A review of CBRN topics related to military and civilian patient exposure and decontamination.

Chemical and biological (CB) warfare have long been practiced, and although these types of warfare are not acceptable in modern times, this does not prevent them from occurring. This makes it important for societies to be able to appropriately respond to these events, including the best way to decontaminate victims to keep them and emergency responders safe. Decontamination methods such as chemical, physical, wet, and dry methods are discussed, as well as their downsides. Secondary contamination, which played a significant role in the Tokyo sarin attacks, has long been noted by anecdotal evidence, although it has been little studied. Biological agents cause more problems after infection has taken place, and thus preventing the spread of infection is the largest concern. There are many differences between military and civilian populations, and the response to mass casualty attacks differs accordingly. There are several emerging technologies that can make this process easier on all parties, such as bioscavengers, antitoxins, and color changing bleach for visualization. A reliable way to quantify decontamination is also needed, which would allow for better care of victims both in normal hospital situations, as well as during aeromedical transport. In addition, several gaps were identified, such as the lack of scientific basis for 90 percent reduction during decontamination, a way to quantify decontamination, and the lack of studies on toxic industrial chemicals and secondary contamination.

Essential Gene Profiles for Human Pluripotent Stem Cells Identify Uncharacterized Genes and Substrate Dependencies.

Human pluripotent stem cells (hPSCs) provide an invaluable tool for modeling diseases and hold promise for regenerative medicine. For understanding pluripotency and lineage differentiation mechanisms, a critical first step involves systematically cataloging essential genes (EGs) that are indispensable for hPSC fitness, defined as cell reproduction in this study. To map essential genetic determinants of hPSC fitness, we performed genome-scale loss-of-function screens in an inducible Cas9 H1 hPSC line cultured on feeder cells and laminin to identify EGs. Among these, we found FOXH1 and VENTX, genes that encode transcription factors previously implicated in stem cell biology, as well as an uncharacterized gene, C22orf43/DRICH1. hPSC EGs are substantially different from other human model cell lines, and EGs in hPSCs are highly context dependent with respect to different growth substrates. Our CRISPR screens establish parameters for genome-wide screens in hPSCs, which will facilitate the characterization of unappreciated genetic regulators of hPSC biology.

Human Embryonic Stem Cell-Derived Cardiomyocytes Regenerate the Infarcted Pig Heart but Induce Ventricular Tachyarrhythmias.

Human embryonic stem cell-derived cardiomyocytes (hESC-CMs) show considerable promise for regenerating injured hearts, and we therefore tested their capacity to stably engraft in a translationally relevant preclinical model, the infarcted pig heart. Transplantation of immature hESC-CMs resulted in substantial myocardial implants within the infarct scar that matured over time, formed vascular networks with the host, and evoked minimal cellular rejection. While arrhythmias were rare in infarcted pigs receiving vehicle alone, hESC-CM recipients experienced frequent monomorphic ventricular tachycardia before reverting back to normal sinus rhythm by 4 weeks post transplantation. Electroanatomical mapping and pacing studies implicated focal mechanisms, rather than macro-reentry, for these graft-related tachyarrhythmias as evidenced by an abnormal centrifugal pattern with earliest electrical activation in histologically confirmed graft tissue. These findings demonstrate the suitability of the pig model for the preclinical development of a hESC-based cardiac therapy and provide new insights into the mechanistic basis of electrical instability following hESC-CM transplantation.

Poly(2-thienyl)borates: An Investigation into the Coordination of Thiophene and Its Derivatives.

The synthesis, characterization, and reactivity of a new sulfur-rich tridentate ligand, tetrakis(2-thienyl)borate (1(-)()), are reported along with a molecular orbital analysis of its coordination to a metal center. Unlike the analogous tetrakis((methylthio)methyl)borate (2(-)()), 1(-)() does not coordinate Mo(CO)(3) when reacted with (C(7)H(8))Mo(CO)(3). The sulfur atoms in both ligands are oriented to coordinate the metal in a pyramidal eta(1) sulfur-bound mode. Approximate molecular orbital calculations are used to compare the metal-ligand interactions in these related species, and the results indicate that the magnitude and polarizability of the electronic charge density of the lone pairs on the sulfur atoms dictate the coordination strength of the ligands. Simple Mulliken atomic charges and orbital occupation numbers are used to determine the extent of charge delocalization. While the conjugation of the sulfur lone pair electrons with adjacent pi bonds in the ligands decreases the corresponding Lewis basicity, the contribution from the aromaticity in the thienyl groups is negligible. During the course of these studies, the structure of K[1] was determined by X-ray diffraction. K[1]: monoclinic space group C2/c, with a = 16.00(2) Å, b = 7.680(7) Å, c = 16.22(2) Å, beta = 118.520(7) degrees, V = 1750(3) Å(3), Z = 4, R(F) = 0.0494, and R(w)(F(2)()) = 0.122. The crystal lattice contains one-dimensional chains of 1(-)() bridged by K ions.

The implementation of novel collaborative structures for the identification and resolution of barriers to pluripotent stem cell translation.

Increased global connectivity has catalyzed technological development in almost all industries, in part through the facilitation of novel collaborative structures. Notably, open innovation and crowd-sourcing-of expertise and/or funding-has tremendous potential to increase the efficiency with which biomedical ecosystems interact to deliver safe, efficacious and affordable therapies to patients. Consequently, such practices offer tremendous potential in advancing development of cellular therapies. In this vein, the CASMI Translational Stem Cell Consortium (CTSCC) was formed to unite global thought-leaders, producing academically rigorous and commercially practicable solutions to a range of challenges in pluripotent stem cell translation. Critically, the CTSCC research agenda is defined through continuous consultation with its international funding and research partners. Herein, initial findings for all research focus areas are presented to inform global product development strategies, and to stimulate continued industry interaction around biomanufacturing, strategic partnerships, standards, regulation and intellectual property and clinical adoption.