The Use of Tissue-on-Chip Technology to Focus the Search for Extracellular Vesicle miRNA Biomarkers in Thyroid Disease.

Small extracellular vesicles (sEVs) contain microRNAs (miRNAs) which have potential to act as disease-specific biomarkers. The current study uses an established method to maintain human thyroid tissue ex vivo on a tissue-on-chip device, allowing the collection, isolation and interrogation of the sEVs released directly from thyroid tissue. sEVs were analysed for differences in miRNA levels released from benign thyroid tissue, Graves' disease tissue and papillary thyroid cancer (PTC), using miRNA sequencing and quantitative reverse transcriptase polymerase chain reaction (qRT-PCR) to identify potential biomarkers of disease. Thyroid biopsies from patients with benign tissue (n = 5), Graves' disease (n = 5) and PTC (n = 5) were perfused with medium containing sEV-depleted serum for 6 days on the tissue-on-chip device. During incubation, the effluents were collected and ultracentrifuged to isolate sEVs; miRNA was extracted and sequenced (miRNASeq). Out of the 15 samples, 14 passed the quality control and miRNASeq analysis detected significantly higher expression of miR-375-3p, miR-7-5p, miR-382-5p and miR-127-3p in the sEVs isolated from Graves' tissue compared to those from benign tissue (false discovery rate; FDR p < 0.05). Similarly, miR-375-3p and miR-7-5p were also detected at a higher level in the Graves' tissue sEVs compared to the PTC tissue sEVs (FDR p < 0.05). No significant differences were observed between miRNA in sEVs from PTC vs. those from benign tissue. These results were supported by Quantitative Reverse Transcriptase Polymerase Chain Reaction (qRT-PCR). The novel findings demonstrate that the tissue-on-chip technology is a robust method for isolating sEVs directly from the tissue of interest, which has permitted the identification of four miRNAs, with which further investigation could be used as biomarkers or therapeutic targets within thyroid disease.

Contextualizing Colossus: Codebreaking Technology and Institutional Capabilities.

The Bletchley Park codebreaking center sits close to the heart of Britain's collective sense of historical greatness. Historians view it as a highly successful but largely ad-hoc institutional response to novel cryptographic challenges, depicting both its reliance on elite mathematicians and a large labor force as ruptures with peacetime practice. In contrast, this article suggests that Bletchley Park's success relied on institutional capabilities established in the prewar British state. It focuses on the celebrated "Colossus" electronic codebreaking devices as one element of a highly successful institutional collaboration between Bletchley Park, where they were used, and the Post Office research station at Dollis Hill, where they were designed and built. Correcting previous accounts, this article shows that this partnership was sponsored at the highest levels of government and supported by managers on both sides.

Analysis of cosmetic results of metopic synostosis: concordance and interobserver variability.

Trigonocephaly is caused by premature fusion of the metopic suture of the calvarium. The resultant facial and skull deformities place a newborn at a higher risk of cerebral impairment. Frontal orbital advancement and remodeling is the accepted surgical management. An analysis was undertaken to assess the cosmetic results for nonsyndromic metopic synostosis following frontal orbital advancement and remodeling and to determine whether the observer technique used had validity.The photographs of 20 consecutive patients with metopic synostosis were assessed preoperatively, postoperatively, and at 3 and 5 years of age. Each photograph was analyzed by 2 pairs of trained rotating observers. The findings were compared and reviewed by the fifth member, who acted as a "referee." Where there were disagreements between the findings, the referee came to a final decision. The presence and severity of trigonocephaly, temporal hollowing, hypotelorism, orbital asymmetry, epicanthic folds, and scarring were assessed. κ Analysis was used to determine the validity of observer concordance when using photographic material.There was a significant overall trend in craniofacial aesthetic improvement with time. However, 12% had some persistence of trigonocephaly. Temporal hollowing was usually persistent. κ Statistics varied among attributes and time period assessed. The greatest concordance was for improvement of epicanthic folds and trigonocephaly, with observers agreeing 84.1% and 82.6% of the time, respectively. There was least concordance for severity of hypotelorism and scarring.This study suggests that observer analysis of photographic records is a valid outcome measure for cosmesis, although it yields variable interobserver concordance according to the feature assessed. Surgery corrected most but not all the features of trigonocephaly. The prognostic indicators for good cosmetic outcome are presented.

Corrigendum to "A Lip Lump: An Unexpected Histological Diagnosis of a Lip Schwannoma".

[This corrects the article DOI: 10.1155/2017/3107362.].

Tracking a painful episode after a joint replacement using patient-reported outcome measures (PROMs).

Patient-reported outcome measures (PROMs) are an important tool in measuring the benefit of a surgery for patients and for clinicians. The results of such assessment tools can be used to monitor patient progress or initiate intervention. The scores also provide a reproducible evaluation of functional recovery and well-being after surgery. We report the case of a 68-year-old woman who underwent left unicondylar knee replacement in November 2011 followed by right unicondylar knee replacement in April 2012. Prospective, web-based electronic PROMs were used preoperatively and every 6-12 months postoperatively to monitor the improvement in pain and function symptoms. These outcome measures were beneficial in helping to monitor an episode of new pain in her left knee, without requiring invasive or extensive investigation.

A Lip Lump: An Unexpected Histological Diagnosis of a Lip Schwannoma.

Schwannomas are benign nerve sheath tumours arising from Schwann cells. They comprise 1% of all benign tumours. In the 2016 World Health Organisation Classification of Central Nervous System, they are classified as a tumour of the cranial and paraspinal nerves, Schwannoma 9560/0. A 23-year-old Caucasian lady presented with a seven-month history of a painless right upper lip lump. Examination revealed a small cystic 0.5 cm diameter lesion within the right upper lip. The clinical impression was that of a mucocele. Excision of the lip lesion was performed under local anaesthetic. Histological examination of the excised lesion demonstrated a circumscribed nodule consisting of spindle cells mixed with vascular spaces containing red blood cells and fibrin. Immunohistochemistry for S100 was strongly positive. The findings were consistent with that of a small benign schwannoma. The current consensus is for surgical excision of a conservative nature with no need for margins. If recurrence does occur one needs to consider whether complete enucleation was achieved or whether malignant transformation has occurred.