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2.
Sci Rep ; 14(1): 14394, 2024 06 22.
Article in English | MEDLINE | ID: mdl-38909141

ABSTRACT

Individuals affected by human immunodeficiency virus (HIV) have a growing demand for coronary artery bypass grafting (CABG) due to heightened risk for cardiovascular diseases and extended life expectancy. However, CABG outcomes in HIV patients are not well-established, with insights only from small case series studies. This study conducted a comprehensive, population-based examination of in-hospital CABG outcomes in HIV patients. Patients underwent CABG were identified in National Inpatient Sample from Q4 2015-2020. Patients with age < 18 years and concomitant procedures were excluded. A 1:5 propensity-score matching was used to address preoperative group differences. Among patients who underwent CABG, 613 (0.36%) had HIV and were matched to 3119 out of 167,569 non-HIV patients. For selected HIV patients, CABG is relatively safe, presenting largely similar outcomes. After matching, HIV and non-HIV patients had comparable in-hospital mortality rates (2.13% vs. 1.67%, p = 0.40). Risk factors associated with mortality among HIV patients included previous CABG (aOR = 14.32, p = 0.01), chronic pulmonary disease (aOR = 8.24, p < 0.01), advanced renal failure (aOR = 7.49, p = 0.01), and peripheral vascular disease (aOR = 6.92, p = 0.01), which can be used for preoperative risk stratification. While HIV patients had higher acute kidney injury (AKI; 26.77% vs. 21.77%, p = 0.01) and infection (8.21% vs. 4.18%, p < 0.01), other complications were comparable between the groups.


Subject(s)
Coronary Artery Bypass , HIV Infections , Hospital Mortality , Humans , Coronary Artery Bypass/adverse effects , Male , Female , Middle Aged , HIV Infections/epidemiology , HIV Infections/surgery , Aged , Risk Factors , Inpatients/statistics & numerical data , Treatment Outcome , Adult , United States/epidemiology , Coronary Artery Disease/surgery , Coronary Artery Disease/mortality
3.
Sci Rep ; 14(1): 11762, 2024 05 23.
Article in English | MEDLINE | ID: mdl-38783030

ABSTRACT

There is limited data on the effect of socioeconomic status (SES) on transcatheter (TAVR) and surgical aortic valve replacement (SAVR) outcomes for aortic stenosis (AS). This study conducted a population-based analysis to assess the influence of SES on valve replacement outcomes. Patients with AS undergoing TAVR or SAVR were identified in National Inpatient Sample from Q4 2015-2020. Multivariable logistic regressions were used to compare in-hospital outcomes between patients living in neighborhoods of income at the lowest and highest quartiles. Of 613,785 AS patients, 9.77% underwent TAVR and 10.13% had SAVR. These rates decline with lower neighborhood income levels, with TAVR/SAVR ratio also declining in lower-income areas. Excluding concomitant procedures, 58,064 patients received isolated TAVR (12,355 low-income and 15,212 high-income) and 43,694 underwent isolated SAVR (10,029 low-income and 10,811 high-income). Low-income patients, in both TAVR and SAVR, were younger but had more comorbid burden. For isolated TAVR, outcomes were similar across income groups. However, for isolated SAVR, low-income patients experienced higher in-hospital mortality (aOR = 1.44, p < 0.01), pulmonary (aOR = 1.13, p = 0.01), and renal complications (aOR = 1.14, p < 0.01). They also had more transfers, longer waits for operations, and extended hospital stays. Lower-income communities had reduced access to TAVR and SAVR, with TAVR accessibility being particularly limited. When given access to TAVR, patients from lower-income neighborhoods had mostly comparable outcomes. However, patients from low-income communities faced worse outcomes in SAVR, possibly due to delays in treatment. Ensuring equitable specialized healthcare resources including expanding TAVR access in economically disadvantaged communities is crucial.


Subject(s)
Aortic Valve Stenosis , Transcatheter Aortic Valve Replacement , Humans , Female , Male , Aged , Aortic Valve Stenosis/surgery , Aged, 80 and over , Healthcare Disparities , Inpatients/statistics & numerical data , Heart Valve Prosthesis Implantation , United States/epidemiology , Hospital Mortality , Middle Aged , Socioeconomic Factors , Social Class , Aortic Valve/surgery , Treatment Outcome , Socioeconomic Disparities in Health
4.
Microbiol Spectr ; 12(6): e0031424, 2024 Jun 04.
Article in English | MEDLINE | ID: mdl-38709058

ABSTRACT

Bacterial isolates from the human urinary microbiome have been extensively studied for their antibiotic resistance; however, little work has been done on those isolates that are difficult to grow in vitro. This study was designed to qualify a serum-based medium, New York City Broth III (NYCIII), and a broth microdilution method to determine the antibiotic susceptibility of previously underreported or undescribed microbes that have a difficult time growing in standard Mueller-Hinton broth. Here, we demonstrate that NYCIII microbroth dilution can be an effective method for the determination of antibiotic susceptibility of species found in the human urinary microbiome. We show that this method serves well to characterize fastidious and anaerobic urinary microbes that have no Clinical and Laboratory Standards Institute (CLSI) guidelines, including several in the families Aerococcaceae, Lactobacillaceae, or Actinomycetaceae. Previous studies using expanded quantitative urine culture reveal that urine samples from clinical patients are commonly polymicrobial in composition. Thus, we test whether NYCIII can serve as a viable harmonized medium, capable of supporting antibiotic susceptibility testing in a range of fastidious, non-fastidious, and anaerobic urinary microbes. We propose this methodology to be standardized comparable to CLSI standards to allow for resistance testing in uncharacterized urinary bacteria. IMPORTANCE: Antibiotic susceptibilities of fastidious and anaerobic bacteria of the human urinary microbiome are largely underreported due to difficulty in growing them in the lab environment. The current standard medium, Muller-Hinton broth, has difficulty supporting the growth of many of these species, leaving microbiologists without a standardized method. To address this need, this study offers a methodology to survey susceptibilities in a high-throughput manner of these understudied microbes with a proposed harmonized medium, NYCIII, which is capable of supporting the growth of both fastidious and non-fastidious urinary microbes. Broader standardization of this method can allow for the development of antibiotic-resistant breakpoints of the many uncharacterized urinary microbes.


Subject(s)
Anti-Bacterial Agents , Bacteria, Anaerobic , Microbial Sensitivity Tests , Microbiota , Humans , Microbial Sensitivity Tests/methods , Anti-Bacterial Agents/pharmacology , Microbiota/drug effects , Bacteria, Anaerobic/drug effects , Bacteria, Anaerobic/isolation & purification , Urine/microbiology , Urinary Tract Infections/microbiology , Bacteria/drug effects , Bacteria/isolation & purification , Bacteria/growth & development , Culture Media/chemistry
5.
Antibiotics (Basel) ; 13(5)2024 May 10.
Article in English | MEDLINE | ID: mdl-38786161

ABSTRACT

The recognition of the Aerococcus urinae complex (AUC) as an emerging uropathogen has led to growing concerns due to a limited understanding of its disease spectrum and antibiotic resistance profiles. Here, we investigated the prevalence of macrolide resistance within urinary AUC isolates, shedding light on potential genetic mechanisms. Phenotypic testing revealed a high rate of macrolide resistance: 45%, among a total of 189 urinary AUC isolates. Genomic analysis identified integrative and conjugative elements (ICEs) as carriers of the macrolide resistance gene ermA, suggesting horizontal gene transfer as a mechanism of resistance. Furthermore, comparison with publicly available genomes of related pathogens revealed high ICE sequence homogeneity, highlighting the potential for cross-species dissemination of resistance determinants. Understanding mechanisms of resistance is crucial for developing effective surveillance strategies and improving antibiotic use. Furthermore, the findings underscore the importance of considering the broader ecological context of resistance dissemination, emphasizing the need for community-level surveillance to combat the spread of antibiotic resistance within the urinary microbiome.

6.
Microbiol Resour Announc ; 13(6): e0015624, 2024 Jun 11.
Article in English | MEDLINE | ID: mdl-38651909

ABSTRACT

Previously identified under the single designation of Aerococcus urinae, three distinct taxonomic species have been distinguished as Aerococcus loyolae, Aerococcus mictus, and Aerococcus tenax. Here, we present the complete genome sequences of the type strains of these species assembled via a combination of short-read and long-read sequencing techniques.Registered at ClinicalTrials.gov (NCT01166438).

7.
J Am Chem Soc ; 146(17): 11605-11609, 2024 May 01.
Article in English | MEDLINE | ID: mdl-38634647

ABSTRACT

The ribosomally synthesized and post-translationally modified peptide (RiPP) superfamily of natural products includes many examples of cyclic peptides with diverse macrocyclization chemistries. The graspetides, one family of macrocyclized RiPPs, harbor side chain-side chain ester or amide linkages. We recently reported the structure and biosynthesis of the graspetide pre-fuscimiditide, a 22-amino-acid (aa) peptide with two ester cross-links forming a stem-loop structure. These cross-links are introduced by a single graspetide synthetase, the ATP-grasp enzyme ThfB. Here we show that ThfB can also catalyze the formation of amide or thioester cross-links in prefuscimiditide, with thioester formation being especially efficient. We further show that upon proteolysis to reveal an N-terminal cysteine residue, the thioester-linked peptide rapidly and quantitatively rearranges via native chemical ligation into an isopeptide-bonded head-to-tail cyclic peptide. The solution structure of this rearranged peptide was determined by using 2D NMR spectroscopy experiments. Our methodology offers a straightforward recombinant route to head-to-tail cyclic peptides.


Subject(s)
Peptides, Cyclic , Peptides, Cyclic/chemistry , Peptides, Cyclic/biosynthesis , Peptides, Cyclic/metabolism
8.
Article in English | MEDLINE | ID: mdl-38052718

ABSTRACT

BACKGROUND: Racial disparities in aortic valve replacement outcomes have been established. However, the current literature lacks comprehensive studies that examine the outcomes for Native Americans, probably due to their limited population size. This study aimed to investigate whether disparities in transcatheter aortic valve replacement (TAVR) and surgical aortic valve replacement (SAVR) also exist for outcomes among Native Americans. METHODS: Patients who underwent SAVR and TAVR were identified in National Inpatient Sample from the last quarter of 2015 to 2020. A 1:5 propensity score matching was conducted between Native Americans and Caucasians. In-hospital perioperative outcomes, length of stay, wait from admission to operation, and total hospital charge, were compared. RESULTS: In TAVR, 51,394 (84.41 %) were Caucasians and 171 (0.28 %) were Native Americans. In SAVR, there were 50,080 (78.52 %) Caucasians and 279 (0.44 %) Native Americans. After propensity matching, no significant difference was found in post-TAVR outcomes between Native Americans and Caucasians. However, Native Americans have a higher risk of neurological complications (2.88 % vs 0.79 %, p < 0.01) with stroke being the primary contributor (2.52 % vs 0.5 %, p < 0.01), as well as a higher incidence of venous thromboembolism (1.8 % vs 0.57 %, p < 0.05) after SAVR. CONCLUSIONS: This study is the first to examine aortic valve replacement outcomes in Native Americans. Native Americans were found to be more likely to undergo SAVR than TAVR. Moreover, Native Americans were found to have five times higher stroke and three times higher VTE after SAVR. These disparities faced by Native Americans underscore the need for increased attention and targeted actions to guarantee health equity.

9.
ACS Chem Biol ; 18(11): 2394-2404, 2023 Nov 17.
Article in English | MEDLINE | ID: mdl-37856788

ABSTRACT

Graspetides are a class of ribosomally synthesized and post-translationally modified peptides (RiPPs) that exhibit an impressive diversity in patterns of side chain-to-side chain ω-ester or ω-amide linkages. Recent studies have uncovered a significant portion of graspetides to contain an additional post-translational modification involving aspartimidylation catalyzed by an O-methyltransferase, predominantly found in the genomes of actinomycetota. Here, we present a comprehensive bioinformatic analysis focused on graspetides harboring aspartimide, for which we propose the name graspimiditides. From protein BLAST results of 5000 methyltransferase sequences, we identified 962 unique putative graspimiditides, which we further classified into eight main clusters based on sequence similarity along with several smaller clusters and singletons. The previously studied graspimiditides, fuscimiditide, and amycolimiditide, are identified in this analysis; fuscimiditide is a singleton, while amycolimiditide is in the fifth largest cluster. Cluster 1, by far the largest cluster, contains 641 members, encoded almost exclusively in the Streptomyces genus. To characterize an example of a graspimiditide in Cluster 1, we conducted experimental studies on the peptide from Streptomyces albus J1074, which we named albusimiditide. By tandem mass spectrometry, hydrazinolysis, and amino acid substitution experiments, we elucidated the structure of albusimiditide to be a large tetracyclic peptide with four ω-ester linkages generating a stem-loop structure with one aspartimide. The ester cross-links form 22-, 46-, 22-, and 44-atom macrocycles, the last of which, the loop, contains the enzymatically installed aspartimide. Further in vitro experiments revealed that the aspartimide hydrolyzes in a 3:1 ratio of isoaspartate to aspartate residues. Overall, this study offers comprehensive insight into the diversity and structural features of graspimiditides, paving the way for future investigations of this unique class of natural products.


Subject(s)
Computational Biology , Peptides , Computational Biology/methods , Peptides/chemistry , Protein Processing, Post-Translational , Methyltransferases/metabolism , Esters
10.
Article in English | MEDLINE | ID: mdl-37755156

ABSTRACT

Average nucleotide identity analysis, based on whole genome sequences of 115 strains previously identified as Aerococcus urinae, an emerging uropathogen, discriminates at least six unique genomic taxa. The whole genome analysis affords clearer species boundaries over 16S rRNA gene sequencing and traditional phenotypic approaches for the identification and phylogenetic organization of Aerococcus species. The newly described species can be differentiated by matrix-assisted laser desorption ionization time-of-flight analysis of protein signatures. We propose the emendation of the description of A. urinae (type strain ATCC 51268T = CCUG 34223T=NCFB 2893) and the names of Aerococcus tenax sp. nov. (ATCC TSD-302T = DSM 115700T = CCUG 76531T=NR-58630T), Aerococcus mictus sp. nov. (ATCC TSD-301T = DSM 115699T = CCUG 76532T=NR-58629T), and Aerococcus loyolae sp. nov. (ATCC TSD-300T = DSM 115698T = CCUG 76533T=NR-58628T) for three of the newly identified genomic taxa.


Subject(s)
Aerococcus , Aerococcus/genetics , Phylogeny , RNA, Ribosomal, 16S/genetics , Sequence Analysis, DNA , DNA, Bacterial/genetics , Bacterial Typing Techniques , Base Composition , Fatty Acids/chemistry
11.
Trends Chem ; 5(8): 620-633, 2023 Aug.
Article in English | MEDLINE | ID: mdl-37614740

ABSTRACT

Graspetides are a class of RiPPs (ribosomally synthesized and post-translationally modified peptides) defined by the presence of ester or amide side chain-side chain linkages resulting in peptide macrocycles. The graspetide name comes from the ATP-grasp enzymes that install the side chain-side chain linkages. This review covers the early, activity-based isolation of the first graspetides, marinostatins and microviridins, as well as the key genomics-driven experiments that established graspetide as RiPPs. The mechanism and structure of graspetide-associated ATP-grasp enzymes is discussed. Genome mining methods to discover new graspetides as well as the analytical techniques used to determine the linkages in graspetides are described. Extant knowledge on the bioactivity of graspetides as protease inhibitors is reviewed. Further chemical modifications to graspetides as well graspetide engineering studies are also described. We conclude with several suggestions about future directions of graspetide research.

12.
J Am Chem Soc ; 144(47): 21628-21639, 2022 11 30.
Article in English | MEDLINE | ID: mdl-36394830

ABSTRACT

Several classes of ribosomally synthesized and post-translationally modified peptides (RiPPs) are composed of multiple macrocycles. The enzymes that assemble these macrocycles must surmount the challenge of installing a single specific set of linkages out of dozens of distinct possibilities. One class of RiPPs that includes multiple macrocycles are the graspetides, named after the ATP-grasp enzymes that install ester or amide linkages between pairs of nucleophilic and electrophilic side chains. Here, using heterologous expression and NMR spectroscopy, we characterize the connectivity and structure of amycolimiditide, a 29 aa graspetide with a stem-loop structure. The stem includes four esters and extends over 20 Å. The loop of amycolimiditide is distinguished by the presence of an aspartimide moiety, installed by a dedicated O-methyltransferase enzyme. We further characterize the biosynthesis of amycolimiditide in vitro, showing that the amycolimiditide ATP-grasp enzyme AmdB operates in a strict vectorial manner, installing esters starting at the loop and proceeding down the stem. Surprisingly, the O-methyltransferase AmdM that aspartimidylates amycolimiditide prefers a substrate with all four esters installed, despite the fact that the most distal ester is ∼30 Å away from the site of aspartimidylation. This study provides insights into the structure and diversity of aspartimidylated graspetides and also provides fresh insights into how RiPP biosynthetic enzymes engage their peptide substrates.


Subject(s)
Amides , Methyltransferases , Adenosine Triphosphate , Esters
13.
Nat Chem ; 14(11): 1325-1334, 2022 11.
Article in English | MEDLINE | ID: mdl-35982233

ABSTRACT

Microviridins and other ω-ester-linked peptides, collectively known as graspetides, are characterized by side-chain-side-chain linkages installed by ATP-grasp enzymes. Here we report the discovery of a family of graspetides, the gene clusters of which also encode an O-methyltransferase with homology to the protein repair catalyst protein L-isoaspartyl methyltransferase. Using heterologous expression, we produced fuscimiditide, a ribosomally synthesized and post-translationally modified peptide (RiPP). NMR analysis of fuscimiditide revealed that the peptide contains two ester cross-links forming a stem-loop macrocycle. Furthermore, an unusually stable aspartimide moiety is found within the loop macrocycle. We fully reconstituted fuscimiditide biosynthesis in vitro including formation of the ester and aspartimide moieties. The aspartimide moiety embedded in fuscimiditide hydrolyses regioselectively to isoaspartate. Surprisingly, this isoaspartate-containing peptide is also a substrate for the L-isoaspartyl methyltransferase homologue, thus driving any hydrolysis products back to the aspartimide form. Whereas an aspartimide is often considered a nuisance product in protein formulations, our data suggest that some RiPPs have aspartimide residues intentionally installed via enzymatic activity.


Subject(s)
Isoaspartic Acid , Protein D-Aspartate-L-Isoaspartate Methyltransferase , Amino Acid Sequence , Protein D-Aspartate-L-Isoaspartate Methyltransferase/genetics , Protein D-Aspartate-L-Isoaspartate Methyltransferase/metabolism , Peptides/chemistry , Methyltransferases/metabolism , Esters
14.
AJR Am J Roentgenol ; 219(3): 407-419, 2022 09.
Article in English | MEDLINE | ID: mdl-35441530

ABSTRACT

BACKGROUND. Deep learning frameworks have been applied to interpretation of coronary CTA performed for coronary artery disease (CAD) evaluation. OBJECTIVE. The purpose of our study was to compare the diagnostic performance of myocardial perfusion imaging (MPI) and coronary CTA with artificial intelligence quantitative CT (AI-QCT) interpretation for detection of obstructive CAD on invasive angiography and to assess the downstream impact of including coronary CTA with AI-QCT in diagnostic algorithms. METHODS. This study entailed a retrospective post hoc analysis of the derivation cohort of the prospective 23-center Computed Tomographic Evaluation of Atherosclerotic Determinants of Myocardial Ischemia (CREDENCE) trial. The study included 301 patients (88 women and 213 men; mean age, 64.4 ± 10.2 [SD] years) recruited from May 2014 to May 2017 with stable symptoms of myocardial ischemia referred for nonemergent invasive angiography. Patients underwent coronary CTA and MPI before angiography with quantitative coronary angiography (QCA) measurements and fractional flow reserve (FFR). CTA examinations were analyzed using an FDA-cleared cloud-based software platform that performs AI-QCT for stenosis determination. Diagnostic performance was evaluated. Diagnostic algorithms were compared. RESULTS. Among 102 patients with no ischemia on MPI, AI-QCT identified obstructive (≥ 50%) stenosis in 54% of patients, including severe (≥ 70%) stenosis in 20%. Among 199 patients with ischemia on MPI, AI-QCT identified nonobstructive (1-49%) stenosis in 23%. AI-QCT had significantly higher AUC (all p < .001) than MPI for predicting ≥ 50% stenosis by QCA (0.88 vs 0.66), ≥ 70% stenosis by QCA (0.92 vs 0.81), and FFR < 0.80 (0.90 vs 0.71). An AI-QCT result of ≥ 50% stenosis and ischemia on stress MPI had sensitivity of 95% versus 74% and specificity of 63% versus 43% for detecting ≥ 50% stenosis by QCA measurement. Compared with performing MPI in all patients and those showing ischemia undergoing invasive angiography, a scenario of performing coronary CTA with AIQCT in all patients and those showing ≥ 70% stenosis undergoing invasive angiography would reduce invasive angiography utilization by 39%; a scenario of performing MPI in all patients and those showing ischemia undergoing coronary CTA with AI-QCT and those with ≥ 70% stenosis on AI-QCT undergoing invasive angiography would reduce invasive angiography utilization by 49%. CONCLUSION. Coronary CTA with AI-QCT had higher diagnostic performance than MPI for detecting obstructive CAD. CLINICAL IMPACT. A diagnostic algorithm incorporating AI-QCT could substantially reduce unnecessary downstream invasive testing and costs. TRIAL REGISTRATION. Clinicaltrials.gov NCT02173275.


Subject(s)
Coronary Artery Disease , Coronary Stenosis , Fractional Flow Reserve, Myocardial , Myocardial Ischemia , Myocardial Perfusion Imaging , Aged , Artificial Intelligence , Computed Tomography Angiography/methods , Constriction, Pathologic , Coronary Angiography/methods , Coronary Stenosis/diagnostic imaging , Female , Humans , Male , Middle Aged , Myocardial Ischemia/diagnostic imaging , Predictive Value of Tests , Prospective Studies , Reference Standards , Retrospective Studies
15.
Front Cardiovasc Med ; 9: 839400, 2022.
Article in English | MEDLINE | ID: mdl-35387447

ABSTRACT

Coronary artery disease is a leading cause of death worldwide. There has been a myriad of advancements in the field of cardiovascular imaging to aid in diagnosis, treatment, and prevention of coronary artery disease. The application of artificial intelligence in medicine, particularly in cardiovascular medicine has erupted in the past decade. This article serves to highlight the highest yield articles within cardiovascular imaging with an emphasis on coronary CT angiography methods for % stenosis evaluation and atherosclerosis quantification for the general cardiologist. The paper finally discusses the evolving paradigm of implementation of artificial intelligence in real world practice.

16.
Biofabrication ; 13(4)2021 09 17.
Article in English | MEDLINE | ID: mdl-34479224

ABSTRACT

The properties of a semipermeable porous membrane, including pore size, pore density, and thickness, play a crucial role in creating a tissue interface in a microphysiological system (MPS) because it dictates multicellular interactions between different compartments. The small pore-sized membrane has been preferentially used in an MPS for stable cell adhesion and the formation of tissue barriers on the membrane. However, it limited the applicability of the MPS because of the hindered cell transmigration via sparse through-holes and the optical translucence caused by light scattering through pores. Thus, there remain unmet challenges to construct a compartmentalized MPS without those drawbacks. Here we report a submicrometer-thickness (∼500 nm) fibrous extracellular matrix (ECM) film selectively condensed on a large pore-sized track-etched (TE) membrane (10µm-pores) in an MPS device, which enables the generation of functional tissue barriers simultaneously achieving optical transparency, intercellular interactions, and transmigration of cells across the membrane. The condensed ECM fibers uniformly covering the surface and 10µm-pores of the TE membrane permitted sufficient surface areas where a monolayer of the human induced pluripotent stem cell-derived brain endothelial cells is formed in the MPS device. The functional maturation of the blood-brain barrier (BBB) was proficiently achieved due to astrocytic endfeet sheathing the brain endothelial cells through 10µm pores of the condensed-ECM-coated TE (cECMTE) membrane. We also demonstrated the extravasation of human metastatic breast tumor cells through the human BBB on the cECMTE membrane. Thus, the cECMTE membrane integrated with an MPS can be used as a versatile platform for studying various intercellular communications and migration, mimicking the physiological barriers of an organ compartment.


Subject(s)
Cell Communication , Endothelial Cells , Extracellular Matrix , Humans , Induced Pluripotent Stem Cells , Positron-Emission Tomography
17.
Biol Open ; 10(8)2021 08 15.
Article in English | MEDLINE | ID: mdl-34387311

ABSTRACT

In recent years, the clinical significance of Aerococcus urinae has been increasingly recognized. A. urinae has been implicated in cases of urinary tract infection (UTI; acute cystitis and pyelonephritis) in both male and female patients, ranging from children to older adults. Aerococcus urinae can also be invasive, causing urosepsis, endocarditis, and musculoskeletal infections. Mechanisms of pathogenesis in A. urinae infections are poorly understood, largely due to the lack of an animal model system. In response to this gap, we developed a model of A. urinae urinary tract infection in mice. We compared A. urinae UTI in female C3H/HeN and C57BL/6 mice and compared four clinical isolates of A. urinae isolated from patients with UTI, urgency urinary incontinence, and overactive bladder. Our data demonstrate that host genetic background modulates A. urinae UTI. Female C57BL/6 female mice rapidly cleared the infection. Female C3H/HeN mice, which have inherent vesicoureteral reflux that flushes urine from the bladder up into the kidneys, were susceptible to prolonged bacteriuria. This result is consistent with the fact that A. urinae infections most frequently occur in patients with underlying urinary tract abnormalities or disorders that make them susceptible to bacterial infection. Unlike uropathogens such as E. coli, which cause infection and inflammation both of the bladder and kidneys in C3H/HeN mice, A. urinae displayed tropism for the kidney, persisting in kidney tissue even after clearance of bacteria from the bladder. Aerococcus urinae strains from different genetic clades displayed varying propensities to cause persistent kidney infection. Aerococcus urinae infected kidneys displayed histological inflammation, neutrophil recruitment and increased pro-inflammatory cytokines. These results set the stage for future research that interrogates host-pathogen interactions between A. urinae and the urinary tract.


Subject(s)
Aerococcus , Gram-Positive Bacterial Infections/microbiology , Host-Pathogen Interactions , Urinary Tract Infections/microbiology , Aerococcus/classification , Aerococcus/genetics , Animals , Disease Models, Animal , Disease Susceptibility , Genetic Background , Genome, Bacterial , Genomics/methods , Gram-Positive Bacterial Infections/pathology , Mice , Mice, Inbred C3H , Mice, Inbred C57BL , Phylogeny , Urinary Tract Infections/pathology
18.
Article in English | MEDLINE | ID: mdl-33746507

ABSTRACT

PURPOSE OF REVIEW: Social media (SoMe) as a means of knowledge dissemination has grown significantly in cardiovascular imaging in recent years. This media platform allows for a free exchange of ideas, the development of new communities, and the ability to disseminate advancements rapidly. While the social media platforms offer limitless potential, their public domain necessitates several important suggestions around best practices. RECENT FINDINGS: In cardiovascular imaging, specific hashtags have emerged to encompass the major modalities to include #EchoFirst, #YesCCT, #WhyCMR, and #CVNuc. Cardiovascular imaging journals have established major presences in the social media space as an avenue to present novel, high-quality, peer-reviewed content to new audiences. SUMMARY: This review paper aims to introduce basic concepts in social media and cardiovascular imaging while highlighting recent topics of high importance, influence, and attention in cardiovascular imaging to include the ISCHEMIA trial, COVID-19, structural imaging, and multimodality advances from throughout 2020.

19.
Nat Chem Biol ; 17(1): 96-103, 2021 01.
Article in English | MEDLINE | ID: mdl-33046851

ABSTRACT

Eukaryotic cells compartmentalize metabolic pathways in organelles to achieve optimal reaction conditions and avoid crosstalk with cytosolic factors. We found that cytosolic expression of norcoclaurine synthase (NCS), the enzyme that catalyzes the first committed reaction in benzylisoquinoline alkaloid biosynthesis, is toxic in Saccharomyces cerevisiae and, consequently, restricts (S)-reticuline production. We developed a compartmentalization strategy that alleviates NCS toxicity while promoting increased (S)-reticuline titer. This strategy is achieved through efficient targeting of toxic NCS to the peroxisome while, crucially, taking advantage of the free flow of metabolite substrates and products across the peroxisome membrane. We demonstrate that expression of engineered transcription factors can mimic the oleate response for larger peroxisomes, further increasing benzylisoquinoline alkaloid titer without the requirement for peroxisome induction with fatty acids. This work specifically addresses the challenges associated with toxic NCS expression and, more broadly, highlights the potential for engineering organelles with desired characteristics for metabolic engineering.


Subject(s)
Benzylisoquinolines/metabolism , Carbon-Nitrogen Ligases/genetics , Gene Expression Regulation, Fungal , Peroxisomes/metabolism , Saccharomyces cerevisiae Proteins/genetics , Saccharomyces cerevisiae/genetics , Bacterial Proteins/genetics , Bacterial Proteins/metabolism , Biological Transport , Carbon-Nitrogen Ligases/metabolism , Cell Compartmentation , Cytosol/metabolism , Genes, Reporter , Luminescent Proteins/genetics , Luminescent Proteins/metabolism , Metabolic Engineering/methods , Metabolic Networks and Pathways , Oleic Acid/metabolism , Saccharomyces cerevisiae/metabolism , Saccharomyces cerevisiae Proteins/metabolism , Transcription Factors/genetics , Transcription Factors/metabolism , Red Fluorescent Protein
20.
Clin Spine Surg ; 34(4): E216-E222, 2021 05 01.
Article in English | MEDLINE | ID: mdl-33122569

ABSTRACT

STUDY DESIGN: This was a retrospective cohort study. OBJECTIVE: Identify the independent risk factors for 30- and 90-day readmission because of surgical site infection (SSI) in patients undergoing elective posterior lumbar fusion (PLF). SUMMARY OF BACKGROUND DATA: SSI is a significant cause of morbidity in the 30- and 90-day windows after hospital discharge. There remains a gap in the literature on independent risk factors for readmission because of SSI after PLF procedures. In addition, readmission for SSI after spine surgery beyond the 30-day postoperative period has not been well studied. METHODS: A retrospective analysis was performed on data from the 2012 to 2014 Healthcare Cost and Utilization Project Nationwide Readmissions Database. The authors identified 65,121 patients who underwent PLF. There were 191 patients (0.30%) readmitted with a diagnosis of SSI in the 30-day readmission window, and 283 (0.43%) patients readmitted with a diagnosis of SSI in the 90-day window. Baseline patient demographics and medical comorbidities were assessed. Bivariate and multivariate analyses were performed to examine the independent risk factors for readmission because of SSI. RESULTS: In the 30-day window after discharge, this study identified patients with liver disease, uncomplicated diabetes, deficiency anemia, depression, psychosis, renal failure, obesity, and Medicaid or Medicare insurance as higher risk patients for unplanned readmission with a diagnosis of SSI. The study identified the same risk factors in the 90-day window with the addition of diabetes with chronic complications, chronic pulmonary disease, and pulmonary circulation disease. CONCLUSIONS: Independent risk factors for readmission because of SSI included liver disease, uncomplicated diabetes, obesity, and Medicaid insurance status. These findings suggest that additional intervention in the perioperative workup for patients with these risk factors may be necessary to lower unplanned readmission because of SSI after PLF surgery.


Subject(s)
Patient Readmission , Spinal Fusion , Aged , Humans , Medicare , Postoperative Complications , Retrospective Studies , Risk Factors , Spinal Fusion/adverse effects , Surgical Wound Infection/etiology , United States
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