The current landscape of imaging recommendations in cardiovascular clinical guidelines: toward an imaging-guided precision medicine

The purpose of this article is to provide an overview on the role of CT scan and MRI according to selected guidelines by the European Society of Cardiology (ESC) and the American College of Cardiology/American Heart Association (ACC/AHA). ESC and ACC/AHA guidelines were systematically reviewed for recommendations to CT and MRI use in specific cardiovascular (CV) clinical categories. All recommendations were collected in a dataset, including the class of recommendation, the level of evidence (LOE), the specific imaging technique, the clinical purpose of the recommendation and the recommending Society. Among the 43 included guidelines (ESC: n = 18, ACC/AHA: n = 25), 26 (60.4%) contained recommendations for CT scan or MRI (146 recommendations: 62 for CT and 84 for MRI). Class of recommendation IIa (32.9%) was the most represented, followed by I (28.1%), IIb (24%) and III (11.9%). MRI recommendations more frequently being of higher class (I: 36.9%, IIa: 29.8%, IIb: 21.4%, III: 11.9%) as compared to CT (I: 16.1%, IIa: 37.1%, IIb: 27.4%, III: 19.4%). Most of recommendation (55.5%) were based on expert opinion (LOE C). The use of cardiac CT and cardiac MR in the risk assessment, diagnosis, therapeutic and procedural planning is in continuous development, driven by an increasing need to evolve toward an imaging-guided precision medicine, combined with cost-effectiveness and healthcare sustainability. These developments must be accompanied by an increased availability of high-performance scanners in healthcare facilities and should emphasize the need of increasing the number of radiologists fully trained in cardiac imaging

Intelligent non-colorimetric indicators for the perishable supply chain by non-wovens with photo-programmed thermal response

Spoiled perishable products, such as food and drugs exposed to inappropriate temperature, cause million illnesses every year. Risks range from intoxication due to pathogen-contaminated edibles, to suboptimal potency of temperature-sensitive vaccines. High-performance and low-cost indicators are needed, based on conformable materials whose properties change continuously and irreversibly depending on the experienced time-temperature profile. However, these systems can be limited by unclear reading, especially for colour-blind people, and are often difficult to be encoded with a tailored response to detect excess temperature over varying temporal profiles. Here we report on optically-programmed, non-colorimetric indicators based on nano-textured non-wovens encoded by their cross-linking degree. This combination allows a desired time-temperature response to be achieved, to address different perishable products. The devices operate by visual contrast with ambient light, which is explained by backscattering calculations for the complex fibrous material. Optical nanomaterials with photo-encoded thermal properties might establish new design rules for intelligent labels

Severe acute respiratory syndrome coronavirus 2 may exploit human transcription factors involved in retinoic acid and interferon-mediated response: a hypothesis supported by an in silico analysis

The pandemic of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) causing coronavirus disease 2019 (COVID-19), resulting in acute respiratory disease, is a worldwide emergency. Because recently it has been found that SARS-CoV is dependent on host transcription factors (TF) to express the viral genes, efforts are required to understand the molecular interplay between virus and host response. By bioinformatic analysis, we investigated human TF that can bind the SARS-CoV-2 sequence and can be involved in viral transcription. In particular, we analysed the key role of TF involved in interferon (IFN) response. We found that several TF could be induced by the IFN antiviral response, specifically some induced by IFN-stimulated gene factor 3 (ISGF3) and by unphosphorylated ISGF3, which were found to promote the transcription of several viral open reading frame. Moreover, we found 22 TF binding sites present only in the sequence of virus infecting humans but not bat coronavirus RaTG13. The 22 TF are involved in IFN, retinoic acid signalling and regulation of transcription by RNA polymerase II, thus facilitating its own replication cycle. This mechanism, by competition, may steal the human TF involved in these processes, explaining SARS-CoV-2's disruption of IFN-I signalling in host cells and the mechanism of the SARS retinoic acid depletion syndrome leading to the cytokine storm. We identified three TF binding sites present exclusively in the Brazilian SARS-CoV-2 P.1 variant that may explain the higher severity of the respiratory syndrome. These data shed light on SARS-CoV-2 dependence from the host transcription machinery associated with IFN response and strengthen our knowledge of the virus's transcription and replicative activity, thus paving the way for new targets for drug design and therapeutic approaches

Melorheostosis and Osteopoikilosis Clinical and Molecular Description of an Italian Case Series

Melorheostosis (MEL) is an uncommon, sclerosing disease, characterised by hyperostosis of long bones, resembling the flowing of candle wax. The disease is sporadic and the pathogenesis is still poorly understood. Occasionally, the same family can include individuals with MEL and Osteopoikilosis (OPK), a disease characterised by multiple round foci of increased bone density. LEMD3 gene mutations are related to OPK and Buschke\u2013Ollendorff Syndrome, a genetic condition in which an association between MEL, OPK and skin lesions is observed. In rare cases, LEMD3 mutations and recently mosaic MAP2K1 gene mutations have been correlated to MEL suggesting that somatic mosaicism could be causative of the disease. In this study, we described the clinical, radiological and molecular findings of 19 individuals with MEL and 8 with OPK and compared the results to the medical literature. The molecular analyses of this case series corroborate the available data in the medical literature, indicating that LEMD3 germline mutations are not a major cause of isolated MEL and reporting five further cases of OPK caused by LEMD3 germline mutations

An integrated approach to the evaluation of patients with asymptomatic or minimally symptomatic hyperCKemia

Currently, there are no straightforward guidelines for the clinical and diagnostic management of hyperCKemia, a frequent and nonspecific presentation in muscle diseases. Therefore, we aimed to describe our diagnostic workflow for evaluating patients with this condition. Methods: We selected 83 asymptomatic or minimally symptomatic patients with persistent hyperCKemia for participation in this Italian multicenter study. Patients with facial involvement and distal or congenital myopathies were excluded, as were patients with suspected inflammatory myopathies or predominant respiratory or cardiac involvement. All patients underwent a neurological examination and nerve conduction and electromyography studies. The first step of the investigation included a screening for Pompe disease. We then evaluated the patients for myotonic dystrophy type II\u2013related CCTG expansion and excluded patients with copy number variations in the DMD gene. Subsequently, the undiagnosed patients were investigated using a target gene panel that included 20 genes associated with isolated hyperCKemia. Results: Using this approach, we established a definitive diagnosis in one third of the patients. The detection rate was higher in patients with severe hyperCKemia and abnormal electromyographic findings. Discussion: We have described our diagnostic workflow for isolated hyperCKemia, which is based on electrodiagnostic data, biochemical screening, and first-line genetic investigations, followed by successive targeted sequencing panels. Both clinical signs and electromyographic abnormalities are associated with increased diagnostic yields

Vitamin D receptor ChIP-seq in primary CD4+ cells: relationship to serum 25-hydroxyvitamin D levels and autoimmune disease

PMCID: PMC3710212This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited