Targeted Destruction of S100A4 Inhibits Metastasis of Triple Negative Breast Cancer Cells.

Most patients who die of cancer do so from its metastasis to other organs. The calcium-binding protein S100A4 can induce cell migration/invasion and metastasis in experimental animals and is overexpressed in most human metastatic cancers. Here, we report that a novel inhibitor of S100A4 can specifically block its increase in cell migration in rat (IC, 46 µM) and human (56 µM) triple negative breast cancer (TNBC) cells without affecting Western-blotted levels of S100A4.

Addressing the challenges of implementing evidence-based prioritisation in global health.

Global health requires evidence-based approaches to improve health and decrease inequalities. In a roundtable discussion between health practitioners, funders, academics and policy-makers, we recognised key areas for improvement to deliver better-informed, sustainable and equitable global health practices. These focus on considering information-sharing mechanisms and developing evidence-based frameworks that take an adaptive function-based approach, grounded in the ability to perform and respond to prioritised needs.

Masked arterial hypertension in a 64-year-old man with primary aldosteronism.

Purpose: Primary aldosteronism is one of the most frequent causes of secondary arterial hypertension, and whether primary aldosteronism is associated with masked hypertension is unknown.

Materials And Methods: We describe a 64-year-old man with a history of hypothyroidism, recurring hypokalaemia, and normal home and office blood pressure values. Ambulatory blood pressure monitoring revealed masked hypertension with strikingly high systolic blood pressure variability and typical hypertension-mediated organ damage.

The Role of the C-Terminal Lysine of S100P in S100P-Induced Cell Migration and Metastasis.

S100P protein is a potent inducer of metastasis in a model system, and its presence in cancer cells of patients is strongly associated with their reduced survival times. A well-established Furth Wistar rat metastasis model system, methods for measuring cell migration, and specific inhibitors were used to study pathways of motility-driven metastasis. Cells expressing C-terminal mutant S100P proteins display markedly-reduced S100P-driven metastasis in vivo and cell migration in vitro.

Investigation and management of pulmonary embolism 1: a probability-based approach.

Pulmonary embolism remains a common and potentially deadly disease, despite advances in diagnostic imaging, treatment and prevention. Managing pulmonary embolism requires a multifactorial approach involving risk stratification, determining appropriate diagnostics and selecting individualised therapy. This article reviews the pathophysiology, risk factors, clinical presentation, diagnostic evaluation and therapeutic management and early outpatient management of pulmonary embolism.

Investigation and management of pulmonary embolism 2: specific clinical conditions.

Pulmonary embolism remains a common and potentially deadly disease, despite advances in diagnostic imaging, treatment and prevention. Managing pulmonary embolism requires a multifactorial approach involving risk stratification, determining appropriate diagnostics and selecting individualised therapy. The first part of this article reviewed the pathophysiology, risk factors, clinical presentation, diagnostic evaluation and therapeutic management and early outpatient management of pulmonary embolism.

Mechanisms Underlying the Association of Chronic Obstructive Pulmonary Disease With Heart Failure.

Objectives: The purposes of this study were to determine why chronic obstructive pulmonary disease (COPD) is associated with heart failure (HF). Specific objectives included whether COPD is associated with myocardial fibrosis, whether myocardial fibrosis is associated with hospitalization for HF and death in COPD, and whether COPD and smoking are associated with myocardial inflammation.

Background: COPD is associated with HF independent of shared risk factors.

Effect of grouping on behaviour of dairy heifers and cows in the transition period.

Regrouping dairy cows is a common feature of dairy farm management. Cows are grouped based on lactation stage, age, milk yield and other factors. Regrouping cows during the dry period (from far-off area to close up area and from close up area to the main herd) brings new challenges.

The behavior of dairy cattle in the transition period: Effects of blood calcium status.

The aim of this study was to use an automated behavior-monitoring system to objectively assess the association between lying and activity behavior in the precalving, calving, and postcalving periods between multiparous and primiparous cows with (1) normocalcemia, (2) subclinical hypocalcemia, or (3) clinical hypocalcemia at calving. Behavioral data and blood serum samples were collected from 51 multiparous and 21 primiparous Holstein dairy cattle. Blood samples from the coccygeal vein were taken within 24 h of calving, and serum was analyzed to measure total calcium concentration.

Altered Levels of mRNAs for Calcium-Binding/Associated Proteins, Annexin A1, S100A4, and TMEM64, in Peripheral Blood Mononuclear Cells Are Associated with Osteoporosis.

Background: Osteoporosis is the most common metabolic bone disease in the world. Since osteoporosis is clinically symptomless until the first fracture occurs, early diagnosis is critical. Calcium, along with calcium-binding and calcium-associated proteins, plays an important role in homeostasis, maintaining healthy bone metabolism.

The behavior of dairy cattle in late gestation: Effects of parity and dystocia.

The aim of this study was to objectively assess, using an automated behavioral monitoring system, any behavioral differences between primiparous and multiparous cows before calving, and to quantify any behavioral differences between assisted (dystocic) and unassisted (eutocic) calvings. Data were collected from 32 multiparous and 12 primiparous Holstein dairy cattle to describe normal calving behavior and parity differences. To quantify behavior related to calving difficulty, the data from 14 animals that had dystocia at calving were matched to cows that had an eutocic calving based on parity, locomotion score, calf breed, calf sex, month, and year of calving.

High AGR2 protein is a feature of low grade endometrial cancer cells.

Background: Biomarkers for identification of endometrial cancers (ECs) with high risk of recurrence are required to reduce the rising EC-related mortality. AGR2 is a prognostic marker in several hormonally-regulated cancers.

Aim: To assess the utility of AGR2 as a prognostic marker in EC.

Cardiac Involvement in Systemic Sclerosis: Diagnostic Tools and Evaluation Methods.

The heart is one of the major organs commonly involved in systemic sclerosis (SSc). Myocardial fibrosis has been identified in a high percentage of these patients. Most SSc patients with cardiac involvement (CI) are subclinical, especially early on in the course of their disease.

Circulating microRNAs as potential diagnostic biomarkers for osteoporosis.

Osteoporosis is the most common age-related bone disease worldwide and is usually clinically asymptomatic until the first fracture happens. MicroRNAs are critical molecular regulators in bone remodelling processes and are stabilised in the blood. The aim of this project was to identify circulatory microRNAs associated with osteoporosis using advanced PCR arrays initially and the identified differentially-expressed microRNAs were validated in clinical samples using RT-qPCR.

Insufficiency of the zona glomerulosa of the adrenal cortex and progressive kidney insufficiency following unilateral adrenalectomy - case report and discussion.

Background: Primary aldosteronism (PA) is the most common cause of secondary hypertension and bilateral adrenal hyperplasia (BAH) and aldosterone-producing adenoma (APA) seem to be the most common causes of PA. Unilateral adrenalectomy (UA) is the preferred treatment for APA, although the benefits are still difficult to assess.

Case Report: We present a case report of a 69-year old man with a 30 year history of hypertension and probably long-standing PA due to APA, with typical organ complications.

Assessing Estrogen-Induced Proliferative Response in an Endometrial Cancer Cell Line Using a Universally Applicable Methodological Guide.

Objective: Translational endometrial cancer (EC) research benefits from an in vitro experimental approach using EC cell lines. We demonstrated the steps that are required to examine estrogen-induced proliferative response, a simple yet important research question pertinent to EC, and devised a pragmatic methodological workflow for using EC cell lines in experimental models.

Methods: Comprehensive review of all commercially available EC cell lines was carried out, and Ishikawa cell line was selected to study the estrogen responsiveness with HEC1A, RL95-2, and MFE280 cell lines as comparators where appropriate, examining relevant differential molecular (steroid receptors) and functional (phenotype, anchorage-independent growth, hormone responsiveness, migration, invasion, and chemosensitivity) characteristics in 2-dimensional and 3-dimensional cultures in vitro using immunocytochemistry, immunofluorescence, quantitative polymerase chain reaction, and Western blotting.

Activation of tissue plasminogen activator by metastasis-inducing S100P protein.

S100P protein in human breast cancer cells is associated with reduced patient survival and, in a model system of metastasis, it confers a metastatic phenotype upon benign mammary tumour cells. S100P protein possesses a C-terminal lysine residue. Using a multiwell assay, S100P is now shown for the first time to exhibit a strong, C-terminal lysine-dependent activation of tissue plasminogen activator (tPA), but not of urokinase-catalysed plasminogen activation.

Gene Expression Meta-Analysis of Potential Metastatic Breast Cancer Markers.

Background: Breast cancer metastasis is a highly prevalent cause of death for European females. DNA microarray analysis has established that primary tumors, which remain localized, differ in gene expression from those that metastasize. Crossanalysis of these studies allow to revile the differences that may be used as predictive in the disease prognosis and therapy.

Ampicillin resistance in from COPD patients in the UK.

Background: is commonly isolated from the airways of COPD patients. Antibiotic treatment may cause the emergence of resistant strains, particularly ampicillin-resistant strains, including β-lactamase-negative ampicillin resistance (BLNAR) strains. Genetic identification using sequencing is the optimum method for identifying mutations within BLNAR strains.

S100A4 Elevation Empowers Expression of Metastasis Effector Molecules in Human Breast Cancer.

Many human glandular cancers metastasize along nerve tracts, but the mechanisms involved are generally poorly understood. The calcium-binding protein S100A4 is expressed at elevated levels in human cancers, where it has been linked to increased invasion and metastasis. Here we report genetic studies in a Drosophila model to define S100A4 effector functions that mediate metastatic dissemination of mutant Ras-induced tumors in the developing nervous system.

The metastasis-inducing protein AGR2 is O-glycosylated upon secretion from mammary epithelial cells.

AGR2 is overexpressed in multiple cancers, particularly those arising from breast and prostate tissues, and higher levels of AGR2 are associated with earlier patient death. Although AGR2 is normally resident within the endoplasmic reticulum, the protein has been found in the extracellular space in several model systems. However, it has never been expressly demonstrated that this extracellular form of the protein is secreted and does not just accumulate in the extracellular space as a result of cell lysis.

Mosquito Communities and Avian Malaria Prevalence in Silvereyes (Zosterops lateralis) Within Forest Edge and Interior Habitats in a New Zealand Regional Park.

Forest fragmentation and agricultural development are important anthropogenic landscape alterations affecting the disease dynamics of malarial parasites (Plasmodium spp.), largely through their effects on vector communities. We compared vector abundance and species composition at two forest edge sites abutting pastureland and two forest interior sites in New Zealand, while simultaneously assessing avian malaria prevalence in silvereyes (Zosterops lateralis).

Joining S100 proteins and migration: for better or for worse, in sickness and in health.

The vast diversity of S100 proteins has demonstrated a multitude of biological correlations with cell growth, cell differentiation and cell survival in numerous physiological and pathological conditions in all cells of the body. This review summarises some of the reported regulatory functions of S100 proteins (namely S100A1, S100A2, S100A4, S100A6, S100A7, S100A8/S100A9, S100A10, S100A11, S100A12, S100B and S100P) on cellular migration and invasion, established in both culture and animal model systems and the possible mechanisms that have been proposed to be responsible. These mechanisms involve intracellular events and components of the cytoskeletal organisation (actin/myosin filaments, intermediate filaments and microtubules) as well as extracellular signalling at different cell surface receptors (RAGE and integrins).

COPD causation and workplace exposures: an assessment of agreement among expert clinical raters.

Background: Although occupational exposure is a known risk factor for Chronic Obstructive Pulmonary Disease (COPD), it is difficult to identify specific occupational contributors to COPD at the individual level to guide COPD prevention or for compensation. The aim of this study was to gain an understanding of how different expert clinicians attribute likely causation in COPD.

Methods: Ten COPD experts and nine occupational lung disease experts assigned occupational contribution ratings to fifteen hypothetical cases of COPD with varying combinations of occupational and smoking exposures.