Thyroglobulin measurement before rhTSH-aided 131I ablation in detecting metastases from differentiated thyroid carcinoma

Aim Thyroidectomy followed by administration of large activities of 131‐iodine (¹³¹I) is the treatment of choice for differentiated thyroid carcinoma (DTC). The serum thyroglobulin (Tg) measurement during hypothyroidism (offT4‐Tg), just before radioiodine thyroid ablation, has proved to be effective for predicting persistent/recurrent disease. However, the Tg measurement cannot be used as a corresponding value for pre‐ablative offT4‐Tg when recombinant human TSH (rhTSH) is used as stimulus before treatment. The present study was undertaken to evaluate if post‐thyroidectomy Tg values, measured before rhTSH‐stimulated radioiodine ablation is of prognostic value in patients affected by DTC. Methods We enrolled 126 patients with DTC submitted to total thyroidectomy. T4 treatment was started just after surgery to suppress TSH levels and Tg levels (onT4‐Tg) were measured just before rhTSH‐aided thyroid ablation by ¹³¹I (3700 MBq). Neck radioiodine uptake (RAIU) was measured just before ablation and a post‐treatment whole body scan (PT‐WBS) was performed. Results A significant relationship was found between thyroid remnants’ RAIU and onT4‐Tg levels (P < 0·001). The 1·10 ng/ml onT4‐Tg threshold selected by ROC curve analysis identifies patients with positive PT‐WBS with 83·3% sensitivity, 65·7% specificity, 44·5% positive predictive value (PPV) and 93·6% negative predictive value (NPV). The 0·65 ng/ml cut‐off level recognizes metastatic patients with 82·9% sensitivity, 55·2% specificity, 43·3% PPV and 97·8% NPV when compared with 12 months restaging results. Among 63 patients with initially undetectable onT4‐Tg (i.e. ≤ 0·2 ng/ml) none had positive PT‐WBS nor DTC relapse at 12‐month restaging (NPV 100%). Conclusions Based on our data we conclude that pre‐ablative onT4‐Tg is a prognostic marker and should be used instead of pre‐ablative TSH‐stimulated Tg measurement when rhTSH‐aided radioiodine ablation is done.     

Clonality and specificity of cryoglobulins associated with HCV: pathophysiological implications

Background/Aims: Hepatitis C virus (HCV) infection plays a central role in the pathogenesis of mixed cryoglobulinemia through molecular mechanisms which remain to be elucidated. The aim of this study was to investigate the role of antibody responses to HCV in the pathogenesis of cryoglobulinemia through characterization of the anti-HCV specificity and immunochemical characteristics of the immunoglobulins involved in cryoprecipitation.Methods: Sera from 50 consecutive patients with chronic HCV infection (RNA positive) were screened for the presence of cryoglobulins. The two major components of cryoprecipitates, IgM rheumatoid factors and IgG, were separated by high performance liquid chromatography and analyzed for immunochemical composition by immunoblotting and antibody specificity by ELISA and immunoblotting using recombinant HCV proteins and synthetic peptides as antigens.Results: Cryoprecipitates were observed in 27 patients and characterized by immunofixation: 13 (48%) were classified as type II and 14 (52%) as type III. Monoclonal immunoglobulins were detected by immunoblotting in 20 cryoprecipitates: IgM in 14 samples and IgG in 14, which a clear preponderance of IgG3 (). Specificity studies on sera and purified IgM and IgG fractions from cryoprecipitates revealed enrichment in cryoglobulins, predominantly polyclonal IgG1, reactive with the HCV structural proteins, whereas specificities for nonstructural viral proteins were relatively less represented compared to whole serum. No restricted pattern of fine specificity was observed. IgG3 subclass was apparently not involved in HCV nucleoprotein binding.Conclusions: Our findings do not support a direct link between monoclonal cryoglobulins and immune response to HCV. According to the proposed pathogenetic model, HCV infection can induce the formation of cryoprecipitable rheumatoid factors, sustain their production, and eventually lead to monoclonal B-cell expansion through several cooperative mechanisms.     

Peyer's Patches Epithelium in the Rat

The epithelial layer covering lymphoid follicles of Peyer's patches consists of cells with a different surface morphology. Some of these cells have been described as a distinct cytotype, the so-called M cells. In order to resolve the controversy on the specific morphological and biochemical markers of M cells, structural, ultrastructural, and morphometrical study of the epithelium covering the rat Peyer's patches were performed. Peyer's patches from healthy rats were processed for light microscopy, immunohistochemistry, in situ nick-end labeling (TUNEL), and scanning and transmission electron microscopy. A morphometric study was also performed to evaluate microvillus density, length, and number of lysosomes in different areas of the epithelium. Peyer's patches were covered by simple columnar/cubical dome epithelium (DE). Scarce goblet cells and a large number of enterocytes were observed. Ultrastructural observations revealed that the DE showed cells with different morphology. The density and length of microvilli and the lysosome number varied along the whole dome without significant differences. The DE cells characterized by short and disorganized microvilli appeared always in close spatial relationship with lymphocytes. In conclusion, the concept that distinct cell types (enterocytes and M cells) can be identified in the rat DE does not appear to be valid based on morphological criteria. It seems correct to consider that in rat Peyer's patches the presence of scarce goblet cells and a large number of enterocytes showing dynamic morphofunctional modifications is related to the functional state and/or to cell cycle.     

Surface Chemistry of Amphiphilic Polysiloxane/Triethyleneglycol‐Modified Poly(pentafluorostyrene) Block Copolymer Films Before and After Water Immersion

New amphiphilic block copolymers Si‐EFSx composed of a poly(dimethyl siloxane) (Si) block and a poly(4‐(triethyleneglycol monomethyl ether)‐2,3,5,6‐tetrafluorostyrene) (EFS) block are synthesized by atom transfer radical polymerization (ATRP) starting from a bromo‐terminated Si macroinitiator. Similarly, new hydrophobic block copolymers Si‐FSy consisting of an Si block and a poly(pentafluorostyrene) (FS) block are prepared for comparison. X‐ray photoelectron spectroscopy (XPS) analysis on block copolymer films reveals that the Si block is concentrated at the polymer–air interface, while the EFS block is located in the layers underneath. The same polymer films undergo a marked surface reconstruction after immersion in water for 7 d, as probed by XPS. This phenomenon involves the exposure of the hydrophilic oxyethylenic chains to contact water. Such surface reconstruction is even more drastic when an amphiphilic block copolymer is dispersed in a cross‐linked poly(dimethyl siloxane) matrix film.

     

Homeostasis maintenance of encapsulated cells

Cell niche homeostasis plays a critical role in many bodily functions including tissue functionality, stem cell maintenance and differentiation, wound healing, cancer development and propagation, and many others. Many tissue engineering approaches overlook the importance of engineered constructs homeostasis, in particular for transplantation purposes. Here, we present a study of the effect of encapsulation duration on engineered tissue maturation and provide a protocol for the evaluation of critical conditions for transplantation purposes. In brief, SHSY5Y human neuroblastoma cells were encapsulated in 2% alginate by electrohydrodynamic jetting method for up to 4 weeks. We evaluated extracellular matrix niche formation and tissue maturation in situ through COL1A1 expression. In in vitro conditions, we studied the ability of cells to maintain their critical functions after being released from alginate beads. Cellular viability was evaluated via an apoptosis/necrosis detection kit and AlamarBlue assay, and functionality via immunocytochemistry. We proved the importance of engineered tissue homeostasis stabilization for future cell recovery, in particular, for our system cells encapsulated for 28 days met all critical requirements for successful tissue transplantation. Maturation of engineered tissue constructs could be accelerated by enriching alginate with growth factors or extracellular matrix molecules.     

Detection of myocardial iron overload by two-dimensional speckle tracking in patients with beta-thalassaemia major: a combined echocardiographic and T2* segmental CMR study

We aimed to evaluate the role of two-dimensional speckle tracking imaging (2DSTI) in detecting early changes of myocardial deformation in patients affected by thalassemia major (TM) and its relation with myocardial iron overload (MIO) detected by T2* cardiovascular magnetic resonance (CMR). We studied 28 TM patients (15 males, 37.4?±?10 years). All patients underwent CMR and echocardiography in the same day. Segmental and global T2* values were measured. Values of global longitudinal strain (GLS) were derived from the three apical views, while radial and circumferential strain were obtained as average strain from the short axis views at basal, mid and apical level. Six patients (21.4%) showed significant MIO (global heart T2*?<?20 ms). GLS showed a significant correlation with T2* values (R?=??0.49; P?=?0.001) and it was significantly lower in patients with a significant MIO than in those with no significant MIO (?18.3?±?2 vs. ?21.3?±?2.7, P?=?0.02). No significant difference was found for radial and circumferential strain in relation to the severity of MIO. Patients with impaired GLS (<?19.5%) had a significant higher risk of showing significant MIO (Odds-ratio-OR?=?17; 95%). GLS is related with global T2* in TM patients. Moreover, GLS can identify TM patients with severe MIO detected by CMR.     

Prenatal and Childhood Traffic-Related Pollution Exposure and Childhood Cognition in the Project Viva Cohort (Massachusetts,USA)

Background

Influences of prenatal and early-life exposures to air pollution on cognition are not well understood.

Objectives

We examined associations of gestational and childhood exposure to traffic-related pollution with childhood cognition.

Methods

We studied 1,109 mother–child pairs in Project Viva, a prospective birth cohort study in eastern Massachusetts (USA). In mid-childhood (mean age, 8.0 years), we measured verbal and nonverbal intelligence, visual motor abilities, and visual memory. For periods in late pregnancy and childhood, we estimated spatially and temporally resolved black carbon (BC) and fine particulate matter (PM_2.5) exposures, residential proximity to major roadways, and near-residence traffic density. We used linear regression models to examine associations of exposures with cognitive assessment scores, adjusted for potential confounders.

Results

Compared with children living ≥ 200 m from a major roadway at birth, those living < 50 m away had lower nonverbal IQ [–7.5 points; 95% confidence interval (CI): –13.1, –1.9], and somewhat lower verbal IQ (–3.8 points; 95% CI: –8.2, 0.6) and visual motor abilities (–5.3 points; 95% CI: –11.0, 0.4). Cross-sectional associations of major roadway proximity and cognition at mid-childhood were weaker. Prenatal and childhood exposure to traffic density and PM_2.5 did not appear to be associated with poorer cognitive performance. Third-trimester and childhood BC exposures were associated with lower verbal IQ in minimally adjusted models; but after adjustment for socioeconomic covariates, associations were attenuated or reversed.

Conclusions

Residential proximity to major roadways during gestation and early life may affect cognitive development. Influences of pollutants and socioeconomic conditions on cognition may be difficult to disentangle.

Citation

Harris MH, Gold DR, Rifas-Shiman SL, Melly SJ, Zanobetti A, Coull BA, Schwartz JD, Gryparis A, Kloog I, Koutrakis P, Bellinger DC, White RF, Sagiv SK, Oken E. 2015. Prenatal and childhood traffic-related pollution exposure and childhood cognition in the Project Viva cohort (Massachusetts, USA). Environ Health Perspect 123:1072–1078; http://dx.doi.org/10.1289/ehp.1408803