Demographic fluctuations in bloodstream lineages configure the mobile gene pool and antimicrobial resistance.

in the bloodstream causes high morbidity and mortality, exacerbated by the spread of multidrug-resistant and methicillin-resistant (MRSA). We aimed to characterize the circulating lineages of from bloodstream infections and the contribution of individual lineages to resistance over time. Here, we generated 852 high-quality short-read draft genome sequences of isolates from patient blood cultures in a single hospital from 2010 to 2022.

Multi-host infection and phylogenetically diverse lineages shape the recombination and gene pool dynamics of Staphylococcus aureus.

Background: Staphylococcus aureus can infect and adapt to multiple host species. However, our understanding of the genetic and evolutionary drivers of its generalist lifestyle remains inadequate. This is particularly important when considering local populations of S.

Prophage-encoded immune evasion factors are critical for host infection, switching, and adaptation.

is a multi-host pathogen that causes infections in animals and humans globally. The specific genetic loci-and the extent to which they drive cross-species switching, transmissibility, and adaptation-are not well understood. Here, we conducted a population genomic study of 437 isolates to identify bacterial genetic variation that determines infection of human and animal hosts through a genome-wide association study (GWAS) using linear mixed models.

Genome Evolution of Invasive Methicillin-Resistant Staphylococcus aureus in the Americas.

Staphylococcus aureus causes a variety of debilitating and life-threatening diseases, and thus remains a challenging global health threat. S. aureus is remarkably diverse, yet only a minority of methicillin-resistant S.

Genomic epidemiology of methicillin-resistant and -susceptible Staphylococcus aureus from bloodstream infections.

Background: Bloodstream infections due to Staphylococcus aureus cause significant patient morbidity and mortality worldwide. Of major concern is the emergence and spread of methicillin-resistant S. aureus (MRSA) in bloodstream infections, which are associated with therapeutic failure and increased mortality.

Decolonizing Global Health Education: Rethinking Institutional Partnerships and Approaches.

Global health often entails partnerships between institutions in low- and middle-income countries (LMICs) that were previously colonized and high-income countries (HICs) that were colonizers. Little attention has been paid to the legacy of former colonial relationships and the influence they have on global health initiatives. There have been recent calls for the decolonization of global health education and the reexamination of assumptions and practices under pinning global health partnerships.

IDS Transposer: A Users Guide.

The Intermediate Data Structure (IDS) provides a standard format for storing and sharing individual-level longitudinal life-course data (Alter and Mandemakers 2014; Alter, Mandemakers and Gutmann 2009). Once the data are in the IDS format, a standard set of programs can be used to extract data for analysis, facilitating the analysis of data across multiple databases. Currently, life-course databases store information in a variety of formats, and the process of translating data into IDS can be long and tedious.

Unhappy Cities.

There are persistent differences in self-reported subjective well-being across US metropolitan areas, and residents of declining cities appear less happy than others. Yet some people continue to move to these areas, and newer residents appear to be as unhappy as longer-term residents. While historical data on happiness are limited, the available facts suggest that cities that are now declining were also unhappy in their more prosperous past.

Simulation in plastic surgery training and education: the path forward.

Computer-based training simulators have been used extensively, most notably in flight simulation. Over the past 20 years, surgical simulators have been developed, initially for training of minimally invasive surgery and more recently for open surgical simulation. The key effort in today's surgical simulation field is to develop metrics to evaluate how well the skills learned in a simulator translate to improvement in real surgical skills, execution of procedures, and team cooperation in the operating room.

The synthetic triterpenoid CDDO-Imidazolide suppresses STAT phosphorylation and induces apoptosis in myeloma and lung cancer cells.

Purpose: Excessive activity of the transcription factors known as signal transducers and activators of transcription (STAT) contributes to the development and progression of malignancy in many organs. It is, therefore, important to develop new drugs to control the STATs, particularly their phosphorylation state, which is required for their transcriptional activity.

Experimental Design: Myeloma and lung cancer cells were treated with the new synthetic triterpenoid CDDO-Imidazolide, and STAT phosphorylation and apoptosis were evaluated by immunoblotting and fluorescence-activated cell sorting analysis.

The synthetic triterpenoids, CDDO and CDDO-imidazolide, are potent inducers of heme oxygenase-1 and Nrf2/ARE signaling.

The synthetic triterpenoid 2-cyano-3,12-dioxooleana-1,9(11)-dien-28-oic acid (CDDO) and its derivative 1-[2-cyano-3-,12-dioxooleana-1,9(11)-dien-28-oyl]imidazole (CDDO-Im) are multifunctional molecules with potent antiproliferative, differentiating, and anti-inflammatory activities. At nanomolar concentrations, these agents rapidly increase the expression of the cytoprotective heme oxygenase-1 (HO-1) enzyme in vitro and in vivo. Transfection studies using a series of reporter constructs show that activation of the human HO-1 promoter by the triterpenoids requires an antioxidant response element (ARE), a cyclic AMP response element, and an E Box sequence.

Synthetic triterpenoids enhance transforming growth factor beta/Smad signaling.

We have studied the effects of two new synthetic triterpenoids, 2-cyano-3,12-dioxooleana-1,9-dien-28-oic acid (CDDO) and its derivative, 1-(2-cyano-3,12-dioxooleana-1,9-dien-28-oyl) imidazole (CDDO-Im), on transforming growth factor (TGF)-beta/Smad signaling. These agents, at nanomolar concentrations, increase the expression of TGF-beta-dependent genes, such as those for plasminogen activator inhibitor 1 and the type II TGF-beta receptor, and they synergize with TGF-beta in this regard. They prolong the activation of Smad2 induced by TGF-beta and markedly enhance the ability of Smad3 to activate a Smad binding element, CAGA-luciferase.

A synthetic triterpenoid, 2-cyano-3,12-dioxooleana-1,9-dien-28-oic acid (CDDO), is a ligand for the peroxisome proliferator-activated receptor gamma.

A novel synthetic triterpenoid, 2-cyano-3,12-dioxooleana-1,9-dien-28-oic acid (CDDO), previously reported to have potent differentiating, antiproliferative, and antiinflammatory activities, has been identified as a ligand for the peroxisome proliferator-activated receptor gamma (PPARgamma). CDDO induces adipocytic differentiation in 3T3-L1 cells, although it is not as potent as the full agonist of PPARgamma, rosiglitazone. Binding studies of CDDO to PPARgamma using a scintillation proximity assay give a Ki between 10(-8) to 10(-7) M.

Methyl Transfer to Mercury Thiolates: Effects of Coordination Number and Ligand Dissociation.

The complexes [(CH(3))(4)N](2)[Hg(SC(6)H(5))(4)] and [(C(4)H(9))(4)N][Hg(SC(6)H(5))(3)] demethylate (CH(3)O)(3)PO as revealed by (1)H, (31)P{(1)H}, and (199)Hg{(1)H} NMR spectroscopy in DMSO-d(6) solution. The products of the [(CH(3))(4)N](2)[Hg(SC(6)H(5))(4)] reaction are CH(3)SC(6)H(5), (CH(3)O)(2)PO(2)(-), and [Hg(SC(6)H(5))(3)](-), whereas [Hg(SC(6)H(5))(3)](-) demethylates (CH(3)O)(3)PO to yield CH(3)SC(6)H(5) and {Hg(SC(6)H(5))(2)[(CH(3)O)(2)PO(2)]}(-). Kinetic and solution studies of [(CH(3))(4)N](2)[Hg(SC(6)H(5))(4)] reveal a rapid equilibrium between bound and free thiolate.