Adv Exp Med Biol
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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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Physiological data from wearable sensors and smartphone are accumulating rapidly, and this provides us the chance to collect dynamic and personalized information as phenotype to be integrated to genotype for the holistic understanding of complex diseases. This integration can be applied to early prediction and prevention of disease, therefore promoting the shifting of disease care tradition to the healthcare paradigm. ⋯ We discuss the challenges of physiological informatics about the storage, the standardization, the analyses, and the applications of the physiological data from the wearable sensors and smartphone. At last, we present our perspectives on the models for disentangling the complex relationship between early disease prediction and the mining of physiological phenotype data.
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Substance addiction (or drug addiction) is a neuropsychiatric disorder characterized by a recurring desire to continue taking the drug despite harmful consequences. Non-substance addiction (or behavioral addiction) covers pathological gambling, food addiction, internet addiction, and mobile phone addiction. Their definition is similar to drug addiction but they differ from each other in specific domains. This review aims to provide a brief overview of past and current definitions of substance and non-substance addiction, and also touches on the topic of diagnosing drug addiction and non-drug addiction, ultimately aiming to further the understanding of the key concepts needed for a foundation to study the biological and psychological underpinnings of addiction disorders.
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Two major guide-line committees (JNC-8 and NICE UK) have dropped beta-blockers as first-line therapy in the treatment of hypertension. Also, recent meta-analyses (that do not take age into account) have concluded that beta-blockers are inappropriate first-line agents in the treatment of hypertension. This review seeks to shed some light on the "rights and wrongs" of such actions and conclusions. ⋯ Primary/essential hypertension in younger/middle-age is underpinned by high sympathetic nerve activity. In this age-group high resting heart rates and high plasma norepinephrine levels (independent of blood pressure) are linked to premature cardiovascular events and death. Thus, anti-hypertensive agents that increase sympathetic nerve activity ie diuretics, dihydropyridine calcium blockers, and ARBs, are inappropriate first-line choices in this younger age-group. Beta-blockers perform well vs randomised placebo and other antihypertensive agents regarding reduced risk of death/stroke/myocardial infarction in younger (<60 years) hypertensive subjects, and are a reasonable first-line choice of therapy (certainly in men). These facts should be reflected in the recommendations of guideline committees around the world.