvement Resulting in Vision Loss.

Mpox, caused by infection with , usually presents as a mild, self-limited illness in immunocompetent persons that resolves within 2-4 weeks. Serious complications have been reported when mpox lesions involve vulnerable anatomic sites, such as the eye, and in those with substantial immunosuppression. We describe a patient with advanced human immunodeficiency virus infection and sustained viral shedding of mpox with ocular involvement, which resulted in vision loss.

Antimicrobial resistance in multistate outbreaks of nontyphoidal infections linked to animal contact-United States, 2015-2018.

Animal contact is an established risk factor for nontyphoidal infections and outbreaks. During 2015-2018, the U.S.

Interaction of mitoxantrone with abasic sites - DNA strand cleavage and inhibition of apurinic/apyrimidinic endonuclease 1, APE1.

Mitoxantrone (1,4-dihydroxy-5,8-bis[2-(2-hydroxyethylamino)ethylamino]-anthracene-9,10-dione) is a clinically-relevant synthetic anthracenedione that functions as a topoisomerase II poison by trapping DNA double-strand break intermediates. Mitoxantrone binds to DNA via both stacking interactions with DNA bases and hydrogen bonding with the sugar-phosphate backbone. It has been shown that mitoxantrone inhibits apurinic/apyrimidinic (AP) endonuclease 1 (APE1)-catalyzed incision of DNA containing a tetrahydrofuran (THF) moiety and more recently, that mitoxantrone forms Schiff base conjugates at AP sites in DNA.

A novel score of IL-13 and age predicts 90-day mortality in severe alcohol-associated hepatitis: A multicenter plasma biomarker analysis.

Background: Severe alcoholic hepatitis (AH) has a high short-term mortality rate. The MELD assesses disease severity and mortality; however, it is not specific for AH. We screened plasma samples from patients with severe AH for biomarkers of multiple pathological processes and identified predictors of short-term mortality.

Prevalence and incidence of Mycoplasma genitalium infection: a systematic review protocol.

Objective: The objective of this review is to determine the prevalence and incidence of Mycoplasma genitalium infection.

Introduction: Mycoplasma genitalium is a sexually transmitted pathogen that can cause reproductive health issues in men and women. Recent US Food and Drug Administration (FDA)-approved testing has improved the capability to more readily diagnose and treat this infection.

Implications of a Supernumerary Nipple Breast Cancer in a BReast CAncer Sequence Variation Carrier: A Case Report.

Supernumerary nipples develop on the chest and abdominopelvic regions along the embryonic milk line. Their anatomy varies from isolated accessory nipples to complete supernumerary nipples (accessory nipple, areola, and underlying glandular breast tissue). Patients with a pathogenic BReast CAncer (BRCA) sequence variation are at an increased cumulative risk of developing breast cancer, and it is the standard of care for them to be offered medical or surgical risk reduction.

Functional analyses of single nucleotide polymorphic variants of the DNA glycosylase NEIL1 in sub-Saharan African populations.

Nei-like glycosylase 1 (NEIL1) is a DNA repair enzyme that initiates the base excision repair (BER) pathway to cleanse the human genome of damage. The substrate specificity of NEIL1 includes several common base modifications formed under oxidative stress conditions, as well as the imidazole ring open adducts that are induced by alkylating agents following initial modification at N7 guanine. An example of the latter is the persistent and mutagenic 8,9-dihydro-8-(2,6-diamino-4-oxo-3,4-dihydropyrimid-5-yl-formamido)-9-hydroxyaflatoxin B (AFB-FapyGua) adduct, resulting from the alkylating agent aflatoxin B (AFB) exo-8-9-epoxide.

Accuracy of ultrasonographic fatty liver index using point-of-care ultrasound in stratifying non-alcoholic fatty liver disease patients.

Background: The prevalence of non-alcoholic fatty liver disease (NAFLD) is increasing in the USA. Some of these patients develop non-alcoholic steatohepatitis (NASH), which can progress to cirrhosis. Ultrasound imaging is one of the most used modalities for diagnosing hepatic steatosis.