Immunomodulation Through Low-Dose Radiation for Severe COVID-19:Lessons From the Past and New Developments

Low-dose radiation therapy (LD-RT) has historically been a successful treatment for pneumonia and is clinically established as an immunomodulating therapy for inflammatory diseases. The ongoing COVID-19 pandemic has elicited renewed scientific interest in LD-RT and multiple small clinical trials have recently corroborated the historical LD-RT findings and demonstrated preliminary efficacy and immunomodulation for the treatment of severe COVID-19 pneumonia. The present review explicates archival medical research data of LD-RT and attempts to translate this into modernized evidence, relevant for the COVID-19 crisis. Additionally, we explore the putative mechanisms of LD-RT immunomodulation, revealing specific downregulation of proinflammatory cytokines that are integral to the development of the COVID-19 cytokine storm induced hyperinflammatory state. Radiation exposure in LD-RT is minimal compared to radiotherapy dosing standards in oncology care and direct toxicity and long-term risk for secondary disease are expected to be low. The recent clinical trials investigating LD-RT for COVID-19 confirm initial treatment safety. Based on our findings we conclude that LD-RT could be an important treatment option for COVID-19 patients that are likely to progress to severity. We advocate the further use of LD-RT in carefully monitored experimental environments to validate its effectiveness, risks and mechanisms of LD-RT

Brain and Head-and-Neck MRI in Immobilization Mask: A Practical Solution for MR-Only Radiotherapy

In brain/head-and-neck radiotherapy (RT), thermoplastic immobilization masks guarantee reproducible patient positioning in treatment position between MRI, CT, and irradiation. Since immobilization masks do not fit in the diagnostic MR head/head-and-neck coils, flexible surface coils are used for MRI imaging in clinical practice. These coils are placed around the head/neck, in contact with the immobilization masks. However, the positioning of these flexible coils is technician dependent, thus leading to poor image reproducibility. Additionally, flexible surface coils have an inferior signal-to-noise-ratio (SNR) compared to diagnostic coils. The aim of this work was to create a new immobilization setup which fits into the diagnostic MR coils in order to enhance MR image quality and reproducibility. For this purpose, a practical immobilization setup was constructed. The performances of the standard clinical and the proposed setups were compared with four tests: SNR, image quality, motion restriction, and reproducibility of inter-fraction subject positioning. The new immobilization setup resulted in 3.4 times higher SNR values on average than the standard setup, except directly below the flexible surface coils where similar SNR was observed. Overall, the image quality was superior for brain/head-and-neck images acquired with the proposed RT setup. Comparable motion restriction in feet-head/left-right directions (maximum motion ≈1 mm) and comparable inter-fraction repositioning accuracy (mean inter-fraction movement 1 ± 0.5 mm) were observed for the standard and the new setup

Medications and addictive substances potentially inducing or attenuating sleep bruxism and/or awake bruxism

Bruxism is a repetitive jaw-muscle activity characterised by clenching or grinding of the teeth and/or by bracing or thrusting of the mandible. It can occur during sleep, indicated as sleep bruxism, or during wakefulness, indicated as awake bruxism. Exogenous risk indicators of sleep bruxism and/or awake bruxism are, among others, medications and addictive substances, whereas also several medications seem to have the potential to attenuate sleep bruxism and/or awake bruxism. The objective of this study was to present a narrative literature on medications and addictive substances potentially inducing or aggravating sleep bruxism and/or awake bruxism and on medications potentially attenuating sleep bruxism and/or awake bruxism. Literature reviews reporting evidence or indications for sleep bruxism and/or awake bruxism as an adverse effect of several (classes of) medications as well as some addictive substances and literature reviews on medications potentially attenuating sleep bruxism and/or awake bruxism were used as starting point and guidelines to describe the topics mentioned. Additionally, two literature searches were established on PubMed. Three types of bruxism were distinguished: sleep bruxism, awake bruxism and non-specified bruxism. Generally, there are insufficient evidence-based data to draw definite conclusions concerning medications and addictive substances inducing or aggravating sleep bruxism and/or awake bruxism as well as concerning medications attenuating sleep bruxism and/or awake bruxism. There are insufficient evidence-based data to draw definite conclusions concerning medications and addictive substances inducing or aggravating sleep bruxism and/or awake bruxism as well as concerning medications attenuating sleep bruxism and/or awake bruxism.Peer reviewe

Low abundance, strong features: Window-dressing crystalline forsterite in the disk wall of HD 100546

Forsterite is one of the crystalline dust species that is often observed in protoplanetary disks and solar system comets. Being absent in the interstellar medium, it must be produced during the disk lifetime. It can therefore serve as a tracer of dust processing and disk evolution, which can lead to a better understanding of the physical processes occurring in the disk, and possibly planet formation. However, the connection of these processes with the overall disk crystallinity remains unclear. We aim to characterize the forsterite abundance and spatial distribution in the disk of the Herbig Be star HD 100546, to investigate if a connection exists with the large disk gap. We use a 2D radiative transfer code, MCMax, to model the circumstellar dust around HD 100546. We use VISIR Q-band imaging to probe the outer disk geometry and mid-infrared features to model the spatial distribution of forsterite. The temperature-dependent shape of the 69 micron feature observed with Herschel PACS is used as a critical tool to constrain this distribution. We find a crystalline mass fraction of 40 - 60 %, located close to the disk wall between 13 and 20 AU, and possibly farther out at the disk surface. The forsterite is in thermal contact with the other dust species. We put an upper limit on the iron content of forsterite of 0.3 %. Optical depth effects play a key role in explaining the observed forsterite features, hiding warm forsterite from view at short wavelengths. The disk wall acts as a showcase: it displays a localized high abundance of forsterite, which gives rise to a high observed crystallinity, while the overall mass fraction of forsterite is a factor of ten lower.Comment: A&A accepted, 17 pages, 14 figure

Recurrences of ventricular tachycardia after stereotactic arrhythmia radioablation arise outside the treated volume: analysis of the swiss cohort

BACKGROUND AND AIMS Stereotactic arrhythmia radioablation (STAR) has been recently introduced for the management of therapy-refractory ventricular tachycardia (VT). VT recurrences have been reported after STAR but the mechanisms remain largely unknown. We analyzed recurrences in our patients after STAR. METHODS From 09.2017 to 01.2020, 20 patients (68±8y, LVEF 37±15%) suffering from refractory VT were enrolled, 16/20 with a history of at least 1 electrical storm. Before STAR, an invasive electro-anatomical mapping (Carto3) of the VT substrate was performed. A mean dose of 23±2Gy was delivered to the planning target volume (PTV). RESULTS The median ablation volume was 26 ml (range 14-115) and involved the interventricular septum in 75% of patients. During the first 6 months after STAR, VT burden decreased by 92% (median value, from 108 to 10 VT/semester). After a median follow-up of 25 months, 12/20 (60%) developed a recurrence and underwent a redo ablation. VT recurrence was located in proximity of the treated substrate in 9 cases, remote from the PTV in 3 cases and involved a larger substrate over ≥3 LV segments in 2 cases. No recurrences occurred inside the PTV. Voltage measurements showed a significant decrease in both bipolar and unipolar signal amplitude after STAR. CONCLUSION STAR is a new tool available for the treatment of VT, allowing for a significant reduction of VT burden. VT recurrences are common during follow-up, but no recurrences were observed inside the PTV. Local efficacy was supported by a significant decrease in both bipolar and unipolar signal amplitude

High-contrast imaging constraints on gas giant planet formation - The Herbig Ae/Be star opportunity

Planet formation studies are often focused on solar-type stars, implicitly considering our Sun as reference point. This approach overlooks, however, that Herbig Ae/Be stars are in some sense much better targets to study planet formation processes empirically, with their disks generally being larger, brighter and simply easier to observe across a large wavelength range. In addition, massive gas giant planets have been found on wide orbits around early type stars, triggering the question if these objects did indeed form there and, if so, by what process. In the following I briefly review what we currently know about the occurrence rate of planets around intermediate mass stars, before discussing recent results from Herbig Ae/Be stars in the context of planet formation. The main emphasis is put on spatially resolved polarized light images of potentially planet forming disks and how these images - in combination with other data - can be used to empirically constrain (parts of) the planet formation process. Of particular interest are two objects, HD100546 and HD169142, where, in addition to intriguing morphological structures in the disks, direct observational evidence for (very) young planets has been reported. I conclude with an outlook, what further progress we can expect in the very near future with the next generation of high-contrast imagers at 8-m class telescopes and their synergies with ALMA.Comment: Accepted by Astrophysics and Space Science as invited short review in special issue about Herbig Ae/Be stars; 12 pages incl. 5 figures, 2 tables and reference

Circumstellar disks and planets. Science cases for next-generation optical/infrared long-baseline interferometers

We present a review of the interplay between the evolution of circumstellar disks and the formation of planets, both from the perspective of theoretical models and dedicated observations. Based on this, we identify and discuss fundamental questions concerning the formation and evolution of circumstellar disks and planets which can be addressed in the near future with optical and infrared long-baseline interferometers. Furthermore, the importance of complementary observations with long-baseline (sub)millimeter interferometers and high-sensitivity infrared observatories is outlined.Comment: 83 pages; Accepted for publication in "Astronomy and Astrophysics Review"; The final publication is available at http://www.springerlink.co

Monitoring and evaluation of malaria in pregnancy – developing a rational basis for control

Monitoring and evaluation of malaria control in pregnancy is essential for assessing the efficacy and effectiveness of health interventions aimed at reducing the major burden of this disease on women living in endemic areas. Yet there is no currently integrated strategic approach on how this should be achieved. Malaria control in pregnancy is formulated in relation to epidemiological patterns of exposure. Current emphasis is on intermittent preventive treatment (IPTp) during pregnancy with sulphadoxine-pyrimethamine in higher transmission areas, combined with insecticide treated bed nets (ITNs) and case management. Emphasis in lower transmission areas is primarily on case management. This paper discusses a rational basis for monitoring and evaluation based on: assessments of therapeutic and prophylactic drug efficacy; proportional reductions in parasite prevalence; seasonal effects; rapid assessment methodologies; birthweight and/or anaemia nomograms; case-coverage methods; maternal mortality indices; operational and programmatic indicators; and safety and pharmacovigilance of antimalarials in pregnancy. These approaches should be incorporated more effectively within National Programmes in order to facilitate surveillance and improve identification of high-risk women. Systems for utilizing routinely collected data should be strengthened, with greater attention to safety and pharmacovigilance with the advent of artemisinin combination therapies, and prospects of inadvertent exposures to artemisinins in the first trimester. Integrating monitoring activities within malaria control, reproductive health and adolescent-friendly services will be critical for implementation. Large-scale operational research is required to further evaluate the validity of currently proposed indicators, and in order to clarify the breadth and scale of implementation to be deployed

Ethnic differences in total and HDL cholesterol among Turkish, Moroccan and Dutch ethnic groups living in Amsterdam, the Netherlands.

<p>Abstract</p> <p>Background</p> <p>High total cholesterol and low HDL (high-density lipoprotein) cholesterol are important determinants of cardiovascular disease. Little is known about dyslipidemia among Turkish and Moroccan migrants, two of the largest ethnic minority groups in several European countries. This study examines ethnic differences in total and HDL cholesterol levels between Dutch, Turkish and Moroccan ethnic groups.</p> <p>Methods</p> <p>Data were collected in the setting of a general health survey, in Amsterdam, the Netherlands, in 2004. Total response rate was 45% (Dutch: 46%, Turks: 50%, Moroccans: 39%). From 1,220 adults information on history of hypercholesterolemia, lifestyle and demographic background was obtained via health interviews. In a physical examination measurements of anthropometry and blood pressure were performed and blood was collected. Total and HDL cholesterol were determined in serum.</p> <p>Results</p> <p>Total cholesterol levels were lower and hypercholesterolemia was less prevalent among the Moroccan and Turkish than the Dutch ethnic population. HDL cholesterol was also relatively low among these migrant groups. The resulting total/HDL cholesterol ratio was particularly unfavourable among the Turkish ethnic group. Controlling for Body Mass Index and alcohol abstinence substantially attenuated ethnic differences in HDL cholesterol levels and total/HDL cholesterol ratio.</p> <p>Conclusions</p> <p>Total cholesterol levels are relatively low in Turkish and Moroccan migrants. However part of this advantage is off-set by their relatively low levels of HDL cholesterol, resulting in an unfavourable total/HDL cholesterol ratio, particularly in the Turkish population. Important factors in explaining ethnic differences are the relatively high Body Mass Index and level of alcohol abstinence in these migrant groups.</p