Adv Exp Med Biol
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Ultrasound (US) allows the non-invasive evaluation of morphological changes of kidney structure (by means of B-Mode) and patterns of renal and extrarenal vascularization (by means of color-Doppler and contrast-enhanced US). In hypertensive subjects it offers a relevant contribution to the diagnosis of early renal damage, acute or chronic nephropathies and nephrovascular disease. However, morphological changes are often detected late and non-specific and in recent years evidence has increased regarding the clinical relevance of renal resistive index (RRI) for the study of vascular and renal parenchymal renal abnormalities. ⋯ The recent claim that systemic (pulse pressure) rather than renal hemodynamic determinants sustain this predictive role of RRI, does not significantly reduce this predictive role of RRI. (c) Doppler ultrasound allows diagnosis and grading of renal stenosis in both fibromuscolar dysplastic and atherosclerotic diseases. Moreover, by RRI assay Doppler ultrasound can indirectly measure the hemodynamic impact of renal artery stenosis on the homolateral kidney, by virtue of the stenosis-related decrease in pulse pressure. However, in elderly subjects with atherosclerotic renal artery stenosis coexisting renal diseases can independently increase RRI by the augmentation in renal vascular stiffness and tubulo-interstitial pressure and hidden changes due to renal artery stenosis.
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Mitochondria are essential double-membraned cytoplasmic organelles to support aerobic respiration and produce cellular energy by oxidative phosphorylation (OXPHOS). Mitochondrial functions are controlled by mitochondrial (mtDNA) and nuclear genomes (nDNA). Mutations of mtDNA result in mitochondrial dysfunction and multisystem diseases through compromising OXPHOS function directly by a point mutation or a large-scale mtDNA rearrangement. ⋯ Unlike diploid nDNA, mtDNA is a multi-copy genome transmitted and maternally inherited through oocyte. The multi-copy nature of mtDNA easily causes the heteroplasmy as a unique aspect of mtDNA, making mitochondrial diseases more complex and heterogeneous. mtDNA-associated mitochondrial dysfunction plays the important role in the development of multisystemic primary mitochondrial disease, neurodegeneration, and cancer. The present article overviews the occurrence of mtDNA mutation, interactions with other factors, and molecular mechanisms of mtDNA-associated diseases.
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Lung cancer is the leader malignancy worldwide accounting 1.5 millions of deaths every year. In the United States the 5 year-overall survival is less than 20% for all the newly diagnosed patients. Cisplatin-based cytotoxic chemotherapy for unresectable or metastatic NSCLC patients in the first line of treatment, and docetaxel in the second line, have achieved positive results but with limited benefit in overall survival. ⋯ In the other side high PD-1 expression patients that undergo immunotherapy treatment achieve better results in terms of survival with lesser toxicity. Combining different immunotherapy treatments, combination of immunotherapy with chemotherapy or with targeted treatment are under research with some promising PRELIMINARY results in non-small cell lung cancer patients. This chapter attempts to summarize the development of immunotherapy treatment in non-small cell lung cancer patients and explain the results that have leaded immunotherapy as a new standard of treatment in selected NSCLC patients.
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Inter-individual variability in response to pharmacotherapy has provoked a higher demand to personalize medical decisions. As the field of pharmacogenomics has served to translate personalized medicine from concept to practice, the contribution of the "omics" disciplines to the era of precision medicine seems to be vital in improving therapeutic outcomes. Although we have observed significant advances in the field of genomics towards personalized medicine , the field of proteomics-with all its capabilities- is still in its infancy towards the area of personalized precision medicine. ⋯ However, other applications in proteomics such as "individual" proteome sequencing with its signature PTMs, have not been fully investigated as compared to the achievements in the genomics discipline This infers that proteomics research work has promising potential, yet to be discovered, in the precision medicine and comprises a major component of the personalized medicine infrastructure as it allows individual characterization of disease at the protein level. To conclude, the field of proteomics-based personalized medicine is still in its infancy compared to genomics field due to several technical and instrumentation-based obstacles; however, we anticipate to have this initiative leading in the coming future. This chapter will discuss briefly how neuroproteomics can impact personalized medicine in the fields of neurodegenerative disorders particularly in Alzheimer's disease and brain injury .
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Acute leukaemia is the major subtype of paediatric cancer with a cumulative risk of 1 in 2000 for children up to the age of 15 years. Childhood acute lymphoblastic leukaemia (ALL) is a biologically and clinically diverse disease with distinctive subtypes; multiple chromosomal translocations exist within the subtypes and each carries its own prognostic relevance. The most common chromosome translocation observed is the t(12;21) that results in an in-frame fusion between the first five exons of ETV6 (TEL) and almost the entire coding region of RUNX1 (AML1). ⋯ It has, however, been possible to backtrack this process through molecular analysis of appropriate clinical samples: (i) leukaemic clones in monozygotic twins that are either concordant or discordant for ALL; (ii) archived neonatal blood spots or Guthrie cards from individuals who later developed leukaemia; and (iii) stored, viable cord blood cells. Here, we outline our studies on the aetiology and pathology of childhood ALL that provide molecular evidence for a monoclonal, prenatal origin of ETV6-RUNX1+ leukaemia in monozygotic identical twins. We provide mechanistic support for the concept that altered patterns of infection during early childhood can deliver the necessary promotional drive for the progression of ETV6-RUNX1+ pre-leukaemic cells into a postnatal overt leukaemia.