Exploring the impact of Osteogenesis Imperfecta on families: A mixed-methods systematic review

Background: Osteogenesis Imperfecta (OI) is a rare genetic condition whose key characteristic is increased bone fragility. OI has the potential to impact upon all family members, making it important to consider the challenges families face, how they cope and their support needs as the affected individual moves from childhood through to adult life. / Objective: To conduct a mixed-methods systematic review investigating the experiences of families when a family member is affected with OI. / Methods: A systematic search of seven electronic databases, relevant patient organisation websites and reference lists was conducted. Data extraction was performed for all studies that met the eligibility and quality criteria. Results were synthesised following the principles of thematic analysis. / Results: One mixed-method, six qualitative and six quantitative studies were included in the review. Three overarching themes were identified through thematic analysis: Impact of OI on the psychosocial wellbeing of families, impact on family life and evolving roles and relationships. Fear of fractures and the uncertainty of when the next fracture will occur are key issues that permeate all areas of family life and impact upon all family members. / Conclusion: The experiences, coping strategies and support needs of families affected by OI were highly variable and changed over time. Future research should address the need for adaptive health and education interventions that support all family members

Unraveling the genomes of ancient Iberian Canis

info:eu-repo/semantics/publishedVersio

Archaeogenomic analysis of the first steps of Neolithization in Anatolia and the Aegean

The Neolithic transition in west Eurasia occurred in two main steps: the gradual development of sedentism and plant cultivation in the Near East and the subsequent spread of Neolithic cultures into the Aegean and across Europe after 7000 cal BCE. Here, we use published ancient genomes to investigate gene flow events in west Eurasia during the Neolithic transition. We confirm that the Early Neolithic central Anatolians in the ninth millennium BCE were probably descendants of local hunter-gatherers, rather than immigrants from the Levant or Iran. We further study the emergence of post-7000 cal BCE north Aegean Neolithic communities. Although Aegean farmers have frequently been assumed to be colonists originating from either central Anatolia or from the Levant, our findings raise alternative possibilities: north Aegean Neolithic populations may have been the product of multiple westward migrations, including south Anatolian emigrants, or they may have been descendants of local Aegean Mesolithic groups who adopted farming. These scenarios are consistent with the diversity of material cultures among Aegean Neolithic communities and the inheritance of local forager know-how. The demographic and cultural dynamics behind the earliest spread of Neolithic culture in the Aegean could therefore be distinct from the subsequent Neolithization of mainland Europe.WoSScopu

Limited effects of growth hormone replacement in patients with GH deficiency during long-term cure of acromegaly

The aim of this study was to assess the effects of replacement with recombinant human growth hormone (rhGH) in patients with GH deficiency (GHD) after treatment of acromegaly. Intervention study. Sixteen patients (8 men, age 56 years), treated for acromegaly by surgery and radiotherapy, with an insufficient GH response to insulin-induced hypoglycaemia, were treated with 1 year of rhGH replacement. Study parameters were assessed at baseline and after 1 year of rhGH replacement. Study parameters were cardiac function, body composition, bone mineral density (BMD), fasting lipids, glucose, bone turnover markers, and Quality of Life (QoL). During rhGH replacement IGF-I concentrations increased from −0.4 ± 0.7 to 1.0 ± 1.5 SD (P = 0.001), with a mean daily dose of 0.2 ± 0.1 mg in men and 0.3 ± 0.2 mg in women. Nonetheless, rhGH replacement did not alter cardiac function, lipid and glucose concentrations, body composition or QoL. Bone turnover markers (PINP and β crosslaps) levels increased (P = 0.005 and P = 0.021, respectively), paralleled by a small, but significant decrease in BMD of the hip. The beneficial effects of rhGH replacement in patients with GHD during cure from acromegaly are limited in this study

Genome sequencing of the extinct Eurasian wild aurochs, Bos primigenius, illuminates the phylogeography and evolution of cattle

Background Domestication of the now-extinct wild aurochs, Bos primigenius, gave rise to the two major domestic extant cattle taxa, B. taurus and B. indicus. While previous genetic studies have shed some light on the evolutionary relationships between European aurochs and modern cattle, important questions remain unanswered, including the phylogenetic status of aurochs, whether gene flow from aurochs into early domestic populations occurred, and which genomic regions were subject to selection processes during and after domestication. Here, we address these questions using whole-genome sequencing data generated from an approximately 6,750-year-old British aurochs bone and genome sequence data from 81 additional cattle plus genome-wide single nucleotide polymorphism data from a diverse panel of 1,225 modern animals. Results Phylogenomic analyses place the aurochs as a distinct outgroup to the domestic B. taurus lineage, supporting the predominant Near Eastern origin of European cattle. Conversely, traditional British and Irish breeds share more genetic variants with this aurochs specimen than other European populations, supporting localized gene flow from aurochs into the ancestors of modern British and Irish cattle, perhaps through purposeful restocking by early herders in Britain. Finally, the functions of genes showing evidence for positive selection in B. taurus are enriched for neurobiology, growth, metabolism and immunobiology, suggesting that these biological processes have been important in the domestication of cattle. Conclusions This work provides important new information regarding the origins and functional evolution of modern cattle, revealing that the interface between early European domestic populations and wild aurochs was significantly more complex than previously thought

Long-Lasting Inhibitory Effects of Fetal Liver Mesenchymal Stem Cells on T-Lymphocyte Proliferation

Human bone marrow mesenchymal stem cells (BM-MSC) are multipotent progenitor cells that have transient immunomodulatory properties on Natural Killer (NK) cells, Dendritic Cells (DC), and T cells. This study compared the use of MSC isolated from bone marrow and fetal liver (FL-MSC) to determine which displayed the most efficient immunosuppressive effects on T cell activation. Although both types of MSC exhibit similar phenotype profile, FL-MSC displays a much more extended in vitro life-span and immunomodulatory properties. When co-cultured with CD3/CD28-stimulated T cells, both BM-MSC and FL-MSC affected T cell proliferation by inhibiting their entry into the cell cycle, by inducing the down-regulation of phospho-retinoblastoma (pRb), cyclins A and D1, as well as up-regulating p27kip1expression. The T cell inhibition by MSC was not due to the soluble HLA-G5 isoform, but to the surface expression of HLA-G1, as shown by the need of cell-cell contact and by the use of neutralizing anti-HLA-G antibodies. To note, in a HLA-G-mediated fashion, MSC facilitated the expansion of a CD4low/CD8low T subset that had decreased secretion of IFN-γ, and an induced secretion of the immunomodulatory cytokine IL-10. Because of their longer lasting in vitro immunosuppressive properties, mainly mediated by HLA-G, and their more efficient induction of IL-10 production and T cell apoptosis, fetal liver MSC could be considered a new tool for MSC therapy to prevent allograft rejection