Submacular Hemorrhage Rates Following Anti-Vascular Endothelial Growth Factor Injections for Exudative Age-Related Macular Degeneration.

Purpose: To examine rates of submacular hemorrhage in patients undergoing anti-vascular endothelial growth factor (VEGF) injections, comparing rates between specific anti-VEGF agents.

Design: Retrospective clinical cohort study.

Methods: All patients in the database from January 2015 to November 2023 with a diagnosis of neovascular age-related macular degeneration and accompanying submacular hemorrhage (SMH).

VITREORETINAL OUTCOMES FOLLOWING SECONDARY INTRAOCULAR LENS IMPLANTATION WITH PARS PLANA VITRECTOMY.

Background: Retrospective cohort study of 561 adult patients undergoing secondary intraocular lens (IOL) implantation by vitreoretinal surgeons at a single institution from April 2015 to December 2020.

Methods: Patient historical factors, intraoperative/postoperative complications, and outcomes of IOL type (anterior chamber IOL versus scleral sutured IOL versus scleral fixated IOL versus. sulcus) were assessed.

Retrospective Cohort Study of Sickle Cell Disease and Large Vessel Retinal Vascular Occlusion Risk in a National United States Database.

Objective: To determine if differences exist in the risk of developing large vessel retinal vascular occlusions in patients with sickle cell states.

Design: Retrospective cohort study.

Participants: Patients with sickle cell disease (SCD) or trait evaluated by an ophthalmologist were compared with matched controls without SCD or sickle cell trait (SCT) also evaluated by an ophthalmologist.

Glyburide confers neuroprotection against age-related macular degeneration (AMD).

Glyburide, a sulfonylurea drug used to treat type 2 diabetes, boasts neuroprotective effects by targeting the sulfonylurea receptor 1 (SUR1) and associated ion channels in various cell types, including those in the central nervous system and the retina. Previously, we demonstrated that glyburide therapy improved retinal function and structure in a rat model of diabetic retinopathy. In the present study, we explore the application of glyburide in non-neovascular ("dry") age-related macular degeneration (AMD), another progressive disease characterized by oxidative stress-induced damage and neuroinflammation that trigger cell death in the retina.

Racial Differences in Choroidal Vascularity Index in Healthy Patients: Novel Insights.

Background And Objective: Choroidal vascularity index (CVI) measures the ratio of blood vessels in the choroid to the total choroidal area. We aimed to compare CVI between young Black and White patients without a history of ocular or systemic disease.

Patients And Methods: We used a previously validated algorithm for shadow compensation and choroidal vessel binarization to measure CVI across the Early Treatment of Diabetic Retinopathy Study grid.

Metformin Use and Age-Related Macular Degeneration in Patients Without Diabetes.

Importance: Metformin use may protect against the development of age-related macular degeneration (AMD) based on results from observational studies. However, its potential effectiveness among patients without diabetes remains unclear.

Objective: To assess the association between metformin use and the development of AMD in patients without diabetes.

Association of Metformin and Other Diabetes Medication Use and the Development of New-Onset Dry Age-Related Macular Degeneration: A Case-Control Study.

Purpose: To investigate if metformin use is associated with decreased odds of developing new non-neovascular ("dry") age-related macular degeneration (AMD).

Methods: Case-control study examining 194,135 cases with diagnoses of new-onset AMD between 2008 and 2017 and 193,990 matched controls in the Merative MarketScan Research Databases. The diabetic subgroup included 49,988 cases and 49,460 controls.

Autologous humanized PDX modeling for immuno-oncology recapitulates features of the human tumor microenvironment.

Background: Interactions between immune and tumor cells are critical to determining cancer progression and response. In addition, preclinical prediction of immune-related drug efficacy is limited by interspecies differences between human and mouse, as well as inter-person germline and somatic variation. To address these gaps, we developed an autologous system that models the tumor microenvironment (TME) from individual patients with solid tumors.

Trends in Secondary Intraocular Lens Surgery among Vitreoretinal Surgeons.

Objective: To identify changes in secondary lens techniques over time and to determine common complications of each technique.

Design: Retrospective cohort study.

Participants: All patients in the database from January 2015 to December 2021 who underwent secondary lens placement (anterior chamber intraocular lens [IOL, ACIOL], scleral-fixated IOL [SFIOL], or scleral-sutured IOL [SSIOL]).

Androstadienone sensitivity is associated with attention to emotions, social interactions, and sexual behavior in older U.S. adults.

Δ 4,16-androstadien-3-one (androstadienone) is a putative human pheromone often linked to sexual attraction in young adults, although specific associations with sexual behavior are not yet established. Androstadienone also serves a broader social-emotional function beyond the sexual domain, specifically tuning the brain to efficiently process emotional information. Whether these effects persist throughout the lifespan into post-reproductive life is unknown.

Computerized Texture Analysis of Optical Coherence Tomography Angiography of Choriocapillaris in Normal Eyes of Young and Healthy Subjects.

Computerized texture analysis uses higher-order mathematics to identify patterns beyond what the naked eye can recognize. We tested its feasibility in optical coherence tomography angiography imaging of choriocapillaris. Our objective was to determine sets of parameters that provide coherent and consistent output when applied to a homogeneous, healthy group of patients.

Transposon Mutagenesis-Guided CRISPR/Cas9 Screening Strongly Implicates Dysregulation of Hippo/YAP Signaling in Malignant Peripheral Nerve Sheath Tumor Development.

Malignant peripheral nerve sheath tumors (MPNSTs) are highly aggressive, genomically complex, have soft tissue sarcomas, and are derived from the Schwann cell lineage. Patients with neurofibromatosis type 1 syndrome (NF1), an autosomal dominant tumor predisposition syndrome, are at a high risk for MPNSTs, which usually develop from pre-existing benign Schwann cell tumors called plexiform neurofibromas. NF1 is characterized by loss-of-function mutations in the gene, which encode neurofibromin, a Ras GTPase activating protein (GAP) and negative regulator of RasGTP-dependent signaling.

R-spondin 2 Drives Liver Tumor Development in a Yes-Associated Protein-Dependent Manner.

Each year, more than 25,000 people succumb to liver cancer in the United States, and this neoplasm represents the second cause of cancer-related death globally. R-spondins (RSPOs) are secreted regulators of Wnt signaling that function in development and promote tissue stem cell renewal. In cancer, RSPOs 2 and 3 are oncogenes first identified by insertional mutagenesis screens in tumors induced by mouse mammary tumor virus and by transposon mutagenesis in the colonic epithelium of rodents.

Recurrent Brain Arteriovenous Malformations (AVMs): A Systematic Review.

Objective: Risk factors for the recurrence of surgically excised brain arteriovenous malformations (AVMs) are poorly understood. In addition, ideal follow-up imaging paradigms to catch AVM recurrences are not well defined. We present a systematic review on risk factors for the recurrence of surgically resected AVMs and identify potential theories of recurrence.

Dual nucleotide specificity determinants of an infection aborting anticodon nuclease.

The anticodon nuclease (ACNase) PrrC is silenced by a DNA restriction-modification (RM) protein and activated by a phage T4-encoded restriction inhibitor. The activation is driven by GTP hydrolysis while dTTP, which accumulates during the infection, stabilizes the active form. We show here, first, that the ABC-ATPase N-domains of PrrC can accommodate the two nucleotides simultaneously.

Phage T4-induced DNA breaks activate a tRNA repair-defying anticodon nuclease.

The natural role of the conserved bacterial anticodon nuclease (ACNase) RloC is not known, but traits that set it apart from the homologous phage T4-excluding ACNase PrrC could provide relevant clues. PrrC is silenced by a genetically linked DNA restriction-modification (RM) protein and turned on by a phage-encoded DNA restriction inhibitor. In contrast, RloC is rarely linked to an RM protein, and its ACNase is regulated by an internal switch responsive to double-stranded DNA breaks.

A DNA break inducer activates the anticodon nuclease RloC and the adaptive immunity in Acinetobacter baylyi ADP1.

Double-stranded DNA breaks (DSB) cause bacteria to augment expression of DNA repair and various stress response proteins. A puzzling exception educes the anticodon nuclease (ACNase) RloC, which resembles the DSB responder Rad50 and the antiviral, translation-disabling ACNase PrrC. While PrrC's ACNase is regulated by a DNA restriction-modification (R-M) protein and a phage anti-DNA restriction peptide, RloC has an internal ACNase switch comprising a putative DSB sensor and coupled ATPase.

The wobble nucleotide-excising anticodon nuclease RloC is governed by the zinc-hook and DNA-dependent ATPase of its Rad50-like region.

The conserved bacterial anticodon nuclease (ACNase) RloC and its phage-excluding homolog PrrC comprise respective ABC-adenosine triphosphatase (ATPase) and ACNase N- and C-domains but differ in three key attributes. First, prrC is always linked to an ACNase silencing, DNA restriction-modification (R-M) locus while rloC rarely features such linkage. Second, RloC excises its substrate's wobble nucleotide, a lesion expected to impede damage reversal by phage transfer RNA (tRNA) repair enzymes that counteract the nick inflicted by PrrC.

Phage T4-induced dTTP accretion bolsters a tRNase-based host defense.

The anticodon nuclease (ACNase) PrrC is silenced in Escherichia coli by an associated DNA restriction-modification protein, activated by the phage T4-encoded anti-DNA restriction factor Stp and counteracted by T4's tRNA repair enzymes polynucleotide kinase and RNA ligase 1. Hence, only tRNA repair-deficient phages succumb to PrrC's restriction. PrrC's ABC-ATPase motor domains are implicated in driving its activation by hydrolyzing GTP and in stabilizing the activated ACNase by avidly binding dTTP.

RloC: a wobble nucleotide-excising and zinc-responsive bacterial tRNase.

The conserved bacterial protein RloC, a distant homologue of the tRNA(Lys) anticodon nuclease (ACNase) PrrC, is shown here to act as a wobble nucleotide-excising and Zn(++)-responsive tRNase. The more familiar PrrC is silenced by a genetically linked type I DNA restriction-modification (R-M) enzyme, activated by a phage anti-DNA restriction factor and counteracted by phage tRNA repair enzymes. RloC shares PrrC's ABC ATPase motifs and catalytic ACNase triad but features a distinct zinc-hook/coiled-coil insert that renders its ATPase domain similar to Rad50 and related DNA repair proteins.

Combined axillary reverse mapping (ARM) technique for breast cancer patients requiring axillary dissection.

Background: The objective of axillary reverse mapping (ARM) is to preserve the main lymphatic chain-with both the nodes and the ducts-in relation to lymphatic arm drainage (LAD) during an axillary dissection (AD).

Methods: From July 2006 to March 2008, 23 patients with stage II or III breast carcinoma requiring an AD underwent an ARM procedure. Identification of the ARM nodes relied on an isotope injection into the web space of the ipsilateral hand.

Parallel dimerization of a PrrC-anticodon nuclease region implicated in tRNALys recognition.

The optional Escherichia coli restriction tRNase PrrC represents a family of potential antiviral devices widespread among bacteria. PrrC comprises a functional C-domain of unknown structure and regulatory ABC/ATPase-like N-domain. The possible involvement of a C-domain sequence in tRNA(Lys) recognition was investigated using a matching end-protected 11-meric peptide.

DNA polymerase epsilon associates with the elongating form of RNA polymerase II and nascent transcripts.

DNA polymerase epsilon co-operates with polymerases alpha and delta in the replicative DNA synthesis of eukaryotic cells. We describe here a specific physical interaction between DNA polymerase epsilon and RNA polymerase II, evidenced by reciprocal immunoprecipitation experiments. The interacting RNA polymerase II was the hyperphosphorylated IIO form implicated in transcriptional elongation, as inferred from (a) its reduced electrophoretic mobility that was lost upon phosphatase treatment, (b) correlation of the interaction with phosphorylation of Ser5 of the C-terminal domain heptapeptide repeat, and (c) the ability of C-terminal domain kinase inhibitors to abolish it.

PrrC-anticodon nuclease: functional organization of a prototypical bacterial restriction RNase.

The tRNA(Lys) anticodon nuclease PrrC is associated in latent form with the type Ic DNA restriction endonuclease EcoprrI and activated by a phage T4-encoded inhibitor of EcoprrI. The activation also requires the hydrolysis of GTP and presence of dTTP and is inhibited by ATP. The N-proximal NTPase domain of PrrC has been implicated in relaying the activating signal to a C-proximal anticodon nuclease site by interacting with the requisite nucleotide cofactors [Amitsur et al.