Selective Targeting of Glucagon-Like Peptide-1 Signalling As a Novel Therapeutic Approach for Cardiovascular Disease in Diabetes

Glucagon-like peptide-1 (GLP-1) is an incretin hormone whose glucose-dependent insulinotropic actions have been harnessed as a novel therapy for glycaemic control in type 2 diabetes. Although it has been known for some time that the GLP-1 receptor is expressed in the cardiovascular system where it mediates important physiological actions, it is only recently that specific cardiovascular effects of GLP-1 in the setting of diabetes have been described. GLP-1 confers indirect benefits in cardiovascular disease (CVD) under both normal and hyperglycaemic conditions via reducing established risk factors, such as hypertension, dyslipidaemia and obesity, which are markedly increased in diabetes. Emerging evidence indicates that GLP-1 also exerts direct effects on specific aspects of diabetic CVD, such as endothelial dysfunction, inflammation, angiogenesis and adverse cardiac remodelling. However, the majority of studies have employed experimental models of diabetic CVD and information on the effects of GLP-1 in the clinical setting are limited although several large-scale trials are ongoing. It is clearly important to gain a detailed knowledge of the cardiovascular actions of GLP-1 in diabetes given the large number of patients currently receiving GLP-1 based therapies. This review will therefore discuss current understanding of the effects of GLP-1 on both cardiovascular risk factors in diabetes and direct actions on the heart and vasculature in this setting, and the evidence implicating specific targeting of GLP-1 as a novel therapy for CVD in diabetes.

Provision for young people who have displayed harmful sexual behaviour

Over the past few decades, children and young people who have sexually harmed others have attracted increasing attention from researchers and policy makers. Although it is known that they form a small, but significant group, there are difficulties in gaining a clear indication of incidence since much of the existing research has involved small and heterogeneous samples, many of which were not UK-based and lack of control groups for comparison. Furthermore, many incidents of sexual abuse are likely to go unreported. The nature, extent and significant negative consequences of harmful sexual behaviour for the victims and perpetrators, make this an important issue for policy development and research investigation. Overall, research and knowledge in this important area are still accumulating and much remains to be confirmed. Although recent decades have seen a movement towards greater understanding of the issue of harmful sex behaviour, a gap remains. The purpose of the project was to help address this gap in knowledge.

Impact of abuse and neglect on the health and wellbeing of children:Child sexual abuse

During the past 30 years, the focus on the extent and nature of child abuse and neglect has been coupled with an increasing interest in the impact on children’s development, health and mental wellbeing. Child maltreatment is both a human rights violation and a complex public health issue, likely caused by a myriad of factors that involve the individual, the family, and the community. Child abuse includes any type of maltreatment or harm inflicted upon children and young people in interactions between adults (or older adolescents). Such maltreatment is likely to cause enduring harm to the child.
The different forms of abuse and neglect often occur together in one family and can affect one or more children. These include, in deceasing level of frequency: neglect; physical abuse and non-accidental injury; emotional abuse; and sexual abuse (Cawson et al, 2000; 2002). Recently, bullying and domestic violence have been included as forms of abuse of children.
There is a sizeable body of literature on the relationship between types of child maltreatment and a variety of negative health and mental health consequences. These include biological, psychological, and social deficits (for reviews, see Crittenden, 1998; Kendall-Tackett, 2001; 2003). Aside from the serious physical and health consequences of child maltreatment, several emotional and behavioural consequences for children have been noted in the literature.

Sexual Abuse in Institutional Contexts

This chapter adopts a cross-national comparative perspective on institutional child sexual abuse. It seeks first to provide a critical overview of a range of high profile inquiries and official reviews into allegations of institutional child abuse and the dominant transnational themes arising from them. It also seeks to highlight the dynamics of what I have previously termed 'institutional grooming' (McAlinden, 2006) and the features of the organisational environment which both facilitate institutional child sexual abuse and help mask its discovery or disclosure. In so doing, the analysis examines the tension between what others have termed 'preferential' or 'situational' sexual offending – that is whether offenders deliberately set out to gain employment which affords access to children or whether the motivation to sexually offend only emerges after they become ensconced in an institutional environment. Finally, the article concludes by offering some suggestions for combatting institutional grooming and sexual abuse.

The Sexual Offences (NI) Order 2008 implications for nurses

This article outlines the changes to the definition of sexual offences in Northern Ireland following the implementation of the Sexual offences Northern Ireland Order 2008 in 2009, and its implications for nurses working with sexually active children in a range of clinical settings. The paper outlines the key changes for practice and addresses the needs of children in three different age groups with emphasis on children aged 13-15 years, and reviews mandatory reporting, the differences between the rights of children to consent and confidentiality, developmental sexual experimentation and sexual health promotion. It reviews related policy and guidance and makes clear the differences between sexual abuse and exploitation, and experimentation. It seeks to advise the Safeguarding Committee of the Department of Health Northern Ireland on how best to support nurses working with sexually active children and when this activity should be discussed with line managers and safeguarding specialists or referred to the safeguarding authorities.

Sexual Health and Sexuality Education Needs of Young People in Care: a Survey of Service-provider Perspectives. Report No 1.

Aim: This study aims to describe the sex education and sexual health needs of young people in care, and to explore the degree to which these needs are being met by current provision.As part of the Department for Children and Youth Affairs ‘National Strategy for Data and Research on Children’s Lives, 2011-2016’, the HSE Crisis Pregnancy Programme (CPP) and HSE Children and Families Social Services Care Group have co-commissioned a team of researchers from UCD School of Nursing, Midwifery & Health Systems, Insights Health and Social Research and Queen’s University Belfast to examine the sex education and sexual health needs of young people in care in the Republic of Ireland. The project is supported by a steering group of senior personnel from both partner organisations (CPP and CFS) and external advisors. The study involves data collection with young people, care providers, birth parents and foster parents using a mixed methods approach. Findings from each stage of the study will be combined to inform recommendations for policy and practice.

Risk, Regulation and the Reintegration of Sexual Offenders

Media reporting of and public concern about sexual offending, particularly relating to children, affects and reflects political, policy and organisational responses to those convicted of such crimes. The development of regulatory policies on sexual offending has taken place within a highly emotive and overtly politicized public and policy discourse. This chapter charts the various ways in which the risks imagined or posed by sexual offenders have been conceptualised within public discourses and regulated and managed under the legislative and organisational ‘risk paradigm.’ Ultimately, it argues that risk-based responses to sexual offending are at best uncertain in their effects and at worst counterproductive, in that they often reduce the potential for successful reintegration. In seeking to look ‘beyond risk’, the chapter also explores the usefulness of restorative and related practices in supporting sex offender reintegration aimed at the primary and secondary levels of harm prevention.

Small leucine rich proteoglycan family regulates multiple signalling pathways in neural development and maintenance

The small leucine-rich repeat proteoglycan (SLRPs) family of proteins currently consists of five classes, based on their structural composition and chromosomal location. As biologically active components of the extracellular matrix (ECM), SLRPs were known to bind to various collagens, having a role in regulating fibril assembly, organization and degradation. More recently, as a function of their diverse proteins cores and glycosaminoglycan side chains, SLRPs have been shown to be able to bind various cell surface receptors, growth factors, cytokines and other ECM components resulting in the ability to influence various cellular functions. Their involvement in several signaling pathways such as Wnt, transforming growth factor-β and epidermal growth factor receptor also highlights their role as matricellular proteins. SLRP family members are expressed during neural development and in adult neural tissues, including ocular tissues. This review focuses on describing SLRP family members involvement in neural development with a brief summary of their role in non-neural ocular tissues and in response to neural injury.

Prenatal hypoxia leads to increased muscle sympathetic nerve activity, sympathetic hyperinnervation, premature blunting of NPY signalling and hypertension in adult life

Adverse conditions prenatally increase the risk of cardiovascular disease, including hypertension. Chronic hypoxia in utero (CHU) causes endothelial dysfunction, but whether sympathetic vasoconstrictor nerve functioning is altered is unknown. We, therefore, compared in male CHU and control (N) rats muscle sympathetic nerve activity, vascular sympathetic innervation density, and mechanisms of sympathetic vasoconstriction. In young (Y)-CHU and Y-N rats (≈3 months), baseline arterial blood pressure was similar. However, tonic muscle sympathetic nerve activity recorded focally from arterial vessels of spinotrapezius muscle had higher mean frequency in Y-CHU than in Y-N rats (0.56±0.075 versus 0.33±0.036 Hz), and the proportions of single units with high instantaneous frequencies (1–5 and 6–10 Hz) being greater in Y-CHU rats. Sympathetic innervation density of tibial arteries was ≈50% greater in Y-CHU than in Y-N rats. Increases in femoral vascular resistance evoked by sympathetic stimulation at low frequency (2 Hz for 2 minutes) and bursts at 20 Hz were substantially smaller in Y-CHU than in Y-N rats. In Y-N only, the neuropeptide Y Y1-receptor antagonist BIBP3226 attenuated these responses. By contrast, baseline arterial blood pressure was higher in middle-aged (M)-CHU than in M-N rats (≈9 months; 139±3 versus 126±3 mmHg, respectively). BIBP3226 had no effect on femoral vascular resistance increases evoked by 2 Hz or 20 Hz bursts in M-N or M-CHU rats. These results indicate that fetal programming induced by prenatal hypoxia causes an increase in centrally generated muscle sympathetic nerve activity in youth and hypertension by middle age. This is associated with blunting of sympathetically evoked vasoconstriction and its neuropeptide Y component that may reflect premature vascular aging and contribute to increased risk of cardiovascular disease