From Metcalf to myeloproliferative neoplasms - a personal journey.

The human myeloproliferative neoplasms constitute a biologically fascinating group of chronic myeloid malignancies. This perspective outlines how a postdoctoral fellowship working in Don Metcalf's unit proved a formative and immensely enjoyable experience for my family and me. It laid the foundation for a subsequent body of work over three decades that revealed the genetic basis of these diseases, defined how these genetic alterations subvert normal hematopoiesis, altered clinical practice, and provided insights of broad biological relevance for cancer and cytokine signaling.

Green Synthesis of Silver Nanoparticles with Antimicrobial Properties Using Plant Extract.

Foodborne illnesses caused by the consumption of food contaminated with foodborne pathogens at infectious doses are becoming a common health issue throughout the world. Metal nanoparticles with potential antimicrobial properties are an area that can be explored to discover novel antimicrobial agents. The traditional synthesis methods of metal nanoparticles involve the use of toxic chemicals and the generation of harmful byproducts.

Ruxolitinib-induced defects in DNA repair cause sensitivity to PARP inhibitors in myeloproliferative neoplasms.

Myeloproliferative neoplasms (MPNs) often carry JAK2(V617F), MPL(W515L), or CALR(del52) mutations. Current treatment options for MPNs include cytoreduction by hydroxyurea and JAK1/2 inhibition by ruxolitinib, both of which are not curative. We show here that cell lines expressing JAK2(V617F), MPL(W515L), or CALR(del52) accumulated reactive oxygen species-induced DNA double-strand breaks (DSBs) and were modestly sensitive to poly-ADP-ribose polymerase (PARP) inhibitors olaparib and BMN673.

The European Hematology Association Roadmap for European Hematology Research: a consensus document.

The European Hematology Association (EHA) Roadmap for European Hematology Research highlights major achievements in diagnosis and treatment of blood disorders and identifies the greatest unmet clinical and scientific needs in those areas to enable better funded, more focused European hematology research. Initiated by the EHA, around 300 experts contributed to the consensus document, which will help European policy makers, research funders, research organizations, researchers, and patient groups make better informed decisions on hematology research. It also aims to raise public awareness of the burden of blood disorders on European society, which purely in economic terms is estimated at €23 billion per year, a level of cost that is not matched in current European hematology research funding.

The evolving genomic landscape of myeloproliferative neoplasms.

Our understanding of the genetic basis of the Philadelphia chromosome-negative myeloproliferative neoplasms (MPNs) has moved forward at a staggering pace over the last decade. With the discoveries of underlying mutations in JAK2, MPL, and, most recently, calreticulin (CALR), that together account for ∼90% of patients with MPNs, these conditions are now among the best characterized of hematological malignancies. While JAK-STAT pathway activation has been shown to be central to the pathogenesis of the MPN phenotype, the mechanism by which mutant CALR alters cellular function to result in myeloid proliferation remains unclear.

Macmillan raises concerns that Liverpool Care Pathway is still used.

Controversial end of life framework the Liverpool Care Pathway (LCP) is still being used in some places six months after it was withdrawn, MPs have been told.

Use spirometry first to improve diagnosis of asthma, says NICE.

Clinicians should use spirometry - the measurement of breath - as the first test for asthma in adults and children over five, says draft guidance by the National Institute for Health and Care Excellence (NICE).

Safe staffing legislation will change behaviour, says RCN Wales director.

Soaring spend on agency nurses in Wales could be cut if minimum staffing levels are introduced in hospitals, Welsh Assembly members have been told.

Innovative nursing research unit to encourage evidence-based practice.

Speaking up about unsafe practice and the use of technology to prevent patient falls are among the initial projects being investigated at a new nursing research unit.

Diagnosis and treatment plan aims to eliminate TB across England.

A national drive to eradicate tuberculosis has been launched amid fears that within four years there could be more cases of the potentially fatal disease in England than in the United States.

PD-1/SHP-2 inhibits Tc1/Th1 phenotypic responses and the activation of T cells in the tumor microenvironment.

Immune rejection of tumors is mediated by IFNγ production and T-cell cytolytic activity. These processes are impeded by PD-1, a coinhibitory molecule expressed on T cells that is elevated in tumor-infiltrating lymphocytes (TIL). PD-1 elevation may reflect T-cell exhaustion marked by decreased proliferation, production of type I cytokines, and poor cytolytic activity.

Stella-Cre mice are highly efficient Cre deleters.

Cre-loxP recombination is widely used for genetic manipulation of the mouse genome. Here, we report generation and characterization of a new Cre line, Stella-Cre, where Cre expression cassette was targeted to the 3' UTR of the Stella locus. Stella is specifically expressed in preimplantation embryos and in the germline.

The Ph-positive and Ph-negative myeloproliferative neoplasms: some topical pre-clinical and clinical issues.

This review focuses on topical issues in the biology and treatment of the myeloproliferative neoplasms (MPNs). Studies in transgenic mice suggest that BCR-ABL1 reduces the fraction of self-renewing 'leukemic' stem cells in the bone marrow but that some of these cells survive treatment with imatinib. This also seems to operate in humans.

Proper training key to defeating Legionella.

The long-awaited report from the Health & Safety Executive (HSE) into the Barrow Legionella outbreak has now been published and is in the public domain. Its conclusions and recommendations clearly recognise that the outbreak cannot, and should not, be attributed purely to one group or to the individuals working within one department. Moreover, the failings which contributed to the outbreak stretched from the lowest levels to the top of the council organisation.

A theoretical description of the polarization dependence of the sum frequency generation spectroscopy of the water/vapor interface.

An improved time correlation function (TCF) description of sum frequency generation (SFG) spectroscopy was developed and applied to theoretically describing the spectroscopy of the ambient water/vapor interface. A more general TCF expression than was published previously is presented-it is valid over the entire vibrational spectrum for both the real and imaginary parts of the signal. Computationally, earlier time correlation function approaches were limited to short correlation times that made signal processing challenging.