Association between thyroid-stimulating hormone (TSH) and proteinuria in relation to thyroid cyst in a euthyroid general population

Background: High normal levels of thyroid-stimulating hormone (TSH) have been reported to be associated with chronic kidney disease (CKD) among euthyroid individuals. However, there has been only limited research on the association between TSH and proteinuria, a major risk factor for the progression of renal disease.Methods: A cross-sectional study of 1595 euthyroid individuals was conducted. All participants were within the normal range for free triiodothyronine (T3), free thyroxine (T4), and TSH. Analyses were stratified by thyroid cyst status to test the hypothesis that the absence of thyroid cysts, an indicator of latent thyroid damage, is associated with declining ability to synthesis thyroid hormone.Results: For participants with thyroid cysts, a significant inverse association between TSH and proteinuria was observed (adjusted odds ratio (95% confidence intervals) of log-transformed TSH for proteinuria 0.40 (0.18, 0.89)). In participants without thyroid cysts, a significant positive association between those two factors was observed (2.06 (1.09, 3.90)).Conclusions: Among euthyroid individuals in the general population, being in the normal range of TSH was found to have an ambivalent association with proteinuria. Thyroid cyst status could be an effect modifier for those associations

The Current Status and Challenges for the Nursing Education with Information and Communication Technology

journal articl

Employment relations in emerging economies: China and India

This chapter presents and analyses the employment relations in China and India, assessed in their broader institutional context as well as in the nature of their integration into the global economy, from a comaparative capitalsit framework. This allows the identification of the similarities and differences of the economic pattersn of development in the two economies with respect to each other as well as with industrialised economies. The main objective is firstly, to show how the two countries have a number of distinctive institutional features underpinned by different social compromises that configure the employment relation in each economy. Secondly, this helps us to analyse the impact of globalisation and multinational firms on the employment relations in these economies

Associations between thyroid-stimulating hormone and hypertension according to thyroid cyst status in the general population: a cross-sectional study

Background: The absence of thyroid cysts may indicate latent thyroid damage, as demonstrated in our previous study. However, the association between the absence of thyroid cysts and latent functional damage of the thyroid is unknown. At low thyroid hormone productivity, which may be associated with latent functional damage of the thyroid, the association between thyroid-stimulating hormone(TSH) and hypertension might be enhanced. Therefore, we evaluated the association between TSH level and hypertension stratified by thyroid cyst status. Methods: We conducted a cross-sectional study of 1724 euthyroid Japanese individuals aged 40?74 years who participated in an annual health checkup in 2014. Results: In the study population, 564 and 686 participants had thyroid cysts and hypertension, respectively. A significant positive association was observed between TSH and hypertension in subjects without a thyroid cyst but not in subjects with thyroid cysts. There was a significant positive association between hypertension and TSH in subjects without a thyroid cyst (odds ratio [OR] 1.27; 95% confidence intervals [CI] 1.01, 1.61) but not in subjects with thyroid cysts (OR 0.79; CI 0.57, 1.09) in the model fully adjusted for known confounding factors. The correlation between the TSH and free triiodothyronine (fee T3) levels (simple correlation coefficient [r] = ? 0.13, p < 0.01) was stronger in the subjects without thyroid cysts than in those with thyroid cysts (r = ? 0.03, p = 0.525). Conclusions: TSH is positively associated with hypertension only in individuals without thyroid cysts. The correlation between the TSH and free T3 levels was stronger in the subjects without thyroid cysts than in those with thyroid cysts. Therefore, the absence of thyroid cysts could be related to the association between TSH level and hypertension, possibly by indicating that the subjects without thyroid cysts had limited thyroid hormone reserves. Therefore, the absence of thyroid cysts could indicate the latent functional damage of the thyroid

Structural and thermodynamic characterization of the binding of isoliquiritigenin to the first bromodomain of BRD4

Bromodomain-containing protein 4 (BRD4) recognizes the acetylated lysineof histone H4 via its bromodomains, leading to the recruitment of positivetranscription elongation factor b. Small molecules that inhibit BRD4 havepotential as anticancer agents by leading to the downregulation of specificoncogenes. Using X-ray crystallographic screening, we identified the BRD4inhibitory activity of isoliquiritigenin (ISL), a natural chalcone found inlicorice. Structural analysis revealed that ISL bound to BRD4 with a novelbinding mode and squeezed out one of the six conserved water moleculesthat form a strong hydrogen bond network. The thermodynamic analysisrevealed that the binding of ISL is enthalpy driven, suggesting that stronghydrogen bonds would compensate for the desolvation penalty. Neutronprotein crystallography further suggested that the favorable bindingenthalpy originates from the stabilization and optimization of the hydrogenbond network of the conserved water molecules. Here, we describe the noveltyand potential of ISL as a template for new BRD4 inhibitors

Neutron crystallographic analysis of the nucleotide-binding domain of Hsp72 in complex with ADP

The 70 kDa heat-shock proteins (Hsp70s) are ATP-dependent molecular chaperones that contain an N-terminal nucleotide-binding domain (NBD) and a C-terminal substrate-binding domain. Hsp70s bind to misfolded/unfolded proteins and thereby prevent their aggregation. The ATP hydrolysis reaction in the NBD plays a key role in allosteric control of the binding of substrate proteins. In the present study, the neutron crystal structure of the NBD of Hsp72, a heat-inducible Hsp70 family member, was solved in complex with ADP in order to study the structure–function relationship with a focus on hydrogens. ADP bound to Hsp72 was fully deprotonated, and the catalytically important residues, including Asp10, Asp199 and Asp206, are also deprotonated. Neutron analysis also enabled the characterization of the water clusters in the NBD. Enzymatic assays and X-ray crystallographic analysis revealed that the Y149A mutation exhibited a higher ATPase activity and caused disruption of the water cluster and incorporation of an additional magnesium ion. Tyr149 was suggested to contribute to the low intrinsic ATPase activity and to stabilize the water cluster. Collectively, these structural studies will help to elucidate the molecular basis of the function of Hsp72

The Structure of Physarum polycephalum Hemagglutinin I Suggests a Minimal Carbohydrate Recognition Domain of Legume Lectin Fold

Physarum polycephalum hemagglutinin I is a 104-residue protein that is secreted to extracellular space. The crystal structure of hemagglutinin I has a β-sandwich fold found among lectin structures, such as legume lectins and galectins. Interestingly, the β-sandwich of hemagglutinin I lacks a jelly roll motif and is essentially composed of two simple up-and-down β-sheets. This up-and-down β-sheet motif is well conserved in other lectins derived from animals, plants, bacteria, and viruses. It is more noteworthy that the up-and-down β-sheet motif includes many residues that make contact with the target carbohydrates. Our NMR data demonstrate that hemagglutinin I lacking a jelly roll motif also binds to its target glycopeptide. Taken together, the up-and-down β-sheet motif provides a fundamental scaffold for the binding of legume lectin-like proteins to the target carbohydrates, and the structure of hemagglutinin I suggests a minimal carbohydrate recognition domain