Setting priorities for EU healthcare workforce IT skills competence improvement

A major challenge for healthcare quality improvement is the lack of IT skills and knowledge of healthcare workforce as well as their ambivalent attitudes towards IT. This paper identifies and prioritises actions needed to improve the IT skills of healthcare workforce across the EU. 46 experts, representing different fields of expertise in healthcare and geolocations systematically list and scored actions that would improve IT skills among healthcare workforce. The Child Health and Nutrition Research Initiative methodology was used for research priority-setting. The participants evaluated the actions using the following criteria: feasibility, effectiveness, deliverability, and maximum impact on IT skills improvement. The leading priority actions were related to appropriate training, integrating eHealth in curricula, involving healthcare workforce in the eHealth solution development, improving awareness of eHealth and learning arrangement. As the different professionals’ needs are prioritised, healthcare workforce should be actively and continuously included in the development of eHealth solutions

Academic freedom: in justification of a universal ideal

This paper examines the justification for, and benefits of, academic freedom to academics, students, universities and the world at large. The paper surveys the development of the concept of academic freedom within Europe, more especially the impact of the reforms at the University of Berlin instigated by Wilhelm von Humboldt. Following from this, the paper examines the reasons why the various facets of academic freedom are important and why the principle should continue to be supported

The use of social interest, activity and affect as reflected in early recollections as predictors of stress in an analogue social situation

EducationDoctor of Education (Ed.D.

Reticular dysgenesis-associated AK2 protects hematopoietic stem and progenitor cell development from oxidative stress.

Adenylate kinases (AKs) are phosphotransferases that regulate the cellular adenine nucleotide composition and play a critical role in the energy homeostasis of all tissues. The AK2 isoenzyme is expressed in the mitochondrial intermembrane space and is mutated in reticular dysgenesis (RD), a rare form of severe combined immunodeficiency (SCID) in humans. RD is characterized by a maturation arrest in the myeloid and lymphoid lineages, leading to early onset, recurrent, and overwhelming infections. To gain insight into the pathophysiology of RD, we studied the effects of AK2 deficiency using the zebrafish model and induced pluripotent stem cells (iPSCs) derived from fibroblasts of an RD patient. In zebrafish, Ak2 deficiency affected hematopoietic stem and progenitor cell (HSPC) development with increased oxidative stress and apoptosis. AK2-deficient iPSCs recapitulated the characteristic myeloid maturation arrest at the promyelocyte stage and demonstrated an increased AMP/ADP ratio, indicative of an energy-depleted adenine nucleotide profile. Antioxidant treatment rescued the hematopoietic phenotypes in vivo in ak2 mutant zebrafish and restored differentiation of AK2-deficient iPSCs into mature granulocytes. Our results link hematopoietic cell fate in AK2 deficiency to cellular energy depletion and increased oxidative stress. This points to the potential use of antioxidants as a supportive therapeutic modality for patients with RD

Super Resolution Microscopy Reveals that Caveolin-1 Is Required for Spatial Organization of CRFB1 and Subsequent Antiviral Signaling in Zebrafish

10.1371/journal.pone.0068759PLoS ONE87-POLN

Zebrafish hoxd4a Acts Upstream of meis1.1 to Direct Vasculogenesis, Angiogenesis and Hematopoiesis

10.1371/journal.pone.0058857PLoS ONE83

Targeting the hypoxic fraction of tumours using hypoxia activated prodrugs

The presence of a microenvironment within most tumours containing regions of low oxygen tension or hypoxia has profound biological and therapeutic implications. Tumour hypoxia is known to promote the development of an aggressive phenotype, resistance to both chemotherapy and radiotherapy and is strongly associated with poor clinical outcome. Paradoxically, it is recognised as a high priority target and one therapeutic strategies designed to eradicate hypoxic cells in tumours are a group of compounds known collectively as hypoxia activated prodrugs (HAPs) or bioreductive drugs. These drugs are inactive prodrugs that require enzymatic activation (typically by 1 or 2 electron oxidoreductases) to generate cytotoxic species with selectivity for hypoxic cells being determined by (i) the ability of oxygen to either reverse or inhibit the activation process and (ii) the presence of elevated expression of oxidoreductases in tumours. The concepts underpinning HAP development were established over 40 years ago and have been refined over the years to produce a new generation of HAPs that are under preclinical and clinical development. The purpose of this article is to describe current progress in the development of HAPs focusing on the mechanisms of action, preclinical properties and clinical progress of leading examples

Characterization of a polymorphism in NAD(P)H: quinone oxidoreductase (DT-diaphorase).

NAD(P)H:quinone oxidoreductase (NQO1, EC 1.6.99.2) is an obligate two-electron reductase that can either bioactivate or detoxify quinones and has been proposed to play an important role in chemoprevention. We have previously characterized a homozygous point mutation in the BE human colon carcinoma cell line that leads to a loss of NQO1 activity. Sequence analysis showed that this mutation was at position 609 of the NQO1 cDNA, conferring a proline to serine substitution at position 187 of the NQO1 enzyme. Using polymerase chain reaction (PCR) analysis, we have found that the H596 human non-small-cell lung cancer (NSCLC) cell line has elevated NQO1 mRNA, but no detectable enzyme activity. Sequencing of the coding region of NQO1 from the H596 cells showed the presence of the identical homozygous point mutation present in the BE cell line. Expression and purification of recombinant wild-type and mutant protein from E. coli showed that mutant protein could be detected using immunoblot analysis and had 2% of the enzymatic activity of the wild-type protein. PCR and Northern blot analysis showed moderate to low levels of expression of the correctly sized transcript in the mutant cells. Immunoblot analysis also revealed that recombinant mutant protein was immunoreactive; however, the mutant protein was not detected in the cytosol of either BE or H596 cells, suggesting that the mutant proteins were either not translated or were rapidly degraded. The absence of any detectable, active protein, therefore, appears to be responsible for the lack of NQO1 activity in cells homozygous for the mutation. A polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) analysis for the mutation at position 609 conducted on 90 human lung tissue samples (45 matched sets of tumour and uninvolved tissue) revealed a 7% incidence of individuals homozygous for the mutation, and 42% heterozygous for the mutation. These data suggest that the mutation at position 609 represents a polymorphism in an important xenobiotic metabolizing enzyme, which has implications for cancer therapy, chemoprevention and chemoprotection

Effects of Pesticide Treatments on Nutrient Levels in Worker Honey Bees (\u3ci\u3eApis mellifera\u3c/i\u3e)

Honey bee colony loss continues to be an issue and no factor has been singled out as to the cause. In this study, we sought to determine whether two beekeeper-applied pesticide products, tau-fluvalinate and Fumagilin-B, and one agrochemical, chlorothalonil, impact the nutrient levels in honey bee workers in a natural colony environment. Treatments were performed in-hive and at three different periods (fall, spring, and summer) over the course of one year. Bees were sampled both at pre-treatment and two and four weeks post-treatment, weighed, and their protein and carbohydrate levels were determined using BCA and anthrone based biochemical assays, respectively. We report that, based on the pesticide concentrations tested, no significant negative impact of the pesticide products was observed on wet weight, protein levels, or carbohydrate levels of bees from treated colonies compared with bees from untreated control colonies

Effects of Pesticide Treatments on Nutrient Levels in Worker Honey Bees (\u3ci\u3eApis mellifera\u3c/i\u3e)

Honey bee colony loss continues to be an issue and no factor has been singled out as to the cause. In this study, we sought to determine whether two beekeeper-applied pesticide products, tau-fluvalinate and Fumagilin-B, and one agrochemical, chlorothalonil, impact the nutrient levels in honey bee workers in a natural colony environment. Treatments were performed in-hive and at three different periods (fall, spring, and summer) over the course of one year. Bees were sampled both at pre-treatment and two and four weeks post-treatment, weighed, and their protein and carbohydrate levels were determined using BCA and anthrone based biochemical assays, respectively. We report that, based on the pesticide concentrations tested, no significant negative impact of the pesticide products was observed on wet weight, protein levels, or carbohydrate levels of bees from treated colonies compared with bees from untreated control colonies