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Anomalous aortic origin of the left coronary artery from an incorrect aortic sinus has been reported as the second most common causes of sudden cardiac arrest in young athletes. Intramural course of the proximal left coronary artery is considered a high-risk morphology. It is associated with a slit-like ostium and elliptical shape of the proximal artery. In this case, all pre-operative cardiac images demonstrated a round ostium and round luminal shape of the left coronary artery, which suggested no evidence of intramural course. On intraoperative inspection, although the ostium and proximal left coronary artery appeared round, the patient had a long intramural course of the left coronary artery which our surgeons performed a successful unroofing procedure. The post-operative images showed a patent new ostium from the correct aortic sinus. These findings are very unusual and proved that we should not exclude intramural course even in the absence of a slit-like ostium and elliptical shape of the proximal left coronary artery.

Surgical repair in anomalous aortic origin of a coronary artery aims at mitigating the risk of sudden cardiac death in a subset of patients. The pattern and behavior of electrocardiogram changes in a large cohort of these patients are lacking. We aim to describe postoperative electrocardiogram changes in this population and its clinical implications on follow-up.All patients aged less than 21 years who underwent surgical repair for anomalous aortic origin of a coronary artery between December 2012 and June 2020 at our institution were considered for inclusion. Electrocardiograms were reviewed at 5 defined time intervals, from preoperative to 90-day follow-up, with attention to significant findings of ST-segment changes, abnormal T waves, and pathologic Q waves. The electrocardiogram changes were analyzed for correlation with surgical reintervention and medium-term outcomes.Sixty-two patients met inclusion criteria (median age 13.7 years, 61% male). ST-segment changes in the initial postoperative period were seen in 52 patients (84%), all resolving over time. Abnormal T waves were seen in 19 patients (31%), occurred commonly at the predischarge period, and mostly resolved over time. Pathologic Q waves were observed in only 1 patient and associated with reintervention due to coronary artery stenosis. There was no association between postoperative electrocardiogram changes and inducible myocardial ischemia, ventricular dysfunction, or restriction from exercise at follow-up.ST-segment changes and T-wave abnormalities are commonly seen in the postoperative period after anomalous aortic origin of a coronary artery repair, tend to resolve over time, and are not associated with adverse medium-term outcomes. Pathologic Q waves were associated with the need for early coronary reintervention.

Sarah Hudson Scholle,1 Tam T Nguyen-Louie,1 Lauren Bifulco,2 Jacquelyn W Blaz,1 Mary L Blankson,2 Veena Channamsetty,2 Daren R Anderson2 1National Committee for Quality Assurance, Washington, DC, USA; 2Weitzman Institute, Community Health Center, Inc., Middletown, CT, USACorrespondence: Sarah Hudson Scholle, National Committee for Quality Assurance (NCQA), 1100 13th St. NW, Third Floor, Washington, DC, 20005, USA, Tel +1-202-955-1726, Fax +1-202-955-3500, Email scholle@ncqa.orgPurpose: To determine if pain screening and functional assessment results are associated with new diagnoses and treatment for pain in primary care.Patients and Methods: Observational study at 13 primary care sites of a statewide federally qualified health center that implemented routine screening and functional assessment for all adults in primary care. The study group included 10,091 adults aged 18+ who had an in-person visit between July 2, 2018, and June 1, 2019, where they screened positive for chronic pain and completed a 3-question functional assessment with the PEG (Pain, Enjoyment of Life, General Activity). Multivariate logistic regressions quantified associations between pain frequency, diagnosis and treatment, sociodemographics, comorbidities, and self-reported severe pain impairment with pain diagnoses and treatment documented after screening.Results: Patients were mostly women (60.3%), Latinx (41.1%), English-speaking (80.1%), and Medicaid-insured (62.0%); they averaged 49.1 years old (SD = 13.7 years). Patients with severe pain impairment or who were Latinx were more likely to get a newly documented pain diagnosis (absolute risk difference [ARD]: 13.2% and 8.6%, ps < 0.0001), while patients with mental health/substance use or medical comorbidities were less likely (ARDs: − 20.0% to − 6.2%, ps < 0.001). Factors most consistently associated with treatment were prior treatment of the same modality (4 of 7 treatments, ARDs = 27.3% to 44.1%, ps < 0.0001), new pain diagnosis (5 of 7, ARDs = 3.2% to 27.4%, ps < 0.001), and severe impairment (4 of 7, ARDs = 2.6% to 6.5%, ps < 0.0001). A new diagnosis had the strongest association with non-opioid pain analgesics and physical medicine (ARD = 27.0% and 27.4%, p < 0.0001). Latinx patients were less likely to receive opioid analgesics and mental health/substance use medications and counseling (ARDs = − 3.3% to 7.5%, ps < 0.0001).Conclusion: Screening and assessment with patient-reported tools may influence pain care. Care for Latinx patients differed from non-Latinx white patients.Keywords: PEG, chronic pain, primary care, patient-reported outcome measures, federally qualified health center, equity

We revise the definition of graph operations in [WDK2018] and adapt correspondingly the construction of graph term algebras. As a first contribution to a prospective research field Universal Graph Algebra, we generalize some basic concepts and results from algebras to graph algebras. To tackle this generalization task, we revise and reformulate traditional set-theoretic definitions, constructions and proofs in Universal Algebra by means of more category-theoretic concepts and constructions. Especially, we generalize the concept generated subalgebra and prove that all monomorphic homomorphisms between graph algebras are regular. Derived graph operations are the other main topic. After an in depth analysis of terms as representations of derived operations in traditional algebras, we identify three basic mechanisms to construct new graph operations out of given ones: parallel composition, instantiation, and sequential composition. As a counterpart of terms, we introduce graph operation expressions with a structure as close as possible to the structure of terms. We show that the three mechanisms allow us to construct for any graph operation expression a corresponding derived graph operation in any graph algebra.

Bacterial restriction-modification (R-M) systems are a first-line immune defense against foreign DNA from viruses and other bacteria. While R-M systems are critical in maintaining genome integrity, R-M nucleases unfortunately present significant barriers to targeted genetic modification. Bacteria of the genus Fusobacterium are oral, Gram-negative, anaerobic, opportunistic pathogens that are implicated in the progression and severity of multiple cancers and tissue infections, yet our understanding of their direct roles in disease have been severely hindered by their genetic recalcitrance. Here, we demonstrate a path to overcome these barriers in Fusobacterium by using native DNA methylation as a host mimicry strategy to bypass R-M system cleavage of transformed plasmid DNA. We report the identification, characterization, and successful use of Fusobacterium nucleatum type II and III DNA methyltransferase (MTase) enzymes to produce a multifold increase in gene knockout efficiency in the strain Fusobacterium nucleatum subsp. nucleatum 23726, as well as the first system for efficient gene knockouts and complementations in F. nucleatum subsp. nucleatum 25586. We show plasmid protection can be accomplished in vitro with purified enzymes, as well as in vivo in an Escherichia coli host that constitutively expresses F. nucleatum subsp. nucleatum MTase enzymes. In summary, this proof-of-concept study characterizes specific MTases that are critical for bypassing R-M systems and has enhanced our understanding of enzyme combinations that could be used to genetically modify clinical isolates of Fusobacterium that have thus far been inaccessible to molecular characterization. IMPORTANCE Fusobacterium nucleatum is an oral opportunistic pathogen associated with diseases that include cancer and preterm birth. Our understanding of how this bacterium modulates human disease has been hindered by a lack of genetic systems. Here, we show that F. nucleatum DNA methyltransferase-modified plasmid DNA overcomes the transformation barrier and has allowed the development of a genetic system in a previously inaccessible strain. We present a strategy that could potentially be expanded to enable the genetic modification of highly recalcitrant strains, thereby fostering investigational studies to uncover novel host-pathogen interactions in Fusobacterium.

Background: Anomalous aortic origin of the left coronary artery (AAOLCA) confers a rare, but significant, risk of sudden cardiac death in children. Surgery is recommended for interarterial AAOLCA, and other subtypes considered benign. We aimed to determine the clinical characteristics and outcomes of 3 AAOLCA subtypes. Methods: All patients with AAOLCA 8 years old or younger if concerning symptoms. Surgery was recommended for group 1 and in select cases in group 2 and group 3. Results: We enrolled 56 patients (64% males) with AAOLCA (group 1, 27; group 2, 20; group 3, 9) at median age of 12 years (interquartile range, 6–15). Intramural course was common in group 1 (93%) compared with group 3 (56%) and group 2 (10%). Seven (13%) presented with aborted sudden cardiac death (group 1, 6/27; group 3, 1/9); 1 (group 3) with cardiogenic shock. Fourteen/42 (33%) had inducible ischemia on provocative testing (group 1, 32%; group 2, 38%; group 3, 29%). Surgery was recommended in 31/56 (56%) patients (group 1, 93%; group 2, 10%; and group 3, 44%). Surgery was performed in 25 patients at a median age 12 (interquartile range, 7–15) years; all have been asymptomatic and free from exercise restrictions at median follow-up of 4 (interquartile range, 1.4–6.3) years. Conclusions: Inducible ischemia was noted in all 3 AAOLCA subtypes while most aborted sudden cardiac deaths occurred in interarterial AAOLCA (group 1). Aborted sudden cardiac death and cardiogenic shock may occur in AAOLCA with left/nonjuxtacommissural origin and intramural course, thus also deemed high-risk. A systematic approach is essential to adequately risk stratify this population.

Background: Anomalous aortic origin of a right coronary artery may cause myocardial ischemia and sudden death in the young. Data on myocardial ischemia or longitudinal outcomes are sparse in pediatric anomalous aortic origin of a right coronary artery population. Methods: Patients 7 years or younger with concern for ischemia. High-risk features included intramural length, slit-like/hypoplastic ostium, exertional symptoms, or evidence of ischemia. Results: A total of 220 patients (60% males) were enrolled December 2012 to April 2020 at a median age 11.4 years (interquartile range, 6.1–14.5), including 168 (76%) with no/nonexertional symptoms (group 1) and 52 (24%) with exertional chest pain/syncope (group 2). Computerized tomography angiography was available in 189/220 (86%), exercise stress test in 164/220 (75%), and sPI in 169/220 (77%). Exercise stress test was positive in 2/164 (1.2%) patients in group 1, both had positive sPI. Inducible ischemia (sPI) was detected in 11/120 (9%) in group 1 and 9/49 (18%) in group 2 ( P =0.09). Intramural length was similar in patients with/without ischemia (5 [interquartile range, 4–7] versus 5 [interquartile range, 4–7] mm; P =0.65). Surgery was recommended in 56/220 (26%) patients with high-risk features. In 52 surgical patients (38 unroofing, 14 reimplantation), all subjects were alive and have returned to exercise at last median follow-up of 4.6 (interquartile range, 2.3–6.5) years. Conclusions: Anomalous aortic origin of a right coronary artery patients can present with inducible ischemia on sPI despite symptoms or intramural length. Exercise stress test is a poor predictor of ischemia and caution should be given to determine low-risk based solely on this assessment. All patients are alive at medium-term follow-up.

This study presents a new approach as an integration of deep neural networks (DNN) into differential evolution (DE) to give the so-called DNN-DE for frequency optimization of laminated functionally graded carbon nanotube (FG-CNT)-reinforced composite quadrilateral plates under free vibration. In the presented approach, the DNN is applied to predict the objective and constraints during the optimization process instead of using the time-consuming finite element analysis (FEA) procedures while the DE is used as an optimizer for solving the optimization problem. Several numerical examples are performed to illustrate the performance of the proposed method. Optimal results obtained by the DNN-DE are compared with those achieved by other methods in order to show the reliability and effectiveness of the proposed methodology. Additionally, the influence of various parameters such as the boundary condition, the carbon nanotube (CNT) volume fraction, the CNT distribution on the optimal results is also investigated. The obtained results indicate that the proposed DNN-DE is an effective and promising method in solving optimization problems of engineering structures.

The goal of this study was to determine minimum selection concentrations of various antibiotics using four manure-originated multi-drug resistant plasmids in a surrogateEscherichia colihost. These plasmids carried genes conferring resistance phenotypes to several antibiotic classes including β-lactams, lincosamides, phenicols, macrolides, sulfonamides and tetracyclines. The minimum selection concentrations of antibiotics tested in nutrient-rich medium were determined: 14.1-28.2 mg/L for penicillin G, 0.1 mg/L for oxytetracycline, 0.45 mg/L for chlortetracycline, 2 mg/L for lincomycin, 1 mg/L for florfenicol, 1.3-4 mg/L for azithromycin, 0.13-0.25 mg/L for tetracycline, 0.004-0.01 mg/L for cefotaxime. Penicillin G, oxytetracycline, chlortetracycline, lincomycin and florfenicol had minimum selection concentrations in nutrient-defined medium slightly changed within 3.5-fold range compared to those in nutrient-rich medium. The minimum selection concentrations of antibiotics interfering folic acid synthesis in bacteria were also determined: 63 mg/L for sulfamethoxazole, 11.2 mg/L for sulfisoxazole and 0.06 mg/L for trimethoprim. Mixing two antibiotics changed minimum selection concentrations within 3.7-fold range compared to those in single antibiotic tests. Relatively high plasmid loss rates (> 90%) were observed when culturing plasmid-bearing strains in antibiotic-free nutrient-rich and nutrient-defined media. Overall results suggested that these plasmids can be maintained at concentrations environmentally relevant in waste water treatment plants, sewage, manure and manured soil although they are not stable in antibiotic-free environments.IMPORTANCEAntibiotic resistance crisis is a grave concern in healthcare systems around the world. To combat this crisis, we sought to find out how likely manure-originated multi-drug resistant plasmids are to be selected and maintained in different environment matrices. Our study showed that these plasmids conferring resistance to β-lactams, lincosamides, phenicols, macrolides, sulfonamides and tetracyclines can be selected at minimum selection concentrations which are lower than minimum inhibition concentrations of theE. colihost strain. Lincomycin, oxytetracycline, chlortetracycline, tetracycline, chloramphenicol, trimethoprim had minimum selection concentrations lower than the antibiotic concentrations in several environment matrices reported previously. Our findings suggest that despite the burden and the high rate of plasmid loss, these plasmids can still be selected, maintained and circulated well in some polluted environments.