Screening the complex biological behavior of late lanthanides through genome-wide interactions.

Despite their similar physicochemical properties, recent studies have demonstrated that lanthanides can display different biological behaviors. Hence, the lanthanide series can be divided into three parts, namely early, mid, and late lanthanides, based on their interactions with biological systems. In particular, the late lanthanides demonstrate distinct, but poorly understood biological activity.

Identifying Toxicity Mechanisms Associated with Early Lanthanide Exposure through Multidimensional Genome-Wide Screening.

Lanthanides are a series of elements essential to a wide range of applications, from clean energy production to healthcare. Despite their presence in multiple products and technologies, their toxicological characteristics have been only partly studied. Recently, our group has employed a genomic approach to extensively characterize the toxicity mechanisms of lanthanides.

Heavy-Ion-Induced Lung Tumors: Dose- & LET-Dependence.

There is a limited published literature reporting dose-dependent data for in vivo tumorigenesis prevalence in different organs of various rodent models after exposure to low, single doses of charged particle beams. The goal of this study is to reduce uncertainties in estimating particle-radiation-induced risk of lung tumorigenesis for manned travel into deep space by improving our understanding of the high-LET-dependent dose-response from exposure to individual ion beams after low particle doses (0.03-0.

Characteristics of circulatory failure after out-of-hospital cardiac arrest: a prospective cohort study.

Background: Circulatory failure after out-of-hospital cardiac arrest (OHCA) as part of the postcardiac arrest syndrome (PCAS) is believed to be caused by an initial myocardial depression that later subsides into a superimposed vasodilatation. However, the relative contribution of myocardial dysfunction and systemic inflammation has not been established. Our objective was to describe the macrocirculatory and microcirculatory failure in PCAS in more detail.

Delineating toxicity mechanisms associated with MRI contrast enhancement through a multidimensional toxicogenomic profiling of gadolinium.

Gadolinium is a metal used in contrast agents for magnetic resonance imaging. Although gadolinium is widely used in clinical settings, many concerns regarding its toxicity and bioaccumulation after gadolinium-based contrast agent administration have been raised and published over the last decade. To date, most toxicological studies have focused on identifying acute effects following gadolinium exposure, rather than investigating associated toxicity mechanisms.

Multidimensional genome-wide screening in yeast provides mechanistic insights into europium toxicity.

Europium is a lanthanide metal that is highly valued in optoelectronics. Even though europium is used in many commercial products, its toxicological profile has only been partially characterized, with most studies focusing on identifying lethal doses in different systems or bioaccumulation in vivo. This paper describes a genome-wide toxicogenomic study of europium in Saccharomyces cerevisiae, which shares many biological functions with humans.

Circulatory trajectories after out-of-hospital cardiac arrest: a prospective cohort study.

Background: Circulatory failure frequently occurs after out-of-hospital cardiac arrest (OHCA) and is part of post-cardiac arrest syndrome (PCAS). The aim of this study was to investigate circulatory disturbances in PCAS by assessing the circulatory trajectory during treatment in the intensive care unit (ICU).

Methods: This was a prospective single-center observational cohort study of patients after OHCA.

Genome-wide toxicogenomic study of the lanthanides sheds light on the selective toxicity mechanisms associated with critical materials.

Lanthanides are a series of critical elements widely used in multiple industries, such as optoelectronics and healthcare. Although initially considered to be of low toxicity, concerns have emerged during the last few decades over their impact on human health. The toxicological profile of these metals, however, has been incompletely characterized, with most studies to date solely focusing on one or two elements within the group.

Transitions Between Circulatory States After Out-of-Hospital Cardiac Arrest: Protocol for an Observational, Prospective Cohort Study.

Background: The post cardiac arrest syndrome (PCAS) is responsible for the majority of in-hospital deaths following cardiac arrest (CA). The major elements of PCAS are anoxic brain injury and circulatory failure.

Objective: This study aimed to investigate the clinical characteristics of circulatory failure and inflammatory responses after out-of-hospital cardiac arrest (OHCA) and to identify patterns of circulatory and inflammatory responses, which may predict circulatory deterioration in PCAS.

Harderian Gland Tumorigenesis: Low-Dose and LET Response.

Increased cancer risk remains a primary concern for travel into deep space and may preclude manned missions to Mars due to large uncertainties that currently exist in estimating cancer risk from the spectrum of radiations found in space with the very limited available human epidemiological radiation-induced cancer data. Existing data on human risk of cancer from X-ray and gamma-ray exposure must be scaled to the many types and fluences of radiations found in space using radiation quality factors and dose-rate modification factors, and assuming linearity of response since the shapes of the dose responses at low doses below 100 mSv are unknown. The goal of this work was to reduce uncertainties in the relative biological effect (RBE) and linear energy transfer (LET) relationship for space-relevant doses of charged-particle radiation-induced carcinogenesis.

Abductor pollicis longus tendon interposition for arthrosis of the first carpo-metacarpal joint. Long-term results.

Background: We performed an interposition arthroplasty using the abductor pollicis longus tendon for arthrosis in the basal joint of the thumb that needed surgery from 1995 to 2010. In 2001 47 patients (55 thumbs) were reviewed after 3.5 (1-5) years.

Validation of the Endopep-MS method for qualitative detection of active botulinum neurotoxins in human and chicken serum.

Botulinum neurotoxins (BoNTs) are highly toxic proteases produced by anaerobic bacteria. Traditionally, a mouse bioassay (MBA) has been used for detection of BoNTs, but for a long time, laboratories have worked with alternative methods for their detection. One of the most promising in vitro methods is a combination of an enzymatic and mass spectrometric assay called Endopep-MS.

An interferon signature identified by RNA-sequencing of mammary tissues varies across the estrous cycle and is predictive of metastasis-free survival.

The concept that a breast cancer patient's menstrual stage at the time of tumor surgery influences risk of metastases remains controversial. The scarcity of comprehensive molecular studies of menstrual stage-dependent fluctuations in the breast provides little insight in this observation. To gain a deeper understanding of the biological changes in mammary tissue and blood during the menstrual cycle and to determine the influence of environmental exposures, such as low-dose ionizing radiation (LDIR), we used the mouse to characterize estrous-cycle variations in mammary gene transcripts by RNA-sequencing, peripheral white blood cell (WBC) counts and plasma cytokine levels.

(238)Pu elimination profiles after delayed treatment with 3,4,3LI(1,2HOPO) in female and male Swiss-Webster mice.

Purpose: To characterize the dose-dependent and sex-related efficacy of the hydroxypyridinonate decorporation agent 3,4,3-LI(1,2-HOPO) at enhancing plutonium elimination when post-exposure treatment is delayed.

Materials And Methods: Six parenteral dose levels of 3,4,3-LI(1,2-HOPO) from 1-300 μmol/kg were evaluated for decorporating plutonium in female and male Swiss-Webster mice administered a soluble citrate complex of (238)Pu and treated 24 hours later. Necropsies were scheduled at four time-points (2, 4, 8, and 15 days post-contamination) for the female groups and at three time-points (2, 4, and 8 days post-contamination) for the male groups.

Mass spectrometric detection of protein-based toxins.

This review focuses on mass spectrometric detection of protein-based toxins, which are among the most toxic substances known. Special emphasis is given to the bacterial toxins botulinum neurotoxin from Clostridium botulinum and anthrax toxins from Bacillus anthracis as well as the plant toxin ricin produced by Ricinus communis. A common feature, apart from their extreme toxicity, is that they are composed of 2 polypeptide chains, one of which is responsible for cell uptake and another that has enzymatic function with the ability to destroy basic cellular functions.

Demand for Zn2+ in acid-secreting gastric mucosa and its requirement for intracellular Ca2+.

Background And Aims: Recent work has suggested that Zn(2+) plays a critical role in regulating acidity within the secretory compartments of isolated gastric glands. Here, we investigate the content, distribution and demand for Zn(2+) in gastric mucosa under baseline conditions and its regulation during secretory stimulation.

Methods And Findings: Content and distribution of zinc were evaluated in sections of whole gastric mucosa using X-ray fluorescence microscopy.

Biomimetic actinide chelators: an update on the preclinical development of the orally active hydroxypyridonate decorporation agents 3,4,3-LI(1,2-HOPO) and 5-LIO(Me-3,2-HOPO).

The threat of a dirty bomb or other major radiological contamination presents a danger of large-scale radiation exposure of the population. Because major components of such contamination are likely to be actinides, actinide decorporation treatments that will reduce radiation exposure must be a priority. Current therapies for the treatment of radionuclide contamination are limited and extensive efforts must be dedicated to the development of therapeutic, orally bioavailable, actinide chelators for emergency medical use.

Bioanalytical investigation of asarone in connection with Acorus calamus oil intoxications.

Preparations of the plant Acorus calamus (calamus or sweet flag) (A. calamus) are available via internet trade and marketed as being hallucinogenic. In 2003-2006, the Swedish Poisons Information Centre received inquiries about 30 clinical cases of intentional intoxication with A.

Bioanalytical and clinical evaluation of 103 suspected cases of intoxications with psychoactive plant materials.

Introduction: Problems associated with the increasing abuse of plant-derived psychoactive substances have recently attracted attention. This study involved bioanalytical and clinical examinations of intoxication cases suspected to be linked to such plant materials.

Methods: Urine samples were collected at emergency wards in Sweden from patients who either admitted or were suspected of ingestion of psychoactive plant materials.

A multi-component LC-MS/MS method for detection of ten plant-derived psychoactive substances in urine.

A sensitive and specific LC-MS/MS method for simultaneous detection of 10 plant-derived psychoactive substances (atropine, N,N-dimethyltryptamine, ephedrine, harmaline, harmine, ibogaine, lysergic acid amide, psilocin, scopolamine and yohimbine) in urine was developed. Direct injection of urine diluted with 3 deuterated internal standards allowed for a readily accessible method suitable for application in clinical intoxication cases. Separation was achieved using reversed phase chromatography and gradient elution with a total analysis time of 14 min.

Mid-infrared reflectivity of experimental atheromas.

We report that the pathologic components present within the atheromatous plaques of ApoE knock-out mice can reflect significant amounts of mid-infrared (mid-IR) light. Furthermore, the reflected light spectra contained the unique signatures of a variety of biologic features including those found in unstable or "vulnerable" plaque. This discovery may represent a unique opportunity to develop a new intravascular diagnostic modality that can detect and characterize sites of atherosclerosis.

Development and clinical application of an LC-MS-MS method for mescaline in urine.

Mescaline (3,4,5-trimethoxyphenylethylamine) is an hallucinogenic psychoactive substance present in several species of cacti. Mescaline has a documented use dating back 5700 years. In more recent years, the interest in hallucinogenic designer drugs such as ecstasy has also triggered interest in the naturally occurring mescaline.

Particle radiation alters expression of matrix metalloproteases resulting in ECM remodeling in human lens cells.

Relatively low doses of space radiation have been correlated with an increased incidence and earlier appearance of cataracts in space travelers. The lens is a radiosensitive organ of the body with a very obvious late end point of radiation damage--cataract. However, many molecular changes occur in the lens soon after radiation exposure and long before the appearance of an opacification.

Synthetic nano-low density lipoprotein as targeted drug delivery vehicle for glioblastoma multiforme.

The low density lipoprotein (LDL) receptor has been shown to be upregulated in GBM tumor cells and is therefore a potential molecular target for the delivery of therapeutic agents. A synthetic nano-LDL (nLDL) particle was developed and tested to determine its utility as a drug delivery vehicle targeted to GBM tumors. nLDL particles were constructed by combining a synthetic peptide containing a lipid binding motif and the LDL receptor (LDLR) binding domain of apolipoprotein B-100 with a lipid emulsion consisting of phosphatidyl choline, triolein, and cholesteryl oleate.