Ion mobility mass spectrometry unveils conformational effects of drug lead EPI-001 on the intrinsically disordered N-terminal domain of the androgen receptor.

Intrinsically disordered proteins (IDPs) are important drug targets as they are key actors within cell signaling networks. However, the conformational plasticity of IDPs renders them challenging to characterize, which is a bottleneck in developing small molecule drugs that bind to IDPs and modulate their behavior. In relation to this, ion mobility mass spectrometry (IM-MS) is a useful tool to investigate IDPs, as it can reveal their conformational preferences.

Corrigendum: Characterising an Alternative Murine Model of Diabetic Cardiomyopathy.

[This corrects the article DOI: 10.3389/fphys.2019.

Characterising an Alternative Murine Model of Diabetic Cardiomyopathy.

The increasing burden of heart failure globally can be partly attributed to the increased prevalence of diabetes, and the subsequent development of a distinct form of heart failure known as diabetic cardiomyopathy. Despite this, effective treatment options have remained elusive, due partly to the lack of an experimental model that adequately mimics human disease. In the current study, we combined three consecutive daily injections of low-dose streptozotocin with high-fat diet, in order to recapitulate the long-term complications of diabetes, with a specific focus on the diabetic heart.

An unusual presentation of atrial myxoma: thromboembolic phenomenon with a recent normal echocardiogram.

Atrial myxomas are the most common primary neoplasms of the heart. Clinical presentation varies from asymptomatic incidental masses to serious life-threatening cardiovascular complications. We describe the case of a 37-year-old man who presented with both coronary and cerebral embolisation secondary to an atrial myxoma in the context of a recent normal transthoracic echocardiogram.

Emotional intelligence: A unique group training in a hematology-oncology unit.

Background: Emotional intelligence (EI) is increasingly viewed as one of the important skills required for a successful career and personal life. Consequently, efforts have been made to improve personal and group performance in EI, mostly in commercial organizations. However, these programs have not been widely applied in the health field.

The Rhodococcus equi virulence protein VapA disrupts endolysosome function and stimulates lysosome biogenesis.

Rhodococcus equi (R. equi) is an important pulmonary pathogen in foals that often leads to the death of the horse. The bacterium harbors a virulence plasmid that encodes numerous virulence-associated proteins (Vaps) including VapA that is essential for intracellular survival inside macrophages.

A pilot study of an emotional intelligence training intervention for a paediatric team.

Objective: Emotional intelligence (EI) is the individual's ability to perceive, understand and manage emotion and to understand and relate effectively to others. We examined the degree to which EI training may be associated with a change in EI among different medical personnel and patient satisfaction.

Design, Setting And Participants: The EI of 17 physicians and 10 nurses in paediatric ward was prospectively evaluated with Bar-On's EI at baseline and after 18 months.

Rab32 restriction of intracellular bacterial pathogens.

Our immune system is engaged in a continuous battle against invading pathogens, many of which have evolved to survive in intracellular niches of mammalian hosts. A variety of cellular processes are involved in preventing bacterial invasion or in killing bacteria that successfully invade host cells. Recently, the Rab GTPase Rab32 emerged as critical regulator of a host defense pathway that can eliminate bacterial pathogens.

Purification of Lysosomes Using Supraparamagnetic Iron Oxide Nanoparticles (SPIONs).

Lysosomes can be rapidly isolated from tissue culture cells using supraparamagnetic iron oxide particles (SPIONs). In this protocol, colloidal iron dextran (FeDex) particles, a type of SPION, are taken up by cultured mouse macrophage cells via the endocytic pathway. The SPIONs accumulate in lysosomes, the end point of the endocytic pathway, permitting the lysosomes to be isolated magnetically.

[EMOTIONAL INTELLIGENCE EQ--A NECESSARY SKILL FOR SUCCESS OF MEDICAL STAFF IN THE 21ST CENTURY].

During the last decade, medical organizations have undergone major changes worldwide and these continue to evolve at a rapid pace. Today the medical profession faces many new challenges that will eventually have an impact on almost every aspect of daily hospital routine. To a large extent, these issues arise from emerging new technologies, the entry of a new generation of trained workers who have different views and characteristics than previous generations, and the introduction of stricter regulations and accreditation procedures in recent years.

[THE WORLD EXPERIENCE OF THE PEDIATRIC INTESTINAL FAILURE PROGRAM: SUCCESSFUL OUTCOMES FROM INTESTINAL REHABILITATION].

Management of children with short bowel syndrome is optimized by interdisciplinary coordination of parenteral and enteral nutrition support, medical management of associated complications, surgical lengthening procedures, and intestinal transplantation. Pediatric Intestinal Failure Centers were established in 14 pediatric hospitals throughout the United States and Canada and the Pediatric Intestinal Failure Consortium has been developed and is implementing prospective, multi-institutional studies to better define the specific aspects of intestinal failure management that optimize long-term outcomes. The published data from these studies suggest that intestinal failure in pediatric patients is quite treatable and provides further evidence that all infants at risk for intestinal failure should be treated aggressively and referred early to a dedicated intestinal rehabilitation center.

[93 YEARS OF CLINICAL EMPATHY, STATE-OF-THE-ART MEDICINE AND RESEARCH EXCELLENCE].

This issue of Harefuah is devoted to articles and reviews written by the medical staff of Bnai Zion Medical Center in Haifa. Celebrating 93 years since its inception, Bnai Zion Medical Center is home to the oldest public hospital in Haifa, and a founding affiliate of the Technion's Faculty of Medicine. Known for its centers of excellence and the impactful clinical and basic research developed, the hospital has a reputation for state-of-the-art medicine, both conventional and complementary.

Isolating phagosomes from tissue culture cells.

Phagocytosis is the process by which receptors at the plasma membrane are used to engulf a particle such as a bacterium, parasite, or dead cell. Phagosomes can be isolated from tissue culture cells by various centrifugation methods, including the use of differential density gradients or sucrose step gradients, but these methods are time-consuming or otherwise difficult. We describe here a protocol that avoids centrifugation and relies instead on the uptake of magnetic beads to rapidly isolate the phagosomal compartment from tissue culture cells.

In vivo measurement, in vitro estimation and fugacity prediction of PAH bioavailability in post-remediated creosote-contaminated soil.

In this study, PAH bioavailability was assessed in creosote-contaminated soil following bioremediation in order to determine potential human health exposure to residual PAHs from incidental soil ingestion. Following 1,000 days of enhanced natural attenuation (ENA), a residual PAH concentration of 871 ± 8 mg kg(-1) (∑16 USEPA priority PAHs in the <250 μm soil particle size fraction) was present in the soil. However, when bioavailability was assessed to elucidate potential human exposure using an in vivo mouse model, the upper-bound estimates of PAH absolute bioavailability were in excess of 65% irrespective of the molecular weight of the PAH.

The heart team approach to coronary revascularization--have we crossed the lines of evidence-based medicine?

Evidence-based medicine demands considerable time and decision-making skills to navigate through the proliferating data. A hierarchical "pyramid of evidence" has been formulated to help categorize data quality. The hierarchical data are processed into recommendations in Practice Guideline statements.

Predicting lead relative bioavailability in peri-urban contaminated soils using in vitro bioaccessibility assays.

In this study, lead (Pb) bioaccessibility was assessed in peri-urban contaminated soils using a variety of established in vitro assays. Bioaccessibility data was then used to predict Pb relative bioavailability (RBA) using published in vivo-in vitro regression models in order to compare calculated estimates and measured values. Lead bioaccessibility varied depending on the in vitro methodology employed with the relative bioavailability leaching procedure (RBALP) and in vitro gastrointestinal (IVG) assays providing more conservative Pb bioaccessibility values compared to those determined using PBET, UBM and Rel-SBRC-I assays.

Molecular insights into vesicle tethering at the Golgi by the conserved oligomeric Golgi (COG) complex and the golgin TATA element modulatory factor (TMF).

Protein sorting between eukaryotic compartments requires vesicular transport, wherein tethering provides the first contact between vesicle and target membranes. Here we map and start to functionally analyze the interaction network of the conserved oligomeric Golgi (COG) complex that mediates retrograde tethering at the Golgi. The interactions of COG subunits with members of transport factor families assign the individual subunits as specific interaction hubs.

Assessment of DDT relative bioavailability and bioaccessibility in historically contaminated soils using an in vivo mouse model and fed and unfed batch in vitro assays.

In this study, DDTr (DDTr = DDT + DDD + DDE) relative bioavailability in historically contaminated soils (n = 7) was assessed using an in vivo mouse model. Soils or reference materials were administered to mice daily over a 7 day exposure period with bioavailability determined using DDTr accumulation in adipose, kidney, or liver tissues. Depending on the target tissue used for its calculation, some variability in DDTr relative bioavailability was observed; however, it did not exceed 25% (range 2-25%).

Antagonistic effects of cadmium on lead accumulation in pregnant and non-pregnant mice.

People are frequently exposed to combinations of contaminants but there is a paucity of data on the effects of mixed contaminants at low doses. This study investigated the influence of cadmium (Cd) on lead (Pb) accumulation in pregnant and non-pregnant mice following exposure to contaminated soil. Exposure to Pb from contaminated soils increased Pb accumulation in both pregnant and non-pregnant mice compared to unexposed control animals (pregnant and non-pregnant).

Prenatal exposure to lipopolysaccharide results in neurodevelopmental damage that is ameliorated by zinc in mice.

There is converging evidence that during pregnancy a maternal immune response to infection can cause neurodevelopmental damage. Lipopolysaccharide (LPS)-mediated induction of metallothionein (MT) and subsequent hypozincaemia has been linked to fetal brain damage. Our group has demonstrated that Zn, when co-administered with LPS in early pregnancy in mice (gestation day (GD) 8), prevents fetal malformations and neurodevelopmental deficits in offspring.

In vivo-in vitro and XANES spectroscopy assessments of lead bioavailability in contaminated periurban soils.

Lead (Pb) bioaccessibility was assessed using 2 in vitro methods in 12 Pb-contaminated soils and compared to relative Pb bioavailability using an in vivo mouse model. In vitro Pb bioaccessibility, determined using the intestinal phase of the Solubility Bioaccessibility Research Consortium (SBRC) assay, strongly correlated with in vivo relative Pb bioavailability (R(2) = 0.88) following adjustment of Pb dissolution in the intestinal phase with the solubility of Pb acetate at pH 6.

Determination of cadmium relative bioavailability in contaminated soils and its prediction using in vitro methodologies.

In this study, cadmium (Cd) relative bioavailability in contaminated (n = 5) and spiked (n = 2) soils was assessed using an in vivo mouse model following administration of feed containing soil or Cd acetate (reference material) over a 15 day exposure period. Cadmium relative bioavailability varied depending on whether the accumulation of Cd in the kidneys, liver, or kidney plus liver was used for relative bioavailability calculations. When kidney plus liver Cd concentrations were used, Cd relative bioavailability ranged from 10.

Assessment of four commonly employed in vitro arsenic bioaccessibility assays for predicting in vivo relative arsenic bioavailability in contaminated soils.

Currently, a number of in vitro methods are in use worldwide to assess arsenic (As) bioaccessibility in soils. However, a dearth of research has been undertaken to compare the efficacy of the in vitro methods for estimating in vivo relative As bioavailability. In this study, As bioaccessibility in contaminated soils (n = 12) was assessed using four in vitro assays (SBRC, IVG, PBET, DIN).