IMPORTANCE Diabetic retinopathy is the leading cause of blindness in working-age adults. Studies have suggested that statins may reduce the risk of developing diabetic retinopathy.OBJECTIVE To investigate the association between statin therapy and the development of diabetic retinopathy in patients with diabetes and dyslipidemia.
Introduction Increased sedentary behavior predicts greater cardiovascular morbidity and mortality, and does so independently of physical activity (PA). This association is only partially explained by BMI and overall body fat, suggesting mechanisms besides general increased adiposity. The purpose of this study was to explore associations of self-reported leisure PA and sitting time with regional fat depositions and abdominal muscle among community-dwelling older adults. Methods Participants were 539 diverse adults (mean age 65) who completed a study visit in 2001-2002. Areas of pericardial, intra-thoracic, subcutaneous, visceral, and intermuscular fat, as well as abdominal muscle, were measured using computed tomography. Leisure PA and sitting hours were entered simultaneously into multivariate regression models to determine associations with muscle and fat areas. Results After adjusting for demographics, smoking, diabetes, hypertension, triglycerides, and cholesterol, greater PA was associated with less intra-thoracic, visceral, subcutaneous, and intermuscular fat (for all p < .05), while greater sedentary time was associated with greater pericardial and intra-thoracic fat (for both p < .05). After further adjusting for BMI, each hour of weekly PA was associated with 1.85 cm2 less visceral fat (p < .01), but was not associated with other fat depositions. Conversely, each hour of daily sitting was associated with 2.39cm2 more pericardial fat (p < .05), but was not associated with any other fat depositions. There were no associations with abdominal muscle area. Adjusting for common inflammatory markers had little effect. Associations between fat and PA were stronger for men. Conclusions Sitting and physical activity have distinct associations with regional fat deposition in older adults. The association between sitting and pericardial fat could partially explain the link between sitting and coronary heart disease.
In many organisms, polo kinases appear to play multiple roles during M-phase progression. To provide new insights into the function of the budding yeast polo kinase Cdc5, we generated novel temperature-sensitive cdc5 mutants by mutagenizing the C-terminal noncatalytic polo box domain, a region that is critical for proper subcellular localization. One of these mutants, cdc5-11, exhibited a temperature-sensitive growth defect with an abnormal spindle morphology. Strikingly, provision of a moderate level of benomyl, a microtubule-depolymerizing drug, permitted cdc5-11 cells to grow significantly better than the isogenic CDC5 wild type in a FEAR (cdc Fourteen Early Anaphase Release)-independent manner. In addition, cdc5-11 required MAD2 for both cell growth and the benomyl-remedial phenotype. These results suggest that cdc5-11 is defective in proper spindle function. Consistent with this view, cdc5-11 exhibited abnormal spindle morphology, shorter spindle length, and delayed microtubule regrowth at the nonpermissive temperature. Overexpression of CDC5 moderately rescued the spc98-2 growth defect. Interestingly, both Cdc28 and Cdc5 were required for the proper modification of the spindle pole body components Nud1, Slk19, and Stu2 in vivo. They also phosphorylated these three proteins in vitro. Taken together, these observations suggest that concerted action of Cdc28 and Cdc5 on Nud1, Slk19, and Stu2 is important for proper spindle functions.
Ocular diseases associated with retinal ganglion cell (RGC) degeneration is the most common neurodegenerative disorder that causes irreversible blindness worldwide. It is characterized by visual field defects and progressive optic nerve atrophy. The underlying pathophysiology and mechanisms of RGC degeneration in several ocular diseases remain largely unknown. RGCs are a population of central nervous system neurons, with their soma located in the retina and long axons that extend through the optic nerve to form distal terminals and connections in the brain. Because of this unique cytoarchitecture and highly compartmentalized energy demand, RGCs are highly mitochondrial-dependent for adenosine triphosphate (ATP) production. Recently, oxidative stress and mitochondrial dysfunction have been found to be the principal mechanisms in RGC degeneration as well as in other neurodegenerative disorders. Here, we review the role of oxidative stress in several ocular diseases associated with RGC degenerations, including glaucoma, hereditary optic atrophy, inflammatory optic neuritis, ischemic optic neuropathy, traumatic optic neuropathy, and drug toxicity. We also review experimental approaches using cell and animal models for research on the underlying mechanisms of RGC degeneration. Lastly, we discuss the application of antioxidants as a potential future therapy for the ocular diseases associated with RGC degenerations.
Body mass index (BMI) may not accurately or adequately reflect body composition or its role in the development of cardiovascular disease (CVD). Ectopic adipose depots may provide a more refined representation of the role of adiposity in CVD. Thus, we examined the association of pericardial and intra-thoracic fat with coronary artery calcium (CAC). Nearly 600 white men and women, as well as Filipina women and African-American women, all without known CVD, had abdominal and chest computed tomography (CT) scans at two time points about four years apart from which CAC presence, severity and progression, as well as pericardial and intra-thoracic fat volumes were obtained. Logistic and linear regression models with staged adjustment were used to assess associations of pericardial and intra-thoracic fat with CAC presence, severity and progression. After adjustment for age, BMI, sex/ethnic group, ever smoking, and lipids, each standard deviation higher increment of intra-thoracic fat, but not pericardial fat, was significantly associated with 3.84-fold higher odds of prevalent CAC (95% CI (1.54, 9.58), p=0.004) and a 38.4% higher CAC score (95% CI (3.5%, 90.0%), p=0.03). Neither pericardial nor intra-thoracic fat were associated with CAC progression. Contrary to previous reports, pericardial fat was not associated with the presence, severity or progression of CAC. We did, however, demonstrate a significant association between intra-thoracic fat and both the presence and severity of CAC. Studies measuring fat in the thoracic cavity may consider defining intra-thoracic fat as a separate entity from pericardial fat.
Background Retinal imaging has been applied for detecting eye diseases and cardiovascular risks using deep learning–based methods. Furthermore, retinal microvascular and structural changes were found in renal function impairments. However, a deep learning–based method using retinal images for detecting early renal function impairment has not yet been well studied. Objective This study aimed to develop and evaluate a deep learning model for detecting early renal function impairment using retinal fundus images. Methods This retrospective study enrolled patients who underwent renal function tests with color fundus images captured at any time between January 1, 2001, and August 31, 2019. A deep learning model was constructed to detect impaired renal function from the images. Early renal function impairment was defined as estimated glomerular filtration rate <90 mL/min/1.73 m2. Model performance was evaluated with respect to the receiver operating characteristic curve and area under the curve (AUC). Results In total, 25,706 retinal fundus images were obtained from 6212 patients for the study period. The images were divided at an 8:1:1 ratio. The training, validation, and testing data sets respectively contained 20,787, 2189, and 2730 images from 4970, 621, and 621 patients. There were 10,686 and 15,020 images determined to indicate normal and impaired renal function, respectively. The AUC of the model was 0.81 in the overall population. In subgroups stratified by serum hemoglobin A1c (HbA1c) level, the AUCs were 0.81, 0.84, 0.85, and 0.87 for the HbA1c levels of ≤6.5%, >6.5%, >7.5%, and >10%, respectively. Conclusions The deep learning model in this study enables the detection of early renal function impairment using retinal fundus images. The model was more accurate for patients with elevated serum HbA1c levels.
The coronavirus disease 2019 (COVID 19) pandemic has presented major challenges to ophthalmologists. Reports have shown that ocular manifestations can be the first presenting symptoms of COVID 19 infection and conjunctiva may be a portal of entry for the severe acute respiratory syndrome (SARS) associated coronavirus 2 (SARS CoV 2). The purpose of this article is to provide general guidance for ophthalmologists to understand the prevalence of ocular presentation in COVID 19 patients and to reduce the risk of transmission during practice. Relevant studies published in the period of November 1, 2019, and July 15, 2020, regarding ocular manifestations of COVID 19 and detection of SARS CoV 2 in the eye were included in this systematic review and meta analysis. The pooled prevalence of the ocular manifestations has been estimated at 7% (95% confidence interval [CI]: 0.03–0.10) among COVID 19 patients. The pooled detection rate of SARS CoV 2 from conjunctiva was low (1%, 95% CI: 0.00–0.03). Conjunctival symptoms were the most common ocular manifestations in COVID 19, but the positive detection rate of the SARS CoV 2 virus by reverse transcription–polymerase chain reaction of conjunctival tears or secretions remained low. No study has shown a definite transmission of COVID 19 through ocular mucosa or secretions. In summary, ocular manifestations in COVID 19 patients commonly comprise ocular surface symptoms. Although a low prevalence of ocular symptoms was encountered among patients infected by SARS CoV 2, it is imperative for all ophthalmologists to understand the full spectrum of COVID 19 symptoms or signs including those of the eyes as well as to adopt appropriate protective measures during clinical practice.
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