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BackgroundGraves' disease is routinely treated with antithyroid drugs, radioiodine, or surgery, but whether the choice of initial therapy influences long-term outcomes is uncertain. We evaluated cardiovascular morbidity and mortality according to the method and effectiveness of primary therapy in Graves' disease.MethodsIn this retrospective cohort study, we identified patients with hyperthyroidism, diagnosed between Jan 1, 1998, and Dec 31, 2013, from a thyroid-stimulating hormone (TSH)-receptor antibody (TRAb) test register in south Wales, UK, and imported their clinical data into the All-Wales Secure Anonymised Information Linkage (SAIL) Databank (Swansea University, Swansea, UK). Patients with Graves' disease, defined by positive TRAb tests, were selected for the study, and their clinical data were linked with outcomes in SAIL. We had no exclusion criteria. Patients were matched by age and sex to a control population (1:4) in the SAIL database. Patients were grouped by treatment within 1 year of diagnosis into the antithyroid drug group, radioiodine with resolved hyperthyroidism group (radioiodine group A), or radioiodine with unresolved hyperthyroidism group (radioiodine group B). We used landmark Kaplan-Meier and Cox regression models to analyse the association of treatment with the primary outcome of all-cause mortality and the secondary outcome of major adverse cardiovascular events (myocardial infarction, heart failure, ischaemic stroke, or death) with the landmark set at 1 year after diagnosis. We analysed the association between outcomes and concentration of TSH using Cox regression and outcomes and free thyroxine (FT4) concentration using restricted cubic-spline regression models.FindingsWe extracted patient-level data on 4189 patients (3414 [81·5%] females and 775 [18·5%] males) with Graves' disease and 16 756 controls (13 656 [81·5%] females and 3100 [18·5%] males). In landmark analyses, 3587 patients were in the antithyroid drug group, 250 were in radioiodine group A, 182 were in radioiodine group B. Patients had increased all-cause mortality compared with controls (hazard ratio [HR] 1·22, 95% CI 1·05–1·42). Compared with patients in the antithyroid drug group, mortality was lower among those in radioiodine group A (HR 0·50, 95% CI 0·29–0·85), but not for those in radioiodine group B (HR 1·51, 95% CI 0·96–2·37). Persistently low TSH concentrations at 1 year after diagnosis were associated with increased mortality independent of treatment method (HR 1·55, 95% CI 1·08–2·24). Spline regressions showed a positive non-linear relationship between FT4 concentrations at 1 year and all-cause mortality.InterpretationRegardless of the method of treatment, early and effective control of hyperthyroidism among patients with Graves' disease is associated with improved survival compared with less effective control. Rapid and sustained control of hyperthyroidism should be prioritised in the management of Graves' disease and early definitive treatment with radioiodine should be offered to patients who are unlikely to achieve remission with antithyroid drugs alone.FundingNational Institute for Social Care and Health Research, Wales.

Heavy metals are ubiquitous in nature, thus constituting a serious environmental problem in many countries. Due to their toxicity, there is an obvious need to determine them at trace levels. Zinc is essential for many cellular processes, including DNA synthesis, transcription, and translation, but excess can be toxic. To analyze the uptake and metabolism of zinc in Escherichia coli , a high affinity FRET (Fluorescence Resonance Energy Transfer)–based nanosensor was developed using the cyanobacterial metallothionein SmtA flanked by CFP (cyan fluorescent protein) and YFP (yellow fluorescent protein). The chimeric sensor protein was expressed in E. coli BL21 (DE3) and purified by affinity chromatography. Following binding of zinc, FRET ratio increased with increasing the Zn 2+ concentration. Affinity mutants were constructed with binding constants ranging from 50 μM to 1 mM. In vitro analysis with bacterially purified sensor showed that it is specific for Zn 2+ and responds only weakly to Cd 2+ with no response for other biological metal ions. Moreover, the sensor activity in vitro was stable with extreme changes in pH. In vivo analysis of nanosensor response in E. coli showed that free Zn 2+ accumulate in the bacterial cells and is slowly metabolized.

Maternal hypothyroidism may adversely affect pregnancy outcomes. International practice guidelines recommend that women with hypothyroidism should attain a preconception and early gestation serum thyroid-stimulating hormone (TSH) level of2.5 mU/L. Our objective was to ascertain what proportion of women realize this target in practice and whether a TSH level above this threshold has adverse fetal and maternal consequences.This was an observational study of women with hypothyroidism referred to an endocrine antenatal clinic between 2008 and 2010 (n = 78; mean age, 30.4 years; range, 19 to 43 years). Thyroid profiles (free thyroxine [FT4] and TSH) before conception and through pregnancy were documented. Obstetrics outcomes were examined, including low birth weight, preterm births, preeclampsia, caesarean sections, and admissions to special care neonatal units.Thyroid testing was undertaken in 80% of subjects before conception, and in 64, 94, and 96% of subjects in the first, second, and third trimesters of pregnancy, respectively. TSH2.5 mU/L was seen in 49% of women before conception and in 68% of women in the first trimester. Six women were overtly hypothyroid before conception, attaining normal thyroid function at gestational ages ranging from 12 to 36 weeks. Neither the preconception nor the first postconception TSH level (2.5 mU/L or ≤2.5 mU/L) was associated with gestational age at delivery, birth weight, or rates of caesarean section or preeclampsia.The majority of women with hypothyroidism do not achieve the recommended preconception and early gestation TSH targets. Preconception and early gestation TSH2.5 mU/L was not associated with adverse fetal and maternal outcomes. Studies in larger cohorts will be required to confirm these findings, however.

This study investigates the modulation of antioxidant defence system of Indian mustard (cv. Pusa Jai Kisan) against the arsenic (As)-induced toxicity in 20-day-old plants, exposed to 5 and 25 microM As for 96 h in hydroponic culture. Reduction in plant growth, measured in terms of root and shoot dry weights, was insignificant with 5 microM, but highly significant with 25 microM As treatment. Shoots accumulated more As than roots. The extent of oxidative stress in the leaves was measured as the rate of lipid peroxidation. The As treatments significantly increased the activities of antioxidative enzymes (superoxide dismutase, ascorbate peroxidase and glutathione reductase) and the contents of antioxidants metabolites (glutathione and ascorbate), the increase being dependent on exposure time. Increase in the activity of catalase was not significant, however. In conclusion, Indian mustard was able to detoxify the low As level through induction of antioxidant defence mechanism.