Comprehensive analysis of naturally occurring radionuclides in well water: Isotopic ratios, mitigation, and dose assessment.

In Sweden, around 20 % of the potable water comes from groundwater sources and about one million people drink water from their private wells. In areas with moderate or high abundance of naturally occurring radionuclides in the bedrock, the groundwater could be enhanced with radio and chemically toxic elements such as uranium, radium, lead and polonium. Therefore, this study aims to carry out a comprehensive analysis of the behaviour and radiological impact of naturally occurring radionuclides in well water.

Usefulness and limitations of various detector systems for estimation ofI thyroid activity following an RN event.

Following a radiological or nuclear (RN) event, rapid measurement ofI in members of the public is of utmost importance, and much equipment is needed for a high throughput. In this study, three gamma cameras (GCs), two thyroid uptake meters (TUMs) and one whole-body counter (WBC) were calibrated for activity measurements ofI in the thyroid. Minimum detectable activity was derived for the GCs, the TUMs and the WBC giving that a committed effective dose (CED) in the interval 2.

Nonparametric distributions of tensor-valued Lorentzian diffusion spectra for model-free data inversion in multidimensional diffusion MRI.

Magnetic resonance imaging (MRI) is the method of choice for noninvasive studies of micrometer-scale structures in biological tissues via their effects on the time- and frequency-dependent (restricted) and anisotropic self-diffusion of water. While new designs of time-dependent magnetic field gradient waveforms have enabled disambiguation between different aspects of translational motion that are convolved in traditional MRI methods relying on single pairs of field gradient pulses, data analysis for complex heterogeneous materials remains a challenge. Here, we propose and demonstrate nonparametric distributions of tensor-valued Lorentzian diffusion spectra, or "D(ω) distributions," as a general representation with sufficient flexibility to describe the MRI signal response from a wide range of model systems and biological tissues investigated with modulated gradient waveforms separating and correlating the effects of restricted and anisotropic diffusion.

Integrated transcriptomics- and structure-based drug repositioning identifies drugs with proteasome inhibitor properties.

Computational pharmacogenomics can potentially identify new indications for already approved drugs and pinpoint compounds with similar mechanism-of-action. Here, we used an integrated drug repositioning approach based on transcriptomics data and structure-based virtual screening to identify compounds with gene signatures similar to three known proteasome inhibitors (PIs; bortezomib, MG-132, and MLN-2238). In vitro validation of candidate compounds was then performed to assess proteasomal proteolytic activity, accumulation of ubiquitinated proteins, cell viability, and drug-induced expression in A375 melanoma and MCF7 breast cancer cells.

Multi-omics analysis identifies repurposing bortezomib in the treatment of kidney-, nervous system-, and hematological cancers.

Repurposing of FDA-approved drugs is a quick and cost-effective alternative to de novo drug development. Here, we identify genes involved in bortezomib sensitivity, predict cancer types that may benefit from treatment with bortezomib, and evaluate the mechanism-of-action of bortezomib in breast cancer (BT-474 and ZR-75-30), melanoma (A-375), and glioblastoma (A-172) cells in vitro. Cancer cell lines derived from cancers of the blood, kidney, nervous system, and skin were found to be significantly more sensitive to bortezomib than other organ systems.

Effects of Recombinant α-Microglobulin on Early Proteomic Response in Risk Organs after Exposure to Lu-Octreotate.

Recombinant α-microglobulin (A1M) is proposed as a protector during Lu-octreotate treatment of neuroendocrine tumors, which is currently limited by bone marrow and renal toxicity. Co-administration of Lu-octreotate and A1M could result in a more effective treatment by protecting healthy tissue, but the radioprotective action of A1M is not fully understood. The aim of this study was to examine the proteomic response of kidneys and bone marrow early after Lu-octreotate and/or A1M administration.

Comparison of Lu-octreotate and Lu-octreotide for treatment in human neuroblastoma-bearing mice.

Background: Patients with high-risk neuroblastoma (NB) have a 5-year event-free survival of less than 50 %, and novel and improved treatment options are needed. Radiolabeled somatostatin analogs (SSTAs) could be a treatment option. The aims of this work were to compare the biodistribution and the therapeutic effects of Lu-octreotate and Lu-octreotide in mice bearing the human CLB-BAR NB cell line, and to evaluate their regulatory effects on apoptosis-related genes.

Repurposing proteasome inhibitors for improved treatment of triple-negative breast cancer.

Triple-negative breast cancer (TNBC) is associated with poor prognosis and limited treatment options due to the lack of important receptors (estrogen receptor [ER], progesterone receptor [PR], and human epidermal growth factor receptor 2 [HER2]) used for targeted therapy. However, high-throughput in vitro drug screening of cell lines is a powerful tool for identifying effective drugs for a disease. Here, we determine the intrinsic chemosensitivity of TNBC cell lines to proteasome inhibitors (PIs), thereby identifying potentially potent 2-drug combinations for TNBC.

Analysis of radioactivity in commercially available products aiming to improve health and wellness.

There are products available on the online market that are claim to contain unique 'energies' that can improve health and wellness by eliminating toxins and pains and energising food and drinking water. We investigated these products by alpha and gamma spectrometry, and the analysis showed that they contained a few to hundreds of kilobecquerels per kilogram of naturally occurring radionuclides from the 232Th and 238U series. The committed effective dose for an adult drinking water that had been in contact with these products just once was estimated to 12 nSv.

Recombinant α-Microglobulin (rA1M) Protects against Hematopoietic and Renal Toxicity, Alone and in Combination with Amino Acids, in a Lu-DOTATATE Mouse Radiation Model.

Lu-DOTATATE peptide receptor radionuclide therapy (PRRT) is used clinically to treat metastasized or unresectable neuroendocrine tumors (NETs). Although Lu-DOTATATE is mostly well tolerated in patients, bone marrow suppression and long-term renal toxicity are still side effects that should be considered. Amino acids are often used to minimize renal radiotoxicity, however, they are associated with nausea and vomiting in patients.

Biodistribution of naturally occurring radionuclides and radiocesium in wild European perch (Perca fluviatilis).

Wild European perch (Perca fluviatilis) is one of the most important freshwater fish species, in Sweden, due to its widespread and his value for recreational fishing. Little it is known regarding the biodistribution of naturally occurring radionuclides such as U, U, Ra, Po in perch. Therefore, in this study, perches from five lakes located in different counties in Sweden were collected to investigate the biodistribution of U, U, Ra, Po and Cs in organs and tissues of perch as well as their radiological impact.

Co-administration with A1M does not influence apoptotic response of Lu-octreotate in GOT1 neuroendocrine tumors.

Recombinant α-microglobulin (A1M) is a proposed radioprotector during Lu-octreotate therapy of neuroendocrine tumors (NETs). To ensure a maintained therapeutic effect, we previously demonstrated that A1M does not affect the Lu-octreotate induced decrease in GOT1 tumor volume. However, the underlying biological events of these findings are still unknown.

Pan-cancer analysis of genomic and transcriptomic data reveals the prognostic relevance of human proteasome genes in different cancer types.

Background: The human proteasome gene family (PSM) consists of 49 genes that play a crucial role in cancer proteostasis. However, little is known about the effect of PSM gene expression and genetic alterations on clinical outcome in different cancer forms.

Methods: Here, we performed a comprehensive pan-cancer analysis of genetic alterations in PSM genes and the subsequent prognostic value of PSM expression using data from The Cancer Genome Atlas (TCGA) containing over 10,000 samples representing up to 33 different cancer types.

Age and sex effects across the blood proteome after ionizing radiation exposure can bias biomarker screening and risk assessment.

Molecular biomarkers of ionizing radiation (IR) exposure are a promising new tool in various disciplines: they can give necessary information for adaptive treatment planning in cancer radiotherapy, enable risk projection for radiation-induced survivorship diseases, or facilitate triage and intervention in radiation hazard events. However, radiation biomarker discovery has not yet resolved the most basic features of personalized medicine: age and sex. To overcome this critical bias in biomarker identification, we quantitated age and sex effects and assessed their relevance in the radiation response across the blood proteome.

Age-related long-term response in rat thyroid tissue and plasma after internal low dose exposure to I.

I is used clinically for therapy, and may be released during nuclear accidents. After the Chernobyl accident papillary thyroid carcinoma incidence increased in children, but not adults. The aims of this study were to compare I irradiation-dependent differences in RNA and protein expression in the thyroid and plasma of young and adult rats, and identify potential age-dependent biomarkers for I exposure.

Hyperfractionated Treatment with Lu-Octreotate Increases Tumor Response in Human Small-Intestine Neuroendocrine GOT1 Tumor Model.

Radionuclide treatment of patients with neuroendocrine tumors has advanced in the last decades with favorable results using Lu-octreotate. However, the gap between the high cure rate in animal studies vs. patient studies indicates a potential to increase the curation of patients.

VERDICT MRI for radiation treatment response assessment in neuroendocrine tumors.

Noninvasive methods to study changes in tumor microstructure enable early assessment of treatment response and thus facilitate personalized treatment. The aim of this study was to evaluate the diffusion MRI model, Vascular, Extracellular and Restricted Diffusion for Cytometry in Tumors (VERDICT), for early response assessment to external radiation treatment and to compare the results with those of more studied sets of parameters derived from diffusion-weighted MRI data. Mice xenografted with human small intestine tumors were treated with external radiation treatment, and diffusion MRI experiments were performed on the day before and up to 2 weeks after treatment.

Correction: Long-term transcriptomic and proteomic effects in Sprague Dawley rat thyroid and plasma after internal low dose 131I exposure.

[This corrects the article DOI: 10.1371/journal.pone.

Neuroblastoma xenograft models demonstrate the therapeutic potential of Lu-octreotate.

Background: Neuroblastoma (NB) is one of the most frequently diagnosed tumors in infants. NB is a neuroendocrine tumor type with various characteristics and features, and with diverse outcome. The most malignant NBs have a 5-year survival rate of only 40-50%, indicating the need for novel and improved treatment options.

Neurochemical properties measured by H magnetic resonance spectroscopy may predict cognitive behaviour therapy outcome in paediatric OCD: a pilot study.

To identify neurochemical factors measured pre-treatment that may predict cognitive behavioural treatment (CBT) outcome, aiming at understanding possible causes of poor CBT response. 1H magnetic resonance spectroscopy was used before treatment with CBT in treatment naïve 11-18 year-old patients with moderate-severe OCD. Diagnoses and assessment of OCD severity were based on semi-structured interviews.

Genetic alterations associated with multiple primary malignancies.

Breast cancer (BC) patients are frequently at risk of developing other malignancies following treatment. Although studies have been conducted to elucidate the etiology of multiple primary malignancies (MPM) after a BC diagnosis, few studies have investigated other previously diagnosed primary malignancies (OPPM) before BC. Here, genome-wide profiling was used to identify potential driver DNA copy number alterations and somatic mutations that promote the development of MPMs.

Long-term transcriptomic and proteomic effects in Sprague Dawley rat thyroid and plasma after internal low dose 131I exposure.

Background: Radioiodide (131I) is commonly used to treat thyroid cancer and hyperthyroidis.131I released during nuclear accidents, have resulted in increased incidence of thyroid cancer in children. Therefore, a better understanding of underlying cellular mechanisms behind 131I exposure is of great clinical and radiation protection interest.

Biodistribution of I in mice is influenced by circadian variations.

Effects of radiation and biodistribution of radionuclides are often studied in animal models. Circadian rhythm affects many biological functions and may influence the biokinetics of radionuclides and observed responses. The aim of this study was to investigate if the time during the day of I injection affects the biodistribution and absorbed dose to tissues in mice.

Effects of different mean arterial pressure targets on plasma volume, ANP and glycocalyx-A randomized trial.

Background: Arterial haematocrit (Hct) has been shown to decrease after anaesthesia induction, most probably because of an increased plasma volume (PV). The primary objective was to quantify change in PV if mean arterial pressure (MAP) was kept at baseline level or allowed to decrease to 60 mm Hg. Our secondary objective was to evaluate underlying mechanisms of this response.