Journal of internal medicine
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Brain oscillations underlie the function of our brains, dictating how we both think and react to the world around us. The synchronous activity of neurons generates these rhythms, which allow different parts of the brain to communicate and orchestrate responses to internal and external stimuli. Perturbations of cognitive rhythms and the underlying oscillator neurons that synchronize different parts of the brain contribute to the pathophysiology of diseases including Alzheimer's disease, (AD), Parkinson's disease (PD), epilepsy and other diseases of rhythm that have been studied extensively by Gyorgy Buzsaki. ⋯ While multiple modalities of neuromodulation are currently clinically indicated for some disorders, nothing is yet approved for improving memory in AD. Recent investigations into novel methods of neuromodulation show potential for improving cognition in memory disorders. Here, we demonstrate that neuronal stimulation using audiovisual sensory stimulation that generated 40-HZ gamma waves reduced AD-specific pathology and improved performance in behavioural tests in mouse models of AD, making this new mode of neuromodulation a promising new avenue for developing a new therapeutic intervention for the treatment of dementia.
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Preeclampsia (PE) is a complex pregnancy syndrome characterised by maternal hypertension and organ damage after 20 weeks of gestation and is associated with an increased risk of cardiovascular disease later in life. Extracellular haemoglobin (Hb) and its metabolites heme and iron are highly toxic molecules and several defence mechanisms have evolved to protect the tissue. ⋯ In PE, oxidative stress causes syncytiotrophoblast (STB) stress and increased shedding of placental STB-derived extracellular vesicles (STBEV). The level in maternal circulation correlates with the severity of hypertension and supports the involvement of STBEVs in causing maternal symptoms in PE. In PE and FGR, iron homeostasis is changed, and iron levels significantly correlate with the severity of the disease. The normal increase in plasma volume taking place during pregnancy is less for PE and FGR and therefore have a different impact on, for example, iron concentration, compared to normal pregnancy. Excess iron promotes ferroptosis is suggested to play a role in trophoblast stress and lipotoxicity. Non-erythroid α-globin regulates vasodilation through the endothelial nitric oxide synthase pathway, and hypoxia-induced α-globin expression in STBs in PE placentas is suggested to contribute to hypertension in PE. Underlying placental pathology in PE with and without FGR might be amplified by iron and heme overload causing oxidative stress and ferroptosis. As the placenta becomes stressed, the release of STBEVs increases and affects the maternal vasculature.
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The functional status of lipoprotein particles contributes to atherogenesis. The tendency of plasma low-density lipoprotein (LDL) particles to aggregate and the ability of igh-density lipoprotein (HDL) particles to induce and mediate reverse cholesterol transport associate with high and low risk for cardiovascular disease in adult patients, respectively. However, it is unknown whether children with familial hypercholesterolemia (FH) display lipoprotein function alterations. ⋯ FH children displayed increased atherogenicity of LDL and disrupted HDL function. These newly observed functional alterations in LDL and HDL add further understanding of the risk for atherosclerotic cardiovascular disease in FH children.
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The SARS-CoV-2 virus is highly contagious, as demonstrated by numerous well-documented superspreading events. The infection commonly starts in the upper respiratory tract (URT) but can migrate to the lower respiratory tract (LRT) and other organs, often with severe consequences. Whereas LRT infection can lead to shedding of virus via breath and cough droplets, URT infection enables shedding via abundant speech droplets. ⋯ Nevertheless, in closed environments with inadequate ventilation, they can accumulate, which elevates the risk of direct LRT infection. Of most concern is the large fraction of speech aerosol that is intermediate-sized because it remains suspended in air for minutes and can be transported over considerable distances by convective air currents. The abundance of this speech-generated aerosol, combined with its high viral load in pre- and asymptomatic individuals, strongly implicates airborne transmission of SARS-CoV-2 through speech as the primary contributor to its rapid spread.
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During the past decade, genome-wide association studies (GWAS) have transformed our understanding of many heritable traits. Three recent large-scale GWAS meta-analyses now further markedly expand the knowledge on coronary artery disease (CAD) genetics in doubling the number of loci with genome-wide significant signals. Here, we review the unprecedented discoveries of CAD GWAS on low-frequency variants, underrepresented populations, sex differences and integrated polygenic risk. ⋯ We draw attention to systems genetics in integrating these loci into gene regulatory networks within and across tissues. We review the traits, biomarkers and diseases scrutinized by Mendelian randomization studies for CAD. Finally, we discuss the potentials and concerns of polygenic scores in predicting CAD risk in patient care as well as future directions of GWAS and post-GWAS studies in the field of precision medicine.