Azole resistance mechanisms and population structure of the human pathogen Aspergillus fumigatus on retail plant products.

Aspergillus fumigatus is a ubiquitous saprotroph and human-pathogenic fungus that is life-threatening to the immunocompromised. Triazole-resistant A. fumigatus was found in patients without prior treatment with azoles, leading researchers to conclude that resistance had developed in agricultural environments where azoles are used against plant pathogens. Previous studies have documented azole-resistant A. fumigatus across agricultural environments, but few have looked at retail plant products. Our objectives were to determine if azole-resistant A. fumigatus is prevalent in retail plant products produced in the United States (U.S.), as well as to identify the resistance mechanism(s) and population genetic structure of these isolates. Five hundred twenty-five isolates were collected from retail plant products and screened for azole resistance. Twenty-four isolates collected from compost, soil, flower bulbs, and raw peanuts were pan-azole resistant. These isolates had the TR34/L98H, TR46/Y121F/T289A, G448S, and H147Y cyp51A alleles, all known to underly pan-azole resistance, as well as WT alleles, suggesting that non-cyp51A mechanisms contribute to pan-azole resistance in these isolates. Minimum spanning networks showed two lineages containing isolates with TR alleles or the F46Y/M172V/E427K allele, and discriminant analysis of principle components identified three primary clusters. This is consistent with previous studies detecting three clades of A. fumigatus and identifying pan-azole-resistant isolates with TR alleles in a single clade. We found pan-azole resistance in U.S. retail plant products, particularly compost and flower bulbs, which indicates a risk of exposure to these products for susceptible populations and that highly resistant isolates are likely distributed worldwide on these products.IMPORTANCEAspergillus fumigatus has recently been designated as a critical fungal pathogen by the World Health Organization. It is most deadly to people with compromised immune systems, and with the emergence of antifungal resistance to multiple azole drugs, this disease carries a nearly 100% fatality rate without treatment or if isolates are resistant to the drugs used to treat the disease. It is important to determine the relatedness and origins of resistant A. fumigatus isolates in the environment, including plant-based retail products, so that factors promoting the development and propagation of resistant isolates can be identified.

Risks and Benefits of the Proposed Amputation Reduction and Compassion Act for Disadvantaged Patients.

Racial, ethnic, and socioeconomic disparities in the major risk factors for vascular disease and access to vascular specialist care are well-documented.1-3 The higher incidence of diabetes, peripheral artery disease (PAD), and related nontraumatic lower extremity amputation among racial and ethnic minority groups, those of low socioeconomic status, and those with poor access to care based on geography (together, referred to below as disadvantaged groups) are particularly pervasive.1,4-9 Practitioners of vascular surgery and endovascular therapy are uniquely positioned to address health inequities in lower extremity screening, medical management, intervention, and limb preservation among the population of adults at the highest risk for limb loss.

Development of Novel Immobilized Copper-Ligand Complex for Click Chemistry of Biomolecules.

Copper-catalyzed azide-alkyne cycloaddition click (CuAAC) reaction is widely used to synthesize drug candidates and other biomolecule classes. Homogeneous catalysts, which consist of copper coordinated to a ligand framework, have been optimized for high yield and specificity of the CuAAC reaction, but CuAAC reaction with these catalysts requires the addition of a reducing agent and basic conditions, which can complicate some of the desired syntheses. Additionally, removing copper from the synthesized CuAAC-containing biomolecule is necessary for biological applications but inconvenient and requires additional purification steps. We describe here the design and synthesis of a PNN-type pincer ligand complex with copper (I) that stabilizes the copper (I) and, therefore, can act as a CuAAC catalyst without a reducing agent and base under physiologically relevant conditions. This complex was immobilized on two types of resin, and one of the immobilized catalyst forms worked well under aqueous physiological conditions. Minimal copper leaching was observed from the immobilized catalyst, which allowed its use in multiple reaction cycles without the addition of any reducing agent or base and without recharging with copper ion. The mechanism of the catalytic cycle was rationalized by density functional theory (DFT). This catalyst's utility was demonstrated by synthesizing coumarin derivatives of small molecules such as ferrocene and sugar.

Facile de Novo Sequencing of Tetrazine-Cyclized Peptides through UV-Induced Ring-Opening and Cleavage from the Solid Phase.

While most FDA-approved peptide drugs are cyclic, the robust cyclization chemistry of peptides and the deconvolution of cyclic peptide sequences by using tandem mass spectrometry render cyclic peptide drug discovery difficult. Here we present the successful design of cyclic peptides on solid phase that addresses both of these problems. We demonstrate that this peptide cyclization method using dichloro-s-tetrazine on solid phase allows successful cyclization of a panel of random peptide sequences with various charges and hydrophobicities. The cyclic peptides can be linearized and cleaved from the solid phase by simple UV light irradiation, and we demonstrate that accurate sequence information can be obtained for the UV-cleaved linearized peptides by using tandem mass spectrometry. The tetrazine linker used in the cyclic peptides can further be explored for inverse electron-demand Diels-Alder (IEDDA) reactions for screening or bioconjugation applications in the future.

Successful Treatment of Prurigo Nodularis by Dupilumab: Report of 24 Patients.

BACKGROUND: Prurigo nodularis (PN) is a chronic pruritic skin disease which is difficult to treat. Current treatment options often lead to limited clinical benefit or severe side effects. OBJECTIVE: The objective of this study was to evaluate the efficacy and safety of dupilumab in the treatment of PN in adults. METHOD: This study is a retrospective cohort study. Twenty-four adult patients with PN were included and treated with dupilumab. The primary outcomes were the mean reduction in the Investigator's Global Assessment (IGA) score and pruritus numeric rating scale (p-NRS) score. Outcomes were assessed at baseline, week 4, week 16, and week 36. RESULTS: The study included 24 patients, of whom 9 (37.5%) were male, and the mean (SD) age of the enrolled patients was 49.88 ± 16.71 years. At the end of the 16-week treatment, the mean p-NRS score decreased from 7.50 ± 2.21 to 1.41 ± 0.91 (p < 0.001), sleeplessness numeric rating scale (s-NRS) score declined from 5.33 ± 3.29 to 0.18 ± 0.59 (p < 0.001), and Dermatology Life Quality Index (DLQI) score decreased from 13.32 ± 4.88 to 0.91 ± 0.81 (p < 0.001). Fourteen (63.6%) of 22 patients achieved IGA 0/1 and 21 (95.5%) patients achieved IGA activity 0/1. Among 14 patients who achieved IGA 0/1, 10 had an elevated serum IgE level, and patients with a high serum IgE level showed a more remarkable reduction in IGA (r = 0.52, p = 0.03). Patients with AD responded faster than those without AD (3.76 ± 1.71 weeks vs. 6.40 ± 1.67 weeks, p = 0.01). Adverse events were recorded in 4/24 (16.6%) patients, with conjunctivitis being the most frequent. CONCLUSION: This study demonstrated that dupilumab is effective and safe for PN and could be a potential therapeutic option.

A controlled forearm washing ex vivo method for assessing the impact of personal cleansing products on skin's acid mantle properties and antimicrobial defence against transient bacteria.

BACKGROUND: An important trend in the personal care industry involves the development of advanced personal cleaning products that not only provide skin mildness but support skin's acid mantle properties and skin's natural antimicrobial defence function. OBJECTIVE: The objective of this study was to develop a controlled forearm washing ex vivo method for assessing the impact of personal cleansing products on skin's acid mantle properties and antimicrobial defence against transient bacteria. METHODS: We developed a controlled forearm washing ex vivo method (ex vivo NET method) to compare the impact of two representative personal cleansing products on skin's acid mantle properties and antimicrobial defence against transient bacteria: one was a low-pH skin cleanser, and the other was high-pH soap cleanser. Skin pH was measured at baseline and 4 h after the product application. Concurrently, D-squame tape stripping procedure was followed to sample the stratum corneum surface layers. Then, two selected transient bacteria, Staphylococcus aureus and Escherichia coli, were inoculated onto the D-squame tapes and incubated under controlled conditions, respectively. The residual bacteria counts can provide an objective measure of skin's acid mantle properties against transient bacteria. Results from the ex vivo NET method were compared with the traditional in vivo cup-scrub RET method. RESULTS: The skin pH was significantly lower 4 h after washing the forearm with the low-pH cleanser versus the high-pH soap, consistent with literatures. Interestingly, the skin surface washed by the low-pH cleanser showed significantly higher hostility against representative transient bacteria as demonstrated by the lower counts of S. aureus by 1.09 log and E. coli by 0.6 log versus the high-pH soap based on the ex vivo NET method. Results from the ex vivo NET method were further supported by the traditional in vivo RET method which also showed the skin washed by the low-pH cleanser had significantly lower counts of S. aureus and E. coli versus the high-pH soap. CONCLUSIONS: The skin's acid mantle properties and antimicrobial defence can be directly impacted by the personal cleansing products. The low-pH skin cleanser works better than the high-pH soap for supporting skin's acid mantle properties and antimicrobial defence against transient bacteria. Results from the ex vivo NET method are consistent with the in vivo RET method. It is important that the ex vivo NET method offers many advantages since it is quicker to run with higher throughput and has better safety without the constraint of inoculating harmful microorganisms onto the human subjects.

CONTEXTE: Une tendance importante du secteur des soins personnels est de développer des produits d'hygiène personnelle sophistiqués qui non seulement rendent la peau plus douce, mais favorisent également les propriétés du manteau acide de la peau et la fonction de défense antimicrobienne naturelle de la peau. OBJECTIF: L'objectif de cette étude était de développer une méthode ex vivo de lavage contrôlé des avant-bras pour évaluer l'impact des produits d'hygiène personnelle sur les propriétés du manteau acide de la peau et la défense antimicrobienne contre les bactéries transitoires. MÉTHODES: Nous avons développé une méthode ex vivo de lavage contrôlé des avant-bras (méthode NET ex vivo) pour comparer l'impact de deux produits d'hygiène personnelle représentatifs sur les propriétés du manteau acide de la peau et la défense antimicrobienne contre les bactéries transitoires: d'une part un nettoyant pour la peau à pH faible, d'autre part un savon nettoyant à pH élevé. Le pH de la peau a été mesuré à l'entrée dans l'étude et quatre heures après l'application du produit. Parallèlement, une procédure de stripping par ruban adhésif D-Squame a été suivie pour prélever des couches de surface de la couche cornée. Ensuite, deux bactéries transitoires sélectionnées, S. aureus et E. coli, ont été inoculées sur les rubans adhésifs D-Squame et incubées dans des conditions contrôlées, respectivement. Le nombre de bactéries résiduelles peut fournir une mesure objective des propriétés du manteau acide de la peau contre les bactéries transitoires. Les résultats de la méthode NET ex vivo ont été comparés à la méthode RET in vivo traditionnelle par coupe-grattage. RÉSULTATS: Le pH de la peau était significativement inférieur quatre heures après le lavage des avant-bras avec le nettoyant à pH faible en comparaison avec le savon à pH élevé, conformément à la littérature. Il est intéressant de noter que la surface de la peau lavée au moyen du nettoyant à pH faible présentait une hostilité significativement plus élevée contre les bactéries transitoires représentatives, comme démontré par le nombre inférieur de S. aureus de 1,09 log et d'E. coli de 0,6 log, en comparaison avec le savon à pH élevé, sur base de la méthode NET ex vivo. Les résultats de la méthode NET ex vivo ont été encore par la méthode RET in vivo traditionnelle, laquelle a également démontré que la peau lavée à l'aide du nettoyant à pH faible présentait des nombres significativement plus faibles de S. aureus et d'E. coli que celle lavée à l'aide du savon à pH élevé. CONCLUSIONS: Les propriétés du manteau acide de la peau et la défense antimicrobienne peuvent être directement affectées par les produits d'hygiène personnelle. Le nettoyant de la peau à pH faible fonctionne mieux que le savon à pH élevé pour ce qui est de favoriser les propriétés du manteau acide de la peau et la défense antimicrobienne contre les bactéries transitoires. Les résultats de la méthode NET ex vivo sont cohérents avec la méthode RET in vivo. Il est important de noter que la méthode NET ex vivo offre de nombreux avantages étant donné qu'elle est plus rapide à exécuter avec une capacité plus élevée et offre une meilleure sécurité sans la contrainte d'inoculer des micro-organismes nocifs à des sujets humains.

Functional and behavioral signatures of Kv7 activator drug subtypes.

OBJECTIVE: Voltage-gated potassium channels of the KCNQ (Kv7) family are targeted by a variety of activator compounds with therapeutic potential for treatment of epilepsy. Exploration of this drug class has revealed a variety of effective compounds with diverse mechanisms. In this study, we aimed to clarify functional criteria for categorization of Kv7 activator compounds, and to compare the effects of prototypical drugs in a zebrafish larvae model. METHODS: In vitro electrophysiological approaches with recombinant ion channels were used to highlight functional properties important for classification of drug mechanisms. We also benchmarked the effects of representative antiepileptic Kv7 activator drugs using behavioral seizure assays of zebrafish larvae and in vivo Ca2+ imaging with the ratiometric Ca2+ sensor CaMPARI. RESULTS: Drug effects on channel gating kinetics, and drug sensitivity profiles to diagnostic channel mutations, were used to highlight properties for categorization of Kv7 activator drugs into voltage sensor-targeted or pore-targeted subtypes. Quantifying seizures and ratiometric Ca2+ imaging in freely swimming zebrafish larvae demonstrated that while all Kv7 activators tested lead to suppression of neuronal excitability, pore-targeted activators (like ML213 and retigabine) strongly suppress seizure behavior, whereas ICA-069673 triggers a seizure-like hypermotile behavior. SIGNIFICANCE: This study suggests criteria to categorize antiepileptic Kv7 activator drugs based on their underlying mechanism. We also establish the use of in vivo CaMPARI as a tool for screening effects of anticonvulsant drugs on neuronal excitability in zebrafish. In summary, despite a shared ability to suppress neuronal excitability, our findings illustrate how mechanistic differences between Kv7 activator subtypes influence their effects on heteromeric channels and lead to vastly different in vivo outcomes.

A cluster of trace-concentration methamphetamine identifications in racehorses associated with a methamphetamine-contaminated horse trailer: A report and analysis.

Three low concentration methamphetamine "positive" tests were linked to use of a methamphetamine-contaminated trailer to transport the affected horses. This incident establishes methamphetamine as a human-use substance that can inadvertently enter the environment of racing horses, resulting in urinary methamphetamine "positives;" an interim regulatory cut-off of 15 ng/mL for methamphetamine in post-race urine is proposed.

Identifications de concentrations de méthamphétamine à l'état de traces chez des chevaux de course associées à une remorque contaminée : rapport et analyse. Trois tests «positifs¼ de faibles concentrations de méthamphétamine ont été associés à l'utilisation d'une remorque contaminée par les méthamphétamines qui était utilisée pour transporter les chevaux affectés. Cet incident établit la méthamphétamine comme une substance à utilisation humaine qui peut pénétrer par inadvertance dans le milieu des chevaux de course, entainant ainsi des tests d'urine «positifs¼; un niveau intérimaire réglementaire de 15 ng/mL pour les méthamphétamines est proposé pour les tests d'urine après la course.(Traduit par Isabelle Vallières).

Association Between Skin Acid Mantle, Natural Moisturizing Factors, and Antibacterial Activity Against S. aureus in the Stratum Corneum.

Purpose: The skin has evolved a system to prevent pathogenic microorganism colonization and infection. This study examined the role of natural moisturizing factors (NMFs) and skin pH on Staphylococcus aureus (S. aureus) growth and colonization on the human stratum corneum (SC). Study Population and Methods: A survey study with 82 female participants was performed. Participants maintained their daily hygiene routine, except for refraining from using leave-on products on their forearms on the day of the test. Skin sampling was performed using adhesive tapes. An ex vivo method was developed to study the viability and growth of S. aureus on human SC sampled from normal skin. NMFs, including pyrrolidone carboxylic acid (PCA), urocanic acid (UCA), histidine, and proline in SC samples, were measured by liquid chromatography with tandem mass spectrometry. The impact of PCA and UCA on S. aureus growth and metabolic activity was measured by optical density and isothermal microcalorimetry, respectively. Results: Heterogeneity of S. aureus viability on human SC samples was observed. Skin pH showed a significant negative association (p<0.05) with SC antibacterial activity in the ex vivo assay. One unit of skin pH decrease corresponded to 68.1% of S. aureus cell death. The levels of PCA and histidine were significantly negatively associated (p<0.05) with skin pH. The addition of 5 mM and 10 mM PCA significantly inhibited S. aureus growth by approximately 25% at 20 hours and reduced its metabolic activity in vitro. Conclusion: The results indicate that PCA, one of the NMFs in human skin, plays an important role in regulating the human skin acid mantle in vivo and contributes to antibacterial activity against S. aureus.

Precision subclassification of type 2 diabetes: a systematic review.

BACKGROUND: Heterogeneity in type 2 diabetes presentation and progression suggests that precision medicine interventions could improve clinical outcomes. We undertook a systematic review to determine whether strategies to subclassify type 2 diabetes were associated with high quality evidence, reproducible results and improved outcomes for patients. METHODS: We searched PubMed and Embase for publications that used 'simple subclassification' approaches using simple categorisation of clinical characteristics, or 'complex subclassification' approaches which used machine learning or 'omics approaches in people with established type 2 diabetes. We excluded other diabetes subtypes and those predicting incident type 2 diabetes. We assessed quality, reproducibility and clinical relevance of extracted full-text articles and qualitatively synthesised a summary of subclassification approaches. RESULTS: Here we show data from 51 studies that demonstrate many simple stratification approaches, but none have been replicated and many are not associated with meaningful clinical outcomes. Complex stratification was reviewed in 62 studies and produced reproducible subtypes of type 2 diabetes that are associated with outcomes. Both approaches require a higher grade of evidence but support the premise that type 2 diabetes can be subclassified into clinically meaningful subtypes. CONCLUSION: Critical next steps toward clinical implementation are to test whether subtypes exist in more diverse ancestries and whether tailoring interventions to subtypes will improve outcomes.

In people with type 2 diabetes there may be differences in the way people present, including for example, their symptoms, body weight or how much insulin they make. We looked at recent publications describing research in this area to see whether it is possible to separate people with type 2 diabetes into different subgroups and, if so, whether these groupings were useful for patients. We found that it is possible to group people with type 2 diabetes into different subgroups and being in one subgroup can be more strongly linked to the likelihood of developing complications over others. This might mean that in the future we can treat people in different subgroups differently in ways that improves their treatment and their health but it requires further study.

Systematic review of precision subclassification of type 2 diabetes.

Heterogeneity in type 2 diabetes presentation, progression and treatment has the potential for precision medicine interventions that can enhance care and outcomes for affected individuals. We undertook a systematic review to ascertain whether strategies to subclassify type 2 diabetes are associated with improved clinical outcomes, show reproducibility and have high quality evidence. We reviewed publications that deployed 'simple subclassification' using clinical features, biomarkers, imaging or other routinely available parameters or 'complex subclassification' approaches that used machine learning and/or genomic data. We found that simple stratification approaches, for example, stratification based on age, body mass index or lipid profiles, had been widely used, but no strategy had been replicated and many lacked association with meaningful outcomes. Complex stratification using clustering of simple clinical data with and without genetic data did show reproducible subtypes of diabetes that had been associated with outcomes such as cardiovascular disease and/or mortality. Both approaches require a higher grade of evidence but support the premise that type 2 diabetes can be subclassified into meaningful groups. More studies are needed to test these subclassifications in more diverse ancestries and prove that they are amenable to interventions.

Second international consensus report on gaps and opportunities for the clinical translation of precision diabetes medicine.

Precision medicine is part of the logical evolution of contemporary evidence-based medicine that seeks to reduce errors and optimize outcomes when making medical decisions and health recommendations. Diabetes affects hundreds of millions of people worldwide, many of whom will develop life-threatening complications and die prematurely. Precision medicine can potentially address this enormous problem by accounting for heterogeneity in the etiology, clinical presentation and pathogenesis of common forms of diabetes and risks of complications. This second international consensus report on precision diabetes medicine summarizes the findings from a systematic evidence review across the key pillars of precision medicine (prevention, diagnosis, treatment, prognosis) in four recognized forms of diabetes (monogenic, gestational, type 1, type 2). These reviews address key questions about the translation of precision medicine research into practice. Although not complete, owing to the vast literature on this topic, they revealed opportunities for the immediate or near-term clinical implementation of precision diabetes medicine; furthermore, we expose important gaps in knowledge, focusing on the need to obtain new clinically relevant evidence. Gaps include the need for common standards for clinical readiness, including consideration of cost-effectiveness, health equity, predictive accuracy, liability and accessibility. Key milestones are outlined for the broad clinical implementation of precision diabetes medicine.

Tobacco crop substitution: pilot effort in China.

In China, approximately 20 million farmers produce the world's largest share of tobacco. Showing that income from crop substitution can exceed that from tobacco growth is essential to persuading farm families to stop planting tobacco, grown abundantly in Yunnan Province. In the Yuxi Municipality, collaborators from the Yuxi Bureau of Agriculture and the University of California at Los Angeles School of Public Health initiated a tobacco crop substitution project. At 3 sites, 458 farm families volunteered to participate in a new, for-profit cooperative model. This project successfully identified an approach engaging farmers in cooperatives to substitute food crops for tobacco, thereby increasing farmers' annual income between 21% and 110% per acre.

Extragenital Bullous Lichen Sclerosus Treated with Fractional CO2 Laser (FxCO2) and Wet Dressing of Halcinonide Solution: A Case Report.

Lichen sclerosis (LS) is an insidious, chronic, relapsing skin disease characterized by atrophic, porcelain-appearing plaques. It usually arises in the anogenital area, but some cases can present in extragenital regions with a variety of presentations, including a bullous variant. Topical corticosteroids are a first-line therapy and are usually the most effective treatment to induce remission of LS. However, there is a subset of patients that does not respond well to topical steroids. Herein, we report an extragenital bullous LS case successfully treated with a fractional CO2 laser (FxCO2) and subsequent wet dressing of halcinonide solution.

Mycobacterium smegmatis Skin Infection Following Cosmetic Procedures: Report of Two Cases.

Mycobacterium smegmatis is an acid-fast bacillus of rapidly growing mycobacteria (RGM) of nontuberculous mycobacteria (NTM). M. smegmatis was considered nonpathogenic to humans until 1986, when the first patient was linked to the infection. To date, fewer than 100 cases have been reported in the literature, mainly related to various surgical procedures. Herein, we report two immunocompetent patients who acquired M. smegmatis infection following cosmetic procedures. Due to the rarity of M. smegmatis infection in routine clinical practice, it is challenging for medical providers to diagnose and treat patients with M. smegmatis infection. M. smegmatis infection should be considered for patients with chronic skin and soft tissue infections at the injection site or surgical site following cosmetic procedures. Histological findings, pathogen identification by molecular testing or bacterial culture are required to make a definitive diagnosis. Medical providers should raise awareness of M. smegmatis infection for patients with chronic skin and soft tissue infections after cosmetic procedures. Stringent sterile procedures for surgical instruments, supplies, and environments should be enforced.

Phylogenomic Analysis of Salmonella enterica subsp. enterica Serovar Bovismorbificans from Clinical and Food Samples Using Whole Genome Wide Core Genes and kmer Binning Methods to Identify Two Distinct Polyphyletic Genome Pathotypes

Salmonella enterica subsp. enterica serovar Bovismorbificans has caused multiple outbreaks involving the consumption of produce, hummus, and processed meat products worldwide. To elucidate the intra-serovar genomic structure of S. Bovismorbificans, a core-genome analysis with 2690 loci (based on 150 complete genomes representing Salmonella enterica serovars developed as part of this study) and a k-mer-binning based strategy were carried out on 95 whole genome sequencing (WGS) assemblies from Swiss, Canadian, and USA collections of S. Bovismorbificans strains from foodborne infections. Data mining of a digital DNA tiling array of legacy SARA and SARB strains was conducted to identify near-neighbors of S. Bovismorbificans. The core genome analysis and the k-mer-binning methods identified two polyphyletic clusters, each with emerging evolutionary properties. Four STs (2640, 142, 1499, and 377), which constituted the majority of the publicly available WGS datasets from >260 strains analyzed by k-mer-binning based strategy, contained a conserved core genome backbone with a different evolutionary lineage as compared to strains comprising the other cluster (ST150). In addition, the assortment of genotypic features contributing to pathogenesis and persistence, such as antimicrobial resistance, prophage, plasmid, and virulence factor genes, were assessed to understand the emerging characteristics of this serovar that are relevant clinically and for food safety concerns. The phylogenomic profiling of polyphyletic S. Bovismorbificans in this study corresponds to intra-serovar variations observed in S. Napoli and S. Newport serovars using similar high-resolution genomic profiling approaches and contributes to the understanding of the evolution and sequence divergence of foodborne Salmonellae. These intra-serovar differences may have to be thoroughly understood for the accurate classification of foodborne Salmonella strains needed for the uniform development of future food safety mitigation strategies.

Electrophysiologic Conservation of Epicardial Conduction Dynamics After Myocardial Infarction and Natural Heart Regeneration in Newborn Piglets.

Newborn mammals, including piglets, exhibit natural heart regeneration after myocardial infarction (MI) on postnatal day 1 (P1), but this ability is lost by postnatal day 7 (P7). The electrophysiologic properties of this naturally regenerated myocardium have not been examined. We hypothesized that epicardial conduction is preserved after P1 MI in piglets. Yorkshire-Landrace piglets underwent left anterior descending coronary artery ligation at age P1 (n = 6) or P7 (n = 7), After 7 weeks, cardiac magnetic resonance imaging was performed with late gadolinium enhancement for analysis of fibrosis. Epicardial conduction mapping was performed using custom 3D-printed high-resolution mapping arrays. Age- and weight-matched healthy pigs served as controls (n = 6). At the study endpoint, left ventricular (LV) ejection fraction was similar for controls and P1 pigs (46.4 ± 3.0% vs. 40.3 ± 4.9%, p = 0.132), but significantly depressed for P7 pigs (30.2 ± 6.6%, p < 0.001 vs. control). The percentage of LV myocardial volume consisting of fibrotic scar was 1.0 ± 0.4% in controls, 9.9 ± 4.4% in P1 pigs (p = 0.002 vs. control), and 17.3 ± 4.6% in P7 pigs (p < 0.001 vs. control, p = 0.007 vs. P1). Isochrone activation maps and apex activation time were similar between controls and P1 pigs (9.4 ± 1.6 vs. 7.8 ± 0.9 ms, p = 0.649), but significantly prolonged in P7 pigs (21.3 ± 5.1 ms, p < 0.001 vs. control, p < 0.001 vs. P1). Conduction velocity was similar between controls and P1 pigs (1.0 ± 0.2 vs. 1.1 ± 0.4 mm/ms, p = 0.852), but slower in P7 pigs (0.7 ± 0.2 mm/ms, p = 0.129 vs. control, p = 0.052 vs. P1). Overall, our data suggest that epicardial conduction dynamics are conserved in the setting of natural heart regeneration in piglets after P1 MI.

Health Care Provider Practices and Perceptions During Family-Centered Rounds With Limited English-Proficient Families.

OBJECTIVE: To increase understanding of current practices and perceptions of family-centered rounds (FCR) by providers for limited English-proficient (LEP) families relative to English-proficient families. METHODS: Using grounded theory methodology, we conducted ethnographic observations of FCR for LEP and English-proficient families on the pediatric wards at an urban teaching hospital. Focused coding of observation fieldnotes was performed independently, followed by regular group meetings to discuss discrepancies, refine codes, and identify theoretical direction. Data informed development of an interview guide used to conduct interviews with pediatric physicians, nurses, and interpreters. The iterative analysis process continued with interview transcriptions. RESULTS: FCR of 36 unique patient families were observed, of which 10 were LEP families. We conducted 20 interviews with 7 residents, 3 attendings, 5 nurses, and 5 interpreters. Major themes included: 1) standardization of FCR is needed to address equity issues for LEP families, 2) redefining the roles of medical interpreters would enhance the interpersonal interactions and relationships between families and health care providers, and 3) improving resources to allow interpreters to be used consistently will increase equity for LEP families. CONCLUSIONS: Many differences exist in FCR for LEP versus English-proficient families. FCR for LEP families may be optimized with standardization and training, redefining the interpreters' roles, and improving access to interpreters.