Coexistence of two main folded G-quadruplexes within a single G-rich domain in the EGFR promoter

EGFR is an oncogene which codifies for a tyrosine kinase receptor that represents an important target for anticancer therapy. Indeed, several human cancers showed an upregulation of the activity of this protein. The promoter of this gene contains some G-rich domains, thus representing a yet unexplored point of intervention to potentially silence this gene. Here, we explore the conformational equilibria of a 30-nt long sequence located at position -272 (EGFR-272). By merging spectroscopic and electrophoretic analysis performed on the wild-type sequence as well as on a wide panel of related mutants, we were able to prove that in potassium ion containing solution this sequence folds into two main G-quadruplex structures, one parallel and one hybrid. They show comparable thermal stabilities and affinities for the metal ion and, indeed, they are always co-present in solution. The folding process is driven by a hairpin occurring in the domain corresponding to the terminal loop which works as an important stabilizing element for both the identified G-quadruplex arrangements

Early detection of biochemically occult autonomous thyroid nodules

Objective: Autonomously functioning thyroid areas may be associated with subclinical or overt hyperthyroidism, but may exist even in the presence of normal TSH. This study was aimed at comparing the rate of autonomously functioning areas and their cardiac sequelae in patients with nodular goitre studied with the usual and a novel approach. Design and methods: In total 490 adult outpatients with thyroid nodular goitre, living in a mild iodine-deficient area, were selected in our referral centre for thyroid diseases from 2009 to 2014 on the basis of a suspicion of thyroid functional autonomy. They were divided in three groups according to a non-conventional approach (excessive response to thyroxine treatment: group 1) or conventional approach (low/normal TSH with clinical suspicion or low TSH: groups 2 and 3). All patients of the study with the suspicion of thyroid functional autonomy underwent thyroid scan with radioactive iodine (I131) uptake (RAIU). Results: The percentage of confirmed thyroid functional autonomy was 319/490, being significantly higher in group 3 than in groups 1 and 2 (81.5 vs 64.7 vs 52.6%; chi-square P < 0.0001). However, the diagnosis with non-conventional approach was made at a significant earlier age (P < 0.0001). Cardiac arrhythmias as well as atrial fibrillation were similarly detected by conventional and non-conventional approaches (chi-square test: P = 0.2537; P = 0.8425). Conclusions: The hyper-responsiveness to thyroxine treatment should induce the suspicion of thyroid functional autonomy at an early stage, allowing to detect autonomous functioning areas in apparently euthyroid patients

Physiological Responses in Reindeer to the Application of a Conducted Electrical Weapon

Conducted Electrical Weapons (CEWs) have potential as effective alternatives to chemical restraint for short-term non-routine capture and handling as well as aversion hazing of wildlife. To assess immediate and delayed physiologic effects of exposure to a CEW, we assigned 15 captive reindeer (Rangifer tarandus tarandus) to one of three treatment groups: immobilized with carfentanil and xylazine (CX), 10 second exposure to a CEW, or exposure to the CEW while immobilized with CX (CEW+CX). Blood samples were collected pre-treatment, immediately post-intervention, 10 min, 20 min, 4 hours, and 24 hours post-intervention. Physiologic effects were evaluated by analysis of blood, clinical observation for signs of physiologic compromise, and vital signs. Parameters that changed significantly (P \u3c 0.05) post-exposure (lactate, glucose, rectal temperature, blood oxygen, cardiac troponin I, cortisol, and catecholamines) were not significantly different from baseline values within 24 hours. Cortisol, glucose, and peak rectal temperature were lower in CEW exposed individuals, while lactate, oxygen, and catecholamines were higher than for the CX exposed individuals. The catecholamine response observed in the CEW only group paralleled the response in the CEW+CX group. No long term health effects were detected from either restraint method. Use of a CEW does not appear to increase the risk of capture myopathy

Myringotomy and ventilation tube insertion with endoscopic or microscopic technique in adults: a pilot study

The purpose of this study is to assess the feasibility of endoscopic-assisted myringotomy and ventilation tube insertion in adults affected by chronic otitis media with effusion, comparing the outcomes of this approach with those obtained with the traditional microscopic technique. Twenty-four patients were enrolled in this trial and alternately assigned to 2 groups of 12 subjects each. In group A, patients underwent myringotomy and ventilation tube insertion under endoscopic view, whereas in group B, the same procedure was performed traditionally using a microscope. All cases were evaluated 1 week after surgery and then monthly until tube extrusion. Type A tympanogram was achieved in 10 of 13 ears in both groups (76.92%). No significant difference in operative times or complication rates was observed (P &gt; .05). Endoscopic technique could be a viable alternative to the microscopic approach for myringotomy and ventilation tube positioning in adults affected by chronic otitis media with effusion

Differences in telomere length between sporadic and familial cutaneous melanoma

BACKGROUND: Several pieces of evidence indicate that a complex relationship exists between constitutional telomere length (TL) and the risk of cutaneous melanoma. Although the general perception is that longer telomeres increase melanoma risk, some studies do not support this association. We hypothesise that discordant data are due to the characteristics of the studied populations. OBJECTIVES: To evaluate the association of telomere length with familial and sporadic melanoma. METHODS: TL was measured by multiplex quantitative PCR in leukocytes from 310 melanoma patients according to familial/sporadic and single/multiple cancers and 216 age-matched controls. RESULTS: Patients with sporadic melanoma were found to have shorter telomeres as compared to those with familial melanoma. In addition, shorter telomeres, while tending to reduce the risk of familial melanoma regardless of single or multiple tumors, nearly trebled the risk of single sporadic melanoma. CONCLUSIONS: This is the first time that TL has been correlated to opposite effects on melanoma risk according to the presence or absence of familial predisposition. Individual susceptibility to melanoma should be taken into account when assessing the role of TL as a risk factor. This article is protected by copyright. All rights reserved

Briefing paper : assessing the Period Products (Free Provision) (Scotland) Act 2021 as model menstruation legislation

This paper is based on ‘Ending Period Poverty in Scotland: A Historical and International Perspective’ funded by the Royal Society of Edinburgh’s Arts and Humanities Research Network Award from 2020 to 2022 (grant number 64992), and administratively based at the University of St Andrews with Principal Investigator Bettina Bildhauer and Co-Investigators Sharra Vostral and Camilla Mørk Røstvik.This briefing paper discusses how to include historical perspectives to assess the potential success for current and future menstruation legislation. The case of Scotland provides an instructive example of law-making about free period products and period poverty. While commercial products are perceived as a solution, historical research suggests that cultural attitudes, lingering stigma, and regional differences affect opportunities for passing laws. To predict the likelihood that proposed menstrual product legislation might be adopted in other locations, historical factors related to attitudes about menstruation, including stigma, must be considered and understood to effect lasting change.Publisher PDFPeer reviewe