Epicardial Space: Comprehensive Anatomy and Spectrum of Disease.

The epicardial space (ES) is the anatomic region located between the myocardium and the pericardium. This space includes the visceral pericardium and the epicardial fat that contains the epicardial coronary arteries, cardiac veins, lymphatic channels, and nerves. The epicardial fat represents the main component of the ES. This fat deposit has been a focus of research in recent years owing to its properties and relationship with coronary gossypiboma plaque and atrial fibrillation. Although this region is sometimes forgotten, a broad spectrum of lesions can be found in the ES and can be divided into neoplastic and nonneoplastic categories. Epicardial neoplastic lesions include lipoma, paraganglioma, metastases, angiosarcoma, and lymphoma. Epicardial nonneoplastic lesions encompass inflammatory infiltrative disorders, such as immunoglobulin G4-related disease and Erdheim-Chester disease, along with hydatidosis, abscesses, coronary abnormalities, pseudoaneurysms, hematoma, lipomatosis, and gossypiboma. Initial imaging of epicardial lesions may be performed with echocardiography, but CT and cardiac MRI are the best imaging modalities to help characterize epicardial lesions. Due to the nonspecific onset of signs and symptoms, the clinical history of a patient can play a crucial role in the diagnosis. A history of malignancy, multisystem diseases, prior trauma, myocardial infarction, or cardiac surgery can help narrow the differential diagnosis. The diagnostic approach to epicardial lesions should be made on the basis of the specific location, characteristic imaging features, and clinical background. ©RSNA, 2024 Test Your Knowledge questions for this article are available in the supplemental material.

Plant-Origin Components: New Players to Combat Antibiotic Resistance in Klebsiella pneumoniae.

Klebsiella pneumoniae (Kpn) is an opportunistic pathogen that causes intrahospital complications such as pneumonia, liver abscesses, soft tissue infections, urinary infections, bacteraemia, and, in some cases, death. Since this bacterium has a higher frequency than other Gram-negative pathogens, it has become an important pathogen to the health sector. The adaptative genome of Kpn likely facilitates increased survival of the pathogen in diverse situations. Therefore, several studies have been focused on developing new molecules, synergistic formulations, and biomaterials that make it possible to combat and control infections with and dispersion of this pathogen. Note that the uncontrolled antibiotic administration that occurred during the pandemic led to the emergence of new multidrug-resistant strains, and scientists were challenged to overcome them. This review aims to compile the latest information on Kpn that generates intrahospital infections, specifically their pathogenicity-associated factors. Furthermore, it explains the natural-product-based treatments (extracts and essential oils) developed for Kpn infection and dispersion control.

Impact of corpus callosum integrity on functional interhemispheric connectivity and cognition in healthy subjects.

To examine the corpus callosum's (CC) integrity in terms of fractional anisotropy (FA) and how it affects resting-state hemispheric connectivity (rs-IHC) and cognitive function in healthy individuals. Sixty-eight healthy individuals were recruited for the study. The global FA (gFA) and FA values of each CC tract (forceps minor, body, tapetum, and forceps major) were evaluated using diffusion-weighted imaging (DWI) sequences. The homotopic functional connectivity technique was used to quantify the effects of FA in the CC tracts on bilateral functional connectivity, including the confounding effect of gFA. Brain regions with higher or lower rs-IHC were identified using the threshold-free cluster enhancement family-wise error-corrected p-value of 0.05. The null hypothesis was rejected if the p-value was ≤ 0.05 for the nonparametric partial correlation technique. Several clusters of increased rs-IHC were identified in relation to the FA of individual CC tracts, each with a unique topographic distribution and extension. Only forceps minor FA values correlated with cognitive scores. The integrity of CC influences rs-IHC differently in healthy subjects. Specifically, forceps minor anisotropy impacts rs-IHC and cognition more than other CC tracts do.

Frequency of respiratory virus-associated infection among children and adolescents from a tertiary-care hospital in Mexico City.

Acute respiratory infections (ARIs) are a major cause of morbidity and mortality among children. The causative pathogens show geographic and seasonal variations. We retrospectively evaluated the frequency and seasonality of respiratory pathogens in children and adolescents (age: 0-19 years) with ARIs treated between January 1, 2021, and March 31, 2022, at a single center in Mexico. Out of 2400 patients, 1,603 were diagnosed with SARS-CoV-2 infection and 797 were diagnosed with other common respiratory pathogens (CRPs). Of the 797 patients, 632 were infected with one CRP and 165 with > 2 CRPs. Deaths occurred only in SARS-CoV-2-infected patients. Rhinovirus/Enterovirus, respiratory syncytial virus B, and parainfluenza virus 3 were the most prevalent in cases with single and multiple infections. CRP showed a high frequency between autumn and winter of 2021, with higher incidence of hospitalization compared to COVID-19. The main comorbidities were immunosuppression, cardiovascular disease (CD), and asthma. The frequency of CRPs showed a downward trend throughout the first half of 2021. CRPs increased in single- and co-infection cases between the fourth and fifth waves of COVID-19, probably due to decreased nonpharmaceutical interventions and changes in diagnostic tests. Age, cyanosis (symptom), and immunosuppression (comorbidity) were found to differentiate between SARS-CoV-2 infection and CRP infection.

Long-term respiratory consequences of COVID-19 related pneumonia: a cohort study.

BACKGROUND: Our aims were to describe respiratory sequelae up to 12 months after discharge in COVID-19 patients with severe pneumonia requiring non-invasive respiratory support therapies. METHODS: This study was undertaken at University Hospital Doctor Josep Trueta (Girona, Spain) between March 2020 and June 2020. Three months after discharge, we evaluated their dyspnoea and performed Saint George's respiratory questionnaire, pulmonary function tests, blood test, 6-min walking test, and a high-resolution CT (HRCT). At the six and 12-month follow-up, we repeated all tests except for pulmonary function, 6-min walking test, and HRCT, which were performed only if abnormal findings had been previously detected. RESULTS: Out of the 94 patients recruited, 73% were male, the median age was 62.9 years old, and most were non-smokers (58%). When comparing data three and 12 months after discharge, the percentage of patients presenting dyspnoea ≥ 2 decreased (19% vs 7%), the quality-of-life total score improved (22.8% vs 18.9%; p = 0.019), there were less abnormal results in the pulmonary function tests (47% vs 23%), the 6-min walking test distance was enhanced (368.3 m vs 390.7 m, p = 0.020), ground glass opacities findings waned (51.6% vs 11.5%), and traction bronchiectasis increased (5.6% vs 15.9%). Only age showed significant differences between patients with and without pulmonary fibrotic-like changes. CONCLUSION: Most patients improved their clinical condition, pulmonary function, exercise capacity and quality of life one year after discharge. Nonetheless, pulmonary fibrotic-like changes were observed during the follow-ups.

Immunized mice naturally process in silico-derived peptides from the nucleocapsid of SARS-CoV-2.

BACKGROUND: The nucleocapsid (N) protein of severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) is an excellent immunogen that promotes the production of high-titer antibodies. N protein-derived peptides identified using a bioinformatics approach can potentially be used to develop a new generation of vaccines or diagnostic methods for detecting SARS-CoV-2 and its variants. However, further studies must demonstrate their capacity to be naturally processed by the immune system. OBJECTIVE: We aimed to examine the in vivo processing and recognition of in silico-identified peptides using the serum of immunized animals with the complete protein. METHODS: Recombinant N (Nrec) protein was subcutaneously administered to six Balb/c mice. Enzyme-linked immunosorbent assay (ELISA), western blotting, dot blotting, and immunoprecipitation were performed to evaluate the recognition of the complete protein and in silico-derived peptides. RESULTS: The serum of immunized mice recognized ~ 62.5 ng/µL of Nrec with high specificity to linear and conformational epitopes. Dot blot analysis showed that peptides Npep2 and Npep3 were the most reactive. CONCLUSION: Our data confirm the high immunogenicity of the SARS-CoV-2 N protein and provide evidence on the antigenicity of two peptides located in the N-arm/RNA-binding domain (Npep2) and oligomerization domain/C-tail (Npep3), considered the biologically active site of the N protein.

Synergy of Plant Essential Oils in Antibiotic Therapy to Combat Klebsiella pneumoniae Infections.

Increased antibiotic resistance presents a health problem worldwide. The World Health Organization published a list of pathogens considered a priority for designing new treatments. Klebsiella pneumoniae (Kp) is a top-priority microorganism, highlighting the strains that produce carbapenemases. Developing new efficient therapies or complementing existing treatments is a priority, and essential oils (EOs) provide an alternative. EOs could act as antibiotic adjuvants and enhance antibiotic activity. Employing standard methodologies, the antibacterial activity of the EOs and their synergic effect with antibiotics were detected. A string test was used to identify the impact of the EOs over the hypermucoviscosity phenotype presented by Kp strains, and Gas Chromatography-Mass Spectrometry analysis identified EOs and the composition of EOs. The potential of EOs for designing synergistic therapies with antibiotics to combat the infection of KPC diseases was demonstrated. In addition, the alteration of the hypermucoviscosity phenotype was shown as the principal mechanism of a synergic action between EOs and antibiotics. The differential composition of the EOs lets us identify some molecules that will be analyzed. Synergic activity of EOs and antibiotics can provide a solid platform for combating multiresistant pathogens that represent a severe health sector problem, such as Kp infections.

Seroprevalence of IgG and Subclasses against the Nucleocapsid of SARS-CoV-2 in Health Workers.

BACKGROUND: The nucleocapsid protein of SARS-CoV-2 participates in viral replication, transcription, and assembly. Antibodies against this protein have been proposed for the epidemiological analysis of the seroprevalence of COVID-19 associated with natural infection by SARS-CoV-2. Health workers were one of the most exposed populations, and some had an asymptomatic form of the disease, so detecting IgG antibodies and subclasses against the N protein can help to reclassify their epidemiological status and obtain information about the effector mechanisms associated with viral elimination. METHODS: In this study, we analyzed 253 serum samples collected in 2021 and derived from health workers, and evaluated the presence of total IgG and subclasses against the N protein of SARS-CoV-2 by indirect ELISA. RESULTS: From the analyzed samples, 42.69% were positive to anti-N IgG antibodies. A correlation between COVID-19 asymptomatic infection and IgG antibodies was observed (p = 0.006). The detected subclasses were: IgG1 (82.4%), IgG2 (75.9%), IgG3 (42.6%), and IgG4 (72.6%). CONCLUSIONS: This work provides evidence about the high seroprevalence of total IgG and subclasses of anti-N and their relations with the asymptomatic infection of SARS-CoV-2 and related symptoms.

Detection of IgA and IgG Antibodies against the Structural Proteins of SARS-CoV-2 in Breast Milk and Serum Samples Derived from Breastfeeding Mothers.

Background: COVID-19 vaccination or natural infection is associated with the development of immunity. The search of IgA and IgG antibodies against all the structural proteins (spike, nucleocapsid, membrane, and envelope) of SARS-CoV-2 in breastfeeding mothers is associated with immunity that can help the newborn avoid development of the infection. Methods: In this study, we analyzed 30 breastfeeding women that provided samples of breast milk and serum and evaluated the presence of IgA, total IgG, and subclasses against the structural proteins of SARS-CoV-2. Results: We reported a high seroprevalence to IgA (76.67-100%) and negativity to IgG against all analyzed proteins in breast milk. Seroprevalence in serum samples was around 10-36.67% to IgA and 23.3-60% to IgG. Finally, we detected the presence of the subclasses IgG1, IgG2, and IgG4 against all the structural proteins of SARS-CoV-2. Conclusions: This work provides evidence of the presence of IgA and IgG antibodies against the four structural proteins of SARS-CoV-2 in breast milk and serum samples derived from breastfeeding women, which can confer immunity to the newborn.

Plasma acylcarnitines and gut-derived aromatic amino acids as sex-specific hub metabolites of the human aging metabolome.

Aging biology entails a cell/tissue deregulated metabolism that affects all levels of biological organization. Therefore, the application of "omic" techniques that are closer to phenotype, such as metabolomics, to the study of the aging process should be a turning point in the definition of cellular processes involved. The main objective of the present study was to describe the changes in plasma metabolome associated with biological aging and the role of sex in the metabolic regulation during aging. A high-throughput untargeted metabolomic analysis was applied in plasma samples to detect hub metabolites and biomarkers of aging incorporating a sex/gender perspective. A cohort of 1030 healthy human adults (45.9% females, and 54.1% males) from 50 to 98 years of age was used. Results were validated using two independent cohorts (1: n = 146, 53% females, 30-100 years old; 2: n = 68, 70% females, 19-107 years old). Metabolites related to lipid and aromatic amino acid (AAA) metabolisms arose as the main metabolic pathways affected by age, with a high influence of sex. Globally, we describe changes in bioenergetic pathways that point to a decrease in mitochondrial ß-oxidation and an accumulation of unsaturated fatty acids and acylcarnitines that could be responsible for the increment of oxidative damage and inflammation characteristic of this physiological process. Furthermore, we describe for the first time the importance of gut-derived AAA catabolites in the aging process describing novel biomarkers that could contribute to better understand this physiological process but also age-related diseases.

Clinical Characteristics of Coronavirus Disease (COVID-19) in Mexican Children and Adolescents.

BACKGROUND: We analyzed the demographic, clinical, and diagnostic data of children and adolescents in Mexico, from the first case of coronavirus disease (COVID-19) to 28 February 2022. METHODS: Using the open databases of the Ministry of Health and a tertiary pediatric hospital, we obtained demographic and clinical data from the beginning of the COVID-19 pandemic until 28 February 2022. In addition, quantitative reverse-transcription polymerase chain reaction outputs were used to determine the viral load, and structural protein-based serology was performed to evaluate IgG antibody levels. RESULTS: Of the total 437,832 children and adolescents with COVID-19, 1187 died. Of these patients, 1349 were admitted to the Hospital Infantil de Mexico Federico Gómez, and 11 died. Obesity, asthma, and immunosuppression were the main comorbidities, and fever, cough, and headache were the main symptoms. In this population, many patients have a low viral load and IgG antibody levels. CONCLUSION: During the first 2 years of the COVID-19 pandemic in Mexico, children and adolescents had low incidence and mortality. They are a heterogeneous population, but many patients had comorbidities such as obesity, asthma, and immunosuppression; symptoms such as fever, cough, and headache; and low viral load and IgG antibodies.

Utility of in silico-identified-peptides in spike-S1 domain and nucleocapsid of SARS-CoV-2 for antibody detection in COVID-19 patients and antibody production.

SARS-CoV-2 contains four structural proteins, two of which, the spike and nucleocapsid, are commonly used for the standardization of novel methods for antibody detection; however, some limitations in their use have been observed due to the homology of this virus with other phylogenetically-related viruses. We performed in silico analysis to search for novel immunogenic and antigenic peptides. A total of twenty-five peptides were preliminarily selected, located in the 3D structure of both proteins. Finally, eight peptides were selected: one located in the N protein and seven in the S1 domain of the spike protein. Additionally, the localization of selected peptides in 2D structures and possible changes in the sequences of these peptides in SARS-CoV-2 variants of concern were analyzed. All peptides were synthetized in MAP8 format, and recombinant S (trimer and RBD) and N proteins were used as antigens to search for antibodies in serum samples derived from COVID-19 patients, and for antibody response in New Zealand rabbits. Results showed high recognition of the serum derived from COVID-19 patients to all selected peptides; however, only the RBD3 peptide induced antibody production. In conclusion, this work provides evidence for a new strategy in peptide selection and its use for antibody detection or antibody production in animals.

Asynchronous online learning as a key tool to adapt to new educational needs in radiology during the COVID-19 pandemic.

The risk of contagion and the lockdown caused by the COVID-19 pandemic forced a change in teaching methodologies in radiology. New knowledge about the disease that was being acquired on a daily basis needed to be rapidly spread worldwide, but the restrictions imposed made it difficult to share this information. This paper describes the methodology applied to design and launch a practice-based course on chest X-ray suggestive of COVID-19 right after the pandemic started, and aims to determine whether asynchronous online learning tools for radiology education are useful and acceptable to general practitioners and other medical personnel during a pandemic. The study was carried out from April to October 2020 and involved 2632 participants. Pre- and post-testing was used to assess the participants' gain of knowledge in the course content (paired t-tests and chi-squared tests of independence). A five-point Likert scale questionnaire inspired by the technological acceptance model (TAM) was provided to evaluate the e-learning methodology (ANOVA tests). The results from the pre- and post-tests showed that there were significant differences in the scores before and after completing the course (sample size = 2632, response rate = 56%, p<0.001). As for the questionnaire, all questions surpassed 4.5 out of 5, including those referring to perceived ease of use and perceived usefulness, and no significant differences were found between experienced and inexperienced participants (sample size = 2535, response rate = 53%, p=0.85). The analysis suggests that the applied methodology is flexible enough to adapt to complex situations, and is useful to improve knowledge on the subject of the course. Furthermore, a wide acceptance of the teaching methodology is confirmed for all technological profiles, pushing for and endorsing a more widespread use of online platforms in the domain of radiology continuing education.

Clinical features and severe acute respiratory syndrome-coronavirus-2 structural protein-based serology of Mexican children and adolescents with coronavirus disease 2019.

Severe acute respiratory syndrome (SARS)-coronavirus (CoV)-2 infection in children and adolescents primarily causes mild or asymptomatic coronavirus disease 2019 (COVID-19), and severe illness is mainly associated with comorbidities. However, the worldwide prevalence of COVID-19 in this population is only 1%-2%. In Mexico, the prevalence of COVID-19 in children has increased to 10%. As serology-based studies are scarce, we analyzed the clinical features and serological response (SARS-CoV-2 structural proteins) of children and adolescents who visited the Hospital Infantil de México Federico Gómez (October 2020-March 2021). The majority were 9-year-old children without comorbidities who were treated as outpatients and had mild-to-moderate illness. Children aged 6-10 years and adolescents aged 11-15 years had the maximum number of symptoms, including those with obesity. Nevertheless, children with comorbidities such as immunosuppression, leukemia, and obesity exhibited the lowest antibody response, whereas those aged 1-5 years with heart disease had the highest levels of antibodies. The SARS-CoV-2 spike receptor-binding domain-localized peptides and M and E proteins had the best antibody response. In conclusion, Mexican children and adolescents with COVID-19 represent a heterogeneous population, and comorbidities play an important role in the antibody response against SARS-CoV-2 infection.

False Lumen Flow Assessment by Magnetic Resonance Imaging and Long-Term Outcomes in Uncomplicated Aortic Dissection.

BACKGROUND: Despite the absence of clinical complications after an acute aortic dissection (AD) with persistent patent false lumen (FL), a high risk for clinical events may persist. OBJECTIVES: The aim of this study was to assess the natural evolution of noncomplicated AD and ascertain whether different FL flow patterns by magnetic resonance imaging (MRI) have independent prognostic value for AD-related events beyond established morphologic parameters. METHODS: One hundred thirty-one consecutive patients, 78 with surgically treated type A dissections and 53 with medically treated type B dissections, were followed up prospectively after acute AD with persistent patent FL in the descending aorta. Maximum aortic diameter, true lumen compression, entry tear, and partial FL thrombosis by computed tomography were assessed. Systolic antegrade true lumen and FL flow volumes and diastolic antegrade and retrograde flows were analyzed by MRI during the first year after AD. RESULTS: After a median follow-up period of 8.0 years (IQR: 4.6-10.9 years), 43 patients presented aorta-related events (25 died and 18 required endovascular treatment). FL systolic antegrade flow ≥30% with respect to total systolic antegrade flow and retrograde diastolic flow ≥80% with respect to total diastolic FL flow were predictors of aortic events. In multivariate analysis, aortic diameter >45 mm (HR: 2.91), type B dissection (HR: 2.44), and MRI flow pattern (HR: 16.87) were independent predictors of AD-related events. CONCLUSIONS: High systolic antegrade flow volume in the FL with significant diastolic retrograde flow assessed by MRI and aortic diameter >45 mm identify patients with higher risk for complications in whom more aggressive management would be indicated.

End-point RT-PCR based on a conservation landscape for SARS-COV-2 detection.

End-point RT-PCR is a suitable alternative diagnostic technique since it is cheaper than RT-qPCR tests and can be implemented on a massive scale in low- and middle-income countries. In this work, a bioinformatic approach to guide the design of PCR primers was developed, and an alternative diagnostic test based on end-point PCR was designed. End-point PCR primers were designed through conservation analysis based on kmer frequency in SARS-CoV-2 and human respiratory pathogen genomes. Highly conserved regions were identified for primer design, and the resulting PCR primers were used to amplify 871 nasopharyngeal human samples with a previous RT-qPCR based SARS-CoV-2 diagnosis. The diagnostic test showed high accuracy in identifying SARS-CoV-2-positive samples including B.1.1.7, P.1, B.1.427/B.1.429 and B.1.617.2/ AY samples with a detection limit of 7.2 viral copies/µL. In addition, this test could discern SARS-CoV-2 infection from other viral infections with COVID-19-like symptomatology. The designed end-point PCR diagnostic test to detect SARS-CoV-2 is a suitable alternative to RT-qPCR. Since the proposed bioinformatic approach can be easily applied in thousands of viral genomes and over highly divergent strains, it can be used as a PCR design tool as new SARS-CoV-2 variants emerge. Therefore, this end-point PCR test could be employed in epidemiological surveillance to detect new SARS-CoV-2 variants as they emerge and propagate.

Implications of Iron Deficiency in STEMI Patients and in a Murine Model of Myocardial Infarction.

In patients with a first anterior ST-segment elevation myocardial infarction treated with primary percutaneous coronary intervention, iron deficiency (ID) was associated with larger infarcts, more extensive microvascular obstruction, and higher frequency of adverse left ventricular remodeling as assessed by cardiac magnetic resonance imaging. In mice, an ID diet reduced the activity of the endothelial nitric oxide synthase/soluble guanylate cyclase/protein kinase G pathway in association with oxidative/nitrosative stress and increased infarct size after transient coronary occlusion. Iron supplementation or administration of an sGC activator before ischemia prevented the effects of the ID diet in mice. Not only iron excess, but also ID, may have deleterious effects in the setting of ischemia and reperfusion.

Pseudotyped Vesicular Stomatitis Virus-Severe Acute Respiratory Syndrome-Coronavirus-2 Spike for the Study of Variants, Vaccines, and Therapeutics Against Coronavirus Disease 2019.

World Health Organization (WHO) has prioritized the infectious emerging diseases such as Coronavirus Disease (COVID-19) in terms of research and development of effective tests, vaccines, antivirals, and other treatments. Severe Acute Respiratory Syndrome-Coronavirus-2 (SARS-CoV-2), the etiological causative agent of COVID-19, is a virus belonging to risk group 3 that requires Biosafety Level (BSL)-3 laboratories and the corresponding facilities for handling. An alternative to these BSL-3/-4 laboratories is to use a pseudotyped virus that can be handled in a BSL-2 laboratory for study purposes. Recombinant Vesicular Stomatitis Virus (VSV) can be generated with complementary DNA from complete negative-stranded genomic RNA, with deleted G glycoprotein and, instead, incorporation of other fusion protein, like SARS-CoV-2 Spike (S protein). Accordingly, it is called pseudotyped VSV-SARS-CoV-2 S. In this review, we have described the generation of pseudotyped VSV with a focus on the optimization and application of pseudotyped VSV-SARS-CoV-2 S. The application of this pseudovirus has been addressed by its use in neutralizing antibody assays in order to evaluate a new vaccine, emergent SARS-CoV-2 variants (delta and omicron), and approved vaccine efficacy against variants of concern as well as in viral fusion-focused treatment analysis that can be performed under BSL-2 conditions.