A discussion of syndromic molecular testing for clinical care

Current molecular detection methods for single or multiplex pathogens by real-time PCR generally offer great sensitivity and specificity. However, many infectious pathogens often result in very similar clinical presentations, complicating the test-order for physicians who have to narrow down the causative agent prior to in-house PCR testing. As a consequence, the intuitive response is to start empirical therapy to treat a broad spectrum of possible pathogens. Syndromic molecular testing has been increasingly integrated into routine clinical care, either to provide diagnostic, epidemiological or patient management information. These multiplex panels can be used to screen for predefined infectious disease pathogens simultaneously within a 1 h timeframe, creating opportunities for rapid diagnostics. Conversely, syndromic panels have their own challenges and must be adaptable to the evolving demands of the clinical setting. Firstly, questions have been raised regarding the clinical relevance of some of the targets included in the panels and secondly, there is the added expense of integration into the clinical laboratory. Here, we aim to discuss some of the factors that should be considered before performing syndromic testing rather than traditional low-plex in-house PCR

Extending Our Knowledge about the Th-229 Nuclear Isomer

The first nuclear excited state in Th-229 possesses the lowest excitation energy of all currently known nuclear levels. The energy difference between the ground- and first-excited (isomeric) state (denoted with Th-229m) amounts only to approximate to 8.2 eV (approximate to 151.2 nm), which results in several interesting consequences: Since the excitation energy is in the same energy range as the binding energy of valence electrons, the lifetime of Th-229m is strongly influenced by the electronic structure of the Th atom or ion. Furthermore, it is possible to potentially excite the isomeric state in Th-229 with laser radiation, which led to the proposal of a nuclear clock that could be used to search for new physics beyond the standard model. In this article, we will focus on recent technical developments in our group that will help to better understand the decay mechanisms of Th-229m, focusing primarily on measuring the radiative lifetime of the isomeric state

The megalithic building of S.Erasmo di Cesi: architecture, astronomy, and landscape

Abstract. One of the most enigmatic megalithic buildings of Italy is the structure which lies on the S. Erasmo hill near Cesi, in Umbria, a huge complex encompassing an area of around 8000 square meters and enclosed by refined cyclopean walls. Although its date is uncertain, suggested dates comprise the Iron Age and archaic period, down to the third century B.C. The building’s function is also uncertain. Usually identified as a fortified structure, in fact there is a megalithic platform at the southern end of the enclosure which could have served as foundation of a temple or palace and, from the top of Monte Torre Maggiore, a complex of temples dating from the fourth century B.C. overlooks the hill. Similar combinations of megalithic buildings resting half-way to temples placed on high peaks are known to exist. In order to clarify the function of this structure and its position in relation to the surrounding landscape, with particular attention to its visibility and to the directions of visibility from the complex, as well as to the possible astronomical alignments, we present a multi-disciplinary approach to the study of the S. Erasmo complex, which includes the mapping of the sky at the various possible epochs of construction, the creation of a digital model of the landscape in forms of digital maps using Geographic Information System technologies, and a 3D model using various 3D software packages

A Challenging Nodular Lesion of the Ear

Skin nodular lesion are really frequent, but rapidly growing ones needs to be quickly removed since they can hide really aggressive skin tumor. Among malignant lesion Merkel cell carcinoma arise. It is a rare neuroendocrine skin tumor highly aggressive, not easy to diagnose at first stage, since at first diagnosis it is already widespreading all over the body. In order to renew interest in this letal skin tumori is mandatory to remind high risk population which include elderly people, white skin, chronically exposed to UV immunocompromised. Our unhappy case was described to increase awareness on this kind of skin tumor, since new drug appeared in the market can give an hope to these patients

Lung regions differently modulate bronchial branching development and extracellular matrix plays a role in regulating the development of chick embryo whole lung.

Normal branching development is dependent on the correlation between cells and extracellular matrix. In this interaction glycosaminoglycans, cytokines and growth factors play a fundamental role. In order to verify the distribution and influence of extracellular matrix and related enzymes on chick embryo lung development, 6 day-old whole lungs were maintained in vitro with testicular hyaluronidase, beta-N-acetyl-D-glucosaminidase and chondrotinase ABC or in linkage with apical, medial and caudal lung regions of 6-day development before and after enzyme treatment. In a separate lung region beta-N-acetyl-D-glucosaminidase and hyaluronidase were determined. Our data show that the whole lung cultures increase bronchial branching development when the medial region is admixed separately, while the separate apical or caudal regions or apical combined with caudal region do not affect bronchial branching development. The enzyme treatment of medial region prevents the branching development in associated whole lung. The bronchial branching development of whole lung cultured in medium containing the enzymes related to glycosaminoglycans turnover is significantly altered. In conclusion, these data show that the different influence of separate apical, medial, caudal lung regions on bronchial branching development is related to the extracellular matrix composition

Effect of school reopening on SARS-CoV-2 incidence in a low-prevalence region:Prospective SARS-CoV-2 testing in healthcare workers with primary school-attending children versus without children living at home

Coronavirus disease 2019 (COVID-19) often presents asymptomatically or milder in children compared to adults. The role of young children in the transmission of severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) remains largely unknown. In the Netherlands, the first action of loosening the partial lockdown that had been implemented to reduce SARS-CoV-2 transmission was the reopening of primary schools on 1 May 2020. We subsequently conducted a prospective cohort study among healthcare workers (HCWs) with primary school-attending children versus HCWs without children living at home. We tested each HCW three times for SARS-CoV-2 from May 20 to June 15 2020 at 1-week intervals. In total, 832 nasopharyngeal swabs were taken from 283 HCWs with primary school-attending children living at home and 864 nasopharyngeal swabs from 285 HCWs without children living at home. All nasopharyngeal swabs tested negative for SARS-CoV-2. In our region with a low population density and low SARS-CoV-2 prevalence, reopening of primary schools did not lead to an increase in infections. The results of this study may serve as an example for the implementation of regional strategies to reduce SARS-CoV-2 transmission in countries with large variations in both population density and SARS-CoV-2 prevalence

Viral load dynamics in intubated patients with COVID-19 admitted to the intensive care unit

Background: Prolonged viral RNA detection in respiratory samples from patients with COVID-19 has been described, but the clinical relevance remains unclear. We studied the dynamics of SARS-CoV-2 on a group and individual level in intubated ICU patients. Methods: In a cohort of 86 patients, we analysed SARS-CoV-2 RT-PCR results on nasopharyngeal and sputum samples (obtained as part of clinical care twice a week) according to time after intubation. Subsequently, we performed survival analyses. Results: 870 samples were tested by RT-PCR. Overall viral load was highest in the first week (median nasopharynx 3.5. IQR 1.5-4.3; median sputum 4.3. IQR 3.3-5.6) and decreased over time. In 20% of patients a relapsing pattern was observed. Nasopharyngeal and sputum PCR status on day 14 was not significantly associated with survival up to day 60 in this small cohort. Conclusion: In general SARS-CoV-2 RNA levels in respiratory samples in patients with severe COVID-19 decease alter the first week after intubation, but individual SARS-CoV-2 RNA levels can show a relapsing pattern. Larger studies are needed to address the association of clearance of SARS-CoV-2 RNA from respiratory samples with survival, because we observed a trend towards better survival in patients with early clearance from sputum. (C) 2021 The Authors. Published by Elsevier Inc

Changes in enterovirus epidemiology after easing of lockdown measures

INTRODUCTION: Public health measures aimed at controlling transmission of SARS-CoV-2, otherwise known as "lockdown" measures, had profound effects on circulation of non-SARS viruses, many of which decreased to very low levels. The interrupted transmission of these viruses may have lasting effects. Some of the influenza clades seem to have disappeared during this period, a phenomenon which is described as a "funnel effect". It is currently unknown if the lockdown measures had any effect on the diversity of circulating viruses, other than influenza. Enteroviruses are especially interesting in this context, as the clinical presentation of an infection with a particular enterovirus-type may be clade-dependent.METHODS AND MATERIALS: Enteroviruses were detected in clinical materials using a 5'UTR-based detection PCR, and partial VP-1 sequences were obtained, using methods described before. All samples with EV detections from a large part of the Netherlands were included in the study. The samples originated from general practitioners, general hospitals, university hospitals and public health offices.RESULTS: Five EV-genotypes circulated in significant numbers before and after the lockdown, EV-D68, E-11, CV-A6, CV-B5 and CV-A2. All five genotypes showed decreased genetic diversity after the lockdown, and four indicate a significant number of sequences clustering together with a very high sequence homology. Moreover, children with E-11 and CV-B5 detections were significantly older after the lockdown than before.CONCLUSIONS: The reduced enterovirus transmission in the Netherlands during the pandemic, seems to have led to a decrease in genetic diversity in the five most commonly detected enterovirus serotypes.</p

Modeling the Probability of Overlap Between Marine Fish Distributions and Marine Renewable Energy Infrastructure Using Acoustic Telemetry Data

Understanding the spatiotemporal distributions of migratory marine species at marine renewable energy sites is a crucial step towards assessing the potential impacts of tidal stream turbines and related infrastructure upon these species. However, the dynamic marine conditions that make tidal channels attractive for marine renewable power development also make it difficult to identify and follow species of marine fishes with existing technologies such as hydroacoustics and optical cameras. Acoustic telemetry can resolve some of these problems. Acoustic tags provide unique individual ID codes at an ultrasonic frequency, which are then detected and recorded by acoustic receivers deployed in the area of interest. By matching detection locations of fish species with environmental conditions at proposed sites for tidal energy infrastructure, species distribution models can be developed to predict the probability of species occurrence at sites of current and planned tidal power development. This information can be used to develop statistically robust encounter rate models to aid in quantifying the risk of tidal power development to migratory fish species. We used this approach to develop a predictive model of striped bass (Morone saxatilis) distribution within Minas Passage in the upper Bay of Fundy, Nova Scotia. Model results suggested increased probability of striped bass presence in Minas Passage during late ebb tide conditions and at relatively high water temperatures. We demonstrate the potential utility of species distribution modeling of acoustic tag detections in predicting interactions with renewable energy infrastructure, and show the importance of physical oceanographic variables influencing species distributions in a highly dynamic marine environment