trans-Diaqua­bis­[5-carb­oxy-4-carboxyl­ato-2-(4-pyridinio)-1H-imidazol-1-ido-κ2 N 3,O 4]zinc(II)

In the title complex, [Zn(C10H6N3O4)2(H2O)2], the ZnII atom is located on a twofold rotation axis and is coordinated by two trans-positioned N,O-bidentate and zwitterionic 5-carb­oxy-4-carboxyl­ato-2-(4-pyridinio)-1H-imidazol-1-ide (H2PIDC−) ligands and two water mol­ecules, defining a distorted octa­hedral environment. The complete solid-state structure can be described as a three-dimensional supra­molecular framework, stabilized by extensive hydrogen-bonding inter­actions involving the coordinated water mol­ecules, uncoordin­ated imidazole N atom, protonated pyridine N and carboxyl­ate O atoms of the H2PIDC− ligands

Novel IKBKG gene mutations in incontinentia pigmenti: report of two cases

Incontinentia pigmenti (IP), an X-chromosome dominant genodermatosis caused by mutations in the IKBKG/NEMO gene, is a rare disease affecting the skin, teeth, eyes, and central nervous system. Here, we report two pedigrees of IP and detection of two novel mutations in the IKBKG gene associated with IP via genetic analysis. In addition, different gene mutation types can present with different clinical phenotypes, and the same gene mutation type can show different clinical phenotypes. This study provides clinical cases for further study of the genotype and phenotype of IP and enriches the mutation spectrum of IKBKG gene, which provides a basis for genetic counseling and genetic diagnosis of IP in the future

Technological strategies to estimate and control diffusive passage times through the mucus barrier in mucosal drug delivery

The final publication is available at Elsevier via https://dx.doi.org/10.1016/j.addr.2017.12.002 © 2018. This manuscript version is made available under the CC-BY-NC-ND 4.0 license https://creativecommons.org/licenses/by-nc-nd/4.0/In mucosal drug delivery, two design goals are desirable: 1) insure drug passage through the mucosal barrier to the epithelium prior to drug removal from the respective organ via mucus clearance: and 2) design carrier particles to achieve a prescribed arrival time and drug uptake schedule at the epithelium. Both goals are achievable if one can control "one-sided" diffusive passage times of drug carrier particles: from deposition at the mucus interface, through the mucosal barrier, to the epithelium. The passage time distribution must be, with high confidence, shorter than the timescales of mucus clearance to maximize drug uptake. For 100 nm and smaller drug-loaded nanoparticulates, as well as pure drug powders or drug solutions, diffusion is normal (i.e., Brownian) and rapid, easily passing through the mucosal barrier prior to clearance. Major challenges in quantitative control over mucosal drug delivery lie with larger drug-loaded nanoparticulates that are comparable to or larger than the pores within the mucus gel network, for which diffusion is not simple Brownian motion and typically much less rapid: in these scenarios, a timescale competition ensues between particle passage through the mucus barrier and mucus clearance from the organ. In the lung, as a primary example, coordinated cilia and air drag continuously transport mucus toward the trachea, where mucus and trapped cargo are swallowed into the digestive tract. Mucus clearance times in lung airways range from minutes to hours or significantly longer depending on deposition in the upper, middle, lower airways and on lung health, giving a wide time window for drug-loaded particle design to achieve controlled delivery to the epithelium. We review the physical and chemical factors (of both particles and mucus) that dictate particle diffusion in mucus, and the technological strategies (theoretical and experimental) required to achieve the design goals. First we describe an idealized scenario - a homogeneous viscous fluid of uniform depth with a particle undergoing passive normal diffusion - where the theory of Brownian motion affords the ability to rigorously specify particle size distributions to meet a prescribed, one-sided, diffusive passage time distribution. Furthermore, we describe how the theory of Brownian motion provides the scaling of one-sided diffusive passage times with respect to mucus viscosity and layer depth, and under reasonable caveats, one can also prescribe passage time scaling due to heterogeneity in viscosity and layer depth. Small-molecule drugs and muco-inert, drug-loaded carrier particles 100 nm and smaller fall into this class of rigorously controllable passage times for drug delivery. Second we describe the prevalent scenarios in which drug-loaded carrier particles in mucus violate simple Brownian motion, instead exhibiting anomalous sub-diffusion, for which all theoretical control over diffusive passage times is lost, and experiments are prohibitive if not impossible to measure one-sided passage times. We then discuss strategies to overcome these roadblocks, requiring new particle-tracking experiments and emerging advances in theory and computation of anomalous, sub diffusive processes that are necessary to predict and control one-sided particle passage times from deposition at the mucosal interface to epithelial uptake. We highlight progress to date, remaining hurdles, and prospects for achieving the two design goals for 200 nm and larger, drug-loaded, non-dissolving, nanoparticulates.Natural Sciences and Engineering Research Council of Canada [DMS-1664645, RGPIN-2014-04255, DMS-1412844, DMS-1517274]National Science Foundation [DMS-1462992]Eshelman Institute of Innovation [DMR-1151477]National Institute of Health [R41GM123897, R56HD095629]Graduate Research Fellowship [DGE-1650116

Atypical SARS and Escherichia coli Bacteremia

We describe a patient with severe acute respiratory syndrome (SARS) whose clinical symptoms were masked by Escherichia coli bacteremia. SARS developed in a cluster of healthcare workers who had contact with this patient. SARS was diagnosed when a chest infiltrate developed and when the patient’s brother was hospitalized with acute respiratory failure. We highlight problems in atypical cases and offer infection control suggestions

Monitoring high spatiotemporal water dynamics by fusing MODIS, Landsat, water occurrence data and DEM

Monitoring the spatiotemporal dynamics of surface water from remote sensing imagery is essential for understanding water's impact on the global ecosystem and climate change. There is often a tradeoff between the spatial and temporal resolutions of imagery acquired from current satellite sensors and as such various spatiotemporal image fusion methods have been explored to circumvent the challenges this situation presents (e.g., STARFM). However, some challenges persist in mapping surface water at the desired fine spatial and temporal resolution. Principally, the spatiotemporal changes of water bodies are often abrupt and controlled by topographic conditions, which are usually unaddressed in current spatiotemporal image fusion methods. This paper proposes the SpatioTemporal Surface Water Mapping (STSWM) method, which aims to predict Landsat-like, 30 m, surface water maps at an 8-day time step (same as the MODIS 8-day composite product) by integrating topographic information into the analysis. In addition to MODIS imagery acquired on the date of map prediction and a pair of MODIS and Landsat images acquired temporally close to the date of prediction, STSWM also uses the surface water occurrence (SWO, which represents the frequency with which water is present in a pixel) and DEM data to provide, respectively, topographic information below and above the water surface. These data are used to translate the coarse spatial resolution water distribution representation observed by MODIS into a 30 m spatial resolution water distribution map. The STSWM was used to generate an 8-day time series surface water maps of 30 m resolution in six inundation regions globally, and was compared with several other state-of-the-art spatiotemporal methods. The stratified random sampling design was used, and unbiased estimators of the accuracies were provided. The results show that STSWM generated the most accurate surface water map in which the spatial details of surface water were well-represented

SUSTAINABLE DEVELOPMENT OF AMOMUM VILLOSUM: A SYSTEMATIC INVESTIGATION ON THREE DIFFERENT PRODUCTION MODES

Background: Amomum Villosum (A. Villosum), called Chunsharen in Chinese, is widely used in treating gastrointestinal disease. Its clinical benefits have been confirmed by both in vitro and in vivo studies. Facing the shortage of wild A. Villosum, artificial cultivating and natural fostering have been practiced in recent years. Therefore, it would be wondered whether the three different types of A. Villosum are comparable or not, particularly the herbal qualities, technological challenges, ecological impacts and economic benefits. Material and methods: In this study, we combined quality research by using GC-MS, and field investigation to provide a systematic assessment about the three types of A. Villosum from these four aspects. Results: It found that the wild type had low output and was in an endangered situation. The artificial cultivation had larger agriculturing area with higher productivity, but faced the ecological challenges. Lastly, the natural fostering type generated the highest economic benefit and relatively low ecological impact. In addition, the natural fostering type had relatively better quality than the other types. Conclusion: Therefore, it suggests that natural fostering can be applied for long-term sustainable development of A. Villosum

Potential of Cellular Therapy for ALS: Current Strategies and Future Prospects

Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disease characterized by progressive upper and lower motor neuron (MN) degeneration with unclear pathology. The worldwide prevalence of ALS is approximately 4.42 per 100,000 populations, and death occurs within 3–5 years after diagnosis. However, no effective therapeutic modality for ALS is currently available. In recent years, cellular therapy has shown considerable therapeutic potential because it exerts immunomodulatory effects and protects the MN circuit. However, the safety and efficacy of cellular therapy in ALS are still under debate. In this review, we summarize the current progress in cellular therapy for ALS. The underlying mechanism, current clinical trials, and the pros and cons of cellular therapy using different types of cell are discussed. In addition, clinical studies of mesenchymal stem cells (MSCs) in ALS are highlighted. The summarized findings of this review can facilitate the future clinical application of precision medicine using cellular therapy in ALS