Spontaneous Coronary Artery Dissection in a 19-Year-Old Male Athlete.

We present a 19-year-old male athlete, without cardiovascular risk factors, with anterior ST-segment elevation myocardial infarction caused by left anterior descending artery spontaneous coronary artery dissection. Symptoms began during a swim practice, and patient endorsed using C4 Ripped (Cellucor), a preworkout supplement to enhance athletic performance. We hypothesize that this was the major contributor to presentation. The patient showed improvement after 4 days.

Correction: Referral for Cardiac Amyloidosis in Patients Who Underwent Transcatheter Aortic Valve Replacement: Results of the Quality Outcome Project.

[This corrects the article DOI: 10.7759/cureus.45024.].

Referral for Cardiac Amyloidosis in Patients Who Underwent Transcatheter Aortic Valve Replacement: Results of the Quality Outcome Project.

Background Transthyretin cardiac amyloidosis (ATTR) is an important comorbidity present in severe aortic stenosis (AS). The purpose of this study was to raise awareness of ATTR in patients who underwent transcatheter aortic valve replacement (TAVR) for severe AS among healthcare providers and patients. Methodology We reviewed 197 consecutive TAVR cases performed from 2019 to 2020. Adapting predefined high-risk features for ATTR based on prior literature, we contacted the patients to discuss our clinical suspicion of ATTR and offered a referral to a cardiac amyloid specialist. Results We identified 125 (69.4%) patients who had high-risk features of ATTR. Of the 105 patients contacted, 44 patients agreed to referral, 46 patients were not able to be contacted after several attempts, and 15 patients declined referral. Of the 44 patients who agreed to the referral, 20 patients completed the evaluation for cardiac amyloidosis, all of whom were negative for transthyretin and light-chain cardiac amyloidosis. Conclusions Our attempt to detect ATTR in prior TAVR patients was unsuccessful two to three years post-TAVR. We believe that early detection of cardiac amyloidosis close to the timing of TAVR is important and the most effective means.

Siderophore Synthetase DesD Catalyzes N-to-C Condensation in Desferrioxamine Biosynthesis.

Desferrioxamine siderophores are assembled by the nonribosomal-peptide-synthetase-independent siderophore (NIS) synthetase enzyme DesD via ATP-dependent iterative condensation of three N1-hydroxy-N1-succinyl-cadaverine (HSC) units. Current knowledge of NIS enzymology and the desferrioxamine biosynthetic pathway does not account for the existence of most known members of this natural product family, which differ in substitution patterns of the N- and C-termini. The directionality of desferrioxamine biosynthetic assembly, N-to-C versus C-to-N, is a longstanding knowledge gap that is limiting further progress in understanding the origins of natural products in this structural family. Here, we establish the directionality of desferrioxamine biosynthesis using a chemoenzymatic approach with stable isotope incorporation and dimeric substrates. We propose a mechanism where DesD catalyzes the N-to-C condensation of HSC units to establish a unifying biosynthetic paradigm for desferrioxamine natural products in Streptomyces.

An acyl-adenylate mimic reveals the structural basis for substrate recognition by the iterative siderophore synthetase DesD.

Siderophores are conditionally essential metabolites used by microbes for environmental iron sequestration. Most Streptomyces strains produce hydroxamate-based desferrioxamine (DFO) siderophores composed of repeating units of N1-hydroxy-cadaverine (or N1-hydroxy-putrescine) and succinate. The DFO biosynthetic operon, desABCD, is highly conserved in Streptomyces; however, expression of desABCD alone does not account for the vast structural diversity within this natural product class. Here, we report the in vitro reconstitution and biochemical characterization of four DesD orthologs from Streptomyces strains that produce unique DFO siderophores. Under in vitro conditions, all four DesD orthologs displayed similar saturation steady-state kinetics (Vmax = 0.9-2.5 µM⋅min-1) and produced the macrocyclic trimer DFOE as the favored product, suggesting a conserved role for DesD in the biosynthesis of DFO siderophores. We further synthesized a structural mimic of N1-hydroxy-N1-succinyl-cadaverine (HSC)-acyl-adenylate, the HSC-acyl sulfamoyl adenosine analog (HSC-AMS), and obtained crystal structures of DesD in the ATP-bound, AMP/PPi-bound, and HSC-AMS/Pi-bound forms. We found HSC-AMS inhibited DesD orthologs (IC50 values = 48-53 µM) leading to accumulation of linear trimeric DFOG and di-HSC at the expense of macrocyclic DFOE. Addition of exogenous PPi enhanced DesD inhibition by HSC-AMS, presumably via stabilization of the DesD-HSC-AMS complex, similar to the proposed mode of adenylate stabilization where PPi remains buried in the active site. In conclusion, our data suggest that acyl-AMS derivatives may have utility as chemical probes and bisubstrate inhibitors to reveal valuable mechanistic and structural insight for this unique family of adenylating enzymes.

Between a Rock and a Hard Place: Percutaneous Aspiration and Debulking for Tricuspid Valve Endocarditis.

Right-sided infective endocarditis (IE) constitutes about 10% of total IE cases. Of these, tricuspid endocarditis comprises about 90% of all right-sided IE cases with intravenous drug use (IVDU) as its strongest risk factor. In patients with larger vegetations (>20 mm) or with persistent bacteremia, surgical intervention is often the standard of care. With FDA approval in 2014 and limited cases with regards to its application in tricuspid endocarditis, AngioVac (AngioDynamics, Latham, NY) has been used as a less invasive, off-label, bridging agent for tricuspid IE treatment. We present a case of a 40-year-old man with a past medical history of IVDU who presented with tricuspid endocarditis. His blood cultures were positive for methicillin-susceptible Staphylococcus aureus bacteremia. A transthoracic echocardiogram showed a 2.7 x 1.1 cm vegetation of the tricuspid valve. The patient was thought to be a poor surgical candidate for multifactorial reasons including patient preference, hemodynamic instability, and a hospital course that was complicated by septic emboli and infectious glomerulonephritis. The patient was unable to clear blood cultures despite appropriate antibiotic therapy. He subsequently underwent an AngioVac procedure with removal of the vegetation from his tricuspid valve achieving adequate source control, clear blood cultures, and resolution of endocarditis. As this case illustrates, AngioVac should be considered an effective alternative to surgical intervention in tricuspid endocarditis. Further research and awareness of the utility of AngioVac in right-sided endocarditis are warranted and should be conducted.

Automated detection and segmentation of intracranial hemorrhage suspect hyperdensities in non-contrast-enhanced CT scans of acute stroke patients.

OBJECTIVES: Artif icial intelligence (AI)-based image analysis is increasingly applied in the acute stroke field. Its implementation for the detection and quantification of hemorrhage suspect hyperdensities in non-contrast-enhanced head CT (NCCT) scans may facilitate clinical decision-making and accelerate stroke management. METHODS: NCCTs of 160 patients with suspected acute stroke were analyzed regarding the presence or absence of acute intracranial hemorrhages (ICH) using a novel AI-based algorithm. Read was performed by two blinded neuroradiology residents (R1 and R2). Ground truth was established by an expert neuroradiologist. Specificity, sensitivity, and area under the curve were calculated for ICH and intraparenchymal hemorrhage (IPH) detection. IPH-volumes were segmented and quantified automatically by the algorithm and semi-automatically. Intraclass correlation coefficient (ICC) and Dice coefficient (DC) were calculated. RESULTS: In total, 79 of 160 patients showed acute ICH, while 47 had IPH. Sensitivity and specificity for ICH detection were 0.91 and 0.89 for the algorithm; 0.99 and 0.98 for R1; and 1.00 and 0.98 for R2. Sensitivity and specificity for IPH detection were 0.98 and 0.89 for the algorithm; 0.83 and 0.99 for R1; and 0.91 and 0.99 for R2. Interreader reliability for ICH and IPH detection showed strong agreements for the algorithm (0.80 and 0.84), R1 (0.96 and 0.84), and R2 (0.98 and 0.92), respectively. ICC indicated an excellent (0.98) agreement between the algorithm and the reference standard of the IPH-volumes. The mean DC was 0.82. CONCLUSION: The AI-based algorithm reliably assessed the presence or absence of acute ICHs in this dataset and quantified IPH volumes precisely. KEY POINTS: • Artificial intelligence (AI) is able to detect hyperdense volumes on brain CTs reliably. • Sensitivity and specificity are highest for the detection of intraparenchymal hemorrhages. • Interreader reliability for hemorrhage detection shows strong agreement for AI and human readers.

SARS-CoV-2 Spike Protein Impairs Endothelial Function via Downregulation of ACE2.

Coronavirus disease 2019 (COVID-19) includes the cardiovascular complications in addition to respiratory disease. SARS-CoV-2 infection impairs endothelial function and induces vascular inflammation, leading to endotheliitis. SARS-CoV-2 infection relies on the binding of Spike glycoprotein (S protein) to angiotensin converting enzyme 2 (ACE2) in the host cells. We show here that S protein alone can damage vascular endothelial cells (ECs) in vitro and in vivo, manifested by impaired mitochondrial function, decreased ACE2 expression and eNOS activity, and increased glycolysis. The underlying mechanism involves S protein downregulation of AMPK and upregulation of MDM2, causing ACE2 destabilization. Thus, the S protein-exerted vascular endothelial damage via ACE2 downregulation overrides the decreased virus infectivity.

SARS-CoV-2 Spike Protein Impairs Endothelial Function via Downregulation of ACE2

Coronavirus disease 2019 (COVID-19) includes the cardiovascular complications in addition to respiratory disease. SARS-CoV-2 infection impairs endothelial function and induces vascular inflammation, leading to endotheliitis. SARS-CoV-2 infection relies on the binding of Spike glycoprotein (S protein) to angiotensin converting enzyme 2 (ACE2) in the host cells. We show here that S protein alone can damage vascular endothelial cells (ECs) in vitro and in vivo, manifested by impaired mitochondrial function, decreased ACE2 expression and eNOS activity, and increased glycolysis. The underlying mechanism involves S protein downregulation of AMPK and upregulation of MDM2, causing ACE2 destabilization. Thus, the S protein-exerted vascular endothelial damage via ACE2 downregulation overrides the decreased virus infectivity.

Availability and performance of image-based, non-contact methods of monitoring heart rate, blood pressure, respiratory rate, and oxygen saturation: a systematic review.

OBJECTIVE: Over the last 15 years, developments in camera technology have coincided with increased availability and affordability. This has led to an increasing interest in using these technologies in healthcare settings. Image-based monitoring methods potentially allow multiple vital signs to be measured concurrently using a non-contact sensor. We have undertaken a systematic review of the current availability and performance of these monitoring methods. APPROACH: A multiple database search was conducted using MEDLINE, Embase, CINAHL, Cochrane Library, OpenGrey, IEEE Xplore Library and ACM Digital Library to July 2018. We included studies comparing image-based heart rate, respiratory rate, oxygen saturation and blood pressure monitoring methods against one or more validated reference device(s). Each included study was assessed using the modified GRRAS criteria for reporting bias. MAIN RESULTS: Of 30 279 identified studies, 161 were included in the final analysis. Twenty studies (20/161, 12%) were carried out on patients in clinical settings, while the remainder were conducted in academic settings using healthy volunteer populations. The 18-40 age group was best represented across the identified studies. One hundred and twenty studies (120/161, 75%) estimated heart rate, followed by 62 studies (62/161, 39%) estimating respiratory rate. Fewer studies focused on oxygen saturation (11/161, 7%) or blood pressure (6/161, 4%) estimation. Fifty-one heart rate studies (51/120, 43%) and 24 respiratory rate studies (24/62, 39%) used Bland-Altman analysis to report their results. Of the heart rate studies, 28 studies (28/51, 55%) showed agreement within industry standards of [Formula: see text]5 beats per minute. Only two studies achieved this within clinical settings. Of the respiratory rate studies, 13 studies (13/24, 54%) showed agreement within industry standards of [Formula: see text]3 breaths per minute, but only one study achieved this in a clinical setting. Statistical analysis was heterogeneous across studies with frequent inappropriate use of correlation. The majority of studies (99/161, 61%) monitored subjects for under 5 min. Three studies (3/161, 2%) monitored subjects for over 60 min, all of which were conducted in hospital settings. SIGNIFICANCE: Heart rate and respiratory rate monitoring using video images is currently possible and performs within clinically acceptable limits under experimental conditions. Camera-derived estimates were less accurate in the proportion of studies conducted in clinical settings. We would encourage thorough reporting of the population studied, details of clinically relevant aspects of methodology, and the use of appropriate statistical methods in future studies. Systematic review registration: PROSPERO CRD42016029167 Protocol: https://systematicreviewsjournal.biomedcentral.com/articles/10.1186/s13643-017-0615-3.

Environmental Toxin Acrolein Alters Levels of Endogenous Lipids, Including TRP Agonists: A Potential Mechanism for Headache Driven by TRPA1 Activation.

Exposure to airborne toxins can trigger headaches, but the mechanisms are not well understood. Some environmental toxins, such as acrolein, activate transient receptor potential ankyrin 1 (TRPA1), a receptor involved in pain sensation that is highly expressed in the trigeminovascular system. It has been shown in rat models that repeated exposure to acrolein induces trigeminovascular sensitization to both TRPA1 and TRP vanilloid 1 (TRPV1) agonists, a phenomenon linked to headache. In this study, we test the hypothesis that the sensitization of trigeminovascular responses in rats after acrolein exposure via inhalation is associated with changes in levels of endogenous lipids, including TRPV1 agonists, in the trigeminal ganglia, trigeminal nucleus, and cerebellum. Lipidomics analysis of 80 lipids was performed on each tissue after acute acrolein, chronic acrolein, or room air control. Both acute and chronic acrolein exposure drove widespread alterations in lipid levels. After chronic acrolein exposure, levels of all 6 N-acyl ethanolamines in the screening library, including the endogenous cannabinoid and TRPV1 agonist, N-arachidonoyl ethanolamine, were elevated in trigeminal tissue and in the cerebellum. This increase in TRPV1 ligands by acrolein exposure may indicate further downstream signaling, in that we also show here that a combination of these TRPV1 endogenous agonists increases the potency of the individual ligands in TRPV1-HEK cells. In addition to these TRPV1 agonists, 3 TRPV3 antagonists, 4 TRPV4 agonists, and 25 orphan lipids were up and down regulated after acrolein exposure. These data support the hypothesis that lipid signaling may represent a mechanism by which repeated exposure to the TRPA1 agonist and environmental toxin, acrolein, drives trigeminovascular sensitization.

WITHDRAWN: Can depth of invasion of pT1 carcinoma of the oral tongue predict occult metastases in the neck? A retrospective study.

This article has been withdrawn at the request of the author(s) and/or editor. The Publisher apologizes for any inconvenience this may cause. The full Elsevier Policy on Article Withdrawal can be found at http://www.elsevier.com/locate/withdrawalpolicy.

Detection of the Bacterial Potato Pathogens Pectobacterium and Dickeya spp. Using Conventional and Real-Time PCR.

Blackleg and soft rot of potato, caused by Pectobacterium and Dickeya spp., are major production constraints in many potato-growing regions of the world. Despite advances in our understanding of the causative organisms, disease epidemiology, and control, blackleg remains the principal cause of down-grading and rejection of potato seed in classification schemes across Northern Europe and many other parts of the world. Although symptom recognition is relatively straightforward and is applied universally in seed classification schemes, attributing disease to a specific organism is problematic and can only be achieved through the use of diagnostics. Similarly as disease spread is largely through the movement of asymptomatically infected seed tubers and, possibly in the case of Dickeya spp., irrigation waters, accurate and sensitive diagnostics are a prerequisite for detection. This chapter describes the diagnostic pathway that can be applied to identify the principal potato pathogens within the genera Pectobacterium and Dickeya.

Diagnosis of Phytoplasmas by Real-Time PCR Using Locked Nucleic Acid (LNA) Probes.

Phytoplasma infections are regularly reported worldwide, and concerns about their threats on agricultural production, especially in relation to global climate change, are increasing. Sensitive and reliable detection methods are important to ensure that propagation material is free of phytoplasma infection and for epidemiological studies that may provide information to limit the extent of phytoplasma diseases and to prevent large-scale crop losses. The detection method described here uses LNA chemistry in real-time PCR. It has been developed and validated for use on potatoes, and its sensitivity and specificity make it suitable for use in postentry potato quarantine and initiation of potato nuclear stocks to ensure that material is phytoplasma-free.

Dickeya solani sp. nov., a pectinolytic plant-pathogenic bacterium isolated from potato (Solanum tuberosum).

Pectinolytic bacteria have been recently isolated from diseased potato plants exhibiting blackleg and slow wilt symptoms found in a number of European countries and Israel. These Gram-reaction-negative, motile, rods were identified as belonging to the genus Dickeya, previously the Pectobacterium chrysanthemi complex (Erwinia chrysanthemi), on the basis of production of a PCR product with the pelADE primers, 16S rRNA gene sequence analysis, fatty acid methyl esterase analysis, the production of phosphatases and the ability to produce indole and acids from α-methylglucoside. Differential physiological assays used previously to differentiate between strains of E. chrysanthemi, showed that these isolates belonged to biovar 3. Eight of the isolates, seven from potato and one from hyacinth, were analysed together with 21 reference strains representing all currently recognized taxa within the genus Dickeya. The novel isolates formed a distinct genetic clade in multilocus sequence analysis (MLSA) using concatenated sequences of the intergenic spacer (IGS), as well as dnaX, recA, dnaN, fusA, gapA, purA, rplB, rpoS and gyrA. Characterization by whole-cell MALDI-TOF mass spectrometry, pulsed field gel electrophoresis after digestion of whole-genome DNA with rare-cutting restriction enzymes, average nucleotide identity analysis and DNA-DNA hybridization studies, showed that although related to Dickeya dadantii, these isolates represent a novel species within the genus Dickeya, for which the name Dickeya solani sp. nov. (type strain IPO 2222(T) = LMG25993(T) = NCPPB4479(T)) is proposed.

Draft genome sequences of 17 isolates of the plant pathogenic bacterium dickeya.

Dickeya (formerly Erwinia chrysanthemi) species cause diseases on a wide range of crops and ornamental plants worldwide. Here we present the draft sequences of 17 Dickeya isolates spanning four Dickeya species, including five isolates that are currently unassigned to a species.

NPY Y1 receptors differentially modulate GABAA and NMDA receptors via divergent signal-transduction pathways to reduce excitability of amygdala neurons.

Neuropeptide Y (NPY) administration into the basolateral amygdala (BLA) decreases anxiety-like behavior, mediated in part through the Y1 receptor (Y1R) isoform. Activation of Y1Rs results in G-protein-mediated reduction of cAMP levels, which results in reduced excitability of amygdala projection neurons. Understanding the mechanisms linking decreased cAMP levels to reduced excitability in amygdala neurons is important for identifying novel anxiolytic targets. We studied the intracellular mechanisms of activation of Y1Rs on synaptic transmission in the BLA. Activating Y1Rs by [Leu(31),Pro(34)]-NPY (L-P NPY) reduced the amplitude of evoked NMDA-mediated excitatory postsynaptic currents (eEPSCs), without affecting AMPA-mediated eEPSCs, but conversely increased the amplitude of GABAA-mediated evoked inhibitory postsynaptic currents (eIPSCs). Both effects were abolished by the Y1R antagonist, PD160170. Intracellular GDP-ß-S, or pre-treatment with either forskolin or 8Br-cAMP, eliminated the effects of L-P NPY on both NMDA- and GABAA-mediated currents. Thus, both the NMDA and GABAA effects of Y1R activation in the BLA are G-protein-mediated and cAMP-dependent. Pipette inclusion of protein kinase A (PKA) catalytic subunit blocked the effect of L-P NPY on GABAA-mediated eIPSCs, but not on NMDA-mediated eEPSCs. Conversely, activating the exchange protein activated by cAMP (Epac) with 8CPT-2Me-cAMP blocked the effect of L-P NPY on NMDA-mediated eEPSCs, but not on GABAA-mediated eIPSCs. Thus, NPY regulates amygdala excitability via two signal-transduction events, with reduced PKA activity enhancing GABAA-mediated eIPSCs and Epac deactivation reducing NMDA-mediated eEPSCs. This multipathway regulation of NMDA- and GABAA-mediated currents may be important for NPY plasticity and stress resilience in the amygdala.

Genotype-phenotype correlation in 153 adult patients with congenital adrenal hyperplasia due to 21-hydroxylase deficiency: analysis of the United Kingdom Congenital adrenal Hyperplasia Adult Study Executive (CaHASE) cohort.

CONTEXT: In congenital adrenal hyperplasia (CAH) due to 21-hydroxylase deficiency, a strong genotype-phenotype correlation exists in childhood. However, similar data in adults are lacking. OBJECTIVE: The objective of the study was to test whether the severity of disease-causing CYP21A2 mutations influences the treatment and health status in adults with CAH. RESEARCH DESIGN AND METHODS: We analyzed the genotype in correlation with treatment and health status in 153 adults with CAH from the United Kingdom Congenital adrenal Hyperplasia Adult Study Executive cohort. RESULTS: CYP21A2 mutations were distributed similarly to previously reported case series. In 7 patients a mutation was identified on only 1 allele. Novel mutations were detected on 1.7% of alleles (5 of 306). Rare mutations were found on 2.3% of alleles (7 of 306). For further analysis, patients were categorized into CYP21A2 mutation groups according to predicted residual enzyme function: null (n = 34), A (n = 42), B (n = 36), C (n = 34), and D (n = 7). Daily glucocorticoid dose was highest in group null and lowest in group C. Fludrocortisone was used more frequently in patients with more severe genotypes. Except for lower female height in group B, no statistically significant associations between genotype and clinical parameters were found. Androgens, blood pressure, lipids, blood glucose, and homeostasis model assessment of insulin resistance were not different between groups. Subjective health status was similarly impaired across groups. CONCLUSIONS: In adults with classic CAH and women with nonclassic CAH, there was a weak association between genotype and treatment, but health outcomes were not associated with genotype. The underrepresentation of males with nonclassic CAH may reflect that milder genotypes result in a milder condition that is neither diagnosed nor followed up in adulthood. Overall, our results suggest that the impaired health status of adults with CAH coming to medical attention is acquired rather than genetically determined and therefore could potentially be improved through modification of treatment.

Variation in the diet and feeding morphology of polyphenic Lepomis macrochirus.

Bluegill Lepomis macrochirus showed variation in their diet and trophic morphology based on habitat. Pelagic L. macrochirus feed almost exclusively on cladocerans; littoral L. macrochirus feed on a variety of benthic invertebrates, molluscs, cladocerans and insects. Fish from the littoral habitat had wider pharyngeal jaws, which probably allowed them to crush gastropods and process benthic invertebrates.

Relationship between endocardial activation sequences defined by high-density mapping to early septal contraction (septal flash) in patients with left bundle branch block undergoing cardiac resynchronization therapy.

AIMS: Early inward motion and thickening/thinning of the ventricular septum associated with left bundle branch block is known as the septal flash (SF). Correction of SF corresponds to response to cardiac resynchronization therapy (CRT). We hypothesized that SF was associated with a specific left ventricular (LV) activation pattern predicting a favourable response to CRT. We sought to characterize the spatio-temporal relationship between electrical and mechanical events by directly comparing non-contact mapping (NCM), acute haemodynamics, and echocardiography. METHODS AND RESULTS: Thirteen patients (63 ± 10 years, 10 men) with severe heart failure (ejection fraction 22.8 ± 5.8%) awaiting CRT underwent echocardiography and NCM pre-implant. Presence and extent of SF defined visually and with M-mode was fused with NCM bull's eye plots of endocardial activation patterns. LV-dP/dt(max) was measured during different pacing modes. Five patients had a large SF, four small SF, and four no SF. Large SF patients had areas of conduction block in non-infarcted regions, whereas those with small or no SF did not. Patients with large SF had greater acute response to LV and biventricular (BIV) pacing vs. those with small/no SF (% increase dP/dt 28 ± 14 vs. 11 ± 19% for LV pacing and 42 ± 28 vs. 22 ± 21% for BIV pacing) (P < 0.05). This translated into a more favourable chronic response to CRT. The lines of conduction block disappeared with LV/BIV pacing while remaining with right ventricle pacing. CONCLUSION: A strong association exists between electrical activation and mechanical deformation of the septum. Correction of both mechanical synchrony and the functional conduction block by CRT may explain the favourable response in patients with SF.