The Flavonoid Cyanidin Shows Immunomodulatory and Broad-Spectrum Antiviral Properties, Including SARS-CoV-2.

New antiviral treatments are needed to deal with the unpredictable emergence of viruses. Furthermore, vaccines and antivirals are only available for just a few viral infections, and antiviral drug resistance is an increasing concern. Cyanidin (a natural product also called A18), a key flavonoid that is present in red berries and other fruits, attenuates the development of several diseases, through its anti-inflammatory effects. Regarding its mechanism of action, A18 was identified as an IL-17A inhibitor, resulting in the attenuation of IL-17A signaling and associated diseases in mice. Importantly, A18 also inhibits the NF-κB signaling pathway in different cell types and conditions in vitro and in vivo. In this study, we report that A18 restricts RSV, HSV-1, canine coronavirus, and SARS-CoV-2 multiplication, indicating a broad-spectrum antiviral activity. We also found that A18 can control cytokine and NF-κB induction in RSV-infected cells independently of its antiviral activity. Furthermore, in mice infected with RSV, A18 not only significantly reduces viral titers in the lungs, but also diminishes lung injury. Thus, these results provide evidence that A18 could be used as a broad-spectrum antiviral and may contribute to the development of novel therapeutic targets to control these viral infections and pathogenesis.

Nonbacterial Thrombotic Endocarditis with Multiple Systemic Emboli in a Patient with Primary Lung Cancer.

Nonbacterial thrombotic endocarditis (NBTE) is a rare condition that refers to a spectrum of noninfectious lesions of cardiac valves that is most commonly seen in advanced malignancy. We describe a case report of a 63-year-old male with NBTE and multiple embolizations (encephalic, coronary, splenic, and renal). The patient was admitted to the emergency department for stroke. During hospitalization, the patient complained of left leg pain and a venous echo color Doppler of the lower limbs was performed, showing bilateral distal deep-vein thrombosis. A thoracoabdominal computed tomography scan, which was performed to rule out pulmonary embolism, revealed a primary lung cancer and subcarinal lymphadenopathy. As collateral findings, multiple ischemic lesions in the spleen and in both kidneys were identified. In addition, areas of subendocardial hypodensity compatible with ischemia were also highlighted. An electrocardiogram showed acute myocardial infarction and focused echocardiographic evaluation displayed hypokinesis of the lateral and posterior in the mid- and distal segments and aortic and mitral valve vegetations, confirmed by a transesophageal echocardiography. Empiric antimicrobial therapy was started; all blood culture sets were negative and the patient was apyretic throughout the hospitalization. These findings supported the hypothesis of NBTE with multiple embolizations during a hypercoagulable state associated with advanced lung cancer.

Point-of-Care and Label-Free Detection of Porcine Reproductive and Respiratory Syndrome and Swine Influenza Viruses Using a Microfluidic Device with Photonic Integrated Circuits.

Swine viral diseases challenge the sector's sustainability by affecting productivity and the health and welfare of the animals. The lack of antiviral drugs and/or effective vaccines renders early and reliable diagnosis the basis of viral disease management, underlining the importance of point-of-care (POC) diagnostics. A novel POC diagnostic device utilizing photonic integrated circuits (PICs), microfluidics, and information and communication technologies for the detection of porcine reproductive and respiratory syndrome virus (PRRSV) and swine influenza A (SIV) was validated using spiked and clinical oral fluid samples. Metrics including sensitivity, specificity, accuracy, precision, positive likelihood ratio (PLR), negative likelihood ratio (NLR), and diagnostic odds ratio (DOR) were calculated to assess the performance of the device. For PRRSV, the device achieved a sensitivity of 83.5%, specificity of 77.8%, and DOR values of 17.66, whereas the values for SIV were 81.8%, 82.2%, and 20.81, respectively. The POC device and PICs can be used for the detection of PRRSV and SIV in the field, paving the way for the introduction of novel technologies in the field of animal POC diagnostics to further optimize livestock biosecurity.

Acute Myocarditis Associated with Legionella Infection: Usefulness of Layer-specific Two-dimensional Longitudinal Speckle-tracking Analysis.

Pneumonia is the most commonly described manifestation of Legionella pneumophila infection (legionellosis), and extrapulmonary manifestations are uncommon. There are a few descriptions of acute myocarditis associated with legionellosis. We present a case of acute myocarditis in a patient admitted for legionellosis with multisystemic involvement (lung, heart, and kidney). Left ventricular (LV) dysfunction was documented by cardiac magnetic resonance (CMR) and two-dimensional speckle-tracking echocardiography; layer-specific strain analyses were performed, which allowed to differentiate subendocardial or subepicardial contractile impairment. Layer-specific strain analyses by echocardiography demonstrated impairment of subepicardial deformation in the inferolateral wall, which mirrored CMR findings, showing late gadolinium enhancement in the subepicardium of the same LV segments. After initiation of appropriate antibiotic therapy with levofloxacin, LV systolic function rapidly improved as assessed by both CMR and strain analyses, with concomitant normalization of both clinical and biochemical abnormalities. The basic mechanisms of myocardial involvement during legionellosis are unclear; we discussed our findings according to the limited available evidence.

Imiquimod suppresses respiratory syncytial virus (RSV) replication via PKA pathway and reduces RSV induced-inflammation and viral load in mice lungs.

Respiratory syncytial virus (RSV) is a leading cause of lower respiratory tract disease and bronchiolitis in children, as well as an important cause of morbidity and mortality in elderly and immunocompromised individuals. However, there is no safe and efficacious RSV vaccine or antiviral treatment. Toll Like Receptors (TLR) are important molecular mediators linking innate and adaptive immunity, and their stimulation by cognate agonists has been explored as antiviral agents. Imiquimod is known as a TLR7 agonist, but additionally acts as an antagonist for adenosine receptors. In this study, we demonstrate that imiquimod, but not resiquimod, has direct anti-RSV activity via PKA pathway in HEp-2 and A549 cells, independently of an innate response. Imiquimod restricts RSV infection after viral entry into the host cell, interfering with viral RNA and protein synthesis. Probably as a consequence of these anti-RSV properties, imiquimod displays cytokine modulating activity in RSV infected epithelial cells. Moreover, in a murine model of RSV infection, imiquimod treatment improves the course of acute disease, evidenced by decreased weight loss, reduced RSV lung titers, and attenuated airway inflammation. Consequently, imiquimod represents a promising therapeutic alternative against RSV infection and may inform the development of novel therapeutic targets to control RSV pathogenesis.

Predictors of poor clinical outcomes in patients with acute myocardial infarction and non-obstructed coronary arteries (MINOCA).

OBJECTIVE: To assess the characteristics and prognosis of patients with myocardial infarction and non-obstructed coronary arteries (MINOCA). METHODS: MINOCA was defined as acute myocardial infarction (AMI) with angiographic coronary stenosis <50%.Cardiomyopathies and myocarditis were - a priori - excluded from the study. Stenoses <30% were considered normal coronary arteries (NCA); stenoses ≥30% but <50% were considered mild coronary artery disease (MCAD). Patients were subdivided in 3 groups: I) NCA (0 vessels; stenosis <30%); II) 1-2 vessels showing MCAD and III) MCAD in 3 vessels or the left main stem (LMS). RESULTS: From January 2006 to December 2014, 7935 consecutive AMI patients were entered into our institutional database;150 (2%) were diagnosed as having MINOCA. At a median follow-up of 7.1 years the composite end-point (cardiovascular death, AMI or acute coronary syndrome, heart failure, stroke) occurred in 23 patients (17.4%). Survival analysis showed no differences between NCA versus MCAD (p = 0.781). When assessed by distribution of CAD, group III had a lower event-free survival compared to group I and group II, respectively 54 ±â€¯14%, 83 ±â€¯4% and 90 ±â€¯5% (p = 0.001). In a multivariate model, only 3 vessel disease or LMS involvement (HR = 23.5, 95% CI 2.59-173.49, P = 0.001) and high C-reactive protein at hospital admission (HR = 1.47, 95% CI 1.06-2.07, P = 0.005) were significant predictors of the study composite endpoint. CONCLUSIONS: In patients with MINOCA, the presence of NCA or 1-2 vessel MCAD was associated with better long-term clinical outcomes compared with patients with MCAD affecting 3 vessels or the LMS. Increased CRP concentrations on hospital admission were also a marker of worse clinical outcome during follow-up.

The lived experience of parents whose children discharged to home after cardiac surgery for congenital heart disease.

BACKGROUND: Congenital Heart Diseases (CHDs) afflicting children are estimated in 8 per 1000 live births. Recent advances in surgery and medical treatments allowed an improvement in survival rates leading to changes in diseases management as chronic conditions. Parents involvement during clinical pathways is considered an essential component of care, but frequently they experience stress and anxiety conditions during the care path. These feelings are typical of the pre and peri-operative period, however they don't disappear easily and sometimes they can increase after hospital discharge, affecting the family environment and its behaviors. AIM OF THE WORK: The purpose of this qualitative study is to examine the lived experience of parents during the time just after their children return home from hospital after undergoing surgery for CHD. METHODS: Parents were enrolled and interviewed as a prepositive sampling until concept saturation using Cohen's phenomenology approach. A quantitative approach was also applied using SF-12 questionnaire. The study was conducted in two Italian hospitals: the Pediatric Heart Surgery Center of the Fondazione Toscana G. Monasterio Institute in Massa and the Pediatric Cardiac Surgery Center of the Federico II University Hospital in Naples. RESULTS: The main themes emerged after the analysis were "happiness and uncertainty"; "chronic psychophysical fatigue"; "the rediscovery of a strong link with health care professionals". CONCLUSIONS: Fully understand the life experience of these families will allow the implementation of targeted health interventions through the implementation of shared strategies and tools to reduce families and children discomfort after hospital discharge.

Amiata Donkey Milk Chain: Animal Health Evaluation and Milk Quality.

This study presents an investigation of Amiata donkey health and quality of milk for human consumption. Thirty-one lactating dairy jennies were examined. The following samples were collected: faecal samples from the rectum of animals for parasitological examination; cervical swabs for the detection of bacteria causing reproductive disorders; and blood samples for serological diagnosis of main zoonotic (Brucella spp., Leptospira spp.) and donkey abortion agents (Brucella spp., Leptospira spp., Salmonella abortus equi, Equine viral arterithis virus, Equine herpesvirus type 1). In addition, individual milk samples were collected and analysed for mastitis-causing pathogens and milk quality. Regarding animal health, we detected a high prevalence of strongyle parasites in donkeys. It is very important to tackle parasitic diseases correctly. Selective control programmes are preferable in order to reduce anthelmintic drug use. For dairy donkeys, withdrawal periods from anthelmintic drugs need to be carefully managed, in accordance with EU and national regulations. The isolation of Staphylococcus aureus in milk highlights the importance of preventing contamination during milking, by adopting appropriate hygiene and safety practices at a farm level. Lysozyme activity was high compared to cow's milk, contributing to the inhibitory activity against certain bacteria. Donkey milk was characterised by high lactose content, low caseins, low fat, higher levels of unsaturated fatty acids compared to ruminant milks. Unsaturated fatty acids and omega 3 fatty acids in particular have become known for their beneficial health effect, which is favourable for human diet. These characteristics make it suitable for infants and children affected by food intolerance/allergies to bovine milk proteins and multiple food allergies as well as for adults with dyslipidemias. It is also recommended to prevent cardiovascular diseases.