Involvement of the WT1 and p16 genes in Wilms' tumour and human malignant mesothelioma

Normal cellular homeostasis is established and maintained by the positive and negative regulatory activities of many genes. When these genes are mutated to forms that can contribute to tumorigenesis, either by dominant, gain of function mutations in positive regulators or recessive, loss of function mutations in negative regulators, they are termed oncogenes or tumour suppressor genes, respectively. Identified human tumour suppressor genes, though still relatively few in number, are found to be active in many different cellular processes. I have studied two such genes, the WT1 and p16 genes, which in their wild type forms are known to contribute to development of the urogenital system and the mesothelium (WTI) and to control of the cell cycle (pi6).WT1 was identified as a gene repeatedly disrupted in Wilms' tumour, a common paediatric renal malignancy. This study is one of many which sought to confirm and understand some of the roles of WTI in both normal development and tumorigenesis. Mutation analysis of WTI in samples from patients with sporadic, bilateral and syndrome-associated Wilms' tumour has produced a pattern of results consistent with the findings of other groups. No mutations were detected in the sporadic and bilateral tumours, however exonic point mutations were detected in 7 out of 9 syndrome-associated Wilms' tumour samples that were analysed in detail. Studies examining parental WTI status, genomic imprinting and allele loss distal to the WTI locus are detailed for the syndrome-associated Wilms' tumour samples. Additionally, analysis of WTI in samples from patients with testicular tumours or malignant mesothelioma did not identify any mutations believed to be significant in tumorigenesis.The contribution, resulting effects and complementary nature of WTI and p16 mutations in Wilms' tumour and malignant mesothelioma is discussed

Oxidative Stress Response to Short Duration Bout of Submaximal Aerobic Exercise in Healthy Young Adults

The purpose of this study was to investigate the oxidative stress response to a short duration bout of submaximal exercise in a cohort of healthy young adults. 15 apparently healthy college age males and females completed a modified Bruce-protocol treadmill test to 75–80% of their heart rate reserve. Blood samples collected immediately before (pre-exercise), immediately after, 30, 60 and 120 minutes post-exercise were assayed for total antioxidant capacity (TAC), superoxide disumutase (SOD), thiobarbituric acid-reactive substances (TBARS), and protein carbonyls (PC). SOD activity was significantly increased from pre-exercise levels at 30 minutes (77%), 60 minutes (33%), and 120 minutes (37%) post-exercise. TAC levels were also significantly increased from pre-exercise levels at 60 minutes (30%) and 120 minutes (33%) post-exercise. There were no significant changes in biomarkers for reactive oxygen/nitrogen species (RONS) mediated damage (TBARS and PC) across all post-exercise time points. In a cohort of healthy young adults, a short duration bout of submaximal aerobic exercise elicited increases in antioxidant activity/concentration, but did not evoke changes in oxidative stress-induced damage. These results may suggest that: (1) short duration bouts of submaximal aerobic exercise are sufficient to induce RONS generation; and (2) the antioxidant defense system is capable of protecting against enhanced RONS production induced by a short duration, submaximal exercise bout in healthy young adults

Adolescents: Orphaned and Vulnerable in the Time of HIV/AIDS

This paper calls for greater attention to orphaned and vulnerable adolescents by agencies working in this field

An Interprofessional Approach to Teaching Evidence-based Practice

Purpose: The purpose of this mixed methods study was to identify students’ engagement and implementation of EBP competencies after exposure to EBP content in an interprofessional online research course. In this research, a diverse, convenience sample of nursing, respiratory care, and social work students were selected. The results aim to assist educators in preparing the next generation for their first professional role in providing care using the best evidence. The research questions that guided the study were: (1) What are the levels of practice, attitude, knowledge and skill regarding EBP among the sample? (2) What are the barriers and facilitators to acquiring EBP competency? (3) What are the differences in EBP attitudes, knowledge, and skills between the diverse disciplines in the sample? Methods: This descriptive mixed methods study employed a cross sectional design that allowed comparisons of programs and the different levels within the program. Quantitative data was collected using the S-EBPQ survey, allowing participants’ the opportunity to self-report on the practice, attitude, and knowledge/skills. Qualitative data was collected through two focus groups of approximately six to ten students from the three programs. Results: Data showed that students within the three selected disciplines had a positive attitude towards EBP. Theme analysis supported this view as participants noted EBP impacts patient safety and quality care. Barriers identified included, “lack of resources, use of research language interchangeably with EBP, quick exposure to EBP and confusion among EBP practices in the clinical setting.” Participants had an awareness of EBP and recognized the value of EBP. However, there may be ways to improve the implementation of EBP throughout the learning process while students are in undergraduate studies. Conclusion: Using an interprofessional online research course to introduce students to EBP was successful. Providing an interprofessional approach to teaching EBP will provide support the implementation of EBP competencies. Further development of additional interprofessional EBP courses or activities should be considered. This study found that if interprofessional care teams’ work together and use the EBP process in their courses it will improve student perceived value of EBP

Social and emotional developmental vulnerability at age five in Aboriginal and non-Aboriginal children in New South Wales: a population data linkage study

Background Early childhood social and emotional development underpins later social, emotional, academic and other outcomes. The first aim of this study was to explore the association between child, family and area-level characteristics associated with developmental vulnerability, amongst Aboriginal and non-Aboriginal children in their first year of school. The second aim was to quantify the magnitude of the social and emotional developmental inequalities between Aboriginal and non-Aboriginal children and the extent to which differences in socioeconomic disadvantage and perinatal characteristics explained this inequality. Methods This retrospective cohort study used cross-sectoral data linkage to identify and follow participants from birth to school age. In this way, social and emotional development was examined in 7,384 Aboriginal and 95,104 non-Aboriginal children who were included in the Australian Early Development Census in their first year of full-time school in New South Wales (NSW) in 2009 or 2012 and had a birth registration and/or perinatal record in NSW. The primary outcome measures were teacher-reported social competence and emotional maturity as measured using the Australian version of the Early Development Instrument. Results The mean age at the start of the school year for children in the study sample was 5.2 years (SD = 0.36 years). While 84% of Aboriginal children scored favourably - above the vulnerability threshold – for social competence and 88% for emotional maturity, Aboriginal children were twice as likely as non-Aboriginal children to be vulnerable on measures of social development (RR = 2.00; 95%CI, 1.89–2.12) and had 89% more risk of emotional vulnerability (RR = 1.89; 95%CI, 1.77–2.02). The inequality between Aboriginal and non-Aboriginal children was largely explained by differences in the socioeconomic and perinatal health characteristics of children and families. Thus, after adjusting for differences in measures of socioeconomic advantage and disadvantage (Model 2), the relative risk was attenuated to 1.31 (95% CI: 1.23–1.40) on the social competence domain and 1.24 (95% CI, 1.15–1.33) on the emotional maturity domain. Child, family and area-level characteristics associated with vulnerability were identified. Conclusions Most of the gap in early childhood social and emotional development between Aboriginal and non-Aboriginal children can be attributed to socioeconomic and early life health disadvantage. Culturally safe health and social policies addressing the socioeconomic and health inequalities experienced by Aboriginal children are urgently required.This work was supported by National Health and Medical Research Council of Australia (NHMRC) Project Grant (#1061713) and a Financial Markets Foundation for Children (Australia) grant (2016–341). AW was supported by a NSW Health Early-Mid Career Fellowship. KF was supported by an NHMRC Early Career Fellowship (#1016475) and an NHMRC capacity building grant (#573122). EB was supported by an NHMRC Principal Research Fellowship (#1136128). SE was supported by an NHMRC Career Development Fellowship (#1013418)

Psychological distress in carers of aboriginal children in urban New South Wales: Findings from search (phase one)

OBJECTIVE: To examine the factors associated with psychological distress in parents and carers of Aboriginal children living in urban communities in New South Wales. DESIGN: Cross-sectional survey (phase one of the Study of Environment on Aboriginal Resilience and Child Health [SEARCH], November 2007 - December 2011). SETTING AND PARTICIPANTS: Primary care; 589 parents and carers of Aboriginal children were recruited when attending one of the four Aboriginal Community Controlled Health Services (ACCHSs) in urban NSW that participated in SEARCH. MAIN OUTCOME MEASURE: Kessler Psychological Distress Scale (K10) scores; a score of 22 or higher was deemed to indicate high levels of psychological distress. RESULTS: High levels of psychological distress were identified in 18% of our sample. The factors most strongly associated with this distress were functional limitations (v those with K10 scores under 22: adjusted odds ratio [aOR], 4.2; 95% CI, 1.3-13.5), previous hospitalisation (aOR, 5.5; 95% CI, 1.5-19.4) or other treatment for social and emotional wellbeing (aOR, 3.3; 95% CI, 1.3-8.4), low satisfaction with feeling part of the community (aOR, 0.83; 95% CI, 0.70-0.98) and low involvement in clubs and groups (aOR, 2.9; 95% CI, 1.2-7.3). CONCLUSIONS: Clinicians should note that those with functional limitations or a history of treatment for mental health problems are at higher risk of psychological distress and may require additional support. Increased funding that allows ACCHSs to provide mental health services, and funding and promoting programs and activities that increase social connectedness should remain focuses for ACCHSs and policy makers

Oxidative stress response to short duration bout of submaximal aerobic exercise in healthy young adults

The purpose of this study was to investigate the oxidative stress response to a short duration bout of submaximal exercise in a cohort of healthy young adults. 15 apparently healthy college age males and females completed a modified Bruce-protocol treadmill test to 75-80% of their heart rate reserve. Blood samples collected immediately before (pre-exercise), immediately after, 30, 60 and 120 minutes post-exercise were assayed for total antioxidant capacity (TAC), superoxide disumutase (SOD), thiobarbituric acid-reactive substances (TBARS), and protein carbonyls (PC). SOD activity was significantly increased from pre-exercise levels at 30 minutes (77%), 60 minutes (33%), and 120 minutes (37%) post-exercise. TAC levels were also significantly increased from pre-exercise levels at 60 minutes (30%) and 120 minutes (33%) post-exercise. There were no significant changes in biomarkers for reactive oxygen/nitrogen species (RONS) mediated damage (TBARS and PC) across all post-exercise time points. In a cohort of healthy young adults, a short duration bout of submaximal aerobic exercise elicited increases in antioxidant activity/concentration, but did not evoke changes in oxidative stress-induced damage. These results may suggest that: (1) short duration bouts of submaximal aerobic exercise are sufficient to induce RONS generation; and (2) the antioxidant defense system is capable of protecting against enhanced RONS production induced by a short duration, submaximal exercise bout in healthy young adults

Increased Nitric Oxide and Attenuated Diastolic Blood Pressure Variability in African Americans with Mildly Impaired Renal Function

We investigated the relationship between renal function, blood pressure variability (BPV), and nitric oxide (NO) in a group of African Americans with normal or mildly impaired renal function. 24-hour ambulatory blood pressure monitoring was performed, NO measured, and glomerular filtration rate (GFR) calculated in 38 African Americans. Participants were categorized as having normal (GFR > 90 mL/min per 1.73 m2) or mildly impaired (GFR 60–89 mL/min per 1.73 m2) renal function. Diastolic BPV was significantly lower in the mildly impaired renal function group. Regression analyses revealed a significant positive association between GFR and diastolic BPV for the entire study group. Plasma NO levels were significantly higher in the mildly impaired renal function group and negatively correlated with diastolic BPV. In conclusion, diastolic BPV was reduced in African Americans with mildly impaired renal function, which may be the result of increased NO production. These results conflict with previous findings in diseased and nonblack populations and could provide rationale for studying BPV early in the disease state when BP-buffering mechanisms are still preserved

Promoting good outcomes in Lesbian, Gay and Bisexual cancer care: a qualitative study of patients’experiences in clinical oncology

EXECUTIVE SUMMARY Cancer inequalities, including differences in cancer outcomes and patient satisfaction, affect a range of groups including lesbian, gay and bisexual (LGB) people. In its strategy to reduce these inequalities, the Department of Health commissioned the Cancer Patient Experience Survey (CPES) providing baseline data in which LGB patients were more likely to say their experiences were less positive than those of heterosexual patients. These differences included accessible information, psychosocial support and the human rights concerns of dignity and respect. The CPES, which was carried out in four successive years (2010-2014), suggesting that these are intractable problems, found that LGB patients were more likely to disagree with statements such as they ‘never felt treated as a set of cancer symptoms rather than as a whole person’ or the ‘doctor never talked about me as if I wasn’t there’. The CPES did not collect qualitative data and consequently the reasons for these differences were not known. This De Montfort University study, funded by Macmillan, illuminates some of the reasons for these survey findings as we were able to gather people’s accounts of their treatment and care. This report identifies key moments in the cancer journey where care provided for LGB cancer patients can contribute to their recovery and well-being. Alongside this evidence of unmet need, NHS England (2017) has recently issued guidance to support the introduction of mechanisms for recording sexual orientation across all health services in England for patients over 16. It recommends that sexual orientation monitoring occurs at every face to face contact with the patient. The collection of this monitoring data has implications; not only for cancer professionals, but also that patients themselves understand why this information is being requested. The report draws on LGB cancer patients’ motivations and methods for disclosing their sexual orientation and the perceived benefits of doing so for their quality of life. The findings will contribute to understanding the health benefits of coming out and how disclosure might be facilitated in hospital settings. This study provides compelling data about some of the factors underpinning inequalities in the experiences and, potentially, cancer outcomes for LGB patients. Managing the worry about whether it is safe to disclose their sexual orientation to professionals and the uncertainty about how this will be received presents an additional burden for LGB people with cancer. Participants in this study were sometimes hesitant to disclose because the opportunity did not arise or they were uncertain about its relevance. The report identifies some moments that matter in the care relationship where professionals could seek to facilitate disclosure thus contributing to Achieving World Class Cancer Outcomes (Department of Health, 2015) for LGB patients. In addition, the findings point to the importance of creating an inclusive care environment; participants noted that even in the Cancer Centres of Excellence, there were few visible signs of inclusion for LGB cancer patients. Steps to promote inclusion may entail a diversity policy statement, imagery on walls or the display of a LGB staff network on a hospital notice-board. participants also shared experiences where they were accepted in an everyday manner by hospital staff. They often talked about a whole hospital approach where they were acknowledged by staff from porters, health care assistants, nurses and consultants. These cancer narratives also highlight the need for LGB cancer support groups and tailored resources. The lack of LGB support groups in the UK mean that some participants were coping with their cancer with few forms of social and emotional support and they found few sources of information which addressed their needs. There was a clear demand for a greater range of LGB support resources that were relevant to the challenges and concerns of specific cancer types and reports of rather patchy provision in this regard, with differences influenced primarily by geographic location and cancer type. Finally, our findings suggest that participants had heterogeneous expectations of cancer care requiring complex .skills from professionals. Yet there is little or no curricula content in university programmes of Medicine or Nursing. This might suggest a lack of recognition of distinctive cancer care needs and may explain why participants reported different patient experiences even within the same hospital. The inclusion of research with LGB patients alongside heterosexual populations and relevant case studies to underpin Learning and Development and Continuous Professional Development to inform understanding of patient experience, psychosocial concerns and cancer risk is urgently needed