• Tyler McCarty posted an update 2 months ago

    The association between age and clinically relevant ocular characteristics was examined in a sizable cohort of free-ranging rhesus macaques at Cayo Santiago, Puerto Rico.

    One hundred twenty rhesus macaques (73 male, 47 female), aged between 0 and 29 years (mean ± standard deviation of 12.6 ± 6.4 years), were evaluated from September through December 2021. Following pupil dilation, the ophthalmic evaluation encompassed intraocular pressure (IOP) assessment, corneal pachymetry, biomicroscopy, A-scan biometry, automated refraction, and fundus photography. Through multilevel mixed-effects models, adjusting for sex and weight, the associations between age and outcomes were examined.

    On average, intraocular pressure, pachymetry measurements, axial length, and automated refraction spherical equivalent measurements were 18.37 ± 0.468 mmHg, 47.44 ± 0.3221 mm, 19.49 ± 0.124 mm, and 0.30 ± 0.170 diopters (D), respectively. Age exhibited a substantial correlation with pachymetry, with a coefficient of -120 and a 95% confidence interval ranging from -227 to -0.014 (P = 0.0026), axial length (coefficient = 0.003; 95% CI, 0.001 to 0.005; P = 0.0002), and spherical equivalent (coefficient = -0.012; 95% CI, -0.022 to -0.002; P = 0.0015). No significant connection was identified in the dataset between age and intraocular pressure. The prevalence of cataracts in either eye was exceptionally high at 1083% (95% confidence interval, 634-1789), significantly linked to age with an odds ratio of 120 (95% confidence interval, 106-136; P = 0.0004). A strong correlation was evident between age and the presence of retinal drusen in either eye, found in 1500% (95% confidence interval, 960-2268) of the animals (odds ratio = 114; 95% confidence interval, 102-127; P = 0.0020).

    Similar to human aging, rhesus macaques demonstrate age-dependent ocular characteristics, including thinner corneas, longer axial lengths, a tendency toward nearsightedness, and a greater incidence of cataracts and retinal deposits.

    Ocular changes linked to aging in rhesus macaques demonstrate parallels with human aging, characterized by reduced corneal thickness, elongated axial lengths, a tendency towards myopia, and increased likelihood of cataracts and retinal drusen.

    Scrutinize the divergent effects of refractive error (RE) and ocular biometrics as risk factors for primary open-angle glaucoma (POAG) within diverse racial and ethnic populations.

    A retrospective analysis of data from the Los Angeles Latino Eye Study (LALES) and the Chinese American Eye Study (CHES), two population-based epidemiological investigations, was conducted. Multivariable logistic regression, incorporating interaction terms, was used to explore the relationships between primary open-angle glaucoma (POAG) and its risk factors, including refractive error (RE) and axial length (AL), while also examining the moderating role of race/ethnicity.

    The LALES and CHES datasets, encompassing 7601 phakic participants (473% from LALES and 527% from CHES), were analyzed, with all subjects being 50 years of age. 606.83 years marked the average age, along with 609% being female. A significantly higher prevalence and unadjusted risk of POAG were observed in the LALES group compared to the CHES group (60% versus 40%, respectively); this difference was statistically significant (odds ratio = 155; P < 0.0001). In a multivariable analysis of POAG risk factors, Latino ethnicity emerged as significant (OR = 225; P < 0.0001). Myopia levels – mild (OR = 154), moderate (OR = 247), and severe (OR = 394) when compared to non-myopes – were also significantly associated with POAG (P = 0.0003). A longer axial length (AL) was independently associated with POAG, with an increasing odds ratio of 137 for every millimeter (P < 0.0001). High myopia status, with a standardized regression coefficient of 0.11, had a 27 times weaker association with POAG than AL, which exhibited a standardized regression coefficient of 0.03. The presence or absence of a racial/ethnic group did not alter the link between refractive error (per diopter), axial length (per millimeter) and the presence of primary open-angle glaucoma (P = 0.049).

    Although the predisposition to POAG due to myopia in the retina and longer axial length is comparable between Latino and Chinese Americans, the actual prevalence discrepancy is narrowed by the higher myopia rates among Chinese Americans. The surge in global myopia could amplify the risk of POAG, particularly among racial and ethnic groups with a higher myopia incidence.

    Even though myopic refractive error (RE) and longer axial lengths (AL) are equally associated with an increased risk of primary open-angle glaucoma (POAG) in both Latino and Chinese American populations, the lower prevalence of POAG in Chinese Americans is impacted by the higher prevalence of myopia within this demographic group. In the context of the burgeoning global myopia epidemic, racial/ethnic groups exhibiting higher myopia rates could become disproportionately affected by primary open-angle glaucoma (POAG).

    Examining the correlation between sex, clinical presentation, and outcomes in acute myocardial infarction (AMI) patients categorized by non-obstructive (MINOCA) or obstructive (MIOCA) coronary artery disease.

    A cohort of 2455 patients with AMI, undergoing coronary angiography, was enrolled in our study spanning the period from January 2017 to September 2021. The MIOCA study population was separated by AMI type and sex, resulting in 1593 male and 607 female patients. Meanwhile, in MINOCA, the distribution was 87 males and 168 females. Further subdividing each cohort by age was performed, with a focus on those over 70 years of age. The primary endpoint, MAE, was a composite of all-cause mortality, repeated acute myocardial infarction (AMI), and hospitalizations for heart failure (HF) during the follow-up period. Additional outcomes evaluated included overall mortality, cardiovascular fatalities, repeat episodes of acute myocardial infarction, rehospitalizations for heart failure, and occurrences of stroke.

    Analysis revealed a statistically meaningful difference in gender distribution, with MINOCA patients being more likely female than MIOCA patients (p<0.0001). The average duration of follow-up spanned 28 months. In both MINOCA and MIOCA cohorts, the unadjusted incidence of MAE was markedly higher among females than males, as evidenced by in MINOCA and in MIOCA. Age displayed an independent relationship with MAE within both study cohorts. In the MINOCA cohort, 70-year-old females experienced a substantially higher rate of MAE (18 cases, 23.7% versus 4 cases, 5.9%; p=0.0003) compared to males. This difference was predominantly due to a higher rate of re-hospitalization for heart failure (p=0.0045) and a higher recurrence rate of acute myocardial infarction (AMI) (p=0.0006). In the subset of MINOCA patients, female sex was an independent factor in predicting MAE, showing a hazard ratio of 309 (95% confidence interval 102-959), with statistical significance (p=0.0040). The 70-year-old MINOCA female demographic experienced poorer health outcomes than their comparable MIOCA female peers.

    70-year-old MINOCA females displayed a statistically more significant incidence of MAE compared to male patients and MIOCA female peers, likely attributable to contrasting pathophysiological mechanisms in the ischemic event.

    The data, part of the AMIPE ongoing observational study concerning acute myocardial infarction, aided in the assessment of prognostic and therapeutic strategies. ClinicalTrials.gov is a valuable resource for individuals researching clinical trials. Recognizing this research project is crucial, and its identifier is NCT03883711.

    The AMIPE Acute Myocardial Infarction, Prognostic and Therapeutic Evaluation ongoing observational study utilized these data. The platform ClinicalTrials.gov facilitates the transparency and accessibility of clinical trial data. The study’s identification number is prominently displayed as NCT03883711.

    Generalized pustular psoriasis (GPP) and myeloperoxidase deficiency were found to share causative genetic defects in the myeloperoxidase (MPO) gene, a connection noted in 2020 medical literature. While the clinical subtypes of GPP patients carrying pathogenic MPO mutations are largely undefined, clarifying these distinctions is clinically significant. This report details a gentle presentation of GPP, characterized by a rare heterozygous missense variant, c.1810C>T p.(Arg604Cys), located within the MPO gene. Based on our structural analysis and functional assays on myeloperoxidase, the current substitution of MPO appears to be a hypomorphic variant. 5-fluorouracil inhibitor The GPP patient’s less severe presentation could potentially be due to a partial loss-of-function hypomorphic variant in the MPO gene. Besides this, the severe, intractable edematous pustules and redness improved substantially after five rounds of granulocyte and monocyte adsorption apheresis (GMA) therapy. According to our current understanding, this marks the first instance of GMA treatment for GPP associated with a pathogenic variant within the MPO gene. Our work indicates that GMA may be a helpful and potent instrument for managing GPP in individuals with myeloperoxidase deficiency.

    In vitro studies reveal that substantial quantities of pollutants impede the connection between thyroid hormones and transthyretin (TTR) through competitive inhibition. Although this binding is unintended, its in vivo influence on free thyroid hormones has not been characterized yet. We have created a method for quantitative in vitro to in vivo extrapolation (QIVIVE), utilizing a competitive binding model, for determining the effect of TTR-binding chemicals on free thyroid hormones within the human blood stream. Among the chemicals chosen for investigation were 25 TTR-binding compounds, including 6 hydroxyl polybromodiphenyl ethers (OH-PDBEs), 6 hydroxyl polychlorobiphenyls (OH-PCBs), 4 halogenphenols, 5 per- and polyfluorinated substances (PFASs), and 4 phenols. Based on in vitro binding parameters and human exposure data, the QIVIVE model is expected to accurately predict in vivo effects on free thyroid hormones. Twenty-five common thyroid receptor-binding chemicals, when encountered together, caused a median rise of 0.80% and 0.60% in the general population’s free thyroxine (FT4) and free triiodothyronine (FT3), respectively.

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