Silver nanoparticles enhance the efficacy of aminoglycosides against antibiotic-resistant bacteria.

As the threat of antimicrobial-resistant bacteria compromises the safety and efficacy of modern healthcare practices, the search for effective treatments is more urgent than ever. For centuries, silver (Ag) has been known to have antibacterial properties and, over the past two decades, Ag-based nanoparticles have gained traction as potential antimicrobials. The antibacterial efficacy of Ag varies with structure, size, and concentration. In the present study, we examined Ag nanoparticles (AgNPs) for their antimicrobial activity and safety. We compared different commercially-available AgNPs against gram-negative Escherichia coli, Pseudomonas aeruginosa, Acinetobacter baumannii, and gram-positive Staphylococcus aureus methicillin-resistant and susceptible strains. The most effective formula of AgNPs tested had single-digit (µg/mL) minimum inhibitory concentrations against gram-negative multidrug-resistant clinical bacterial isolates with novel and emerging mechanisms of resistance. The mode of killing was assessed in E. coli and was found to be bactericidal, which is consistent with previous studies using other AgNP formulations. We evaluated cytotoxicity by measuring physiological readouts using the Caenorhabditis elegans model and found that motility was affected, but not the lifespan. Furthermore, we found that at their antibacterial concentrations, AgNPs were non-cytotoxic to any of the mammalian cell lines tested, including macrophages, stem cells, and epithelial cells. More interestingly, our experiments revealed synergy with clinically relevant antibiotics. We found that a non-toxic and non-effective concentration of AgNPs reduced the minimum inhibitory concentrations of aminoglycoside by approximately 22-fold. Because both aminoglycosides and Ag are known to target the bacterial ribosome, we tested whether Ag could also target eukaryotic ribosomes. We measured the rate of mistranslation at bactericidal concentration and found no effect, indicating that AgNPs are not proteotoxic to the host at the tested concentrations. Collectively, our results suggest that AgNPs could have a promising clinical application as a potential stand-alone therapy or antibiotic adjuvants.

Effects of easing shelter-in-place restrictions and the lingering COVID-19 pandemic on orthopaedic trauma at a community level 2 trauma center.

OBJECTIVES: Evaluate the effect of easing "shelter-in-place" restrictions and coronavirus-2019 (COVID-19) cases on orthopaedic trauma encounters (OTEs) at a community level II trauma center. METHODS: A retrospective analysis was conducted of OTEs from March-June of 2016 to 2020. Injuries were classified by high or low severity. Admission and surgical intervention rates were also compared year to year. Data were statistically analyzed and compared with external data for traffic counts near the hospital and COVID-19 cases in Michigan as well as a timeline for enacting and easing of shelter-in-place orders in the state of Michigan. RESULTS: There was no difference in the number of OTEs May to June, 2020 compared with the average of those same months 2016 to 2019. March to June, 2020 showed no change in proportion of injury severity, admissions, or surgical interventions when compared with the average of March-June, 2016 to 2019, although the overall quantity of each was decreased in March and April. A significant negative correlation was found between the daily number of COVID-19 cases in Michigan and OTEs. CONCLUSIONS: The quantity of OTEs normalized to pre-COVID-19 levels in May and June of 2020 compared with 2016 to 2019 despite a previously documented 45.1% drop in March and April. A negative correlation was noted between the number of reported Michigan COVID-19 cases and volume of OTEs. There were no significant changes noted to admission rates or rates of surgical intervention on OTEs throughout the time period studied.

Effect of Shelter-in-Place Orders and the COVID-19 Pandemic on Orthopaedic Trauma at a Community Level II Trauma Center.

OBJECTIVES: To evaluate the effect of the COVID-19 pandemic and the "shelter-in-place" order on orthopaedic trauma presenting to a community level II trauma center. It is hypothesized that the overall number of orthopaedic trauma encounters (OTEs), the number of OTEs related to both high and low severity injuries, and the proportion of OTEs related to high severity versus low severity injuries decreased compared with previous years. METHODS: A retrospective analysis was conducted of OTEs between 2016 and 2020. High and low severity OTEs were classified according to an algorithm created by the researchers. Data were statistically analyzed and compared with external data for traffic counts, motor vehicle accidents, and Transportation Security Administration checkpoints. RESULTS: A 45.1% decrease (P = 0.0005) was seen in OTEs from March and April 2016-2019 compared with 2020. The decrease began approximately 12 days before the shelter-in-place order. There was a 58.8% decrease in high severity injuries with a fracture (P = 0.013) and a 42.9% decrease in low severities injuries (P = 0.0003). The proportion of high to low severity OTEs was unchanged. CONCLUSIONS: The quantity of OTEs was significantly affected by the COVID-19 pandemic and Michigan shelter-in-place order. A decrease in both high and low severity OTEs was found; however, there was no statistically significant change in the ratio of high to low severity OTEs compared with previous years. Although it is difficult to determine what portion of the decrease in OTE is attributable to the shelter-in-place order versus the COVID-19 pandemic in general, data suggest both play a role. LEVEL OF EVIDENCE: Therapeutic Level III. See Instructions for Authors for a complete description of Levels of Evidence.

Impact of the physical environment on patient outcomes of genetic counseling: An exploratory study.

The psychology literature shows that the physical space in which counseling sessions are conducted influences outcomes of the interaction. However, this phenomenon has not been quantitatively explored in genetic counseling (GC). Through retrospective review of naturalistic data from a psychiatric GC clinic (where data on patient outcomes are routinely tracked from pre- to 1 month post-appointment using the Genetic Counseling Outcome Scale (GCOS, empowerment) and the Illness Management Self Efficacy Scale (IMSES), we tested the hypotheses that patients seen in comfortably furnished counseling (C-type) rooms would have greater increases in (a) empowerment and (b) self-efficacy after GC than patients seen in medically oriented (M-type) rooms. We matched each patient with complete GCOS and/or IMSES who was seen in a C-type room between February 2012 and December 2017 to four M-type room controls where possible. We used t tests to compare change in outcome scale scores between groups. There were no significant differences in change in scores between patients seen in M-type (GCOS n = 84, IMSES n = 56) and C-type rooms (GCOS n = 22, IMSES n = 18) (p = 0.241, d = 0.26, and p = 0.602, d = 0.14, respectively). The effect sizes we demonstrate allow estimation of sample size calculations for the design of future prospective studies.

Genetic Coupling of Female Mate Choice with Polygenic Ecological Divergence Facilitates Stickleback Speciation.

Ecological speciation with gene flow is widespread in nature [1], but it presents a conundrum: how are associations between traits under divergent natural selection and traits that contribute to assortative mating maintained? Theoretical models suggest that genetic mechanisms inhibiting free recombination between loci underlying these two types of traits (hereafter, "genetic coupling") can facilitate speciation [2-4]. Here, we perform a direct test for genetic coupling by mapping both divergent traits and female mate choice in a classic model of ecological speciation: sympatric benthic and limnetic threespine stickleback (Gasterosteus aculeatus). By measuring mate choice in F2 hybrid females, we allowed for recombination between loci underlying assortative mating and those under divergent ecological selection. In semi-natural mating arenas in which females had access to both benthic and limnetic males, we found that F2 females mated with males similar to themselves in body size and shape. In addition, we found two quantitative trait loci (QTLs) associated with female mate choice that also predicted female morphology along the benthic-limnetic trait axis. Furthermore, a polygenic genetic model that explains adaptation to contrasting benthic and limnetic feeding niches [5] also predicted F2 female mate choice. Together, these results provide empirical evidence that genetic coupling of assortative mating with traits under divergent ecological selection helps maintain species in the face of gene flow, despite a polygenic basis for adaptation to divergent environments.

Extent of QTL Reuse During Repeated Phenotypic Divergence of Sympatric Threespine Stickleback.

How predictable is the genetic basis of phenotypic adaptation? Answering this question begins by estimating the repeatability of adaptation at the genetic level. Here, we provide a comprehensive estimate of the repeatability of the genetic basis of adaptive phenotypic evolution in a natural system. We used quantitative trait locus (QTL) mapping to discover genomic regions controlling a large number of morphological traits that have diverged in parallel between pairs of threespine stickleback (Gasterosteus aculeatus species complex) in Paxton and Priest lakes, British Columbia. We found that nearly half of QTL affected the same traits in the same direction in both species pairs. Another 40% influenced a parallel phenotypic trait in one lake but not the other. The remaining 10% of QTL had phenotypic effects in opposite directions in the two species pairs. Similarity in the proportional contributions of all QTL to parallel trait differences was about 0.4. Surprisingly, QTL reuse was unrelated to phenotypic effect size. Our results indicate that repeated use of the same genomic regions is a pervasive feature of parallel phenotypic adaptation, at least in sticklebacks. Identifying the causes of this pattern would aid prediction of the genetic basis of phenotypic evolution.

Conserved Arabidopsis ECHIDNA protein mediates trans-Golgi-network trafficking and cell elongation.

Multiple steps of plant growth and development rely on rapid cell elongation during which secretory and endocytic trafficking via the trans-Golgi network (TGN) plays a central role. Here, we identify the ECHIDNA (ECH) protein from Arabidopsis thaliana as a TGN-localized component crucial for TGN function. ECH partially complements loss of budding yeast TVP23 function and a Populus ECH complements the Arabidopsis ech mutant, suggesting functional conservation of the genes. Compared with wild-type, the Arabidopsis ech mutant exhibits severely perturbed cell elongation as well as defects in TGN structure and function, manifested by the reduced association between Golgi bodies and TGN as well as mislocalization of several TGN-localized proteins including vacuolar H(+)-ATPase subunit a1 (VHA-a1). Strikingly, ech is defective in secretory trafficking, whereas endocytosis appears unaffected in the mutant. Some aspects of the ech mutant phenotype can be phenocopied by treatment with a specific inhibitor of vacuolar H(+)-ATPases, concanamycin A, indicating that mislocalization of VHA-a1 may account for part of the defects in ech. Hence, ECH is an evolutionarily conserved component of the TGN with a central role in TGN structure and function.