Aminoacyl-tRNA synthetases (AARSs) are an important family of enzymes that catalyze tRNA aminoacylation reaction (Ibba and Soll in Annu Rev Biochem 2000, 69:617-650) [1]. AARSs are grouped into two broad classes (class I and II) based on sequence/structural homology and mode of their interactions with the tRNA molecule (Ibba and Soll in Annu Rev Biochem 2000, 69:617-650) [1]. As protein dynamics play an important role in enzyme function, we explored the intrinsic dynamics of these enzymes using normal mode analysis and investigated if the two classes and six subclasses (Ia-c and IIa-c) of AARSs exhibit any distinct patterns of motion. The present study found that the intrinsic dynamics-based classification of these enzymes is similar to that obtained based on sequence/structural homology for most enzymes. However, the classification of seryl-tRNA synthetase was not straightforward; the internal mobility patterns of this enzyme are comparable to both IIa and IIb AARSs. This study revealed only a few general mobility patterns in these enzymes--(1) the insertion domain is generally engaged in anticorrelated motion with respect to the catalytic domain for both classes of AARSs and (2) anticodon binding domain dynamics are partly correlated and partly anticorrelated with respect to other domains for class I enzymes. In most of the class II AARSs, the anticodon binding domain is predominately engaged in anticorrelated motion with respect to the catalytic domain and correlated to the insertion domain. This study supports the notion that dynamic-based classification could be useful for functional classification of proteins.
Purpose of review Treatment of diabetic dyslipidemia is necessary because of its impact on cardiovascular disease, which is the leading cause of death in patients with diabetes. In the past, standard treatment of diabetic dyslipidemia focused only on correcting lipids. Although this remains the mainstay of treatment, because new antihyperglycemic treatments reduce cardiovascular events with minimal effect on dyslipidemia, a new approach is both timely and relevant. Recent findings LDL-lowering remains the focus of treatment for diabetic dyslipidemia, especially in patients with both diabetes and cardiovascular disease (CVD). Higher intensity statin therapy or lower LDL cholesterol goals are recommended in these patients. Combination therapy, especially with ezetimibe, fibrates, bile acid sequestrants, PCSK9 inhibitors and omega 3 fatty acids should be considered along with selected new agents to reduce glycemia. Summary As diabetic dyslipidemia plays a key role in CVD, aggressive treatment is indicated. New research targets include apo-CIII and lipoprotein(a) [Lp(a)]. In addition, new antihyperglycemic therapy is changing diabetes care and altering treatment guidelines. The most recent American Diabetes Association Standards of Care has expanded its recommendations for people with CVD and diabetes, suggesting that medications validated to improve cardiac health should be strongly considered.
Purpose Exposure to endocrine disrupting chemicals (EDCs) are associated with underactive thyroid glands, and possibly autoimmunity. Firefighters are exposed to EDCs from flame retardants; however, the prevalence and risk factor associations of thyroid antibodies among firefighters are unknown. Methods Firefighters attending professional health and safety conferences between November 2018 and January 2020, and with no prior diagnosis of thyroid disease were invited (n=278) to submit a health survey, blood samples, and complete a thyroid ultrasound. The survey assessed for sociodemographic and occupational characteristics, including a history of familial thyroid disease, smoking, firefighter tenure, and job rank, radiation exposure, and mitigation practices of occupational exposures. Serum thyroid peroxidase antibody (TPOAb) was also assessed. Results Approximately 39.9% firefighters evaluated had a positive TPOAb test. The mean age for those TPOAb positive was lower than those who tested negative (41.4 ±7.9 vs 43.1 ±7.9 years, p=0.07) but this difference was not significant. Firefighters with a family history of thyroid disease had a statistically significant higher prevalence of TPOAb compared to those without a family history (60.0% vs. 37.5%, p=0.02); this association remained significant after adjusting for sociodemographic and occupational factors (Odds Ratio 2.99; Confidence interval 1.31 – 6.85). Main conclusions The prevalence of TPOAb is high among firefighters in our study, and family history is a significant determinant of testing positive for TPOAb. Firefighters may benefit from TPOAb and thyroid stimulating hormone tests, and screening for family history of thyroid disease at baseline employee medical check-ups. This finding suggests the need for further studies.
Introduction Checkpoint Inhibitor Immunotherapy (CII) has been linked to multiple endocrinopathies. Thyroid dysfunction is more frequently associated with anti-PD-1 and anti-PD-L1 monoclonal antibody use, yet there are no good predictors for the development of thyroid complications after immunotherapy treatment. Iodinated contrast studies have been related to the development of thyroid dysfunction, and are frequently used in the oncology patient population for surveillance of malignancy and response to treatment. Methodology and Results We conducted a retrospective observational study to identify any potential association between the development of thyroid dysfunction and exposure to iodinated contrast studies in patients receiving CII. A chart review was conducted from 2012-2020. Data analysis was performed using Chi-square. Using ICD codes, 236 patients with new thyroid dysfunction after initiation of CII, and no alternative etiology for the thyroid dysfunction, were included. Out of these, 162 (68.6%) patients developed hypothyroidism, 71 (30%) developed thyrotoxicosis initially and subsequently developed hypothyroidism, and 3 (1.27%) developed hyperthyroidism. Of the total patients who developed thyroid dysfunction following CII, 145 vs.91 patients received ≥3 contrast studies, (p. 0. 0004). Discussion These findings suggest that there is an association with the use of three or more iodinated contrast studies and the development of thyroid dysfunction in patients receiving CII. More research is needed to identify additional predictors that could be utilized in clinical practice for earlier detection of patients at risk of developing CII related thyroid dysfunction. Conclusion Thyroid dysfunction following the use of CII, namely anti-PD-1 and anti-PD-L1 therapies, remains prevalent; however, it has been difficult to identify who is most at risk for this complication. This is the first study examining exposure to iodinated contrast and its potential contribution to CII thyroid endocrinopathy, and it warrants further investigation. Presentation: No date and time listed
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