Journal of internal medicine
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Severe acute respiratory syndrome coronavirus (SARS-CoV)-2, a novel coronavirus from the same family as SARS-CoV and Middle East respiratory syndrome coronavirus, has spread worldwide leading the World Health Organization to declare a pandemic. The disease caused by SARS-CoV-2, coronavirus disease 2019 (COVID-19), presents flu-like symptoms which can become serious in high-risk individuals. Here, we provide an overview of the known clinical features and treatment options for COVID-19. ⋯ The main therapies being used to treat the disease are antiviral drugs, chloroquine/hydroxychloroquine and respiratory therapy. In conclusion, although many therapies have been proposed, quarantine is the only intervention that appears to be effective in decreasing the contagion rate. Specifically designed randomized clinical trials are needed to determine the most appropriate evidence-based treatment modality.
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The RAS genes, which include H, N, and KRAS, comprise the most frequently mutated family of oncogenes in cancer. Mutations in KRAS - such as the G12C mutation - are found in most pancreatic, half of colorectal and a third of lung cancer cases and is thus responsible for a substantial proportion of cancer deaths. Consequently, KRAS has been the subject of exhaustive drug-targeting efforts over the past 3-4 decades. ⋯ The drug inhibits the in vivo growth of multiple KRASG12C -mutant cell line xenografts, causes tumour regression in patient-derived xenograft models and shows striking responses in combination with other agents. It has also produced objective responses in patients with mutant-specific lung and colorectal cancer. In this review, we discuss the history of RAS drug-targeting efforts, the discovery of MRTX849, and how this drug provides an exciting and long-awaited opportunity to selectively target mutant KRAS in patients.
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Psychiatric and neurocognitive symptoms due to hypercortisolism were already described by Harvey Cushing in his original paper on patients with Cushing's syndrome (CS). Nowadays, it is well known that psychiatric and cognitive complaints are two of the most common, and most distressing, symptoms in patients with CS. Psychiatric symptoms are indeed a major clinical manifestation of CS. ⋯ Neuroimaging studies have also illustrated the deleterious effects of hypercortisolism on the brain by demonstrating reduced grey matter volumes and cortical thickness, altered resting-state functional responses and during cognitive tasks, as well as widespread reduced white matter integrity, especially in structures important for cognitive function and emotional processing, both before and after successful abrogation of hypercortisolism. In this paper, we summarize the current knowledge on the psychiatric and neurocognitive consequences of hypercortisolism in patients with CS, both before, and after successful treatment. In addition, we review the structural and functional brain abnormalities associated with hypercortisolism and discuss the influence of these factors on quality of life.
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Review
Epigenetic regulation of insulin action and secretion - role in the pathogenesis of type 2 diabetes.
The prevalence of type 2 diabetes (T2D) is rapidly increasing worldwide. Obesity, physical inactivity and ageing increase the risk of T2D. Epigenetic modifications can change due to environmental exposures and may thereby predispose to disease. ⋯ Several of these SNPs are also associated with T2D. Recent data also support that DNA methylation of some sites in blood may be developed into biomarkers that predict T2D since methylation of, for example TXNIP, ABCG1 and SREBF1 associated with future T2D. Future studies should use this information for development of new therapies and biomarkers and thereby improve prediction, prevention and treatment of T2D and its complications.