Drug Repositioning in Inflammatory Bowel Disease Based on Genetic Information

Background:Currently, 200 genetic risk loci have been identified for inflammatory bowel disease (IBD). Although these findings have significantly advanced our insight into IBD biology, there has been little progress in translating this knowledge toward clinical practice, like more cost-efficient drug development. Our aim was to use genetic knowledge to identify drugs that warrant further investigation in IBD treatment.Methods:We hypothesized that proteins encoded by IBD candidate genes are potential IBD drug targets because genetic information can increase successful drug identification. We identified drugs that target the proteins encoded by IBD candidate genes using the DrugBank. We included proteins that are in direct protein-protein interaction with proteins encoded by IBD risk genes. Promising potential IBD drugs were selected based on a manual literature search of all identified drugs (PubMed, ClinicalTrials.gov).Results:We have identified 113 drugs that could potentially be used in IBD treatment. Fourteen are known IBD drugs, 48 drugs have been, or are being investigated in IBD, 19 are being used or being investigated in other inflammatory disorders treatment, and 32 are investigational new drugs that have not yet been registered for clinical use.Conclusions:We confirm that proteins encoded by IBD candidate genes are targeted by approved IBD therapies. Furthermore, we show that Food and Drug Administration-approved drugs could possibly be repositioned for IBD treatment. We also identify investigational new drugs that warrant further investigation for IBD treatment. Incorporating this process in IBD drug development will improve the utilization of genetic data and could lead to the improvement of IBD treatment

Aboriginal and Torres Strait Islander adolescents and their\ud attitudes and behaviours around relationships, contraception and pregnancy: lessons for policy and practice

Aims: \ud The “U Mob Yarn Up” project emerged from expressed needs of young Indigenous mothers at Townsville Aboriginal and Islander Health Service (TAIHS), and investigated attitudes and behaviours of young Indigenous people around relationships and pregnancy.\ud \ud Method:\ud An innovative consultative methodology and participatory action techniques were used. A Young Mums’ Group functioned as project designers, key participants and peer interviewers, and as a social support group. A multi-method design involved semi-structured interviews (individual and smallgroup) and a multimedia self-administered survey with peer assistance. 186 Indigenous students from 3 high schools and a homeless youth shelter, and 10 further young mothers took part.\ud \ud Results:\ud Key results from young mothers and never-pregnant young people will be summarised. These highlight the extremely disadvantaged backgrounds of the young women prior to pregnancy and the transformative effect of motherhood in terms of providing purpose for their lives and impetus for\ud change (contingent upon adequate professional and psychosocial support). In addition, the educational aspirations and attitudes and behaviours around sexual relationships and contraceptive use of these young people will be discussed.\ud \ud Implications:\ud However, the main focus of this paper will be on the implications of the findings in terms of clinical practice for primary health care providers, and policy around sexual and reproductive health care and education for this population. For health care providers these include: the importance of providing sensitive and non-judgemental\ud antenatal and postnatal health care; linking with local Young Mums’ Groups; facilitating access to the category of “good mothers”; increasing access for young Indigenous people to contraception, STI testing and abortion; and providing adequate and realistic family planning information for young people. For policy makers priorities include: the provision of broadly based and culturally appropriate sexuality education (through schools and other networks); further training and support for young mothers; programs to prevent violence and abuse within Indigenous families; and reinforcing broader pedagogical initiatives to increase the range of educational and vocational options for Indigenous\ud young people

Educational aspirations and views about pregnancy of Aboriginal and Torres Strait Islander young people in Townsville, Australia

In this article the authors discuss attitudes to schooling, aspirations and views about teenage pregnancy in a group of Indigenous young people in Townsville, Australia, using novel mixed-methods to investigate complex social attitudes and behaviours. A Young Mums' Group operating on participatory action principles designed the instruments, including a computer-assisted survey with peer interviewers, focus group discussions and individual interviews with school students, homeless youth shelter residents and young mothers. The authors found that many young people, especially young women, had high educational aspirations, as did their parents. However. they were lacking in role models and clear pathways to help them achieve these aims, making them seem unattainable. The majority wanted to avoid pregnancy as a teenager, recognising difficulties inherent in this path, but if they became pregnant, most would receive family support, and would not consider options other than having the child. Parenthood as a teenager had fewer costs in terms of negative judgement or limitations on educational achievement than it had for more advantaged young people. The authors conclude that improving educational pathways and transitions may increase intra-community role models and mentors. broadening options, and empowering young women to take the steps required to defer motherhood

The transformative potential of young motherhood for disadvantaged Aboriginal and Torres Strait Islander women in Townsville, Australia

Objective: To explore attitudes to pregnancy and parenthood among a group of Indigenous young people in Townsville, Australia.\ud \ud Design and participants: Mixed methods and a cross-sectional design involving Indigenous women from a Young Mums Group designing the research instruments and\ud acting as peer interviewers. Data were collected in 2004 from young Indigenous people who had never been pregnant (171 students at three high schools and 15 people at a\ud homeless youth shelter) using a computer-assisted self-administered survey; from 59 of this group who also participated in single sex focus group discussions; and from 10 pregnant and parenting young women in individual semi-structured interviews.\ud \ud Main outcome measure: Self-reported attitudes and behaviour about aspirations, pregnancy and parenthood.\ud Results: Only eight of 186 young Indigenous people who had never been pregnant reported wanting to have a child as a teenager. Large proportions of this group of 186\ud reported idealised views about pregnancy, particularly young men, with 50.5% reporting that being a parent would always be enjoyable, and 62.6% reporting that being a mother\ud or a father would not change their lives. Idealised views were associated with earlier sexual initiation (P =0.001). Issues identified in the narratives of young mothers related to difficult backgrounds, pregnancy "just happening" to them, and the transformative impact of having a child on their lives and aspirations.\ud \ud Conclusions: Accurate parenting information may be necessary to address unrealistic views about parenting among Indigenous young people. Young Indigenous parents\ud often come from extremely disadvantaged backgrounds, and becoming a parent may be the impetus for positive change

Attitudes and behaviours of young indigenous people in Townsville concerning relationships, sex and contraception: the "U Mob Yarn Up" project

Objective:\ud To gain some understanding of the attitudes and behaviours of Indigenous young people in Townsville concerning relationships, contraception and safe sex.\ud \ud Design:\ud Cross-sectional study using a computer-assisted self-administered survey and single-sex focus group discussions designed by a Young Mums’ Group operating on participatory action principles and acting as peer interviewers.\ud Participants and setting:\ud \ud 171 Indigenous students in Years 9–11 at three high schools and 15 residents of a homeless youth shelter in Townsville, Queensland, 27 April – 8 December 2004.\ud \ud Main outcome measures:\ud Self-reported attitudes and behaviour about relationships, sexual intercourse and contraception.\ud \ud Results:\ud 84/183 participants (45.9%) reported past sexual intercourse, with 56.1% commencing intercourse at age 13–14 years. The likelihood of having had sex increased with being male (P = 0.001), increasing age, increased perceived sexual activity of peer group (both P = 0.000), and drinking alcohol at least weekly (P = 0.015). Young women were more likely to report unwanted sexual touching (P = 0.031), and less likely to report enjoying sexual intercourse (P = 0.001). The main qualitative themes concerned females’ reputations, coercion, and denial of female desire. Only 49/80 participants (61.3%) reported always using condoms. The main reasons for not using contraception were “just not thinking about it”, shame, and problems with access. Despite having reasonable knowledge about contraception, most lacked the confidence and negotiation skills to communicate with partners about condom use.\ud \ud Conclusions:\ud Like teenagers elsewhere, Indigenous teenagers in Townsville are becoming sexually active at a young age, and not practising safe sex reliably. The need to protect their reputations puts young women at risk by not being prepared for safe sex by carrying condoms.\u

Protein activation mapping of human sun-protected epidermis after an acute dose of erythemic solar simulated light

Ultraviolet radiation is an important etiologic factor in skin cancer and a better understanding of how solar stimulated light (SSL) affects signal transduction pathways in human skin which is needed in further understanding activated networks that could be targeted for skin cancer prevention. We utilized Reverse Phase Protein Microarray Analysis (RPPA), a powerful technology that allows for broad-scale and quantitative measurement of the activation/phosphorylation state of hundreds of key signaling proteins and protein pathways in sun-protected skin after an acute dose of two minimal erythema dose (MED) of SSL. RPPA analysis was used to map the altered cell signaling networks resulting from acute doses of solar simulated radiation (SSL). To that end, we exposed sun-protected skin in volunteers to acute doses of two MED of SSL and collected biopsies pre-SSL and post-SSL irradiation. Frozen biopsies were subjected to laser capture microdissection (LCM) and then assessed by RPPA. The activation/phosphorylation or total levels of 128 key signaling proteins and drug targets were selected for statistical analysis. Coordinate network-based analysis was performed on specific signaling pathways that included the PI3k/Akt/mTOR and Ras/Raf/MEK/ERK pathways. Overall, we found early and sustained activation of the PI3K-AKT-mTOR and MAPK pathways. Cell death and apoptosis-related proteins were activated at 5 and 24 h. Ultimately, expression profile patterns of phosphorylated proteins in the epidermal growth factor receptor (EGFR), AKT, mTOR, and other relevant pathways may be used to determine pharmacodynamic activity of new and selective topical chemoprevention agents administered in a test area exposed to SSL to determine drug-induced attenuation or reversal of skin carcinogenesis pathways.National Cancer Institute, National Institutes of Health [P01 CA027502, K07 CA132956, P30 CA023074]6 month embargo; Published online: 21 September 2017.This item from the UA Faculty Publications collection is made available by the University of Arizona with support from the University of Arizona Libraries. If you have questions, please contact us at [email protected]