Newborn bloodspot screening (NBS) programs have improved neonatal healthcare since the 1960s. Genomic sequencing now offers potential to generate polygenic risk score (PRS) that could be incorporated ...into NBS programs, shifting the focus from treatment to prevention of future noncommunicable disease (NCD). However, Australian parents' knowledge and attitudes regarding PRS for NBS is currently unknown.
Parents with at least one Australian-born child under 18 years were invited via social media platforms to complete an online questionnaire aimed at examining parents' knowledge of NCDs, PRS, and precision medicine, their opinions on receiving PRS for their child, and considerations of early-intervention strategies to prevent the onset of disease.
Of 126 participants, 90.5% had heard the term "non-communicable disease or chronic condition," but only 31.8% and 34.4% were aware of the terms "polygenic risk score" and "precision medicine" respectively. A large proportion of participants said they would consider screening their newborn to receive a PRS for allergies (77.9%), asthma (81.0%), cancer (64.8%), cardiovascular disease (65.7%), mental illness (56.7%), obesity (49.5%), and type 2 diabetes (66.7%). Additionally, participants would primarily consider diet and exercise as interventions for specific NCDs.
The results from this study will inform future policy for genomic NBS, including expected rate of uptake and interventions that parents would consider employing to prevent the onset of disease.
The ability to capture and convert sunlight, water and nutrients into useful compounds make photosynthetic microbes ideal candidates for the bio‐industrial factories of the future. However, the ...suitability of isolates from temperate regions to grow under Nordic conditions is questionable. In this work, we explore the chemotaxonomy of Nordic strains of cyanobacteria and one green alga and evaluate their potential as raw materials for the production of lipid‐based bio‐industrial compounds. Thin‐layer chromatography was used to identify the presence of triacylglycerol, which were detected in the majority of strains. Fatty acid methyl ester profiles were analysed to determine the suitability of strains for the production of biodiesel or the production of polyunsaturated fatty acids for the nutraceutical industry. The Nordic Synechococcus strains were unique in demonstrating fatty acid profiles comprised mostly C14:0, C16:0 and C16:1 and lacking polyunsaturated fatty acids. These properties translated to superior predicted biodiesel qualities, including cetane number, cold filter plugging point and oxidative stability compared to the other evaluated strains. Polyunsaturated fatty acids were detected at high levels (38–53%), with Calothrix sp. 336/3 being abundant in two essential fatty acids, linoleic and alpha‐linolenic acid (21 and 17%, respectively). Gamma‐linoleic acid was the predominant polyunsaturated fatty acid for the remaining strains (13–21%). In addition to assessing the potential of Nordic strains for bio‐industrial production, this work also discusses issues such as taxonomy and predictive modelling, which can affect the identification of prospective high‐performing strains.
Fat cells or adipocytes are distributed ubiquitously throughout the body and are often regarded purely as energy stores. However, recently it has become clear that these adipocytes are engine rooms ...producing large numbers of metabolically active substances with both endocrine and paracrine actions. White adipocytes surround almost every blood vessel in the human body and are collectively termed perivascular adipose tissue (PVAT). It is now well recognized that PVAT not only provides mechanical support for any blood vessels it invests, but also secretes vasoactive and metabolically essential cytokines known as adipokines, which regulate vascular function. The emergence of obesity as a major challenge to our healthcare systems has contributed to the growing interest in adipocyte dysfunction with a view to discovering new pharmacotherapeutic agents to help rescue compromised PVAT function. Very few PVAT studies have been carried out on human tissue. This review will discuss these and the hypotheses generated from such research, as well as highlight the most significant and clinically relevant animal studies showing the most pharmacological promise.
LINKED ARTICLES This article is part of a themed section on Fat and Vascular Responsiveness. To view the other articles in this section visit http://dx.doi.org/10.1111/bph.2012.165.issue‐3
Kaposiform lymphangiomatosis is a rare lymphatic anomaly that occurs in children and is associated with life-threatening complications. The somatic mutation
NRAS
Q61R (c.182A>G) has been identified ...in lesional tissue samples of patients with kaposiform lymphangiomatosis, and can be used to differentiate this condition from other complex lymphatic anomalies and to guide treatment. Tissue sampling in this lymphatic anomaly is inherently risky due to its involvement of thoracic and abdominal organs and associated coagulopathy. Analysis of cell-free DNA isolated from blood plasma presents a promising noninvasive diagnostic strategy. Here, we describe the use of this approach using a commercial assay.
Abstract Individuals with ADHD and comorbid hoarding disorder are vulnerable to severe consequences from hoarding symptoms. Despite this, and the early onset of hoarding disorder, the nature of ...hoarding symptoms in children with comorbid ADHD is unknown. We therefore explored the phenomenology of hoarding symptoms among ten 8–12 year olds with ADHD and clinically significant hoarding symptoms through parental perceptions. Parents completed in-depth semi-structured interviews. The data was analyzed using Interpretative Phenomenological Analysis. Six superordinate themes were identified: emotional distress; parental avoidance and accommodating behaviors; family impacts of hoarding; excessive acquisition and saving; executive functioning; parental insight and intervention. In contrast to previous suggestions that emotional distress was not associated with hoarding in ADHD, these findings highlight that emotional distress appeared to be core to the hoarding disorder profile of the present sample of children with ADHD. This has important implications for health practitioners who may consider conceptualizing, assessing, and treating hoarding symptoms in children with comorbid ADHD using a cognitive behavioral model of hoarding disorder.
Aging is associated with immune dysfunction and the related development of conditions with an inflammatory pathogenesis. Some of these immune changes are also observed in HIV infection, but the ...interaction between immune changes with aging and HIV infection are unknown. Whilst sex differences in innate immunity are recognized, little research into innate immune aging has been performed on women.
This cross-sectional study of HIV positive and negative women used whole blood flow cytometric analysis to characterize monocyte and CD8(+) T cell subsets. Plasma markers of innate immune activation were measured using standard ELISA-based assays.
HIV positive women exhibited elevated plasma levels of the innate immune activation markers CXCL10 (p<0.001), soluble CD163 (sCD163, p = 0.001), sCD14 (p = 0.022), neopterin (p = 0.029) and an increased proportion of CD16(+) monocytes (p = 0.009) compared to uninfected controls. Levels of the innate immune aging biomarkers sCD163 and the proportion of CD16(+) monocytes were equivalent to those observed in HIV negative women aged 14.5 and 10.6 years older, respectively. CXCL10 increased with age at an accelerated rate in HIV positive women (p = 0.002) suggesting a synergistic effect between HIV and aging on innate immune activation. Multivariable modeling indicated that age-related increases in innate immune biomarkers CXCL10 and sCD163 are independent of senescent changes in CD8(+) T lymphocytes.
Quantifying the impact of HIV on immune aging reveals that HIV infection in women confers the equivalent of a 10-14 year increase in the levels of innate immune aging markers. These changes may contribute to the increased risk of inflammatory age-related diseases in HIV positive women.
Implementing genomic sequencing into newborn screening programs allows for significant expansion in the number and scope of conditions detected. We sought to explore public preferences and ...perspectives on which conditions to include in genomic newborn screening (gNBS).
We recruited English-speaking members of the Australian public over 18 years of age, using social media, and invited them to participate in online focus groups.
Seventy-five members of the public aged 23-72 participated in one of fifteen focus groups. Participants agreed that if prioritisation of conditions was necessary, childhood-onset conditions were more important to include than later-onset conditions. Despite the purpose of the focus groups being to elicit public preferences, participants wanted to defer to others, such as health professionals or those with a lived experience of each condition, to make decisions about which conditions to include. Many participants saw benefit in including conditions with no available treatment. Participants agreed that gNBS should be fully publicly funded.
How many and which conditions are included in a gNBS program will be a complex decision requiring detailed assessment of benefits and costs alongside public and professional engagement. Our study provides support for implementing gNBS for treatable childhood-onset conditions.
IntroductionAs routine genomic testing expands, so too does the opportunity to look for additional health information unrelated to the original reason for testing, termed additional findings (AF). ...Analysis for many different types of AF may be available, particularly to families undergoing trio genomic testing. The optimal model for service delivery remains to be determined, especially when the original test occurs in the acute care setting.Methods and analysisFamilies enrolled in a national study providing ultrarapid genomic testing to critically ill children will be offered analysis for three types of AF on their stored genomic data: paediatric-onset conditions in the child, adult-onset conditions in each parent and reproductive carrier screening for the parents as a couple. The offer will be made 3–6 months after diagnostic testing. Parents will have access to a modified version of the Genetics Adviser web-based decision support tool before attending a genetic counselling appointment to discuss consent for AF. Parental experiences will be evaluated using qualitative and quantitative methods on data collected through surveys, appointment recordings and interviews at multiple time points. Evaluation will focus on parental preferences, uptake, decision support use and understanding of AF. Genetic health professionals’ perspectives on acceptability and feasibility of AF will also be captured through surveys and interviews.Ethics and disseminationThis project received ethics approval from the Melbourne Health Human Research Ethics Committee as part of the Australian Genomics Health Alliance protocol: HREC/16/MH/251. Findings will be disseminated through peer-review journal articles and at conferences nationally and internationally.
This study aims to identify the potential mechanisms by which perivascular adipose tissue (PVAT) reduces tone in small arteries. Small mesenteric arteries from wild-type and large-conductance Ca
2+
...-activated K
+
(BK
Ca
) channel knockout mice were mounted on a wire myograph in the presence and absence of PVAT, and contractile responses to norepinephrine were assessed. Electrophysiology studies were performed in isolated vessels to measure changes in membrane potential produced by adiponectin. Contractile responses from wild-type mouse small arteries were significantly reduced in the presence of PVAT. This was not observed in the presence of a BK
Ca
channel inhibitor or with nitric oxide synthase (NOS) inhibition or in BK
Ca
or adiponectin knockout mice. Solution transfer experiments demonstrated the presence of an anticontractile factor released from PVAT. Adiponectin-induced vasorelaxation and hyperpolarization in wild-type arteries were not evident in the absence of or after inhibition of BK
Ca
channels. PVAT from BK
Ca
or adiponectin knockout mice failed to elicit an anticontractile response in wild-type arteries. PVAT releases adiponectin, which is an anticontractile factor. Its effect on vascular tone is mediated by activation of BK
Ca
channels on vascular smooth muscle cells and adipocytes and by endothelial mechanisms.
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