Transient remission of hyperparathyroidism after fine-needle aspiration biopsy.

Primary hyperparathyroidism (PHPT) is the unregulated overproduction of parathyroid hormone (PTH), resulting in abnormal calcium homeostasis. PHPT is most commonly caused by a single adenoma of the parathyroid gland, which can have an intrathyroid location in rare cases. The measurement of intact PTH in the washout fluid obtained by ultrasound (US)-guided fineneedle aspiration (FNA) can be useful in clarifying the aetiology of these lesions. This study presented a 48-year-old man with a background history of symptomatic renal stone disease who was diagnosed with PHPT and referred to our Endocrinology department. A neck US revealed a thyroid nodule with a size of 21 mm in the right lobe. The patient underwent US-guided FNA of the lesion. The measurement of PTH in the washout fluid was significantly elevated. Following the procedure, he reported neck pain and noticed distal paraesthesias in the upper limbs. Blood test results showed significant hypocalcaemia and supplementation with calcium and calcitriol was started. The patient was closely monitored. Recurrence of hypercalcaemia was later observed, and the patient was submitted to surgery. We present a case of FNAinduced transitory remission of PHPT in a patient with an intrathyroid parathyroid adenoma. We conjecture that intra-nodular haemorrhage might have occurred, which temporarily affected the viability of the autonomous parathyroid tissue. A few similar cases of spontaneous or induced remission of PHPT after FNA have been previously described in the literature. This remission can be transitory or permanent, depending on the degree of cellular damage thus follow-up of these patients is recommended.

Antimicrobial coating of spider silk to prevent bacterial attachment on silk surgical sutures.

Microbial infections from post-surgery or other medical-related procedure is a serious health problem. Nowadays, the research is focused on the development of new drug-free materials with antibacterial properties to prevent or minimize the risk of infections. Spider silk is known for its unique biomechanical properties allied with biocompatibility. Recombinant DNA technology allows to bioengineering spider silk with antimicrobial peptides (AMP). Thus, our goal was to bioengineered spider silk proteins with AMP (6mer-HNP1) as an antibacterial drug-free coating for commercial silk sutures (Perma-Hand®) for decreasing bacterial infections. Perma-Hand® sutures were coated with 6mer-HNP1 by dip coating. In vitro tests, using human fetal lung fibroblasts (MRC5), showed that coated sutures sustained cell viability, and also, the contact with red blood cells (RBCs) demonstrate blood compatibility. Also, the coatings inhibited significantly the adherence and formation of biofilm, where sutures coated with 6mer-HNP1 produced a 1.5 log reduction of Methicillin-Resistant Staphylococcus aureus (MRSA) and a 2 log reduction of Escherichia coli (E. coli) compared to the uncoated Perma-Hand® suture. The mechanical properties of Perma-Hand® sutures were not affected by the presence of bioengineered spider silk proteins. Thus, the present work demonstrated that using spider silk drug-free coatings it is possible to improve the antibacterial properties of the commercial sutures. Furthermore, a new class of drug-free sutures for reducing post-implantation infections can be developed. STATEMENT OF SIGNIFICANCE: Microbial infections from post-surgery or other medical-related procedure is a serious health problem. Developing new drug-free materials with antibacterial properties is an approach to prevent or minimize the risk of infections. Spider silk is known for its unique biomechanical properties allied with biocompatibility. Recombinant DNA technology allow to bioengineering spider silk with antimicrobial peptides (AMP). Our goal is bioengineered spider silk proteins with AMP as an antibacterial coating for silk sutures. The coatings showed exceptional antibacterial properties and maintained intrinsic mechanical features. In vitro studies showed a positive effect of the coated sutures on the cell behavior. With this new drug-free bioengineered spider silk coating is possible to develop a new class of drug-free sutures for reducing post-implantation infections.

Association of Vitamin D Pathway Genetic Variation and Thyroid Cancer.

Vitamin D is mostly known for its role in bone and calcium metabolism. However, studies have suggested that it also has inhibitory effects on tumor development and progression. Genetic variants close to genes that encode crucial enzymes for the synthesis (DHCR7 rs12785878), metabolism (CYP2R1 rs2060793) and degradation (CYP24A1 rs6013897) of vitamin D have been associated with serum levels of vitamin D. The aim of this case-control study was to determine the effect of these variants in the vitamin D pathway on the susceptibility to thyroid cancer. Five hundred patients with differentiated thyroid cancer and 500 controls were genotyped for the DHCR7 rs12785878, CYP2R1 rs2060793, and CYP24A1 rs6013897 variants. Genotype and allele frequencies were compared between patients and controls. The DHCR7 rs12785878 minor allele was associated with thyroid cancer under an additive (OR 1.38, 95% CI 1.15-1.65, p = 0.0004) and codominant (OR 1.88, 95% CI 1.30-2.74, p = 0.0021) model. These findings suggest that DHCR7 polymorphisms may be associated with an increased risk of thyroid cancer due to an effect of this gene on circulating vitamin D levels.

Silk-Based Antimicrobial Polymers as a New Platform to Design Drug-Free Materials to Impede Microbial Infections.

Surgical site infections (SSI) represent a serious health problem that occur after invasive surgery, thus new antimicrobial biomaterials able to prevent SSI are needed. Silks are natural biopolymers with excellent biocompatibility, low immunogenicity and controllable biodegradability. Spider silk-based materials can be bioengineered and functionalized with specific peptides, such as antimicrobial peptides, creating innovative polymers. Herein, we explored new drug-free multifunctional silk films with antimicrobial properties, specifically tailored to hamper microbial infections. Different spider silk domains derived from the dragline sequence of the spider Nephila clavipes (6mer and 15mer, 27 and 41 kDa proteins, respectively) were fused with the two antimicrobial peptides, Hepcidin (Hep) and Human Neutrophil peptide 1 (HNP1). The self-assembly features of the spider silk domains (ß-sheets) were maintained after functionalization. The bioengineered 6mer-HNP1 protein demonstrated inhibitory effects against microbial pathogens. Silk-based films with 6mer-HNP1 and different contents of silk fibroin (SF) significantly reduced bacterial adhesion and biofilm formation, whereas higher bacterial counts were found on the films prepared with 6mer or SF alone. The silk-based films showed no cytotoxic effects on human foreskin fibroblasts. The positive cellular response, together with structural and antimicrobial properties, highlight the potential of these multifunctional silk-based films as new materials for preventing SSI.

Association of FOXE1 polyalanine repeat region with thyroid cancer is dependent on tumour size.

OBJECTIVE: Polymorphisms in the thyroid transcription factor forkhead factor E1 (FOXE1) gene have been implicated in the genetic susceptibility to differentiated thyroid cancer, but little is known about their effect on tumour characteristics. The objective of this study was to determine the contribution of the FOXE1 polyalanine repeat region to the susceptibility to thyroid cancer and to its clinical characteristics. DESIGN, PATIENTS AND MEASUREMENTS: A total of 500 patients with sporadic thyroid cancer (440 papillary and 60 follicular thyroid carcinoma) and 502 healthy controls were included in this case-control association study. The number of FOXE1 alanine repeats in each subject was determined by PCR and multiplex fragment analysis by capillary electrophoresis. FOXE1 genotype and allele frequencies among groups were compared by logistic regression and adjusted for sex and age at diagnosis. Data were analysed according to cancer subtype, tumour size and the presence of lymph node or distant metastasis. RESULTS: FOXE1 alleles with 16 or more alanine repeats were more frequent in patients with tumour size > 1 cm compared to tumour size ≤ 1 cm (adjusted OR 1·44; 95% CI 1·05-1·88; P = 0·019). Genotypes containing at least one allele with 16 or more alanine repeats were associated with larger tumour size (adjusted OR 1·71; 95% CI 1·15-2·57; P = 0·009). No significant differences were observed between cancer subtypes or the presence/absence of metastasis. CONCLUSIONS: FOXE1 polyalanine repeat polymorphisms are associated with thyroid cancer, but only for tumours larger than 1 cm, suggesting a role in disease progression.

Unveiling the effect of three-dimensional bioactive fibre mesh scaffolds functionalized with silanol groups on bacteria growth.

The need to replace or repair deteriorating bones and simultaneously prevent the formation of bacteria biofilm without impairing local tissue integration has pushed scientists to look for new designs and processing methods to develop innovative biomaterials. Silicon-based biomaterials, widely studied for application in bone regeneration, have demonstrated antibacterial properties. Herein, the aim of this work is to investigate the potential of the functionalization of biomaterials surfaces with silanol groups to prevent the bacterial biofilm formation. For that, we evaluated the adherence and biofilm formation of Escherichia coli (E. coli, Gram negative) and Staphylococcus aureus (S. aureus, Gram positive) on starch-based scaffolds. Three-dimensional fibre meshes scaffolds were developed by wet-spinning and functionalized with silanol (Si-OH) groups using a calcium silicate solution as a nonsolvent. The functionalization of the scaffolds was confirmed by X-ray photoelectron spectroscopy. The developed scaffolds showed no biocide activity against the bacterial tested, although the colony-forming units (CFU) mL(-1) counts were significant lower between 4 and 12 h of incubation for both bacteria. The adherence of E. coli and S. aureus to the scaffolds was also investigated. After a growth period of 12 h, the SPCL scaffolds functionalized with Si-OH groups showed a reduced bacterial adherence of E. coli and S. aureus. The functionalized scaffolds showed a positive effect in preventing the formation of biofilm in the case of S. aureus, however, in the case of E. coli this was not observed, suggesting that silanol groups may only have a positive effect in preventing the proliferation of gram-positive bacteria. The in vitro biological assessment of the functionalized materials showed that these materials sustained cell proliferation and induced their osteogenic differentiation. The outcome of this work suggests that the presence of Si-OH groups in SPCL scaffolds maintained bactericidal activity against S. aureus. Further research is still needed in order to understand the full antibacterial potential of Si-OH groups. © 2016 Wiley Periodicals, Inc. J Biomed Mater Res Part A: 104A: 2189-2199, 2016.

Association of RET genetic polymorphisms and haplotypes with papillary thyroid carcinoma in the Portuguese population: a case-control study.

Thyroid cancer has a multifactorial aetiology resulting from the interaction of genetic and environmental factors. Several low penetrance susceptibility genes have been identified but their effects often vary between different populations. Somatic point mutations and translocations of the REarranged during Transfection (RET) proto-oncogene are frequently found in thyroid cancer. The aim of this case-control study was to determine the effect of four well known RET single nucleotide polymorphisms (SNPs) on the risk for differentiated thyroid carcinoma. A total of 545 Portuguese patients and 543 controls were genotyped by PCR and restriction enzyme analysis, for the following SNPs: G691S (exon 11, rs1799939 G/A), L769L (exon 13, rs1800861 T/G), S836S (exon 14, rs1800862 C/T), and S904S (exon 15, rs1800863 C/G). The minor allele of S836S was overrepresented in patients with papillary thyroid carcinoma (PTC) when compared to controls (OR 1.57; 95% CI 1.05-2.35; p = 0.026). The GGTC haplotype was also overrepresented in PTC (OR 2.51; 95% CI 1.07-5.91; p = 0.029). No associations were found in follicular thyroid carcinoma (FTC). Multivariate logistic regression analysis showed no differences regarding gender, age at diagnosis, lymph node or distant metastasis. However, a near significant overrepresentation of the minor alleles of G691S and S904S was found in patients with tumours greater than 10 mm of diameter at diagnosis. These data suggest that the RET S836S polymorphism in exon 14 and the GGTC haplotype are risk factors for PTC, but not FTC, and that the G691S/S904S polymorphisms might be associated with tumour behaviour.

Early onset of medullary thyroid carcinoma in a kindred with multiple endocrine neoplasia type iia associated with cutaneous lichen amyloidosis.

OBJECTIVE: To describe the molecular characterization of a kindred affected by the rare variant of multiple endocrine neoplasia type IIA (MEN IIA) associated with cutaneous lichen amyloidosis and to discuss the clinical implications in the management of this syndrome. METHODS: A kindred with four affected family members was identified, and DNA analysis was performed by sequencing exon 11 of the RET proto-oncogene. Presymptomatic genetic screening was offered to all first-degree relatives. RESULTS: Sequencing analysis of the RET proto-oncogene revealed a Cys634Trp (TGC->TGG) mutation in all clinically affected family members and in an asymptomatic 5-year-old child who, after thyroidectomy, was found to have multicentric medullary thyroid carcinoma and C-cell hyperplasia. A Gly691Ser (GGT->AGT) polymorphism was also detected in this family but did not segregate with the disease. CONCLUSION: To our knowledge, this is the earliest detection of medullary thyroid carcinoma reported thus far in a kindred with MEN IIA associated with cutaneous lichen amyloidosis, and this finding suggests that prophylactic thyroidectomy, in kindreds with this variant, should be performed before the age of 5 years.