Homoharringtonine demonstrates a cytotoxic effect against triple-negative breast cancer cell lines and acts synergistically with paclitaxel.

The lack of targeted therapies for triple-negative breast cancer (TNBC) contributes to their high mortality rates and high risk of relapse compared to other subtypes of breast cancer. Most TNBCs (75%) have downregulated the expression of CREB3L1 (cAMP-responsive element binding protein 3 like 1), a transcription factor and metastasis suppressor that represses genes that promote cancer progression and metastasis. In this report, we screened an FDA-approved drug library and identified four drugs that were highly cytotoxic towards HCC1806 CREB3L1-deficient TNBC cells.

Reduced CREB3L1 expression in triple negative and luminal a breast cancer cells contributes to enhanced cell migration, anchorage-independent growth and metastasis.

Women with metastatic breast cancer have a disheartening 5-year survival rate of only 28%. CREB3L1 (cAMP-responsive element binding protein 3 like 1) is a metastasis suppressor that functions as a transcription factor, and in an estrogen-dependent model of rat breast cancer, it repressed the expression of genes that promote breast cancer progression and metastasis. In this report, we set out to determine the expression level of CREB3L1 across different human breast cancer subtypes and determine whether CREB3L1 functions as a metastasis suppressor, particularly in triple negative breast cancers (TNBCs).

People living with moderate-to-severe COPD prefer improvement of daily symptoms over the improvement of exacerbations: a multicountry patient preference study.

Introduction: This patient preference study sought to quantify the preferences of people living with COPD regarding symptom improvement in the UK, USA, France, Australia and Japan.

Methods: The inclusion criteria were people living with COPD aged 40 years or older who experienced ≥1 exacerbation in the previous year with daily symptoms of cough and excess mucus production. The study design included: 1) development of an attributes and levels grid through qualitative patient interviews; and 2) implementation of the main online quantitative survey, which included a discrete choice experiment (DCE) to allow assessment of attributes and levels using hypothetical health state profiles.

Social character, interdependence, and the dualities of other-directedness.

David Riesman's exploration of the other-directed characterological form, suited to corporate capitalism and the rise of the service sector, became one of the most influential sociological analyses of the twentieth century. Yet sociologists interested in the contemporary fate of those dispositional qualities suited to mutual adjustment confront a paradox: why, in an age of increasing interdependencies apparently conducive to the sustenance of other-directedness, are we witnessing rising concerns about the resurgence of social sectarianism? Most accounts of this tension rely upon structuralist explanations of late modernity's disruptive impact, or psychologistic accounts of group allegiance. In contrast, we develop a meso-level analysis that highlights an increasingly consequential duality at the heart of other-directedness itself: the qualities associated with this characterological form still facilitate selective forms of mutuality, but the demands it places upon people in the current era have also prompted growing levels of resentment and antagonism.

New Graduate Registered Nurses and the Spectrum of Comfort in Clinical Practice.

The comfort zone is where a person consistently performs his or her role in an affective state devoid of anxiety and without a feeling of risk. This study challenges the notion of a singular comfort zone and suggests that a spectrum of comfort is a more accurate reflection of the new graduate experience. A grounded theory methodology was used to identify and explain the spectrum of comfort considerations helpful to nine new graduates amid their transition to professional practice.

Providing 'the bigger picture': benefits and feasibility of integrating remote monitoring from smartphones into the electronic health record.

Objectives: To establish the acceptability and feasibility of collecting daily patient-generated health data (PGHD) using smartphones and integrating PGHD into the electronic health record, using the example of RA.

Methods: The Remote Monitoring of RA smartphone app was co-designed with patients, clinicians and researchers using qualitative semi-structured interviews and focus groups, including selection of question sets for symptoms and disease impact. PGHD were integrated into the electronic health record of one hospital and available in graphical form during consultations.

Rejuvenation of RBCs: validation of a manufacturing method suitable for clinical use.

Background: Rejuvenation of stored red blood cells (RBCs) increases levels of adenosine 5'-triphosphate (ATP) and 2,3-diphosphoglycerate (2,3-DPG) to those of fresh cells. This study aimed to optimize and validate the US-approved process to a UK setting for manufacture and issue of rejuvenated RBCs for a multicenter randomized controlled clinical trial in cardiac surgery.

Study Design And Methods: Rejuvenation of leukoreduced RBC units involved adding a solution containing pyruvate, inosine, phosphate, and adenine (Rejuvesol, Zimmer Biomet), warming at 37°C for 60 minutes, then "manual" washing with saline adenine glucose mannitol solution.

Insight into the PTEN - p85α interaction and lipid binding properties of the p85α BH domain.

The phosphatidylinositol 3-kinase (PI3K) pathway plays a key role in regulating cell growth and cell survival and is frequently deregulated in cancer cells. p85α regulates the p110α lipid kinase, and also stabilizes and stimulates PTEN, the lipid phosphatase that downregulates this pathway. In this report, we determined that the p85α BH domain binds several phosphorylated phosphoinositide lipids, an interaction that could help localize p85α to membranes rich in these lipids.

Impact of p85α Alterations in Cancer.

The phosphatidylinositol 3-kinase (PI3K) pathway plays a central role in the regulation of cell signaling, proliferation, survival, migration and vesicle trafficking in normal cells and is frequently deregulated in many cancers. The p85α protein is the most characterized regulatory subunit of the class IA PI3Ks, best known for its regulation of the p110-PI3K catalytic subunit. In this review, we will discuss the impact of p85α mutations or alterations in expression levels on the proteins p85α is known to bind and regulate.

Patient-derived mutations within the N-terminal domains of p85α impact PTEN or Rab5 binding and regulation.

The p85α protein regulates flux through the PI3K/PTEN signaling pathway, and also controls receptor trafficking via regulation of Rab-family GTPases. In this report, we determined the impact of several cancer patient-derived p85α mutations located within the N-terminal domains of p85α previously shown to bind PTEN and Rab5, and regulate their respective functions. One p85α mutation, L30F, significantly reduced the steady state binding to PTEN, yet enhanced the stimulation of PTEN lipid phosphatase activity.

A serosurvey of bluetongue and epizootic haemorrhagic disease in a convenience sample of sheep and cattle herds in Zimbabwe.

A convenience sample of sheep and cattle herds around the cities of Harare, Kwekwe and Bulawayo, located in the Highveld region of Zimbabwe, was used to estimate the seroprevalence and sero-incidence of bluetongue virus (BTV) and epizootic haemorrhagic disease virus (EHDV) antibodies. A competitive enzyme-linked immunosorbent assay was used to identify serum antibodies against BTV and EHDV across three rainy seasons. The median sero-prevalence of BTV and EHDV antibodies in cattle was 62% (interquartile range [IQR]: 30-89) and 56% (IQR: 5-77), respectively.

Qualification of oil-spill treatment products - Adopting the Baffled Flask Test for testing of dispersant efficacy in the UK.

The UK Marine Management Organisation (MMO) tasked the Centre for Environment, Fisheries & Aquaculture Science (Cefas) with reviewing the current UK dispersant efficacy testing procedures. The aim was to identify possibilities to increase standardisation, improve health and safety performance and explore harmonisation possibilities with international dispersant efficacy testing procedures. The US EPA 'Baffled Flask Test' (BFT) was adopted, implemented and validated as a new standard method in the UK.

A novel non-azole topical treatment reduces Malassezia numbers and associated dermatitis: a short term prospective, randomized, blinded and placebo-controlled trial in naturally infected dogs.

Background: Malassezia yeast overgrowth on the skin is a common and often recurrent cause of dermatitis in dogs; it can be an exacerbating factor of atopic dermatitis. Anti-fungal drugs have been a standard treatment, but there is some concern that resistance may be evolving in a spectrum of Malassezia species. Safe, efficient and easy-to-use alternatives are needed.

Strategies new graduate registered nurses require to care and advocate for themselves: A literature review.

Background: New graduate registered nurses (NGRNs) are confronted with a complex, demanding and resource-constrained environment where gaining acceptance into the workplace culture may be difficult. Existing evidence suggests that preparing undergraduate nursing students for this reality can assist with adjustment.

Objectives: To identify the strategies that NGRNs require to care and advocate for themselves during their first year of practice.

The role of PTEN - HCV core interaction in hepatitis C virus replication.

Hepatitis C virus (HCV) infection leads to severe liver diseases including hepatocellular carcinoma (HCC). Phosphatase and tensin homolog deleted on chromosome 10 (PTEN), a tumour suppressor, is frequently mutated or deleted in HCC tumors. PTEN has previously been demonstrated to inhibit HCV secretion.

Molecular characterization of breast cancer cell lines through multiple omic approaches.

Background: Breast cancer cell lines are frequently used as model systems to study the cellular properties and biology of breast cancer. Our objective was to characterize a large, commonly employed panel of breast cancer cell lines obtained from the American Type Culture Collection (ATCC 30-4500 K) to enable researchers to make more informed decisions in selecting cell lines for specific studies. Information about these cell lines was obtained from a wide variety of sources.

The sero-prevalence and sero-incidence of African horse sickness and equine encephalosis in selected horse and donkey populations in Zimbabwe.

Sentinel herds and samples submitted by private equine practitioners were used to determine the sero-prevalence and sero-incidence of African horse sickness virus (AHSV) and equine encephalosis virus (EEV) in horse and donkey populations in the Highveld region of Zimbabwe. The sero-prevalence and sero-incidence of antibodies against these viruses were determined using the competitive enzyme-linked immunosorbent assay (ELISA) for the detection of serum antibodies. In donkeys, the median sero-prevalence of AHSV antibodies, across the three rainy seasons under study, was 75% (inter quartile range [IQR] 67-83), with a seasonal median sero-incidence of 45% (IQR 40-63).

Using a sedimentation scanner to determine mangrove health responses to sedimentation derived from dredging. An example from northwestern Australia.

A sedimentation scanner was used to measure daily sediment height at 10 sites associated with a 14 million cubic metre dredging project in Port Hedland harbour, Western Australia, between July 2011 and May 2012. Data were collected from seven potential impact sites, where up to 35 mm of additional sedimentation was predicted via modelling to result from dredging and at three reference sites, where background variation was monitored. A variety of mangrove habitat health indices from each site (including leaf area and health, pneumatophore and faunal burrow density) were collected before, during and after dredging.

Involving healthcare professionals and family carers in setting research priorities for end-of-life care.

It is important to ensure regional variances are considered when setting future end-of-life research priorities, given the differing demographics and service provision. This project sought to identify end-of-life research priorities within Greater Manchester (United Kingdom). Following an initial scoping exercise, six topics within the 10 national priorities outlined by The Palliative and end-of-life care Priority Setting Partnership were selected for exploration.

African Horse Sickness Virus: History, Transmission, and Current Status.

African horse sickness virus (AHSV) is a lethal arbovirus of equids that is transmitted between hosts primarily by biting midges of the genus Culicoides (Diptera: Ceratopogonidae). AHSV affects draft, thoroughbred, and companion horses and donkeys in Africa, Asia, and Europe. In this review, we examine the impact of AHSV critically and discuss entomological studies that have been conducted to improve understanding of its epidemiology and control.

Dispositional mindfulness and employment status as predictors of resilience in third year nursing students: a quantitative study.

Background: Nursing students will graduate into stressful workplace environments and resilience is an essential acquired ability for surviving the workplace. Few studies have explored the relationship between resilience and the degree of innate dispositional mindfulness, compassion, compassion fatigue and burnout in nursing students, including those who find themselves in the position of needing to work in addition to their academic responsibilities.

Aim: This paper investigates the predictors of resilience, including dispositional mindfulness and employment status of third year nursing students from three Australian universities.

Ways of Being: Preparing Nursing Students for Transition to Professional Practice.

Background: The new graduate registered nurse (NGRN) does not work in isolation but within an organizational environment. Unfortunately for the NGRN, transition-to-practice programs are often variable and underresourced, which means that promised support is unlikely to eventuate. Many NGRNs learn the skills required to navigate the nursing culture on the job without support and by trial and error.

Using shared needles for subcutaneous inoculation can transmit bluetongue virus mechanically between ruminant hosts.

Bluetongue virus (BTV) is an economically important arbovirus of ruminants that is transmitted by Culicoides spp. biting midges. BTV infection of ruminants results in a high viraemia, suggesting that repeated sharing of needles between animals could result in its iatrogenic transmission.

Epigenetic silencing of CREB3L1 by DNA methylation is associated with high-grade metastatic breast cancers with poor prognosis and is prevalent in triple negative breast cancers.

Background: CREB3L1 (cAMP-responsive element-binding protein 3-like protein 1), a member of the unfolded protein response, has recently been identified as a metastasis suppressor in both breast and bladder cancer.

Methods: Quantitative real time PCR (qPCR) and immunoblotting were used to determine the impact of histone deacetylation and DNA methylation inhibitors on CREB3L1 expression in breast cancer cell lines. Breast cancer cell lines and tumor samples were analyzed similarly, and CREB3L1 gene methylation was determined using sodium bisulfite conversion and DNA sequencing.

The occurrence of Culicoides species, the vectors of arboviruses, at selected trap sites in Zimbabwe.

A study of the distribution of Culicoides species was conducted by establishing 12 light trap sites over five rainy seasons between 1998 and 2003 covering all the geo-climatic natural regions of Zimbabwe. In total, 279 919 specimens of Culicoides were trapped over a total of 163 trapping nights. The highest median counts of Culicoides per trapping night were recorded in natural region III, which has climatic conditions conducive to the successful development of the larvae.