Developing an intervention to facilitate family communication about inherited genetic conditions, and training genetic counsellors in its delivery.

Many families experience difficulty in talking about an inherited genetic condition that affects one or more of them. There have now been a number of studies identifying the issues in detail, however few have developed interventions to assist families. The SPRinG collaborative have used the UK Medical Research Council's guidance on Developing and Evaluating Complex Interventions, to work with families and genetic counsellors (GCs) to co-design a psycho-educational intervention to facilitate family communication and promote better coping and adaptation to living with an inherited genetic condition for parents and their children (<18 years). The intervention is modelled on multi-family discussion groups (MFDGs) used in psychiatric settings. The MFDG was developed and tested over three phases. First focus groups with parents, young people, children and health professionals discussed whether MFDG was acceptable and proposed a suitable design. Using evidence and focus group data, the intervention and a training manual were developed and three GCs were trained in its delivery. Finally, a prototype MFDG was led by a family therapist and co-facilitated by the three GCs. Data analysis showed that families attending the focus groups and intervention thought MFDG highly beneficial, and the pilot sessions had a significant impact on their family' functioning. We also demonstrated that it is possible to train GCs to deliver the MFDG intervention. Further studies are now required to test the feasibility of undertaking a definitive randomised controlled trial to evaluate its effectiveness in improving family outcomes before implementing into genetic counselling practice.The National Institute of Health Research funded the study but any views expressed do not necessarily reflect those of the Authority. Funded by NIHR reference number: RP-DG-1211-10015

Training Genetic Counsellors to Deliver an Innovative Therapeutic Intervention: their views and experience of facilitating multi-family discussion groups

Innovations in clinical genetics have increased diagnosis, treatment and prognosis of inherited genetic conditions (IGCs). This has led to an increased number of families seeking genetic testing and / or genetic counselling and increased the clinical load for genetic counsellors (GCs). Keeping pace with biomedical discoveries, interventions are required to support families to understand, communicate and cope with their Inherited Genetic Condition. The Socio-Psychological Research in Genomics (SPRinG) collaborative have developed a new intervention, based on multi-family discussion groups (MFDGs), to support families affected by IGCs and train GCs in its delivery. A potential challenge to implementing the intervention was whether GCs were willing and able to undergo the training to deliver the MFDG. In analysing three multi-perspective interviews with GCs, this paper evaluates the training received. Findings suggests that MFDGs are a potential valuable resource in supporting families to communicate genetic risk information and can enhance family function and emotional well-being. Furthermore, we demonstrate that it is feasible to train GCs in the delivery of the intervention and that it has the potential to be integrated into clinical practice. Its longer term implementation into routine clinical practice however relies on changes in both organisation of clinical genetics services and genetic counsellors' professional development

Luminescent Ruthenium(II) Polypyridyl Functionalized Gold Nanoparticles; Their DNA Binding Abilities and Application As Cellular Imaging Agents

The synthesis and photophysical and biological investigation of Ru(II)-polypyridyl stabilized watersoluble, luminescent gold nanoparticles (AuNPs) are described. These structures bind to DNA and undergo rapid cellular uptake, being localized within the cell cytoplasm and nucleus within 4 h

Mismatches in Scale Between Highly Mobile Marine Megafauna and Marine Protected Areas

Marine protected areas (MPAs), particularly large MPAs, are increasing in number and size around the globe in part to facilitate the conservation of marine megafauna under the assumption that large-scale MPAs better align with vagile life histories; however, this alignment is not well established. Using a global tracking dataset from 36 species across five taxa, chosen to reflect the span of home range size in highly mobile marine megafauna, we show most MPAs are too small to encompass complete home ranges of most species. Based on size alone, 40% of existing MPAs could encompass the home ranges of the smallest ranged species, while only \u3c 1% of existing MPAs could encompass those of the largest ranged species. Further, where home ranges and MPAs overlapped in real geographic space, MPAs encompassed \u3c 5% of core areas used by all species. Despite most home ranges of mobile marine megafauna being much larger than existing MPAs, we demonstrate how benefits from MPAs are still likely to accrue by targeting seasonal aggregations and critical life history stages and through other management techniques

Mismatches in Scale Between Highly Mobile Marine Megafauna and Marine Protected Areas

Marine protected areas (MPAs), particularly large MPAs, are increasing in number and size around the globe in part to facilitate the conservation of marine megafauna under the assumption that large-scale MPAs better align with vagile life histories; however, this alignment is not well established. Using a global tracking dataset from 36 species across five taxa, chosen to reflect the span of home range size in highly mobile marine megafauna, we show most MPAs are too small to encompass complete home ranges of most species. Based on size alone, 40% of existing MPAs could encompass the home ranges of the smallest ranged species, while only \u3c 1% of existing MPAs could encompass those of the largest ranged species. Further, where home ranges and MPAs overlapped in real geographic space, MPAs encompassed \u3c 5% of core areas used by all species. Despite most home ranges of mobile marine megafauna being much larger than existing MPAs, we demonstrate how benefits from MPAs are still likely to accrue by targeting seasonal aggregations and critical life history stages and through other management techniques

The ARID1B spectrum in 143 patients: from nonsyndromic intellectual disability to Coffin–Siris syndrome

Purpose: Pathogenic variants in ARID1B are one of the most frequent causes of intellectual disability (ID) as determined by large-scale exome sequencing studies. Most studies published thus far describe clinically diagnosed Coffin–Siris patients (ARID1B-CSS) and it is unclear whether these data are representative for patients identified through sequencing of unbiased ID cohorts (ARID1B-ID). We therefore sought to determine genotypic and phenotypic differences between ARID1B-ID and ARID1B-CSS. In parallel, we investigated the effect of different methods of phenotype reporting. Methods: Clinicians entered clinical data in an extensive web-based survey. Results: 79 ARID1B-CSS and 64 ARID1B-ID patients were included. CSS-associated dysmorphic features, such as thick eyebrows, long eyelashes, thick alae nasi, long and/or broad philtrum, small nails and small or absent fifth distal phalanx and hypertrichosis, were observed significantly more often (p < 0.001) in ARID1B-CSS patients. No other significant differences were identified. Conclusion: There are only minor differences between ARID1B-ID and ARID1B-CSS patients. ARID1B-related disorders seem to consist of a spectrum, and patients should be managed similarly. We demonstrated that data collection methods without an explicit option to report the absence of a feature (such as most Human Phenotype Ontology-based methods) tended to underestimate gene-related features

Development of a validation protocol of enzyme immunoassay kits used for the analysis of steroid hormones in fish plasma

The analysis of steroid hormones 17β-estradiol, testosterone and 11-ketotestosterone in fish plasma provide insight into fish reproductive behavior and development. Typically, steroid hormones are analyzed using gold standard approaches, such as radioimmunoassay and liquid chromatography coupled with tandem mass spectrometry. However, these methods are not always available to small-to-medium research facilities due to their large capital outlay, expensive running costs and ongoing maintenance needs, in addition to requiring a costly radioisotope license and skilled staff to handle and perform the assays. One approach being increasingly used by researchers is commercial enzyme immunoassay (EIA) kits (also known as ELISA kits), analyzed with the use of a UV–vis spectrometer. However, with their increased use, many studies fail to validate their EIA kits or fail to report on the kits sensitivity, accuracy and precision. As such, the aim of this paper is to propose a standardized protocol for reporting EIA kit validation. The proposed protocol was then applied to three fish species in order to demonstrate parallelism, accuracy and precision. Specifically, we tested plasma concentrations of 17β-estradiol for the red and black anemonefish Amphiprion melanopus, and 17β-estradiol, testosterone and 11-keto-testosterone for the barramundi Lates calcarifer and the common coral trout Plectropomus leopardus. Steroid hormones were extracted from fish plasma using a liquid-liquid solvent extraction method with ethyl acetate and n-hexane (50:50 v:v). Following extraction, the plasma dilution curves showed good linearity and parallelism, steroid recoveries were found to be within 90–120% accuracy, and precision variance was < 10% in the majority of assays, for the species and steroids measured. Utilization of the proposed standardized validation protocol of EIA kits will assist scientific, fisheries and aquaculture researchers in obtaining reliable steroid hormone measurements, particularly in the field and in smaller research laboratories

Gut Microbial Perturbation and Host Response Induce Redox Pathway Upregulation along the Gut–Liver Axis during Giardiasis in C57BL/6J Mouse Model

Apicomplexan infections, such as giardiasis and cryptosporidiosis, negatively impact a considerable proportion of human and commercial livestock populations. Despite this, the molecular mechanisms of disease, particularly the effect on the body beyond the gastrointestinal tract, are still poorly understood. To highlight host–parasite–microbiome biochemical interactions, we utilised integrated metabolomics-16S rRNA genomics and metabolomics–proteomics approaches in a C57BL/6J mouse model of giardiasis and compared these to Cryptosporidium and uropathogenic Escherichia coli (UPEC) infections. Comprehensive samples (faeces, blood, liver, and luminal contents from duodenum, jejunum, ileum, caecum and colon) were collected 10 days post infection and subjected to proteome and metabolome analysis by liquid and gas chromatography–mass spectrometry, respectively. Microbial populations in faeces and luminal washes were examined using 16S rRNA metagenomics. Proteome–metabolome analyses indicated that 12 and 16 key pathways were significantly altered in the gut and liver, respectively, during giardiasis with respect to other infections. Energy pathways including glycolysis and supporting pathways of glyoxylate and dicarboxylate metabolism, and the redox pathway of glutathione metabolism, were upregulated in small intestinal luminal contents and the liver during giardiasis. Metabolomics-16S rRNA genetics integration indicated that populations of three bacterial families—Autopobiaceae (Up), Desulfovibrionaceae (Up), and Akkermanasiaceae (Down)—were most significantly affected across the gut during giardiasis, causing upregulated glycolysis and short-chained fatty acid (SCFA) metabolism. In particular, the perturbed Akkermanasiaceae population seemed to cause oxidative stress responses along the gut–liver axis. Overall, the systems biology approach applied in this study highlighted that the effects of host–parasite–microbiome biochemical interactions extended beyond the gut ecosystem to the gut–liver axis. These findings form the first steps in a comprehensive comparison to ascertain the major molecular and biochemical contributors of host–parasite interactions and contribute towards the development of biomarker discovery and precision health solutions for apicomplexan infections