Air pollution influences the incidence of otitis media in children: A national population-based study - Fig 1

<p><b>Trends in weekly national otitis media (OM) cases per 1000 children in South Korea in total (A), by age (B), and by sex (C).</b> In 2011 and 2012, the weekly incidence of OM remained steady with seasonal variation, and the average was 12.6 cases per 1000 children. For age and sex, it was much higher in children <5 years, and comparable or somewhat higher in boys than in girls.</p

Adjusted association between exposure to ambient air pollutants and the incidences of otitis media in a nationwide population study for children in South Korea.

<p>Adjusted association between exposure to ambient air pollutants and the incidences of otitis media in a nationwide population study for children in South Korea.</p

Regulatory Activities of Dopamine and Its Derivatives toward Metal-Free and Metal-Induced Amyloid‑β Aggregation, Oxidative Stress, and Inflammation in Alzheimer’s Disease

A catecholamine neurotransmitter, dopamine (<b>DA</b>), is suggested to be linked to the pathology of dementia; however, the involvement of <b>DA</b> and its structural analogues in the pathogenesis of Alzheimer’s disease (AD), the most common form of dementia, composed of multiple pathogenic factors has not been clear. Herein, we report that <b>DA</b> and its rationally designed structural derivatives (<b>1</b>–<b>6</b>) based on <b>DA</b>’s oxidative transformation are able to modulate multiple pathological elements found in AD [i.e., metal ions, metal-free amyloid-β (Aβ), metal-bound Aβ (metal–Aβ), and reactive oxygen species (ROS)], with demonstration of detailed molecular-level mechanisms. Our multidisciplinary studies validate that the protective effects of <b>DA</b> and its derivatives on Aβ aggregation and Aβ-mediated toxicity are induced by their oxidative transformation with concomitant ROS generation under aerobic conditions. In particular, <b>DA</b> and the derivatives (i.e., <b>3</b> and <b>4</b>) show their noticeable anti-amyloidogenic ability toward metal-free Aβ and/or metal–Aβ, verified to occur via their oxidative transformation that facilitates Aβ oxidation. Moreover, in primary pan-microglial marker (CD11b)-positive cells, the major producers of inflammatory mediators in the brain, <b>DA</b> and its derivatives significantly diminish inflammation and oxidative stress triggered by lipopolysaccharides and Aβ through the reduced induction of inflammatory mediators as well as upregulated expression of heme oxygenase-1, the enzyme responsible for production of antioxidants. Collectively, we illuminate how <b>DA</b> and its derivatives could prevent multiple pathological features found in AD. The overall studies could advance our understanding regarding distinct roles of neurotransmitters in AD and identify key interactions for alleviation of AD pathology

Tuning Structures and Properties for Developing Novel Chemical Tools toward Distinct Pathogenic Elements in Alzheimer’s Disease

Multiple pathogenic factors [e.g., amyloid-β (Aβ), metal ions, metal-bound Aβ (metal–Aβ), reactive oxygen species (ROS)] are found in the brain of patients with Alzheimer’s disease (AD). In order to elucidate the roles of pathological elements in AD, chemical tools able to regulate their activities would be valuable. Due to the complicated link among multiple pathological factors, however, it has been challenging to invent such chemical tools. Herein, we report novel small molecules as chemical tools toward modulation of single or multiple target(s), designed via a rational structure-property-directed strategy. The chemical properties (e.g., oxidation potentials) of our molecules and their coverage of reactivities toward the pathological targets were successfully differentiated through a minor structural variation [i.e., replacement of one nitrogen (N) or sulfur (S) donor atom in the framework]. Among our compounds (<b>1</b>–<b>3</b>), <b>1</b> with the lowest oxidation potential is able to noticeably modify the aggregation of both metal-free Aβ and metal–Aβ, as well as scavenge free radicals. Compound <b>2</b> with the moderate oxidation potential significantly alters the aggregation of Cu­(II)–Aβ₄₂. The hardly oxidizable compound, <b>3</b>, relative to <b>1</b> and <b>2</b>, indicates no noticeable interactions with all pathogenic factors, including metal-free Aβ, metal–Aβ, and free radicals. Overall, our studies demonstrate that the design of small molecules as chemical tools able to control distinct pathological components could be achieved via fine-tuning of structures and properties

Additional file 1: of Substitution of ethambutol with linezolid during the intensive phase of treatment of pulmonary tuberculosis: study protocol for a prospective, multicenter, randomized, open-label, phase II trial

SPIRIT checklist. (DOC 126 kb

Additional file 1 of The Korean undiagnosed diseases program phase I: expansion of the nationwide network and the development of long-term infrastructure

Additional file 1. Detailed information of genetically confirmed patients