Significance of Size of Lymph Node Metastasis on Postsurgical Stimulated Thyroglobulin Levels After Prophylactic Unilateral Central Neck Dissection in Papillary Thyroid Carcinoma

published_or_final_versionSpringer Open Choice, 28 May 201

Is there a role for unstimulated thyroglobulin velocity in predicting recurrence in papillary thyroid carcinoma patients with detectable thyroglobulin after radioiodine ablation?

BACKGROUND: In the follow-up of papillary thyroid cancer (PTC) patients treated with curative thyroidectomy and radioiodine ablation, raised thyroglobulin (Tg) predicts recurrence with reasonable sensitivity and specificity. However, a proportion of patients present with raised Tg level but no other clinical evidence of disease. Only limited data on Tg kinetics have been reported to date. Here we aim to evaluate the prognostic and predictive significance of nonstimulated serum Tg velocity (TgV). METHODS: Consecutive PTC patients treated with curative thyroidectomy and radioiodine ablation between 2003 and 2010 were analyzed. Patients with at least one detectable Tg measurement (>0.2 ng/mL) were included. TgV was defined as the annualized rate of Tg change. Logistic regression analyses were performed to evaluate the role of TgV in the prediction of disease recurrence. The optimal TgV cutoff was assigned by receiver-operating characteristic curve analysis. Overall survival of patients above versus below the TgV cutoff were determined by the Kaplan-Meier method and compared. RESULTS: Of a total of 501 patients, 87 had at least one Tg value >0.2 ng/mL; in these latter patients, 29 (33.3 %) developed recurrence. TgV was an independent predictor of the recurrence. TgV >/=0.3 ng/mL per year predicted recurrence with a sensitivity of 83.3 % and specificity of 94.4 %. Patients with TgV below the cutoff had a significantly better overall survival (p = 0.038). CONCLUSIONS: TgV predicts recurrence with high sensitivity and specificity, and is a prognosticator of survival in postthyroidectomy and postablation PTC patients with raised Tg.published_or_final_versio

Semiconductor photocatalysis to engineering deuterated N-alkyl pharmaceuticals enabled by synergistic activation of water and alkanols

Precisely controlled deuterium labeling at specific sites of N-alkyl drugs is crucial in drug-development as over 50% of the top-selling drugs contain N-alkyl groups, in which it is very challenging to selectively replace protons with deuterium atoms. With the goal of achieving controllable isotope-labeling in N-alkylated amines, we herein rationally design photocatalytic water-splitting to furnish [H] or [D] and isotope alkanol-oxidation by photoexcited electron-hole pairs on a polymeric semiconductor. The controlled installation of N-CH3, -CDH2, -CD2H, -CD3, and -13CH3 groups into pharmaceutical amines thus has been demonstrated by tuning isotopic water and methanol. More than 50 examples with a wide range of functionalities are presented, demonstrating the universal applicability and mildness of this strategy. Gram-scale production has been realized, paving the way for the practical photosynthesis of pharmaceuticals

Fonofos Exposure and Cancer Incidence in the Agricultural Health Study

BACKGROUND: The Agricultural Health Study (AHS) is a prospective cohort study of licensed pesticide applicators from Iowa and North Carolina enrolled 1993–1997 and followed for incident cancer through 2002. A previous investigation in this cohort linked exposure to the organophosphate fonofos with incident prostate cancer in subjects with family history of prostate cancer. OBJECTIVES: This finding along with findings of associations between organophosphate pesticides and cancer more broadly led to this study of fonofos and risk of any cancers among 45,372 pesticide applicators enrolled in the AHS. METHODS: Pesticide exposure and other data were collected using self-administered questionnaires. Poisson regression was used to calculate rate ratios (RRs) and 95% confidence intervals (CIs) while controlling for potential confounders. RESULTS: Relative to the unexposed, leukemia risk was elevated in the highest category of lifetime (RR = 2.24; 95% CI, 0.94–5.34, p(trend) = 0.07) and intensity-weighted exposure-days (RR = 2.67; 95% CI, 1.06–6.70, p(trend) = 0.04), a measure that takes into account factors that modify pesticide exposure. Although prostate cancer risk was unrelated to fonofos use overall, among applicators with a family history of prostate cancer, we observed a significant dose–response trend for lifetime exposure-days (p(trend) = 0.02, RR highest tertile vs. unexposed = 1.77, 95% CI, 1.03–3.05; RR(interaction) = 1.28, 95% CI, 1.07–1.54). Intensity-weighted results were similar. No associations were observed with other examined cancer sites. CONCLUSIONS: Further study is warranted to confirm findings with respect to leukemia and determine whether genetic susceptibility modifies prostate cancer risk from pesticide exposure

The influence of pre-existing health conditions on short-term mortality risks of temperature: Evidence from a prospective Chinese elderly cohort in Hong Kong

Background: Both cold and hot temperatures are associated with adverse health outcomes. Less is known about the role of pre-existing medical conditions to confer individual's susceptibility to temperature extremes. Methods: We studied 66,820 subjects aged ≥65 who were enrolled and interviewed in all the 18 Elderly Health Centers of Department of Health, Hong Kong from 1998 to 2001, and followed up for 10–13 years. The distributed lag nonlinear model (DLNM) combined with a nested case-control study design was applied to estimate the nonlinear and delayed effects of cold or hot temperature on all natural mortality among subjects with different pre-existing diseases. Results: The relative risk of all natural mortality associated with a decrease of temperature from 25th percentile (19.5 °C) to 1st percentile (11.3 °C) over 0–21 lag days for participants who reported to have an active disease at the baseline was 2.21 (95% confidence interval (CI): 1.19, 4.10) for diabetes mellitus (DM), 1.59 (1.12, 2.26) for circulatory system diseases (CSD), and 1.23 (0.53, 2.84) for chronic obstructive pulmonary disease (COPD), whereas 1.04 (0.59, 1.85) for non-disease group (NDG). Compared with NDG, elders with COPD had excess risk of mortality associated with thermal stress attributable to hot temperature, while elders with DM and CSD were vulnerable to both hot and cold temperatures. Conclusions: Elders with pre-existing health conditions were more vulnerable to excess mortality risk to hot and/or cold temperature. Preventative measures should target on elders with chronic health problems.postprin

Novel role for the innate immune receptor toll-like receptor 4 (TLR4) in the regulation of the wnt signaling pathway and photoreceptor apoptosis

Recent evidence has implicated innate immunity in regulating neuronal survival in the brain during stroke and other neurodegenerations. Photoreceptors are specialized light-detecting neurons in the retina that are essential for vision. In this study, we investigated the role of the innate immunity receptor TLR4 in photoreceptors. TLR4 activation by lipopolysaccharide (LPS) significantly reduced the survival of cultured mouse photoreceptors exposed to oxidative stress. With respect to mechanism, TLR4 suppressed Wnt signaling, decreased phosphorylation and activation of the Wnt receptor LRP6, and blocked the protective effect of the Wnt3a ligand. Paradoxically, TLR4 activation prior to oxidative injury protected photoreceptors, in a phenomenon known as preconditioning. Expression of TNFα and its receptors TNFR1 and TNFR2 decreased during preconditioning, and preconditioning was mimicked by TNFα antagonists, but was independent of Wnt signaling. Therefore, TLR4 is a novel regulator of photoreceptor survival that acts through the Wnt and TNFα pathways. © 2012 Yi et al

Glycogen Synthase Kinase 3 Beta (GSK3β) Phosphorylates the RNAase III Enzyme Drosha at S300 and S302

The canonical microRNA (miRNA) pathway commences with the enzymatic cleavage of the primary gene transcript (pri-miRNA) by the RNAase III enzyme Drosha in the nucleus into shorter pre-miRNA species that are subsequently exported to the cytoplasm for further processing into shorter, mature miRNA molecules. Using a series of reporter constructs, we have previously demonstrated that phosphorylation of Drosha at Ser 300 and 302 was required for its nuclear localization. Here, we identify GSK3β as the culprit kinase. We demonstrate that Drosha is unable to selectively localize to the nucleus in cells deficient in GSK3β. These findings expand the substrate base of GSK3β to include a central component of the miRNA biogenesis pathway

Synthesis and characterisation of lamellar ZnS nanosheets containing intercalated diamines

A solvothermal method has been used to preparehybrid inorganic-organic composites with a lamellar structure in which layers of wurtzite ZnS are separated by intercalated diamine molecules. A hybrid composite prepared with diethylenetriamine has been isolated and characterisedand its structure and properties compared with those of the composite prepared using ethylenediamine. Comparative structural and morphological studies of the two lamellar hybrid composites are described on the basis of powder XRD, electron and scanning probe microscopies and thermal analysis of the materials