Adv Exp Med Biol
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Autism spectrum disorder (ASD), one of the most common childhood neurodevelopmental disorders (NDDs), is diagnosed in 1 of every 68 children. ASD is incredibly heterogeneous both clinically and aetiologically. The etiopathogenesis of ASD is known to be complex, including genetic, environmental and epigenetic factors. ⋯ In this chapter we aim to summarize some of the important literature that supports a role for epigenetics in the underlying molecular mechanism of ASD. We provide evidence from work in genetics, from environmental exposures and finally from more recent studies aimed at directly determining ASD-specific epigenetic patterns, focusing mainly on DNA methylation (DNAm). Finally, we briefly discuss some of the implications of current research on potential epigenetic targets for therapeutics and novel avenues for future work.
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Interleukin-2 (IL-2) is a very well-known cytokine that has been studied for the past 35 years. It plays a major role in the growth and proliferation of many immune cells such NK and T cells. It is an important immunotherapy cytokine for the treatment of various diseases including cancer. ⋯ OS, our disease of interest, has a peak incidence in the adolescent and young adult years. Our goal is to complete this trial in the next 2 years. In this chapter, we summarize the different effects of IL-2 and cover the advantages of the aerosol delivery route for diseases of the lung with an emphasis on some of our most recent work using combination therapy aerosol IL-2 and NK cells for the treatment of OS lung metastases.
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Hypertension remains the most important risk factor for cardiovascular disease. If antihypertensive drugs choice is well guided today, blood pressure (BP) target still a subject of controversies. Residual risk is matter of debate and the lower- the better dogma is come back again regarding to data reported from recent trials. ⋯ In diabetic patients, SBP target should be less than 140 mmHg according to ACCORD trial. However, for patients with protein-creatinine ratio >500 mg/g (albumin-creatinine ratio > 300 mg/g), with or without diabetes, lower SBP target should be proposed for renal protection aiming SBP < 130 mmHg as recommended by KDIGO guidelines. In patients at low or intermediate risk, without cardiovascular disease, SBP should start to be treated when SBP is above 140 mmHg, and when treated, target BP should be less than 140 mmHg as reported by HOPE-3 trial.
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Basic knowledge of pulmonary embolism is relevant to most practicing physicians. Many medical specialties care for patients with increased risk of pulmonary embolism, why recognition of relevant symptoms, a thorough medical history, assessment of the clinical condition of the patient and possibly referral to a relevant facility should be a part of the skills of all clinicians. ⋯ The information available from the medical history, clinical assessment and basic investigation form the basis on which the decision about further diagnostic imaging and intensity of treatment and monitoring can be made. These decisions can be guided by clinical scoring systems like the Wells score, revised Geneva score and the PESI.
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Huntington's disease (HD) is a genetic, fatal autosomal dominant neurodegenerative disorder typically occurring in midlife with symptoms ranging from chorea, to dementia, to personality disturbances (Philos Trans R Soc Lond Ser B Biol Sci 354:957-961, 1999). HD is inherited in a dominant fashion, and the underlying mutation in all cases is a CAG trinucleotide repeat expansion within exon 1 of the HD gene (Cell 72:971-983, 1993). ⋯ The rate-limiting mechanism(s) of neurodegeneration in HD still remains elusive: many different processes are commonly disrupted in HD cell lines and animal models, as well as in HD patient cells (Eur J Neurosci 27:2803-2820, 2008); however, epigenetic-chromatin deregulation, as determined by the analysis of DNA methylation, histone modifications, and noncoding RNAs, has now become a prevailing feature. Thus, the overarching goal of this chapter is to discuss the current status of the literature, reviewing how an aberrant epigenetic landscape can contribute to altered gene expression and neuronal dysfunction in HD.