Disorders of sex development : insights from targeted gene sequencing of a large international patient cohort

Background: Disorders of sex development (DSD) are congenital conditions in which chromosomal, gonadal, or phenotypic sex is atypical. Clinical management of DSD is often difficult and currently only 13% of patients receive an accurate clinical genetic diagnosis. To address this we have developed a massively parallel sequencing targeted DSD gene panel which allows us to sequence all 64 known diagnostic DSD genes and candidate genes simultaneously. Results: We analyzed DNA from the largest reported international cohort of patients with DSD (278 patients with 46, XY DSD and 48 with 46, XX DSD). Our targeted gene panel compares favorably with other sequencing platforms. We found a total of 28 diagnostic genes that are implicated in DSD, highlighting the genetic spectrum of this disorder. Sequencing revealed 93 previously unreported DSD gene variants. Overall, we identified a likely genetic diagnosis in 43% of patients with 46, XY DSD. In patients with 46, XY disorders of androgen synthesis and action the genetic diagnosis rate reached 60%. Surprisingly, little difference in diagnostic rate was observed between singletons and trios. In many cases our findings are informative as to the likely cause of the DSD, which will facilitate clinical management. Conclusions: Our massively parallel sequencing targeted DSD gene panel represents an economical means of improving the genetic diagnostic capability for patients affected by DSD. Implementation of this panel in a large cohort of patients has expanded our understanding of the underlying genetic etiology of DSD. The inclusion of research candidate genes also provides an invaluable resource for future identification of novel genes

Contextualising the social capital of Australian Aboriginal and non-Aboriginal men in prison

© 2016Social capital is a valuable resource that has received little attention in the prison context. Differences in the construct and accessibility of bonding, bridging, and linking social capital exist for Aboriginal Australians in mainstream society, but were previously unexplored in prison. This study seeks to understand contextual differences of social capital for Australian Aboriginal and non-Aboriginal men in prison. Thirty male inmates participated in qualitative interviews across three New South Wales (NSW) correctional centres. Interviews were completed between November 2014 and March 2015. Experiences of bonding and linking social capital varied among Aboriginal and non-Aboriginal participants. Opportunities for bridging social capital were limited for all participants. There is greater scope for building bonding social capital among male inmates than either bridging or linking social capital. Bonding social capital, particularly among Aboriginal men in prison, should be utilised to promote health and other programs to inmates

Social capital strategies to enhance hepatitis C treatment awareness and uptake among men in prison

Prisoner populations are characterized by high rates of hepatitis C (HCV), up to thirty times that of the general population in Australia. Within Australian prisons, less than 1% of eligible inmates access treatment. Public health strategies informed by social capital could be important in addressing this inequality in access to HCV treatment. Twenty-eight male inmates participated in qualitative interviews across three correctional centres in New South Wales, Australia. All participants had recently tested as HCV RNA positive or were receiving HCV treatment. Analysis was conducted with participants including men with experiences of HCV treatment (n=10) (including those currently accessing treatment and those with a history of treatment) and those who were treatment naïve (n=18). Social capital was a resourceful commodity for inmates considering and undergoing treatment while in custody. Inmates were a valuable resource for information regarding HCV treatment, including personal accounts and reassurance (bonding social capital), while nurses a resource for the provision of information and care (linking social capital). Although linking social capital between inmates and nurses appeared influential in HCV treatment access, there remained opportunities for increasing linking social capital within the prison setting (such as nurse-led engagement within the prisons). Bonding and linking social capital can be valuable resources in promoting HCV treatment awareness, uptake and adherence. Peer-based programmes are likely to be influential in promoting HCV outcomes in the prison setting. Engagement in prisons, outside of the clinics, would enhance opportunities for linking social capital to influence HCV treatment outcomes.The first author (LL) is a recipient of a National Health & Medical Research Council Scholarship (Grant No. 1075727). The Centre for Social Research in Health is supported by a grant from the Australian Government Department of Health

Obesity and asthma at school entry: Co-morbidities and temporal trends

Aim: A decline in asthma prevalence from 2000 to 2005 was reported previously. The objective is to examine the temporal trends for the prevalence of obesity and other childhood disorders and consider the extent to which associations between asthma and other co-morbidities can be accounted for by body mass index. Methods: Serial cross-sectional surveys of primary school entrants (n = 18 999) in the Australian Capital Territory between 2001 and 2005 were used. Asthma, recent respiratory symptoms and diabetes data were extracted from parental reports. Anthropometric measurements were obtained from health assessments by school nurses. Child obesity was defined using the age and sex-specific Cole criteria. Time trends for the prevalence of obesity and other disorders, and the association between ‘current asthma’ and co-morbidities were analysed using multiple logistic regression and other analyses. Results: Obesity prevalence was 5.24% in 2001 decreasing to 3.60% in 2005 (test of linear trend P = 0.02). Overweight (adjusted odds ratio (AOR) 1.30 (95% confidence interval (CI) 1.16, 1.46), P < 0.001) and obese (AOR 1.36 (95% CI 1.13, 1.62), P = 0.001) children were more likely to report ‘asthma ever’. Children with diabetes (AOR 9.35 (95% CI 3.11, 28.12, P < 0.001)) and attention deficit (AOR 3.39 (95% CI 2.04, 5.64), P < 0.001) were more likely to report ‘current asthma’. Conclusions: The pattern of association with co-morbidities was different for asthma and obesity. The temporal decline/plateau effect in ‘current asthma’ could not be explained by concurrent body mass index changes. The decline in obesity was largely driven by the 2005 findings. Longer term trends need to be evaluated further

The B'Active programme for overweight primary school children in Glasgow: determining the prevalence of overweight and obesity and piloting an activity intervention.

The aim of this study was to determine the prevalence of overweight and obesity in primary school children in Glasgow and to evaluate a pilot activity programme for overweight and obese children. BMI was measured in 1548 children. Overweight, obesity and severe obesity were defined as BMI &gt; or =85th, 95th and 98th centile, respectively. Overweight and obese children were then invited to participate in a 10-week school-based activity programme. The programme was evaluated by recording weekly attendance, intensity (using the Children's Effort Rating Scale) and enjoyment (scale 1-10). Focus groups were used to explore the experiences and views of the children, teachers, coaches and parents. Of the 1548 children, 31.4% were overweight, 19.1% were obese and 12.4% were severely obese; 38% of those invited attended the activity programme. Weekly programme attendance was 83% (range 56-99%). Mean enjoyment rating (scale 1-10) was 8 for boys and 9 for girls. The intensity of activity sessions were rated 'very easy' by boys and 'just feeling a strain' by girls. Common themes emerging from the focus groups related to perceived positive and negative aspects of the programme (fun, concerns about stigmatising children); physical and psychological outcomes (fitter, more confident); and future recommendations (involve parents). In summary, the prevalence of overweight and obesity was high. The activity programme was successful in terms of attendance and enjoyment, and overall views of the initiative were positive and there was compelling support for its continuation

Measuring Social Capital in the Prison Setting: Lessons Learned From the Inmate Social Capital Questionnaire

© The Author(s) 2018. Social capital has been associated with improved health outcomes. Measures of social capital have been developed specifically for different population groups, cultures, and contexts; however, there is no readily available measure for use among inmates in the prison setting. This study sought to translate a community concept into the prison setting through the development and piloting of the Inmate Social Capital Questionnaire (ISCQ). Thirty male inmates (living with hepatitis C) participated in the pilot phase of the ISCQ (n = 23 sentenced and n = 7 held on remand). Dimensions of social capital were influenced by length of incarceration (time already served as well as time to release), connections with family, and duration at current prison

MYBA and MYBPA transcription factors co-regulate anthocyanin biosynthesis in blue-coloured berries

The regulatory network of R2R3 MYB transcription factors in anthocyanin biosynthesis is not fully understood in blue-coloured berries containing delphinidin compounds. We used blue berries of bilberry (Vaccinium myrtillus) to comprehensively characterise flavonoid-regulating R2R3 MYBs, which revealed a new type of co-regulation in anthocyanin biosynthesis between members of MYBA-, MYBPA1- and MYBPA2-subgroups. VmMYBA1, VmMYBPA1.1 and VmMYBPA2.2 expression was elevated at berry ripening and by abscisic acid treatment. Additionally, VmMYBA1 and VmMYBPA1.1 expression was strongly downregulated in a white berry mutant. Complementation and transient overexpression assays confirmed VmMYBA1 and VmMYBA2 to induce anthocyanin accumulation. Promoter activation assays showed that VmMYBA1, VmMYBPA1.1 and VmMYBPA2.2 had similar activity towards dihydroflavonol 4-reductase (DFR) and anthocyanidin synthase (ANS), but differential regulation activity for UDP-glucose flavonoid 3-O-glucosyltransferase (UFGT) and flavonoid 3′5′-hydroxylase (F3′5′H) promoters. Silencing of VmMYBPA1.1 in berries led to the downregulation of key anthocyanin and delphinidin biosynthesis genes. Functional analyses of other MYBPA regulators, and a member of novel MYBPA3 subgroup, associated them with proanthocyanidin biosynthesis and F3′5′H expression. The existence of 18 flavonoid-regulating MYBs indicated gene duplication, which may have enabled functional diversification among MYBA, MYBPA1 and MYBPA2 subgroups. Our results provide new insights into the intricate regulation of the complex anthocyanin profile found in blue-coloured berries involving regulation of both cyanidin and delphinidin branches