• Gauthier Mcclure posted an update a month ago

    Breast cancer is a remarkably complex and diverse disease. Subtyping based on morphology, genomics, biomarkers and/or clinical parameters seeks to stratify optimal approaches for management, but it is clear that every breast cancer is fundamentally unique. Intra-tumour heterogeneity adds further complexity and impacts a patient’s response to neoadjuvant or adjuvant therapy. Here, we review some established and more recent evidence related to the complex nature of breast cancer evolution. We describe morphologic and genomic diversity as it arises spontaneously during the early stages of tumour evolution, and also in the context of treatment where the changing subclonal architecture of a tumour is driven by the inherent adaptability of tumour cells to evolve and resist the selective pressures of therapy.Human cytomegalovirus (HCMV) is a ubiquitous herpesvirus (the human herpesvirus 5) and an opportunistic pathogen that primarily infects HIV-positive and other immuno-compromised patients. Retrospective studies in the field of inflammatory bowel disease (IBD) have suggested a relationship between a concomitant colonic HCMV infection and poor outcomes in patients with an ulcerative colitis (UC) due to the presence of HCMV in surgical specimens of patients with a toxic megacolon or a steroid-resistant UC. Therefore, gastroenterologists have focused on the contribution of HCMV infections in the exacerbation of UC. Numerous studies have addressed the benefits of treating colonic HCMV reactivation in UC using an antiviral treatment. However, its clinical relevance remains uncertain as only a few prospective studies have assessed the direct relationship between clinical outcomes and the viral load of HCMV in colonic tissues. HCMV reactivation can be triggered by inflammation according to fundamental research studies. Selleckchem EVT801 Thus, optimal control of intestinal inflammation is essential for preventing an HCMV reactivation in the intestinal mucosa. Indeed, several reports have indicated the effectiveness of an anti-tumor necrosis factor-alpha (TNFα) treatment in patients with an active UC and concomitant HCMV infections. In this review, we describe the mechanism of HCMV reactivation in UC cases and discuss the current issues regarding diagnosis and treatment of HCMV infections in UC patients.Neurodevelopmental disorders are a challenge in medical genetics due to genetic heterogeneity and complex genotype-phenotype correlations. For this reason, the resolution of single cases not belonging to well-defined syndromes often requires an integrated approach of multiple whole-genome technologies. Such an approach has also unexpectedly revealed a complex molecular basis in an increasing number of patients, for whom the original suspect of a pleiotropic syndrome has been resolved as the summation effect of multiple genes. We describe a 10-year-old boy, the third son of first-cousin parents, with global developmental delay, facial dysmorphism, and bilateral deafness. SNP-array analysis revealed regions of homozygosity (ROHs) in multiple chromosome regions. Whole-exome sequencing prioritized on gene-mapping into the ROHs showed homozygosity for the likely pathogenic c.1097_1098delAG p. (Arg366Thrfs*2) frameshift substitution in LARP7 and the likely pathogenic c.5743C>T p.(Arg1915*) nonsense variant in OTOG. Recessive variants in LARP7 cause Alazami syndrome, while variants in OTOG cause an extremely rare autosomal recessive form of neurosensorial deafness. Previously unreported features were acrocyanosis and palmoplantar hyperhidrosis. This case highlights the utility of encouraging technological updates in medical genetics laboratories involved in the study of neurodevelopmental disorders and integrating laboratory outputs with the competencies of next-generation clinicians.Environmental valuation refers to a variety of techniques to assign monetary values to environmental impacts, especially non-market impacts. It has experienced a steady growth in the number of publications on the subject in the last 30 years. We performed a search for papers containing the term “environmental valuation” in the title, abstract, or keywords. The search was conducted with an online literature search engine of the Web of Science (WoS) electronic databases. A search of this database revealed that the term “environmental valuation” appeared for the first time in 1987. Since then, a large number of studies have been published, including significant breakthroughs in theory and applications. In the present work, 661 publications were selected for a review of the literature on environmental valuation over the period 1987-2019. This paper analyzes the evolution of the leading methodologies and authors, highlights the preference for the choice experiment method over the contingent valuation method, and shows that relatively few papers have had a strong impact on the researchers in this area.AIMS We aimed to validate the pathogenicity of genetic variants identified in inherited retinal dystrophy (IRD) patients, which were located in non-canonical splice sites (NCSS). METHODS After next generation sequencing (NGS) analysis (target gene panels or whole exome sequencing (WES)), NCSS variants were prioritized according to in silico predictions. In vivo and in vitro functional tests were used to validate their pathogenicity. RESULTS Four novel NCSS variants have been identified. They are located in intron 33 and 34 of ABCA4 (c.4774-9G>A and c.4849-8C>G, respectively), intron 2 of POC1B (c.101-3T>G) and intron 3 of RP2 (c.884-14G>A). Functional analysis detected different aberrant splicing events, including intron retention, exon skipping and intronic nucleotide addition, whose molecular effect was either the disruption or the elongation of the open reading frame of the corresponding gene. CONCLUSIONS Our data increase the genetic diagnostic yield of IRD patients and expand the landscape of pathogenic variants, which will have an impact on the genotype-phenotype correlations and allow patients to opt for the emerging gene and cell therapies.Background The idea of reusing dispensed medicines is appealing to the general public provided its benefits are illustrated, its risks minimized, and the logistics resolved. For example, medicine reuse could help reduce medicinal waste, protect the environment and improve public health. However, the associated technologies and legislation facilitating medicine reuse are generally not available. The availability of suitable technologies could arguably help shape stakeholders’ beliefs and in turn, uptake of a future medicine reuse scheme by tackling the risks and facilitating the practicalities. A literature survey is undertaken to lay down the groundwork for implementing technologies on and around pharmaceutical packaging in order to meet stakeholders’ previously expressed misgivings about medicine reuse (‘stakeholder requirements’), and propose a novel ecosystem for, in effect, reusing returned medicines. Methods A structured literature search examining the application of existing technologies on pharmaceutical packaging to enable medicine reuse was conducted and presented as a narrative review.

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