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The projected existence and magnitude of carcinogenic effects of ionizing radiation at low doses and low-dose rates is perhaps the most important issue in radiation protection today. Studies of childhood cancer and natural background radiation have the potential to throw direct light on this question, into a dose range below a few tens of mSv. This paper describes the studies that have been undertaken and their context, discusses some problems that arise and summarizes the present position.

Many such studies have been undertaken, but most were too small to have a realistic chance of detecting the small effects expected from such low doses, based on risk projections from higher exposures. Case-control or cohort studies are to be preferred methodologically to ecological studies but can be prone to problems of registration/participation bias. Interview-based studies of the requisite size would be prohibitively expensive and would undoubtedly also run into problems of participation bias. Register-based studie models rather than individual measurements in the homes of those concerned. At present, no firm conclusions can be drawn from the studies that have been published to date. Further data and perhaps pooled studies offer a way forward.

Uncertainties regarding the magnitude of health effects following exposure to low doses of ionizing radiation remain a matter of concern both for professionals and for the public. There is consensus within the international radiation research community that more research is required on biological effects of radiation doses below 100 mGy applied at low dose rates. Moreover, there is a demand for increasing education and training of future radiation researchers and regulators. Research, education and training is primarily carried out at universities but university-based radiation research is often hampered by limited access to radiation sources. The aim of the present report is to describe small and cost-effective low activity gamma and alpha sources that can easily be installed and used in university laboratories.

A gamma radiation source was made from an euxenite-(Y) rock (Y,Ca,Ce,U,Th)(Nb,Ta,Ti)

O

) that was found in an abandoned mine in Sweden. It allows exposing cells grown in culture dishes to radiation at a dose rate of 50

Gy/h and lower. Three alpha sources were custom-made and yield a dose rate of 1 mGy/h each. The construction, dosimetry and cellular effects of the sources are described.

We hope that the report will stimulate research and training activities in the low dose field by facilitating access to radiation sources.

We hope that the report will stimulate research and training activities in the low dose field by facilitating access to radiation sources.Acute isolated optic neuritis can be the initial presentation of demyelinating inflammatory central nervous system disease related to multiple sclerosis (MS), neuromyelitis optica (NMO) or myelin oligodendrocyte glycoprotein antibody disease (MOG-AD). In addition to the well-characterized brain and spinal cord imaging features, important and characteristic differences in the radiologic appearance of the optic nerves in these disorders are being described, and magnetic resonance imaging (MRI) of the optic nerves is becoming an essential tool in the differential diagnosis of optic neuritis. Whereas typical demyelinating optic neuritis is a relatively mild and self-limited disease, atypical optic neuritis in NMO and MOG-AD is potentially much more vision-threatening and merits a different treatment approach. Thus, differentiation based on MRI features may be particularly important during the first attack of optic neuritis, when antibody status is not yet known. This review discusses the optic nerve imaging in the major demyelinating disorders with an emphasis on clinically relevant differences that can help clinicians assess and manage these important neuro-ophthalmic disorders. It also reviews the utility of optic nerve MRI as a prognostic indicator in acute optic neuritis.Objectives Serum uric acid (UA) and arterial lactate acid (LA) are markers of oxidative stress and tissue hypoxia that are present in patients with obstructive sleep apnea syndrome (OSAS). The aim of the study was to evaluate the associations between UA and LA levels and OSAS characteristics as well as the effect of their levels after continuous positive airway pressure (CPAP) treatment.Methods This is a retrospective of newly diagnosed patients with OSAS. UA and LA levels were measured the night before the diagnostic sleep study, and 6 months after CPAP therapy.Results We evaluated 604 individuals with OSAS and 98 controls (i.e. individuals without sleep-related breathing disorders). Baseline median (IQR) serum UA levels were higher in OSAS patients compared to controls; 7.0 (6.4, 8.1) mg/dL vs 6.3 (6.1, 6.4) mg/dL, respectively (p less then 0.001). This difference remained significant, after adjustment of serum UA to creatinine ratio (UA/Cr) (p less then 0.001). Patients with OSAS had higher LA levels at baseline compared to controls; 2.26 (2.25, 2.31) mmol/L vs 1.90 (1.87, 1.97) mmol/L, respectively (p less then 0.001). Both UA and LA levels decreased significantly after CPAP treatment [median (IQR) 7.0 (6.4, 8.1) mg/dL vs 6.4 (6.2, 6.8) mg/dL, p less then 0.001 and 2.26 (2.25, 2.31) mmol/L vs 2.08 (2.07, 2.31) mmol/L, p less then 0.001]. Several sleep parameters were independent predictors of UA and LA levels.Conclusion In OSAS patients increased serum UA and arterial LA levels are found. CPAP therapy resulted in significant reductions in levels of both biomarkers.Introduction Exosomes are nanovesicles that play important functions in a variety of physiological and pathological conditions. They are powerful cell-to-cell communication tool thanks to the protein, mRNA, miRNA, and lipid cargoes they carry. They are also emerging as valuable diagnostic and prognostic biomarker sources. Urinary exosomes carry information from all the cells of the urinary tract, downstream of the podocyte. Rare kidney diseases are a subset of an inherited diseases whose genetic diagnosis can be unclear, and presentation can vary due to genetic, epigenetic, and environmental factors. Areas covered In this review, we focus on a group of rare and often neglected kidney diseases, for which we have sufficient available literature data on urinary exosomes. The analysis of their content can help to comprehend pathological mechanisms and to identify biomarkers for diagnosis, prognosis, and therapeutic targets. Expert opinion The foreseeable large-scale application of system biology approach to the profiling of exosomal proteins as a source of renal disease biomarkers will be also useful to stratify patients with rare kidney diseases whose penetrance, phenotypic presentation, and age of onset vary sensibly. This can ameliorate the clinical management.Introduction In 2013, riociguat a potent and specific stimulator of the soluble guanylyl cyclase (sGC) was approved as first in class sGC stimulator which reflected a first culmination of intense research and development efforts starting in the mid 1990ies. In the meantime, it turned out that triggering cGMP production by sGC stimulators could have a broad treatment potential. In consequence, various pharmaceutical companies are still very active in identifying novel chemistry for sGC stimulators. After the first generation of sGC stimulators like riociguat or lificiguat, new compound classes with different physicochemical and kinetic profiles were identified, like the sGC stimulators vericiguat or praliciguat.Area covered Patent literature on sGC stimulators with a focus on recent compounds of the years 2014-2019 as on claimed use and formulations of these compounds. The information was collected from publicly available data sources only (MedLine, EmBase, Chemical Abstracts, Orbit, Dolphin).Expert Opinion With the recent advancements reported in the patent literature, sGC stimulators might be differentiated due to tissue selectivity or route of application although exhibiting the same molecular mode of action. The indication space of these compounds is potentially very broad and multiple indications in cardiovascular diseases and beyond are under investigation.

Risk assessment of chemical mixtures or complex substances remains a major methodological challenge due to lack of available hazard or exposure data. Therefore, risk assessors usually infer hazard or risk from data on the subset of constituents with available toxicity values.

We evaluated the validity of the widely used traditional mixtures risk assessment paradigms, Independent Action (IA) and Concentration Addition (CA), with new approach methodologies (NAMs) data from human cell-based

assays.

A diverse set of 42 chemicals was tested both individually and as mixtures for functional and cytotoxic effects

. A panel of induced pluripotent stem cell (iPSCs)-derived models (hepatocytes, cardiomyocytes, endothelial, and neurons) and one primary cell type (HUVEC) were used. Bayesian concentration-response modeling of individual chemicals or their mixtures was performed for a total of 47 phenotypes to derive point-of-departure (POD) values. Probabilistic IA or CA was conducted to estimate the mixture effects based on the bioactivity profiles from the individual chemicals and compared with mixture bioactivity.