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The development of trait‐based approaches has accelerated our understanding of how communities assemble, respond to environmental change and may best be managed in the Anthropocene. Understanding the magnitude and pattern of interspecific variability forms a critical underpinning of trait‐based approaches while exploring intraspecific variability can identify the potential of species to adapt to changing environmental drivers. Our work is motivated by the critical need for a novel conceptual framework for understanding the functional ecology of macroalgae, as the current paradigm is still mired in functional group models developed in the 1980s.Our objective was to quantify interspecific and intraspecific functional trait variability in three common and morphologically diverse species of tropical marine macroalgae by exploring traits relating to the ecological functions of resource acquisition, resistance to herbivory, and resistance to physical disturbance and the trade‐offs between them.We quantified intraspecific and interspecific variability of 11 functional traits for three common and morphologically diverse species of tropical macroalgae from five fringing reefs of Mo'orea, French Polynesia that were likely to capture a wide range of environmental variability. Differences in traits among species and sites were determined with PERMANOVA, visualised with non‐metric multidimensional scaling, and trade‐offs between pairs of traits explored with correlation. Finally, spatial patterns among select traits across all species were quantified.Species clustered together in distinctly different trait spaces driven by trade‐offs among suites of functional traits. Two of three species had considerable intraspecific variability, though this variability occurred at different scales, while one clustered tightly. Exploration of individual traits across species and sites revealed trade‐offs between two strategies for resource acquisition, growing tall and strong versus investing in large surface area.Synthesis. We captured novel patterns of interspecific and intraspecific variability for tropical marine macroalgae. We found fundamental differences in traits between species that may represent ecological strategies while considerable intraspecific variability demonstrates a wide range in abilities to respond to environmental drivers. Overall, our work provides novel insights into intra and interspecific trait variation that form an essential underpinning for using a trait‐based framework in a taxon that is increasingly dominant on tropical reefs. [ABSTRACT FROM AUTHOR]

The brain and the gut work synergistically with each other and other organs. Reviewing nutrition systemically (rather than by single organs) is a holistic way for dietitians to evaluate their clients' health status. Nutrition influences the genetic onset and consequences of many chronic diseases. With identification of up to 500 000 single nucleotide polymorphisms in an individual, the population-level potential for nutrigenomic optimization is astounding. The reader will be able to describe how several specific nutrients can maintain or improve health through supporting or suppressing gene expression. [ABSTRACT FROM AUTHOR]

This article is designed for the clinician practicing in the dermatology setting in which patients are likely to be prescribed teratogenic medications. Educating patients, taking a sexual health history, and counseling are discussed, as well as the importance of providing these services. It is hoped that the content presented will enhance the practitioner's skills in taking a sexual health history as well as provide information on basic counseling strategies that can be employed to enhance patient safety and improve the standard of care. [ABSTRACT FROM AUTHOR]

Monofluoroacetate is a highly lethal toxin that causes death by inhibiting cellular adenosine triphosphate (ATP) production. The heart and brain are the primary target organs. Acute death is attributed to cardiac fibrillation and/or convulsions. Although it occurs naturally in some plants, a major source of animal intoxication is access to sodium monofluoroacetate (NaMFA) pesticide, which continues to be a concern in the USA and around the world despite restricted use in some countries including the USA. There are also concerns about misuse of this pesticide for malicious poisoning. Currently, a tissue-based diagnostic method for NaMFA intoxication in animals is lacking. There is a critical need by the veterinary diagnostic community for a simple, sensitive and reliable tissue-based diagnostic test to confirm NaMFA poisoning in animals. We have developed and extensively evaluated a sensitive novel liquid chromatography combined with tandem mass spectrometry method suitable for this purpose. The limits of detection and limits of quantitation are 1.7 and 5.0 ng/g, respectively. The accuracy and precision met or exceeded expectations. The method performance was verified using the incurred kidney obtained from animal diagnostic cases. This novel kidney-based method is now available for clinical use and can help with diagnostic purposes, including detecting potential issues related to animal foods., (© The Author(s) 2024. Published by Oxford University Press. All rights reserved. For commercial re-use, please contact reprints@oup.com for reprints and translation rights for reprints. All other permissions can be obtained through our RightsLink service via the Permissions link on the article page on our site–for further information please contact journals.permissions@oup.com.)

Background: Humans are exposed to hazardous chemicals found in consumer products. In 2019, the Pollution Prevention for Healthy People and Puget Sound Act was passed in Washington State. This law is meant to reduce hazardous chemicals in consumer products and protect human health and the environment. The law directs the Washington State Department of Ecology to assess chemicals and chemical classes found in products, determine whether there are safer alternatives, and make regulatory determinations., Objectives: To implement the law, the Department of Ecology developed a hazard-based framework for identifying safer alternatives to classes of chemicals., Methods: We developed a hazard-based framework, termed the "Criteria for Safer," to set a transparent bar for determining whether new chemical alternatives are safer than existing classes of chemicals. Our "Criteria for Safer" is a framework that builds on existing hazard assessment methodologies and published approaches for assessing chemicals and chemical classes., Discussion: We describe implementation of our criteria using a case study on the phthalates chemical class in two categories of consumer products: vinyl flooring and fragrances used in personal care and beauty products. Additional context and considerations that guided our decision-making process are also discussed, as well as benefits and limitations of our approach. This paper gives insight into our development and implementation of a hazard-based framework to address classes of chemicals in consumer products and will aid others working to build and employ similar approaches. https://doi.org/10.1289/EHP13549.

This announcement contains the whole genome sequences of five Ackermannviridae that infect members of the Enterobacteriaceae family of bacteria. Four of the five phages were isolated using Salmonella enterica serovar Typhimurium as a bacterial host: AR2819, Sajous1, SilasIsHot, and FrontPhageNews. ChubbyThor was isolated using Shigella boydii ., Competing Interests: The authors declare no conflict of interest.

Healthcare-acquired infections and multi-drug resistance in pathogens pose a major crisis for the healthcare industry. Novel antibiotics which are effective against resistant strains and unlikely to elicit strong resistance are sought after in these settings. We have previously developed synthetic mimics of ubiquitous antimicrobial peptides and have worked to apply a lead compound, CSA-131, to the crisis. We aimed to generate a system of CSA-131-containing coatings for medical devices that can be adjusted to match elution and compound load for various environments and establish their efficacy in preventing the growth of common pathogens in and around these devices. Peripherally inserted central catheter (PICC) lines were selected for our substrate in this work, and a polyurethane-based system was used to establish coatings for evaluation. Microbial challenges by methicillin-resistant Staphylococcus aureus , Pseudomonas aeruginosa , Klebsiella pneumoniae , and Candida albicans were performed and SEM was used to evaluate coating structure and colonization. The results indicate that selected coatings show activity against selected planktonic pathogens that extend between 16 and 33 days, with similar periods of biofilm prevention.

Visual cues are important in both interspecific and intraspecific communication. The species confidence hypothesis proposes that animals are more attracted to conspecific colors and repelled by colors, not on their bodies. Studies on terrestrial lizards and birds have tested the species confidence hypothesis and shown that conspecific colors elicit reduced antipredator behavior. To date, the species confidence hypothesis has not been tested in the marine environment, specifically on coral reefs where color communication is of vital importance. We addressed this knowledge gap by measuring flight initiation distance (the distance an individual moves away from an approaching threat) in dusky damselfish ( Stegastes nigricans ) in response to an approaching disc of 1 of 4 different color treatments: conspecific, blue, yellow, and black. If the species confidence hypothesis explained variation in damselfish flight initiation distance, then we expected individuals to tolerate closer approaches when approached by a conspecific color. In addition, we calculated the color difference between each stimulus and its corresponding background as a potential alternative explanation for flight responses. Damselfish tolerated the closest approach from the conspecific color stimulus; there were no significant differences between other colors and there was no support for the alternative color difference hypothesis. As with similar terrestrial studies, these results are relevant to ecotourists' choice of swimsuit and wetsuit colors because color choice may modify natural antipredator behavior., Competing Interests: The authors declare no conflict of interest., (© The Author(s) 2023. Published by Oxford University Press on behalf of Editorial Office, Current Zoology.)

A series of 10-alkoxy-Anthryl-isoxazole-pyrrole-doubletails (RO-AIMs) were synthesized using a crown ether assisted nucleophilic aromatic substitution followed by a modified Schotten-Baumann reaction. The novel RO-AIMs described here exhibit robust growth inhibition for the human SNB19 CNS glioblastoma cell line, and biphenyl analog 8c had activity in the nanomolar regime, which represents the most efficacious compound in the AIM series to date. Computational modeling for RO-AIMs binding in a ternary complex with c-myc quadruplex DNA and its helicase DHX36 is presented which represents our current working hypothesis., (Copyright © 2022 Elsevier Ltd. All rights reserved.)

Objective: To describe the clinical course and novel biochemical findings in 3 dogs with amitraz toxicosis., Case Series Summary: Three Labrador Retrievers developed acute onset obtundation to stupor after being in a rice field. On admittance to the hospital, they all displayed bradycardia, hyperglycemia, hyperlactatemia, respiratory acidosis, and metabolic alkalosis. All clinical signs resolved in 18-48 hours with supportive care. One dog represented with similar clinical signs and biochemical abnormalities 3 days after discharge following spending time in a different rice field owned by the same owner. Toxicological analysis of serum from all 3 dogs and vomitus from 1 dog returned positive for amitraz and one of its metabolites., New or Unique Information Provided: This is the first case series of dogs with confirmed amitraz toxicosis following an environmental exposure. Novel biochemical findings of hyperlactatemia, respiratory acidosis, and metabolic alkalosis were documented in all 3 dogs. Clinicians should be concerned for amitraz toxicosis when presented with an animal with the constellation of signs including decreased mental status, bradycardia, and hyperglycemia, particularly if relevant acid-base abnormalities are also detected., (© Veterinary Emergency and Critical Care Society 2021.)

Objective: To describe changes in the environmental microbiota of a new neonatal intensive care unit (NICU) and potential implications for infection prevention and control (IPC) efforts., Design: Prospective observational study., Setting: A newly constructed level IV neonatal cardiac intensive care unit (NCICU) before and after patient introduction and the original NICU prior to patient transfer., Methods: Environmental samples were obtained from the original NICU prior to patient transfer to a new NCICU. Serial sampling of patient rooms and provider areas of the new NICU was conducted immediately prior to patient introduction and over an 11-month study period. Microbiota at each sampling point were characterized using Illumina sequencing of the V3/V4 region of the 16S rRNA gene. Microbiota characteristics (α and β diversity and differential abundance) were compared based on time, location, and clinical factors (room-level antibiotic use and patient turnover)., Results: An immediate increase in the environmental differential abundance of gut anaerobes were seen after patient introduction. There was an increase in the relative abundance of Staphylococcus spp, Klebsiella spp, Pseudomonas spp, and Streptococcus spp over time. The new NCICU consistently showed more diverse microbiota and remained distinct from the original NICU. The microbiota of the provider areas of the NCICU eventually formed a cluster separate from the patient rooms. Patient turnover increased room-level microbiota diversity., Conclusion: Microbiota characteristics of the new NICU were distinct from the original ICU despite housing similar patients. Patient and provider areas developed distinct microbiota profiles. Non-culture-based methods may be a useful adjunct to current IPC practice.

Introduction: Although the microbiome is altered in various esophageal diseases, there is no direct evidence for a link between the oral or esophageal microbiome and underlying esophageal tissue. Here, we aimed to address these gaps through use of an antimicrobial mouth rinse to modify the esophageal microbiome and tissue gene expression., Methods: In this randomized controlled trial, patients scheduled to undergo endoscopy for clinical indications used chlorhexidine mouth rinse or no treatment for 2 weeks before endoscopy. Oral swabs and saliva were collected at baseline and at follow-up, and the esophagus was sampled on the day of endoscopy. The microbiome was analyzed by 16S rRNA gene sequencing, and esophageal tissue gene expression was ascertained by RNA-Seq., Results: Twenty subjects were enrolled and included in the analyses. Within individuals, the oral and esophageal microbiome composition was significantly correlated. Chlorhexidine treatment associated with significant alterations to the relative abundance of several esophageal bacterial taxa, and to expression of genes in the esophagus including reductions in periostin, claudin-18, chemokines CXCL1 and CXCL13, and several members of the tumor necrosis factor receptor superfamily. A taxon in genus Haemophilus in the esophagus also associated with significant changes in tissue gene expression., Discussion: The oral and esophageal microbiomes are closely related within individuals, and esophageal microbiome alterations correlate with tissue gene expression changes. The esophageal microbiome may act as an important cofactor that influences pathogenesis and outcomes of diseases such as eosinophilic esophagitis, gastroesophageal reflux, and Barrett's esophagus.

A novel series of anthracenyl-isoxazole amide (AIM) antitumor agents containing N-heterocycles in the 10 position (N-het) were synthesized using palladium cross-coupling. The unique steric environment of the N-het-AIMs required individual optimization in each case. Lanthanide mediated double activation was used to couple the dimethylamino pyrrole moiety, required for antitumor action. Robust antitumor activity was observed against breast and brain cancer cell lines. The compounds were docked with the c-myc oncogene promoter sequence, which adopts a G4 quadruplex DNA conformation, and represents the working hypothesis for biological action. The N-het-AIMs have useful fluorescence properties, allowing for observation of their distribution within tumor cells., (Copyright © 2020 Elsevier Ltd. All rights reserved.)

Background: Gut microbial imbalance may contribute to endotoxemia, inflammation, and oxidative stress in heart failure (HF). Changes occurring in the intestinal microbiota and inflammatory/oxidative milieu during HF progression and following left ventricular assist device (LVAD) or heart transplantation (HT) are unknown. We aimed to investigate variation in gut microbiota and circulating biomarkers of endotoxemia, inflammation, and oxidative stress in patients with HF (New York Heart Association, Class I-IV), LVAD, and HT., Methods: We enrolled 452 patients. Biomarkers of endotoxemia (lipopolysaccharide and soluble [sCD14]), inflammation (C-reactive protein, interleukin-6, tumor necrosis factor-α, and endothelin-1 adiponectin), and oxidative stress (isoprostane) were measured in 644 blood samples. A total of 304 stool samples were analyzed using 16S rRNA sequencing., Results: Gut microbial community measures of alpha diversity were progressively lower across worsening HF class and were similarly reduced in patients with LVAD and HT (p < 0.05). Inflammation and oxidative stress were elevated in patients with Class IV HF vs all other groups (all p < 0.05). Lipopolysaccharide was elevated in patients with Class IV HF (vs Class I-III) as well as in patients with LVAD and HT (p < 0.05). sCD14 was elevated in patients with Class IV HF and LVAD (vs Class I-III, p < 0.05) but not in patients with HT., Conclusions: Reduced gut microbial diversity and increased endotoxemia, inflammation, and oxidative stress are present in patients with Class IV HF. Inflammation and oxidative stress are lower among patients with LVAD and HT relative to patients with Class IV HF, whereas reduced gut diversity and endotoxemia persist in LVAD and HT., (Copyright © 2020 International Society for Heart and Lung Transplantation. Published by Elsevier Inc. All rights reserved.)

Background: Polymyxins are antimicrobials of last resort for the treatment of carbapenem-resistant Enterobacteriaceae, but resistance in 5% to >40% isolates has been reported. We conducted a genomic survey of clinical polymyxin-resistant (PR) Klebsiella pneumoniae to determine the molecular mechanisms of PR and the role of polymyxin exposure versus transmission in PR emergence., Methods: We included 88 patients with PR K. pneumoniae from 2011-2018 and collected demographic, antimicrobial exposure, and infection data. Whole-genome sequencing was performed on 388 isolates, including 164 PR isolates. Variant calling and insertion sequence detection were performed, focusing on key genes associated with PR (mgrB, crrAB, phoPQ, and pmrAB). We conducted phylogenetic analyses of key K. pneumoniae multi-locus sequence types (ST258, ST17, ST307, and ST392)., Results: Polymyxin exposure was documented in 53/88 (60%) patients prior to PR detection. Through an analysis of key PR genes, we detected 129 individual variants and 72 unique variant combinations in PR isolates. This included multiple, distinct changes in 36% of patients with serial PR isolates. Insertion sequence disruption was limited to mgrB (P < .001). Polymyxin minimum inhibitory concentrations showed stepwise increases with the number of PR genes affected (P < .001). When clusters containing PR isolates in ≥2 patients were analyzed, 10/14 had multiple genetic events leading to PR., Conclusions: Molecular mechanisms leading to PR in clinical K. pneumoniae isolates are remarkably heterogenous, even within clusters or individual patients. Polymyxin exposure with de novo PR emergence led to PR in the majority of patients, rather than transmission. Optimizing polymyxin use should be a key strategy in stopping the spread of PR., (© The Author(s) 2019. Published by Oxford University Press for the Infectious Diseases Society of America. All rights reserved. For permissions, e-mail: journals.permissions@oup.com.)

Despite the increasing reliance on polymyxin antibiotics (polymyxin B and colistin) for treatment of multidrug-resistant Gram-negative infections, many clinical laboratories are unable to perform susceptibility testing due to the lack of accurate and reliable methods. Although gradient agar diffusion is commonly performed for other antimicrobials, its use for polymyxins is discouraged due to poor performance characteristics. Performing gradient agar diffusion with calcium enhancement of susceptibility testing media has been shown to improve the identification of polymyxin-resistant isolates with plasmid-mediated resistance ( mcr-1 ). We therefore sought to evaluate the broad clinical applicability of this approach for colistin susceptibility testing by assessing a large and diverse collection of resistant and susceptible patient isolates collected from multiple U.S. medical centers. Among 217 isolates, the overall categorical and essential agreement for calcium-enhanced gradient agar diffusion were 73.7% and 65.5%, respectively, compared to the results for reference broth microdilution. Performance varied significantly by organism group, with agreement being highest for Enterobacterales and lowest for Pseudomonas aeruginosa Nevertheless, even for Enterobacterales , there was a high rate of very major errors (9.2%). Performance was similarly poor for calcium-enhanced broth microdilution. While calcium enhancement did allow for more accurate categorization of mcr-1 -resistant isolates, there were unacceptably high rates of errors for both susceptible and non- mcr-1 -resistant isolates, raising serious doubts about the suitability of these calcium-enhanced methods for routine colistin susceptibility testing in clinical laboratories., (Copyright © 2020 American Society for Microbiology.)

Susceptibility testing of the polymyxins (colistin and polymyxin B) is challenging for clinical laboratories. The Clinical and Laboratory Standards Institute (CLSI) Antimicrobial Susceptibility Testing Subcommittee evaluated two methods to enable accurate testing of these agents. These methods were a colistin broth disk elution (CBDE) and a colistin agar test (CAT), the latter of which was evaluated using two inoculum volumes, 1 μl (CAT-1) and 10 μl (CAT-10). The methods were evaluated using a collection of 270 isolates of Enterobacterales , 122 Pseudomonas aeruginosa isolates, and 106 Acinetobacter spp. isolates. Overall, 94.4% of CBDE results were in essential agreement and 97.9% in categorical agreement (CA) with reference broth microdilution MICs. Nine very major errors (VME; 3.2%) and 3 major errors (ME; 0.9%) were observed. With the CBDE, 98.6% CA was observed for Enterobacterales (2.5% VME, 0% ME), 99.3% CA was observed for P. aeruginosa (0% VME, 0.7% ME), and 93.1% CA was observed for Acinetobacter spp. (5.6% VME, 3.3% ME). Overall, CA was 94.9% with 6.8% VME using CAT-1 and improved to 98.3% with 3.9% VME using CAT-10. No ME were observed using either CAT-1 or CAT-10. Using the CAT-1/CAT-10, the CA observed was 99.4%/99.7% for Enterobacterales (1%/0.5% VME), 98.7%/100% for P. aeruginosa (8.3%/0% VME), and 88.5%/92.3% for Acinetobacter spp. (21.4%/14.3% VME). Based on these data, the CLSI antimicrobial susceptibility testing (AST) subcommittee endorsed the CBDE and CAT-10 methods for colistin testing of Enterobacterales and P. aeruginosa ., (Copyright © 2019 American Society for Microbiology.)

Infections by multidrug-resistant bacteria (MDRB) remain a leading cause of morbidity and mortality after liver transplantation (LT). Gut dysbiosis characteristic of end-stage liver disease may predispose patients to intestinal MDRB colonization and infection, in turn exacerbating dysbiosis. However, relationships between MDRB colonization and dysbiosis after LT remain unclear. We prospectively recruited 177 adult patients undergoing LT at a single tertiary care center. 16 S V3-V4 rRNA sequencing was performed on 723 fecal samples collected pre-LT and periodically until one-year post-LT to test whether MDRB colonization was associated with decreased microbiome diversity. In multivariate linear mixed-effect models, MDRB colonization predicts reduced Shannon α-diversity, after controlling for underlying liver disease, antibiotic exposures, and clinical complications. Importantly, pre-LT microbial markers predict subsequent colonization by MDRB. Our results suggest MDRB colonization as a major, previously unrecognized, marker of persistent dysbiosis. Therapeutic approaches accounting for microbial and clinical factors are needed to address post-transplant microbiome health.

Background: The incidence of esophageal adenocarcinoma has risen dramatically over the past half century, and the underlying reasons are incompletely understood. Broad shifts to the upper gastrointestinal microbiome may be partly responsible. The goal of this study was to describe alterations in the esophageal microbiome that occur with progression from Barrett's esophagus to esophageal adenocarcinoma., Methods: A case-control study was performed of patients with and without Barrett's esophagus who were scheduled to undergo upper endoscopy. Demographic, clinical, and dietary intake data were collected, and esophageal brushings were collected during the endoscopy. 16S rRNA gene sequencing was performed to characterize the microbiome., Results: A total of 45 patients were enrolled and included in the analyses [16 controls; 14 Barrett's esophagus without dysplasia (NDBE); 6 low-grade dysplasia (LGD); 5 high-grade dysplasia (HGD); and 4 esophageal adenocarcinoma]. There was no difference in alpha diversity between non-Barrett's esophagus and Barrett's esophagus, but there was evidence of decreased diversity in patients with esophageal adenocarcinoma as assessed by Simpson index. There was an apparent shift in composition at the transition from LGD to HGD, and patients with HGD and esophageal adenocarcinoma had decreased Firmicutes and increased Proteobacteria. In addition, patients with HGD or esophageal adenocarcinoma had increased Enterobacteriaceae and Akkermansia muciniphila and reduced Veillonella . In the study population, patients taking proton pump inhibitors had increased Streptococcus and decreased Gram-negative bacteria overall., Conclusions: Shifts in the Barrett's esophagus-associated microbiome were observed in patients with HGD and esophageal adenocarcinoma, with increases in certain potentially pathogenic bacteria., Impact: The microbiome may play a role in esophageal carcinogenesis., (©2019 American Association for Cancer Research.)

The c-MYC oncogene mediates multiple tumor cell survival pathways and is dysregulated or overexpressed in the majority of human cancers. The NHE III1 region of the c-MYC promoter forms a DNA quadruplex. Stabilization of this structure with small molecules has been shown to reduce expression of c-MYC, and targeting the c-MYC quadruplex has become an emerging strategy for development of antitumor compounds. Previous solution NMR studies of the c-MYC quadruplex have assigned the major conformer and topology of this important target, however, regions outside the G-quartet core were not as well-defined. Here, we report a high-resolution crystal structure (2.35 Å) of the major quadruplex formed in the NHE III1 region of the c-MYC promoter. The crystal structure is in general agreement with the solution NMR structure, however, key differences are observed in the position of nucleotides outside the G-quartet core. The crystal structure provides an alternative model that, along with comparisons to other reported quadruplex crystal structures, will be important to the rational design of selective compounds. This work will aid in development of ligands to target the c-MYC promoter quadruplex with the goal of creating novel anticancer therapies., Competing Interests: The authors have declared that no competing interests exist.

Treatment options for carbapenem-resistant Enterobacteriaceae (CRE) are limited. While Klebsiella pneumoniae strains harboring bla KPC account for most CRE, recent evidence points to increasing diversification of CRE. We determined whether the CRE species and antibiotic resistance genotype influence the response to relebactam (REL), a novel beta-lactamase inhibitor with class A/C activity, combined with imipenem-cilastatin (IMI). We carried out broth microdilution testing with IMI alone or in the presence of 4 μg/ml REL against 154 clinical isolates collected at a New York City hospital with a high prevalence of organisms carrying bla KPC , including Enterobacter spp. ( n = 96), K. pneumoniae ( n = 44), Escherichia coli ( n = 1), Serratia marcescens ( n = 9), and Citrobacter spp. ( n = 4). Resistance gene profiles and the presence of major porin gene disruptions were ascertained by whole-genome sequencing. Addition of REL decreased the IMI MIC to the susceptible range (≤1 μg/ml) against 88% of isolates. However, S. marcescens IMI-REL MICs were 4- to 8-fold higher than those for other organisms. Most bla KPC -positive isolates had IMI-REL MICs of ≤1 μg/ml (88%), including isolates of Enterobacter cloacae ST171 (93%) and K. pneumoniae ST258 (82%). Nineteen isolates had IMI-REL MICs of ≥2 μg/ml, among which 84% harbored bla KPC and one was bla NDM-1 positive. Isolates with IMI-REL MICs of ≥2 μg/ml versus those with MICs of ≤1 μg/ml were significantly more likely to demonstrate disruption of at least one porin gene (42% versus 19%; P = 0.04), although most S. marcescens isolates (67%) had intact porin genes. In conclusion, while REL reduced IMI MICs in a majority of diverse CRE isolates, including high-risk clones, chromosomal factors had an impact on IMI-REL susceptibilities and may contribute to elevated MICs for S. marcescens ., (Copyright © 2018 American Society for Microbiology.)

Ceftazidime-avibactam (CAZ-AVI) is a promising novel treatment for infections caused by carbapenem-resistant Enterobacteriaceae (CRE). Despite improved treatment outcomes compared to those achieved with aminoglycoside- and colistin-based regimens, the rapid evolution of CAZ-AVI resistance during treatment has previously been reported in Klebsiella pneumoniae sequence type 258 (ST258) bla KPC-3 -harboring isolates. Here, we report the stepwise evolution and isolation of two phenotypically distinct CAZ-AVI-resistant Klebsiella pneumoniae isolates from a patient with pancreatitis. All susceptible ( n = 3) and resistant ( n = 5) isolates were of the ST307 clonal background, a rapidly emerging clone. Taking advantage of short-read Illumina and long-read Oxford Nanopore sequencing and full-length assembly of the core chromosome and plasmids, we demonstrate that CAZ-AVI resistance first occurred through a 532G → T bla KPC-2 point mutation in bla KPC-2 (D179Y protein substitution) following only 12 days of CAZ-AVI exposure. While subsequent isolates exhibited substantially decreased meropenem (MEM) MICs (≤2 μg/ml), later cultures demonstrated a second CAZ-AVI resistance phenotype with a lower CAZ-AVI MIC (12 μg/ml) but also MEM resistance (MIC > 128 μg/ml). These CAZ-AVI- and MEM-resistant isolates showed evidence of multiple genomic adaptations, mainly through insertions and deletions. This included amplification and transposition of wild-type bla KPC-2 into a novel plasmid, an IS 1 insertion upstream of ompK36 , and disruption of the rfb gene locus in these isolates. Our findings illustrate the potential of CAZ-AVI resistance to emerge in non- K. pneumoniae ST258 clonal backgrounds and alternative bla KPC variants. These results raise concerns about the strong selective pressures incurred by novel carbapenemase inhibitors, such as avibactam, on isolates previously considered invulnerable to CAZ-AVI resistance. There is an urgent need to further characterize non-KPC-mediated modes of carbapenem resistance and the intrinsic bacterial factors that facilitate the rapid emergence of resistance during treatment., (Copyright © 2018 American Society for Microbiology.)

Methicillin-susceptible Staphylococcus aureus (MSSA) bloodstream infections (BSIs) often lead to severe complications despite the availability of effective antibiotics. It remains unclear whether elevated vancomycin MICs are associated with worse outcomes. We conducted a 2-year retrospective cohort study ( n = 252) of patients with MSSA BSIs at a tertiary care hospital. We defined reduced vancomycin susceptibility (RVS) as a Microscan MIC of 2 mg/liter. All strains were genotyped ( spa ) and assessed for agr functionality. Multivariable logistic regression models were used to examine the impact of RVS phenotype and strain genotype on 30-day all-cause mortality and complicated bacteremia (metastatic spread, endovascular infection, or duration ≥3 days). One-third of patients (84/252) were infected with RVS isolates. RVS Infections were more frequently associated with metastatic or embolic sites of infection (36% versus 17%, P < 0.001), and endovascular infection (26% versus 12%, P = 0.004). These infections occurred more often in patients with fewer underlying comorbidities (Charlson comorbidity index of ≥3 [73% versus 88%, P = 0.002]). Genotyping identified 127 spa -types and 14 Spa-clonal complexes (Spa-CCs). Spa-CC002 and Spa-CC008 were more likely to exhibit the RVS phenotype versus other Spa-CCs (OR = 2.2, P < 0.01). The RVS phenotype was not significantly associated with 30-day mortality; however, it was associated with complicated bacteremia (adjusted odds ratio of 2.35 [range, 1.26 to 4.37]; P = 0.007) in adjusted analyses. The association of RVS strains with complicated infection and fewer underlying comorbidities suggests the phenotype as a potential marker of strain virulence in MSSA BSIs. The RVS phenotype itself was not a significant predictor of mortality in this patient cohort. Further studies are necessary to explore this host-pathogen relationship., (Copyright © 2017 American Society for Microbiology.)

Using the structure-activity relationship emerging from previous Letter, and guided by pharmacokinetic properties, new AIMs have been prepared with both improved efficacy against human glioblastoma cells and cell permeability as determined by fluorescent confocal microscopy. We present our first unambiguous evidence for telomeric G4-forming oligonucleotide anisotropy by NMR resulting from direct interaction with AIMs, which is consistent with both our G4 melting studies by CD, and our working hypothesis. Finally, we show that AIMs induce apoptosis in SNB-19 cells., (Copyright © 2015 Elsevier Ltd. All rights reserved.)

Seven goats and one ram presented with clinical signs including regurgitation, obtundation, anorexia, apparent pain, and bloat. The animals had escaped from their barn, and it was discovered that they had ingested leaves of Pieris japonica, Japanese pieris, a grayanotoxin-containing plant. Animals were treated with antibiotics, calcium borogluconate, B vitamins, and activated charcoal within the first 24-h postexposure, which was followed by the recovery of the ram and two goats and the death of two goats. Approximately 36 h after Japanese pieris ingestion, one of the three remaining anorectic goats was dosed with intravenous lipid emulsion (ILE). This goat recovered within a few hours. The remaining two goats were given ILE the next day and appeared to recover, but one died a week later of aspiration pneumonia.

Diisocyanates, commonly used in the production of polyurethane foams, paints, elastomers, varnishes, and coatings, are considered among the most hazardous inhalation toxicants. The present report describes 2 unusual cases of mortality in pigeon chicks associated with nesting material contaminated by diisocyanates. Case 1 was submitted by a racing pigeon breeder who had lost all the hatchlings (n = 125) following replacement of the nesting material with a different lot. All adult birds appeared healthy, and hatchability was not significantly affected, but hatchlings became lethargic and dyspneic after a day of hatch. At necropsy, dark wet lungs were found in the hatchlings. Case 2 was submitted by a show-roller pigeon breeder. In this case, the owner reported lower hatchability, and all hatchlings (approximately 100) died within 2 days of hatching with clinical signs similar to the first case. Necropsy did not reveal any significant findings. For both cases, nesting materials were screened for toxic compounds using gas chromatography-mass spectrometry. Toluene-2,4-diisocyanate (approximately 190-290 ppm) and 4,4'-methylene diphenyl diisocyanate (unquantified) were detected in the nesting pads. While there is very limited information on toxicosis in birds, there are reports of inhalant exposure of diisocyanates causing pulmonary edema and death in various mammalian species. Although cause-effect relationship of mortality and the nesting material was not established in the present cases, the presence of toxic compounds in the nesting materials is a cause for concern. Further investigation is needed to determine the prevalence and toxicity of diisocyanates-contaminated nesting material in avian species.

Objectives: To (1) determine whether different types of thin film used to occlude congenital portosystemic shunts are cellophane, and (2) evaluate the influence of saline immersion and sterilization on the tensile properties of cellophane., Study Design: Ex vivo spectroscopic evaluation and mechanical testing., Sample Population: Rectangular strips of thin film from 4 sources., Methods: Samples were evaluated with Fourier Transform Infrared Spectroscopy and microscopy with a polarizing lens. Samples consistent with cellophane were divided into 5 sterilization groups: non-sterile, autoclave, gamma irradiation, hydrogen peroxide and ethylene oxide. Samples were tested while dry or after saline solution immersion. Tensile properties were compared using ANOVA, unpaired t-tests, Mann-Whitney U-tests and Fisher's exact tests. P < 0.05 was considered significant., Results: One thin film was consistent with cellophane and it could be differentiated from the other thin films by visible striations. Cellophane was strongest when strips were oriented parallel with its fiber direction and saline immersion reduced its strength by 48% (P < .001). All sterilization methods except autoclave significantly weakened wet cellophane (ethylene oxide [P < .001], gamma irradiation [P < .001], and hydrogen peroxide [P < .001])., Conclusions: Thin film from most sources was not consistent with cellophane. Autoclave sterilization is the best way to preserve the strength of wet cellophane., (© Copyright 2013 by The American College of Veterinary Surgeons.)

Background: The alarming rise in childhood obesity has resulted in a number of bariatric surgical initiatives. To interpret the outcomes, a comparison with a nonoperative approach is prudent., Methods: In 2003, 2004, and 2005, we measured the outcomes produced by an isolated summer camp in North Carolina for 74, 99, and 89 obese children and adolescents with a mean age of 12.7 +/- 2.3, 13.0 +/- 1.9, and 13.2 +/- 1.8 years and initial body mass index (BMI) of 33.1 +/- 5.7, 33.4 +/- 6.4, and 32.9 +/- 7.0 kg/m2, respectively. The camp featured a 1700/d caloric diet, daily aerobic and resistance weight training exercise, nutrition classes, and weekly sessions with a psychologist. The changes in weight, BMI, body shape measurements, and fitness level were assessed. The average length of stay was 4.3, 4.2, and 4.4 weeks, respectively, in 2003, 2004, and 2005., Results: The BMI, body shape, and weight change measures significantly improved during each of the summers. The campers lost 1.6, 2.0, and 1.8 kg/wk during each of the 3 years. Their waist measurements decreased by 9.1 +/- 5.12 cm, 9.9 +/- 5.6 cm, and 8.1 +/- 5.8 cm. Significant improvements occurred in the timed sprints, .5-mile (0.8-km) run, and vertical jump. Of those campers staying for two summers, 4.4% continued to reduce their BMI despite growth, 56.5% maintained their BMI at less than the initial baseline measurement, and 39.1% increased their BMI to greater than the baseline. The co-morbidities also improved. One camper, aged 15 years, weighing 211 kg, progressed from being able to walk 3 steps to managing the 100-yard (91-m) dash in 42 seconds after losing 35 kg in 8 weeks., Conclusion: Diets, exercise, and behavioral modification are useful approaches in severely obese children that can, in some, produce significant albeit expensive long-term results. Recidivism is a problem. Surgical outcomes must compare favorably with these outcomes.

Standardized terminology and digital sources of evidence are essential for evidence-based practice. Dieticians desire concise and consistent documentation of nutrition diagnoses, interventions and outcomes that will be fit for electronic health records. Building on more than 5 years of work to generate the Nutrition Care Process and Model as a road map to quality nutrition care and outcomes, and recognizing existing standardized languages serving other health professions, a task force of the American Dietetic Association (ADA) has begun to develop and disseminate standardized nutrition language. This paper will describe the group's working logic model, the Nutrition Care Process, and the current status of the nutrition language with comparisons to nursing process and terminology.

When an association faces its future, the information its board and leadership have about the world in which it must operate will shape their perceptions and influence their strategic thinking. One of the primary purposes of an environmental scan is to elucidate emerging issues and trends so that strategic attention can be focused on them. An environmental scan can also suggest emerging opportunities and challenges.

Educational and community health systems are social systems composed of a group or collection of entities for which there is a unifying principle. The purpose of this paper is to briefly explain chaos theory and to apply it to the Interdisciplinary Rural Health Training Program (IRHTP) as a case study. The IRHTP is an existing rural, community based educational program for baccalaureate and graduate health care students. Chaos theory attempts to understand the underlying order in processes that appear to not have any guidelines or principles. These processes typically involve the interaction of several elements over time. Chaos theory provided the university with a method of anticipating the natural flux between order and chaos to allow the system to function at its highest level. To thrive in such a complex dynamic environment the authors recommend application of Ockerman's Five Factors.

Objectives: After studying this article, the reader should be able to: 1. Describe the relationship of sexual history taking and counseling to the safe prescription of teratogenic drugs. 2. Define the scope of the problem of unintended pregnancy and the importance of sexual history taking and counseling. 3. Review the skills of sexual counseling and taking a sexual health history. Although the need to take a sexual history and counsel patients about conception and contraception appears in several clinical situations, the process can be uncomfortable, and some physicians may avoid it or do it incompletely. When a patient is receiving a teratogenic agent, the need for proper history taking and counseling is critical. This article reviews ways to make the process more comfortable and rewarding for both the patient and physician.

Within the last years psychosocial care in acute medicine has become more and more important. Therefore different conceptional structures are discussed to optimize the integration into primary care medicine, especious psychosomatic or psychosocial consultation and liaison services. Having resumed the concepts and practice of psychosocial care in oncology this paper describes a psychosocial liaison service accompanying a research project in psychooncology. The representation focuses the experience with psychosocial care of cancer patients over the last three years. Based on a systematic clinical documentation the activities are described with regard to psychosocial indication, patient assignment, patients needs during acute treatment and the different kinds of psychosocial interventions applied. The experiences are evaluated regarding the target groups (patients, relatives, medical staff) and associated problems of cooperation and organisation met with medical staff. Finally needs, possibilities and limits of psychosocial liaison services are discussed comparing the experiences with others reported in the literature.

An inexpensive interface is described that performs direct transfer of digitized data from the digital audio processor and video cassette recorder based data acquisition system designed by Bezanilla (1985, Biophys. J., 47:437-441) to an IBM PC/XT microcomputer. The FORTRAN callable software that drives this interface is capable of controlling the video cassette recorder and starting data collection immediately after recognition of a segment of previously collected data. This permits piecewise analysis of long intervals of data that would otherwise exceed the memory capability of the microcomputer.