Do No Harm in Global Health Engagement.

This manuscript examines the principle of "Do No Harm" in DoD Global Health Engagement (GHE) efforts. It highlights the potential positive and negative consequences of health investments and explores how unintentional harm is addressed in a global health context. The manuscript also discusses the involvement of the U.S. military in global health and the concept of dual loyalty faced by military GHE practitioners. The goal is to understand the challenges of doing no harm and identify methods to mitigate or avoid unintended negative consequences in DoD GHE activities.

Experiences with an Inquiry-Based Ionic Liquid Module in an Undergraduate Physical Chemistry Laboratory.

The topic of ionic liquids is typically not taught at the undergraduate level. Many properties, such as conductivity, vapor pressure, and viscosity, of these so-called "green solvents" are unique compared to traditional molecular solvents. Using active learning techniques, we introduced an ionic liquid module in the physical chemistry laboratory where their structures and physical properties, namely, viscosity, conductivity, and vapor pressure, were explored in relation to molecular solvents. Summative and formative assessments show that a majority of the participants were able to grasp the key concepts of ionic liquids. We envision that our methods and strategies can be one of the building blocks of introducing ionic liquids into the undergraduate chemistry curriculum.

Hydrogen-Bonded Complexes in Binary Mixture of Imidazolium-Based Ionic Liquids with Organic Solvents.

Though local structures in ionic liquids are dominated by strong Coulomb forces, directional hydrogen bonds can also influence the physicochemical properties of imidazolium-based ionic liquids. In particular, the C-2 position of the imidazolium cation is acidic and can bind with suitable hydrogen bond acceptor sites of molecular solvents dissolved in imidazolium-based ionic liquids. In this report, we identify hydrogen-bonded microenvironments of the model ionic liquid, 1-ethyl-3-methylimidazolium tris(pentafluoroethyl) trifluorophosphate, and the changes that occur when molecular solvents are dissolved in it by using a C-D infrared reporter at the C-2 position of the cation. Our linear and nonlinear infrared experiments, along with computational studies, indicate that the molecular solvent dimethyl sulfoxide can form strong hydrogen-bonded dimers with the cation of the ionic liquid at the C-2 position. In contrast, acetone, which is also a hydrogen bond acceptor similar to dimethyl sulfoxide, does not show evidence of cation-solvent hydrogen-bonded conformers at the C-2 position. The outcome of our study on a broad scale strengthens the importance of cation-solute interactions in ionic liquids.

Highly Selective Electrochemical Synthesis of Urea Derivatives Initiated from Oxygen Reduction in Ionic Liquids.

The development of more efficient and sustainable methods for synthesizing substituted urea compounds and directly utilizing CO2 has long been a major focus of synthetic organic chemistry as these compounds serve critical environmental and industrial roles. Herein, we report a green approach to forming the urea compounds directly from CO2 gas and primary amines, triggered by oxygen electroreduction in ionic liquids (ILs). These reactions were carried out under mild conditions, at very low potentials, and achieved high conversion rates. The fact that O2 gas was utilized as the sole catalyst in this electrochemical loop, without additional reagents, is a significant milestone for eco-friendly syntheses of C-N compounds and establishes an effective and green CO2 scavenging method.

Fentanyl Assay Derived from Intermolecular Interaction-Enabled Small Molecule Recognition (iMSR) with Differential Impedance Analysis for Point-of-Care Testing.

Rapid and effective differentiation and quantification of a small molecule drug, such as fentanyl, in bodily fluids are major challenges for diagnosis and personal medication. However, the current toxicology methods used to measure drug concentration and metabolites require laboratory-based testing, which is not an efficient or cost-effective way to treat patients in a timely manner. Here, we show an assay for monitoring fentanyl levels by combining the intermolecular interaction-enabled small molecule recognition (iMSR) with differential impedance analysis of conjugated polymers. The differential interactions with the designed anchor interface were transduced through the perturbance of the electric status of the flexible conducting polymer. This assay showed excellent fentanyl selectivity against common interferences, as well as in variable body fluids through either testing strips or skin patches. Directly using the patient blood, the sensor provided 1%-5% of the average deviation compared to the "gold" standard method LC-MS results in the medically relevant fentanyl range of 20-90 nM. The superior sensing properties, in conjunction with mechanical flexibility and compatibility, enabled point-of-care detection and provided a promising avenue for applications beyond the scope of biomarker detection.

Worker Injuries in Southern California's Warehousing Industry: How to Better Protect Workers in This Burgeoning Industry?

Dangerous conditions and worker injuries in the rapidly growing warehousing industry have gained attention in recent years, with accounts typically drawing on worker reports and investigative journalism. We analyzed workers' compensation injury claims and California Division of Occupational Safety and Health (Cal/OSHA) citations in Southern California's large warehousing sector. Claims increased from 2014 to 2018, with a majority of injuries caused by repetitive motion, lifting and other ergonomic risk factors. Cal/OSHA cited employers for violating standards to protect workers from unsafe vehicle operations, dangerous machinery and equipment, and falls; and for failing to implement injury prevention programs. These citations address the causes of some worker injuries; however, no Cal/OSHA citations were issued for violating the state's Repetitive Motion Injuries prevention standard. Nor do enforcement activities address the underlying causes highlighted by workers-high production quotas and a relentless work pace-that characterize the industry. We discuss the value and limitations of our approach and the implications of our results.

Using workers' compensation claims to investigate occupational injuries among residential day laborers and domestic workers.

BACKGROUND: While many states have legal provisions to extend workers' compensation eligibility to day laborers or domestic workers hired directly by homeowners or families, little is known about the nature or frequency of injury claims submitted on behalf of these "residential employees." METHODS: We examined California workers' compensation claims records for injuries that appear to have occurred in residential settings between 2008 and 2018 and where the employer of record was an individual or family. We examined the demographic, occupational, and injury characteristics of our sample and analyzed factors that contribute to the likelihood of a claim resulting in some sort of payment. RESULTS: We identified 5,463 workers' compensation claims that were likely submitted on behalf of residential employees. Claims most commonly reflected injuries to workers performing housekeeping tasks, followed by construction/maintenance and caregiving. Workers performing construction/maintenance or gardening/landscaping tasks were more likely to be injured on the same day of hire and were more likely to require hospitalization or emergency treatment for their injuries; however, these workers also had a smaller proportion of claims that resulted in payment. We found that employment tenure had the biggest impact on the likelihood of payment, with the odds increasing sharply after the first day of work. CONCLUSIONS: Although the claims in our data set likely represent only a small fraction of all injuries to residential day laborers and domestic workers during this period, we suggest that workers' compensation claims can provide valuable clues for better understanding occupational injuries among workers in this largely informal sector.

C-D Vibration at C2 Position of Imidazolium Cation as a Probe of the Ionic Liquid Microenvironment.

Unlike molecular solvents, imidazolium-based ionic liquids are entirely made of ions with spatial heterogeneity. There is a need for spectroscopic probes that can assess the microenvironment near the cations of these complex liquids. In this manuscript, we describe simple chemical procedures to label the C2 position of imidazolium cation with a C-D vibrational probe and show, through linear and nonlinear vibrational spectroscopies, that this C-D stretching mode can be a useful analytical tool to assess both the solvent microenvironment and solute-solvent interactions in imidazolium-based ionic liquids from the cation point of view. It is expected that this C-D vibration probe on the cation will lead to the development of innovative experimental strategies that can provide a better understanding of such ionic liquids.

Implications of Social and Legal Status on Immigrants' Health in Disaster Zones.

This commentary highlights how immigrants who are linguistically isolated, have limited social networks, and lack legal immigration status experience unique health risks in disaster zones. Research on immigrants and disasters tends to focus on immigrants with these characteristics who are residents of disaster-affected areas, disaster recovery workers, or both. We review the sparse research literature and provide examples of innovative but underresourced programs that reduce immigrants' exposure to disaster-related health hazards and economic exploitation in the recovery. We conclude with recommendations for advancing these initiatives while, simultaneously, addressing the anti-immigrant policies that contribute to these disaster-related inequities.

Crystal structures of the hexa-fluorido-phosphate salts of the isomeric 2-, 3- and 4-cyano-1-methyl-pyridinium cations and determination of solid-state inter-action energies.

The synthesis and crystal structures of the isomeric mol-ecular salts 2-, 3- and 4-cyano-1-methyl-pyridinium hexa-fluorido-phosphate, C7H7N2+·PF6-, are reported. In 2-cyano-1-methyl-pyridinium hexa-fluorido-phosphate, C-H⋯F hydrogen bonds form chains extending along the c-axis direction, which are associated through C-H⋯F hydrogen bonds and P-F⋯π(ring) inter-actions into stepped layers. For 3-cyano-1-methyl-pyridinium hexa-fluorido-phosphate, corrugated sheets parallel to [001] are generated by C-H⋯F hydrogen bonds and P-F⋯π(ring) inter-actions. The sheets are weakly associated by a weak inter-action of the cyano group with the six-membered ring of the cation. In 4-cyano-1-methyl-pyridinium hexa-fluorido-phosphate, C-H⋯F hydrogen bonds form a more open three-dimensional network in which stacks of cations and of anions are aligned with the b-axis direction. Dispersion-corrected density functional theory (DFT-D) calculations were carried out in order to elucidate some of the energetic aspects of the solid-state structures. The results indicate that the distribution of charge within a mol-ecular ionic cation can play a large role in determining the strength of a cation-anion inter-action within a crystal structure. Crystals of 2-cyano-1-methyl-pyridinium hexa-fluorido-phosphate are twinned by a 180° rotation about the c* axis. The anion in 3-cyano-1-methyl-pyridinium hexa-fluorido-phosphate is rotationally disordered by 38.2 (1)° in an 0.848 (3):0.152 (3) ratio.

Point-of-Care Determination of Acetaminophen Levels with Multi-Hydrogen Bond Manipulated Single-Molecule Recognition (eMuHSiR).

This work aims to face the challenge of monitoring small molecule drugs accurately and rapidly for point-of-care (POC) diagnosis in current clinical settings. Overdose of acetaminophen (AP), a commonly used over the counter (OTC) analgesic drug, has been determined to be a major cause of acute liver failure in the US and the UK. However, there is no rapid and accurate detection method available for this drug in the emergency room. The present study examined an AP sensing strategy that relies on a previously unexplored strong interaction between AP and the arginine (Arg) molecule. It was found that as many as 4 hydrogen bonds can be formed between one Arg molecule and one AP molecule. By taking advantages of this structural selectivity and high tenability of hydrogen bonds, Arg, immobilized on a graphene surface via electrostatic interactions, was utilized to structurally capture AP. Interestingly, bonded AP still remained the perfect electrochemical activities. The extent of Arg-AP bonds was quantified using a newly designed electrochemical (EC) sensor. To verify the feasibility of this novel assay, based on multihydrogen bond manipulated single-molecule recognition (eMuHSiR), both pharmaceutical and serum sample were examined. In commercial tablet measurement, no significant difference was seen between the results of eMuHSiR and other standard methods. For measuring AP concentration in the mice blood, the substances in serum, such as sugars and fats, would not bring any interference to the eMuHSiR in a wide concentration range. This eMuHSiR method opens the way for future development of small molecule detection for the POC testing.

Mortality and Morbidity during Extreme Heat Events and Prevalence of Outdoor Work: An Analysis of Community-Level Data from Los Angeles County, California.

Heat is a well-recognized hazard for workers in many outdoor settings, yet few investigations have compared the prevalence of outdoor work at the community level and rates of heat-related mortality and morbidity. This analysis examines whether heat-related health outcomes occur more frequently in communities with higher proportions of residents working in construction, agriculture, and other outdoor industries. Using 2005-2010 data from Los Angeles County, California, we analyze associations between community-level rates of deaths, emergency department (ED) visits, and hospitalizations during summer heat events and the prevalence of outdoor work. We find generally higher rates of heat-related ED visits and hospitalizations during summer heat events in communities with more residents working outdoors. Specifically, each percentage increase in residents working in construction resulted in an 8.1 percent increase in heat-related ED visits and a 7.9 percent increase in heat-related hospitalizations, while each percentage increase in residents working in agriculture and related sectors resulted in a 10.9 percent increase in heat-related ED visits. The findings suggest that outdoor work may significantly influence the overall burden of heat-related morbidity at the community level. Public health professionals and healthcare providers should recognize work and employment as significant heat risk factors when preparing for and responding to extreme heat events.

Strength, character, and directionality of halogen bonds involving cationic halogen bond donors.

Halogen bonds involving cationic halogen bond donors and anionic halogen bond acceptors have recently been recognized as being important in stabilizing the crystal structures of many salts. Theoretical characterization of these types of interactions, most importantly in terms of their directionality, has been limited. Here we generate high-quality symmetry adapted perturbation theory potential energy curves of a H3N-C[triple bond, length as m-dash]C-Br+Cl- model system in order to characterize halogen bonds involving charged species, in terms of contributions from electrostatics, exchange, induction, and dispersion, with special emphasis on analyzing contributions that are most responsible for the directionality of these interactions. It is found that, as in the case of neutral halogen bonds, exchange forces are important contributors to the directionality of charged halogen bonds, however, it is also found that induction effects, which contribute little to the stability and directionality of neutral halogen bonds, play a large role in the directionality of halogen bonds involving charged species. Potential energy curves based on the ωB97X-D/def2-TZVP/C-PCM method, which includes an implicit solvation model in order to mimic the effects of the crystal medium, are produced for both the H3N-C[triple bond, length as m-dash]C-Br+Cl- model system and for the 4-bromoaniliniumCl- dimer, which is based on the real 4-bromoanilinium chloride salt, whose crystal structure has been determined experimentally. It is found that, within a crystal-like medium, charged halogen bond are significantly weaker than in the gas phase, having optimum interaction energies up to approximately -20 kcal mol-1.

Osteoinductive effects of glyceollins on adult mesenchymal stromal/stem cells from adipose tissue and bone marrow.

BACKGROUND: While current therapies for osteoporosis focus on reducing bone resorption, the development of therapies to regenerate bone may also be beneficial. Promising anabolic therapy candidates include phytoestrogens, such as daidzein, which effectively induce osteogenesis of adipose-derived stromal cells (ASCs) and bone marrow stromal cells (BMSCs). PURPOSE: To investigate the effects of glyceollins, structural derivatives of daidzein, on osteogenesis of ASCs and BMSCs. STUDY DESIGN: Herein, the osteoinductive effects of glyceollin I and glyceollin II were assessed and compared to estradiol in ASCs and BMSCs. The mechanism by which glyceollin II induces osteogenesis was further examined. METHODS: The ability of glyceollins to promote osteogenesis of ASCs and BMSCs was evaluated in adherent and scaffold cultures. Relative deposition of calcium was analyzed using Alizarin Red staining, Bichinchoninic acid Protein Assay, and Alamar Blue Assay. To further explore the mechanism by which glyceollin II exerts its osteoinductive effects, docking studies of glyceollin II, RNA isolation, cDNA synthesis, and quantitative RT-PCR (qPCR) were performed. RESULTS: In adherent cultures, ASCs and BMSCs treated with estradiol, glyceollin I, or glyceollin II demonstrated increased calcium deposition relative to vehicle-treated cells. During evaluation on PLGA scaffolds seeded with ASCs and BMSCs, glyceollin II was the most efficacious in inducing ASC and BMSC osteogenesis compared to estradiol and glyceollin I. Dose-response analysis in ASCs and BMSCs revealed that glyceollin II has the highest potency at 10nM in adherent cultures and 1µM in tissue scaffold cultures. At all doses, osteoinductive effects were attenuated by fulvestrant, suggesting that glyceollin II acts at least in part through estrogen receptor-mediated pathways to induce osteogenesis. Analysis of gene expression demonstrated that, similar to estradiol, glyceollin II induces upregulation of genes involved in osteogenic differentiation. CONCLUSION: The ability of glyceollin II to induce osteogenic differentiation in ASCs and BMSCs indicates that glyceollins hold the potential for the development of pharmacological interventions to improve clinical outcomes of patients with osteoporosis.

Ligands of Therapeutic Utility for the Liver X Receptors.

Liver X receptors (LXRs) have been increasingly recognized as a potential therapeutic target to treat pathological conditions ranging from vascular and metabolic diseases, neurological degeneration, to cancers that are driven by lipid metabolism. Amidst intensifying efforts to discover ligands that act through LXRs to achieve the sought-after pharmacological outcomes, several lead compounds are already being tested in clinical trials for a variety of disease interventions. While more potent and selective LXR ligands continue to emerge from screening of small molecule libraries, rational design, and empirical medicinal chemistry approaches, challenges remain in minimizing undesirable effects of LXR activation on lipid metabolism. This review provides a summary of known endogenous, naturally occurring, and synthetic ligands. The review also offers considerations from a molecular modeling perspective with which to design more specific LXRß ligands based on the interaction energies of ligands and the important amino acid residues in the LXRß ligand binding domain.

Ortho-Methylarylamines as Time-Dependent Inhibitors of Cytochrome P450 1A1 Enzyme.

BACKGROUND: Members of the cytochrome P450 1A family metabolize many procarcinogens such as polycyclicaromatic hydrocarbons and heterocyclic amines. Inactivation of these enzymes is a prerequisite for cancer prevention and treatment in certain cases. Mechanism-based inhibition (time and co-factor dependent) is an effective method for the inactivation of these enzymes. Our recent study on emodin analogs revealed an anthraquinone with ortho-methylarylamine moiety that exhibited timedependent inhibition of P450 enzymes 1A1 and 1A2. METHODS: To determine whether the amino group or the methyl group or both were responsible for the time-dependent inhibition of these enzymes, a set of eleven compounds containing the orthomethylarylamine moiety were identified through a database search, and studied for the inhibition of the P450 enzymes 1A1, 1A2, 2A6 and 2B1. Our earlier studies on carbazole derivatives provided us with highly selective P450 1A2 inhibitors. Glycine scanning studies were performed on the docked proteinligand complexes of compounds 1-20 in order to understand the contribution of different protein residues towards the ligand binding. RESULTS: Four compounds were found to cause selective time-dependent inhibition of P450 1A1 with KI values ranging from 0.24 to 8.25 mM. These compounds exhibited only direct inhibition of P450 1A2. Molecular modeling studies of these molecules indicated that the shapes of the molecules, their binding modes, and the methyl substituent in close proximity (4.5-5.7 Å) to the heme-Fe all contributed to their selective time-dependent inhibition activity on P450 1A1. Glycine scanning studies for P450 1A1 indicated that ligand interaction with Phe123 was the strongest binding contributor and similar studies for P450 1A2 indicated that ligand interactions with the phenylalanine residues 226 and 260 were the largest binding contributors. CONCLUSION: Four compounds have been identified that exhibit selective time-dependent inhibition of P450 1A1. Modeling studies have indicated that the proximity of the aromatic methyl group to the heme-Fe could be the main contributor for time-dependent inhibition. Future studies will focus on the confirmation of the involvement of the aromatic methyl group in enzyme inactivation.

Exploring the (Very Flat) Potential Energy Landscape of R-Br⋠⋠⋠π Interactions with Accurate CCSD(T) and SAPT Techniques.

Halogen bonds involving an aromatic moiety as an acceptor, otherwise known as R-X⋅⋅⋅π interactions, have increasingly been recognized as being important in materials and in protein-ligand complexes. These types of interactions have been the subject of many recent investigations, but little is known about the ways in which the strengths of R-X⋅⋅⋅π interactions vary as a function of the relative geometries of the interacting pairs. Here we use the accurate CCSD(T) and SAPT2+3δMP2 methods to investigate the potential energy landscapes for systems of HBr, HCCBr, and NCBr complexed with benzene. It is found that only the separation between the complexed molecules have a strong effect on interaction strength while other geometric parameters, such as tilting and shifting R-Br⋅⋅⋅π donor relative to the benzene plane, affect these interactions only mildly. Importantly, it is found that the C6v (T-shaped) configuration is not the global minimum for any of the dimers investigated.