To assess the relationship between serum vitamin D levels and myopia in people aged 12-50 years using the National Health and Nutrition Examination Survey (NHANES) database.
Demographics, vision, and ...serum vitamin D levels from NHANES (2001-2006) were analyzed. Multivariate analyses were performed to examine the relationship between serum vitamin D levels and myopia while controlling for sex, age, ethnicity, education level, serum vitamin A, and poverty status. The main outcome was presence or absence of myopia, defined as a spherical equivalent of -1 diopters or more.
Of the 11669 participants, 5,310 (45.5%) had myopia. The average serum vitamin D concentration was 61.6 ± 0.9 nmol/L for the myopic group and 63.1 ± 0.8 nmol/L for the non-myopic group (p = .01). After adjusting for all covariates, having higher serum vitamin D was associated with lower odds of having myopia (odds ratio 0.82 0.74-0.92, p = .0007). In linear regression modeling that excluded hyperopes (spherical equivalent > +1 diopters), there was a positive relationship between spherical equivalent and serum vitamin D levels. Specifically, as serum vitamin D doubled, spherical equivalent increased by 0.17 (p = .02) indicating a positive dose-response relationship between vitamin D and myopia.
Participants with myopia, on average, had lower serum concentrations of vitamin D compared to those without myopia. While further studies are needed to determine the mechanism, this study suggests that higher vitamin D levels are associated with lower incidence of myopia.
Age-related macular degeneration (AMD) is the leading cause of irreversible blindness among people age 60 years or older in developed countries. Current standard-of-care anti-vascular endothelial ...growth factor (VEGF) therapy, which inhibits angiogenesis and vascular permeability, has been shown to stabilize choroidal neovascularization and increase visual acuity in neovascular AMD. However, therapeutic limitations of anti-VEGF therapy include limited durability with consequent need for frequent intravitreal injections, and a ceiling of efficacy. Current strategies under investigation include targeting VEGF-C and VEGF-D, integrins, tyrosine kinase receptors, and the Tie2/angiopoietin-2 pathway. A literature search was conducted through November 30, 2021 on PubMed, Medline, Google Scholar, and associated digital platforms with the following keywords: wet macular degeneration, age-related macular degeneration, therapy, VEGF-A, VEGF-C, VEGF-D, integrins, Tie2/Ang2, and tyrosine kinase inhibitors.
The authors provide a comprehensive review of AMD disease pathways and mechanisms involved in wet AMD as well as novel targets for future therapies.
With novel targets and advancements in drug delivery, there is potential to address treatment burden and to improve outcomes for patients afflicted with neovascular AMD.
Predictive models have been used to aid early diagnosis of PCOS, though existing models are based on small sample sizes and limited to fertility clinic populations. We built a predictive model using ...machine learning algorithms based on an outpatient population at risk for PCOS to predict risk and facilitate earlier diagnosis, particularly among those who meet diagnostic criteria but have not received a diagnosis.
This is a retrospective cohort study from a SafetyNet hospital's electronic health records (EHR) from 2003-2016. The study population included 30,601 women aged 18-45 years without concurrent endocrinopathy who had any visit to Boston Medical Center for primary care, obstetrics and gynecology, endocrinology, family medicine, or general internal medicine. Four prediction outcomes were assessed for PCOS. The first outcome was PCOS ICD-9 diagnosis with additional model outcomes of algorithm-defined PCOS. The latter was based on Rotterdam criteria and merging laboratory values, radiographic imaging, and ICD data from the EHR to define irregular menstruation, hyperandrogenism, and polycystic ovarian morphology on ultrasound.
We developed predictive models using four machine learning methods: logistic regression, supported vector machine, gradient boosted trees, and random forests. Hormone values (follicle-stimulating hormone, luteinizing hormone, estradiol, and sex hormone binding globulin) were combined to create a multilayer perceptron score using a neural network classifier. Prediction of PCOS prior to clinical diagnosis in an out-of-sample test set of patients achieved an average AUC of 85%, 81%, 80%, and 82%, respectively in Models I, II, III and IV. Significant positive predictors of PCOS diagnosis across models included hormone levels and obesity; negative predictors included gravidity and positive bHCG.
Machine learning algorithms were used to predict PCOS based on a large at-risk population. This approach may guide early detection of PCOS within EHR-interfaced populations to facilitate counseling and interventions that may reduce long-term health consequences. Our model illustrates the potential benefits of an artificial intelligence-enabled provider assistance tool that can be integrated into the EHR to reduce delays in diagnosis. However, model validation in other hospital-based populations is necessary.
Biomarkers of ocular blood flow originating from a wide variety of imaging modalities have been associated with glaucoma onset and progression for many decades. Advancements in imaging platforms ...including optical coherence tomography angiography (OCTA) have provided the ability to quantify vascular changes in glaucoma patients, alongside traditional measures such as retinal nerve fibre layer thickness and optic nerve head structure. Current literature on vascular biomarkers, as measured by OCTA, indicates significant relationships between glaucoma and blood flow and capillary density in the retina and ONH. The data currently available, however, are highly diverse and lack robust longitudinal data on OCTA vascular outcomes and glaucoma progression. Herein we discuss and summarize the relevant current literature on OCTA vascular biomarkers and glaucoma reviewed through March 1, 2021. Associations between OCTA vascular biomarkers and clinical structural and functional glaucoma outcomes as well as differences between glaucoma patients and healthy controls are reviewed and summarized. The available data identify significantly decreased flow density, flow index and vessel density in the ONH, peripapillary vascular layer and macula of glaucoma patients compared with controls. Whole image vessel density is also significantly decreased in glaucoma patients compared with controls, and this outcome has been found to correspond to severity of visual field loss. OCTA vascular biomarkers alongside clinical structural outcomes may aid in assessing overall risk for glaucoma in patients.
Signaling by innate immune receptors initiates and orchestrates the overall immune responses to infection. Macrophage receptors recognizing pathogens can be broadly grouped into surface receptors and ...receptors restricted to intracellular compartments, such as phagosomes and the cytoplasm. There is an expectation that ingestion and degradation of microorganisms by phagocytes contributes to activation of intracellular innate receptors, although direct demonstrations of this are rare, and many model ligands are studied in soluble form, outside of their microbial context. By comparing a wild-type strain of Staphylococcus aureus and a lysozyme-sensitive mutant, we have been able directly to address the role of degradation of live bacteria by mouse macrophages in determining the overall innate cellular inflammatory response. Our investigations revealed a biphasic response to S. aureus that consisted of an initial signal resulting from the engagement of surface TLR2, followed by a later, second wave on inflammatory gene induction. This second wave of inflammatory signaling was dependent on and correlated with the timing of bacterial degradation in phagosomes. We found that TLR2 signaling followed by TLR2/TLR9 signaling enhanced sensitivity to small numbers of bacteria. We further found that treating wild-type bacteria with the peptidoglycan synthesis-inhibiting antibiotic vancomycin made S. aureus more susceptible to degradation and resulted in increased inflammatory responses, similar to those observed for mutant degradation-sensitive bacteria.
Complex posttraumatic stress disorder (CPTSD) has been proposed as a diagnosis for capturing the diverse clusters of symptoms observed in survivors of prolonged trauma that are outside the current ...definition of PTSD. Introducing a new diagnosis requires a high standard of evidence, including a clear definition of the disorder, reliable and valid assessment measures, support for convergent and discriminant validity, and incremental validity with respect to implications for treatment planning and outcome. In this article, the extant literature on CPTSD is reviewed within the framework of construct validity to evaluate the proposed diagnosis on these criteria. Although the efforts in support of CPTSD have brought much needed attention to limitations in the trauma literature, we conclude that available evidence does not support a new diagnostic category at this time. Some directions for future research are suggested.
Neuroblastoma (NB) is a childhood cancer arising from sympatho-adrenal neural crest cells. MYCN amplification is found in half of high-risk NB patients; however, no available therapies directly ...target MYCN. Using multi-dimensional metabolic profiling in MYCN expression systems and primary patient tumors, we comprehensively characterized the metabolic landscape driven by MYCN in NB. MYCN amplification leads to glycerolipid accumulation by promoting fatty acid (FA) uptake and biosynthesis. We found that cells expressing amplified MYCN depend highly on FA uptake for survival. Mechanistically, MYCN directly upregulates FA transport protein 2 (FATP2), encoded by SLC27A2. Genetic depletion of SLC27A2 impairs NB survival, and pharmacological SLC27A2 inhibition selectively suppresses tumor growth, prolongs animal survival, and exerts synergistic anti-tumor effects when combined with conventional chemotherapies in multiple preclinical NB models. This study identifies FA uptake as a critical metabolic dependency for MYCN-amplified tumors. Inhibiting FA uptake is an effective approach for improving current treatment regimens.
The Centers for Disease Control and Prevention's (CDC) Learn the Signs. Act Early. program, funded the American Academy of Pediatrics (AAP) to convene an expert working group to revise its ...developmental surveillance checklists. The goals of the group were to identify evidence-informed milestones to include in CDC checklists, clarify when most children can be expected to reach a milestone (to discourage a wait-and-see approach), and support clinical judgment regarding screening between recommended ages. Subject matter experts identified by the AAP established 11 criteria for CDC milestone checklists, including using milestones most children (≥75%) would be expected to achieve by specific health supervision visit ages and those that are easily observed in natural settings. A database of normative data for individual milestones, common screening and evaluation tools, and published clinical opinion was created to inform revisions. Application of the criteria established by the AAP working group and adding milestones for the 15- and 30-month health supervision visits resulted in a 26.4% reduction and 40.9% replacement of previous CDC milestones. One third of the retained milestones were transferred to different ages; 67.7% of those transferred were moved to older ages. Approximately 80% of the final milestones had normative data from ≥1 sources. Social-emotional and cognitive milestones had the least normative data. These criteria and revised checklists can be used to support developmental surveillance, clinical judgment regarding additional developmental screening, and research in developmental surveillance processes. Gaps in developmental data were identified particularly for social-emotional and cognitive milestones.
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