How close is the dose? Manipulation of 10 mg hydrocortisone tablets to provide appropriate doses to children

This study explores the methodology advised by healthcare professionals and the methods used by parents/carers to identify whether there is a best practice method for manipulation of 10 mg hydrocortisone tablets to provide an accurate dose to children. Bespoke surveys were used to identify methods recommended and used in manipulation of tablets. Hydrocortisone tablets were manipulated to provide a specified dose by both naïve participants and parents/carers. The accuracy of manipulation was assessed using HPLC analysis. Competed surveys were received from 159 parent/carers reporting doses that ranged from 0.25 to 15 mg. Parents/carers most commonly reported splitting the tablet and administering the solid fraction; however more than 30% of those reporting physically splitting tablets were preparing doses that were not simply halving or quartering tablets. In a naïve population the dose accuracy, defined as percent of doses within 20% of the theoretical dose ranged from 57 to 58% depending on the tablet brand and the method of manipulation used. Almost three-quarters (74.1%) of parent/carers (n = 27) were able to produce a dose within 20% of the theoretical value and the most accurate method was to split tablets and administer the solid fraction. This study shows that a lack of age-appropriate medicines results in children being at risk of sub-optimal dosing

Heterotrophy mitigates the response of the temperate coral

Anthropogenic increases in atmospheric carbon dioxide concentration have caused global average sea surface temperature (SST) to increase by approximately 0.11°C per decade between 1971 and 2010 - a trend that is projected to continue through the 21st century. A multitude of research studies have demonstrated that increased SSTs compromise the coral holobiont (cnidarian host and its symbiotic algae) by reducing both host calcification and symbiont density, among other variables. However, we still do not fully understand the role of heterotrophy in the response of the coral holobiont to elevated temperature, particularly for temperate corals. Here, we conducted a pair of independent experiments to investigate the influence of heterotrophy on the response of the temperate scleractinian coral Oculina arbuscula to thermal stress. Colonies of O. arbuscula from Radio Island, North Carolina, were exposed to four feeding treatments (zero, low, moderate, and high concentrations of newly hatched Artemia sp. nauplii) across two independent temperature experiments (average annual SST (20°C) and average summer temperature (28°C) for the interval 2005-2012) to quantify the effects of heterotrophy on coral skeletal growth and symbiont density. Results suggest that heterotrophy mitigated both reduced skeletal growth and decreased symbiont density observed for unfed corals reared at 28°C. This study highlights the importance of heterotrophy in maintaining coral holobiont fitness under thermal stress and has important implications for the interpretation of coral response to climate change

Oxidative Stress Alters the Morphology and Toxicity of Aortic Medial Amyloid

The aggregation and fibril deposition of amyloid proteins have been implicated in a range of neurodegenerative and vascular diseases, and yet the underlying molecular mechanisms are poorly understood. Here, we use a combination of cell-based assays, biophysical analysis, and atomic force microscopy to investigate the potential involvement of oxidative stress in aortic medial amyloid (AMA) pathogenesis and deposition. We show that medin, the main constituent of AMA, can induce an environment rich in oxidative species, increasing superoxide and reducing bioavailable nitric oxide in human cells. We investigate the role that this oxidative environment may play in altering the aggregation process of medin and identify potential posttranslational modification sites where site-specific modification and interaction can be unambiguously demonstrated. In an oxidizing environment, medin is nitrated at tyrosine and tryptophan residues, with resultant effects on morphology that lead to longer fibrils with increased toxicity. This provides further motivation to investigate the role of oxidative stress in AMA pathogenicity

Internet Facilitated Rape: A Multivariate Model of Offense Behavior

In recent years there has been a significant increase in individuals reporting they have been raped by someone they have met through the internet (IFR). Previous literature has primarily focused on child victims, hence, the overriding aim of this study is to further our understanding of IFR in terms of overt crime scene behaviour. The sample consisted of 144 single IFR cases and two comparative samples of age-matched non-IFR offenders (confidence approach and surprise approach). Thirty-eight crime scene actions were coded as either present or absent for each offence. Findings suggest that the platforms IFR offenders use to meet their victims were not suggestive of the behaviour they were likely to display. In terms of specific offence behaviours, the IFR and confidence approach samples were considerably similar and both samples were comparatively different from the surprise approach cases. A smallest space analysis of the IFR sample revealed three distinct themes of behaviour with 71% of cases being assigned to a dominant behavioural theme. The practical and theoretical implications of the findings will be discussed

Is There Enough Evidence to Support the Role of Glycosaminoglycans and Proteoglycans in Thoracic Aortic Aneurysm and Dissection?—A Systematic Review

Altered proteoglycan (PG) and glycosaminoglycan (GAG) distribution within the aortic wall has been implicated in thoracic aortic aneurysm and dissection (TAAD). This review was conducted to identify literature reporting the presence, distribution and role of PGs and GAGs in the normal aorta and differences associated with sporadic TAAD to address the question; is there enough evidence to establish the role of GAGs/PGs in TAAD? 75 studies were included, divided into normal aorta (n = 51) and TAAD (n = 24). There is contradictory data regarding changes in GAGs upon ageing; most studies reported an increase in GAG sub-types, often followed by a decrease upon further ageing. Fourteen studies reported changes in PG/GAG or associated degradation enzyme levels in TAAD, with most increased in disease tissue or serum. We conclude that despite being present at relatively low abundance in the aortic wall, PGs and GAGs play an important role in extracellular matrix maintenance, with differences observed upon ageing and in association with TAAD. However, there is currently insufficient information to establish a cause-effect relationship with an underlying mechanistic understanding of these changes requiring further investigation. Increased PG presence in serum associated with aortic disease highlights the future potential of these biomolecules as diagnostic or prognostic biomarkers.</jats:p

Exploring the potential of rapid evaporative ionization mass spectrometry (Intelligent Knife) for point-of-care testing in aortic surgery

Abstract OBJECTIVES Many intraoperative decisions regarding the extent of thoracic aortic surgery are subjective and are based on the appearance of the aorta, perceived surgical risks and likelihood of early recurrent disease. Our objective in this work was to carry out a cross-sectional study to demonstrate that rapid evaporative ionization mass spectrometry (REIMS) of electrosurgical aerosol is able to empirically discriminate ex vivo aneurysmal human thoracic aorta from normal aorta, thus providing supportive evidence for the development of the technique as a point-of-care test guiding intraoperative surgical decision-making. METHODS Human aortic tissue was obtained from patients undergoing surgery for thoracic aortic aneurysms (n = 44). Normal aorta was obtained from a mixture of post-mortem and punch biopsies from patients undergoing coronary surgery (n = 13). Monopolar electrocautery was applied to samples and surgical aerosol aspirated and analysed by REIMS to produce mass spectral data. RESULTS Models generated from REIMS data can discriminate aneurysmal from normal aorta with accuracy and precision of 88.7% and 85.1%, respectively. In addition, further analysis investigating aneurysmal tissue from patients with bicuspid and tricuspid aortic valves was discriminated from normal tissue and each other with accuracies and precision of 93.5% and 91.4% for control, 83.8% and 76.7% for bicuspid aortic valve and 89.3% and 86.0% for tricuspid aortic valve, respectively. CONCLUSIONS Analysis of electrosurgical aerosol from ex vivo aortic tissue using REIMS allowed us to discriminate aneurysmal from normal aorta, supporting its development as a point-of-care test (Intelligent Knife) for guiding surgical intraoperative decision-making. </jats:sec

Comparisons with amyloid-β reveal an aspartate residue that stabilizes fibrils of the aortic amyloid peptide medin

Aortic medial amyloid (AMA) is the most common localized human amyloid, occurring in virtually all of the Caucasian population over the age of 50. The main protein component of AMA, medin, readily assembles into amyloid-like fibrils in vitro. Despite the prevalence of AMA, little is known about the self-assembly mechanism of medin or the molecular architecture of the fibrils. The amino acid sequence of medin is strikingly similar to the sequence of the Alzheimer's disease (AD) amyloid-beta (Aβ) polypeptides around the structural turn region of Aβ where mutations associated with familial, early onset AD, have been identified. D25 and K30 of medin align with residues D23 and K28 of Aβ that are known to form a stabilizing salt bridge in some fibril morphologies. Here we show that substituting D25 of medin with asparagine (D25N) impedes assembly into fibrils and stabilizes non-cytotoxic oligomers. Wild-type medin, by contrast, aggregates into β-sheet rich amyloid-like fibrils within 50 h. A structural analysis of wild-type fibrils by solid-state NMR suggests a molecular repeat unit comprising at least two extended β-strands, separated by a turn stabilized by a D25-K30 salt-bridge. We propose that D25 drives the assembly of medin by stabilizing the fibrillar conformation of the peptide, and is thus reminiscent of the influence of D23 on the aggregation of Aβ. Pharmacological comparisons of wild-type medin and D25N will help to ascertain the pathological significance of this poorly under-stood protein

Variant connective tissue (joint hypermobility) and its relevance to depression and anxiety in adolescents: a cohort-based case-control study

Objective: To test whether variant connective tissue structure, as indicated by the presence of joint hypermobility, poses a developmental risk for mood disorders in adolescence. Design: Cohort-based case-control study. Setting: Data from the Avon Longitudinal Study of Parents and Children (ALSPAC) were interrogated. Participants: 6105 children of the ALSPAC cohort at age 14 years old, of whom 3803 also were assessed when aged 18 years. Main outcome measures: In a risk analysis, we examined the relationship between generalised joint hypermobility (GJH) at age 14 years with psychiatric symptoms at age 18 years. In an association analysis, we examined the relationship between presence of symptomatic joint hypermobility syndrome (JHS) and International Classification of Diseases (ICD-10) indication of depression and anxiety (Clinical Interview Schedule Revised [CIS-R], Anxiety Sensitivity Index [ASI]) at age 18 years. Results: GJH was more common in females (n=856, 28%) compared to males (n=319, 11%; OR 3.20 (95% CI 2.78 to 3.68); P<0.001). In males only, GJH at age 14 years was associated with depression at 18 years (OR 2.10 (95%CI 1.17 to 3.76); P=0.013). An index of basal physiological arousal, elevated resting heart rate, mediated this effect. Across genders, the diagnosis of JHS at age 18 years was associated with the presence of depressive disorder (adjusted OR 3.53 (95%CI 1.67 to 7.40); P=0.001), anxiety disorder (adjusted OR 3.14 (95% CI 1.52 to 6.46); P=0.002), level of anxiety (B=8.08, t(3278)=3.95; P<0.001), and degree of psychiatric symptomatology (B=5.89, t(3441)=0.093; p<0.001). Conclusions: Variant collagen, indexed by joint hypermobility, is linked to the emergence of depression and anxiety in adolescence, an effect mediated by autonomic factors in males. Recognition of this association may motivate further evaluation, screening, and interventions to mitigate development of psychiatric disorders and improve health outcomes