Effect of a pharmacist intervention on asthma control. A cluster randomised trial.

Introduction: Achievement and maintenance of good asthma control is a major objective in asthma management. However, asthma control in many patients is suboptimal, due to improper use of asthma medications and non-adherence. The aim of this study was to evaluate the effect of a pharmacist intervention on asthma control in adult patients.

The Irish National Joint Registry: where are we now?

Background: Ireland is currently in the process of establishing a National Joint Registry.

Aim: We aim to determine which implants and surgical techniques are currently being used by Irish orthopaedic surgeons and to examine the impact that a National Joint Registry may have on arthroplasty practice in Ireland.

Methods: The study consisted of a postal questionnaire sent to all public service consultant orthopaedic surgeons in The Republic of Ireland.

ClogP(alk): a method for predicting alkane/water partition coefficient.

Alkane/water partition coefficients (P(alk)) are less familiar to the molecular design community than their 1-octanol/water equivalents and access to both data and prediction tools is much more limited. A method for predicting alkane/water partition coefficient from molecular structure is introduced. The basis for the ClogP(alk) model is the strong (R² = 0.

TACE-dependent TGFα shedding drives triple-negative breast cancer cell invasion.

The epidermal growth factor receptor (EGFR) is frequently expressed in triple-negative breast cancer (TNBC) and is a marker of poor prognosis in this patient population. Because activating mutations in this kinase are very rare events in breast cancer, we screened breast tumor gene expression profiles to examine the distribution of EGFR ligand expression. Of the six known EGFR ligands, transforming growth factor alpha (TGFα) was expressed more highly in triple-negative breast tumors than in tumors of other subtypes.

Dopamine D2 receptors and striatopallidal transmission in addiction and obesity.

Drug addiction and obesity share the core feature that those afflicted by the disorders express a desire to limit drug or food consumption yet persist despite negative consequences. Emerging evidence suggests that the compulsivity that defines these disorders may arise, to some degree at least, from common underlying neurobiological mechanisms. In particular, both disorders are associated with diminished striatal dopamine D2 receptor (D2R) availability, likely reflecting their decreased maturation and surface expression.

MicroRNAs and Drug Addiction.

Drug addiction is considered a disorder of neuroplasticity in brain reward and cognition systems resulting from aberrant activation of gene expression programs in response to prolonged drug consumption. Non-coding RNAs (ncRNAs) are key regulators of almost all aspects of cellular physiology. MicroRNAs (miRNAs) are small (∼21-23 nucleotides) ncRNAs transcripts that regulate gene expression at the post-transcriptional level.

Translating genomic research into clinical practice: promise and pitfalls.

Breast cancer is a heterogeneous disease associated with variable clinical outcomes despite standard local therapy for the primary tumor and systemic adjuvant therapy to prevent distant recurrence. Management decisions are typically made using classical prognostic and predictive clinicopathologic factors, and more recently gene expression profiling assays are commonly used in practice. Recent advances in genomic sequencing-often referred to collectively as next-generation sequencing (NGS)-have facilitated more in-depth evaluation of the cancer genome than could be afforded by the initial generation of gene expression studies, including DNA single nucleotide variants, small insertions and deletions, structural alterations, and copy number alterations (CNAs).

Targeted deletion of the mouse α2 nicotinic acetylcholine receptor subunit gene (Chrna2) potentiates nicotine-modulated behaviors.

Baseline and nicotine-modulated behaviors were assessed in mice harboring a null mutant allele of the nicotinic acetylcholine receptor (nAChR) subunit gene α2 (Chrna2). Homozygous Chrna2(-/-) mice are viable, show expected sex and Mendelian genotype ratios, and exhibit no gross neuroanatomical abnormalities. A broad range of behavioral tests designed to assess genotype-dependent effects on anxiety (elevated plus maze and light/dark box), motor coordination (narrow bean traverse and gait), and locomotor activity revealed no significant differences between mutant mice and age-matched wild-type littermates.

Mitochondrial calcium uniporter silencing potentiates caspase-independent cell death in MDA-MB-231 breast cancer cells.

The mitochondrial calcium uniporter (MCU) transports free ionic Ca(2+) into the mitochondrial matrix. We assessed MCU expression in clinical breast cancer samples using microarray analysis and the consequences of MCU silencing in a breast cancer cell line. Our results indicate that estrogen receptor negative and basal-like breast cancers are characterized by elevated levels of MCU.

Biomarkers for smoking cessation.

One way to enhance therapeutic development is through the identification and development of evaluative tools such as biomarkers. This review focuses on putative diagnostic, pharmacodynamic, and predictive biomarkers for smoking cessation. These types of biomarkers may be used to more accurately diagnose a disease, personalize treatment, identify novel targets for drug discovery, and enhance the efficiency of drug development.

Variations in magnetic resonance venographic anatomy of the dorsal dural venous sinus system in 51 dogs.

Variations in intracranial dural venous sinus anatomy have been widely reported in humans, but there have been no studies reporting this in dogs. The purpose of this retrospective study was to describe variations in magnetic resonance (MR) venographic anatomy of the dorsal dural venous sinus system in a sample population of dogs with structurally normal brains. Medical records were searched for dogs with complete phase contrast, intracranial MR venograms and a diagnosis of idiopathic epilepsy.

Intra-articular dislocation of the patella.

We present an unusual case of a chronic, irreducible intra-articular dislocation of the patella in an elderly nursing home resident. The patient had been unable to weight bear for 3 weeks. Radiographs in the emergency department (ED) confirmed the intra-articular dislocation with the superior pole lodged in the intercondylar notch.

miR-21 mediates hematopoietic suppression in MDS by activating TGF-β signaling.

Myelodysplastic syndromes (MDS) are characterized by ineffective hematopoiesis that leads to peripheral cytopenias. We observed that SMAD7, a negative regulator of transforming growth factor-beta (TGF-β) receptor-I kinase, is markedly reduced in MDS and leads to ineffective hematopoiesis by overactivation of TGF-β signaling. To determine the cause of SMAD7 reduction in MDS, we analyzed the 3'UTR of the gene and determined that it contains a highly conserved putative binding site for microRNA-21.

Successful intravenous immunoglobulin treatment of atypical lichen myxedematosus associated with hypothyroidism and central nervous system involvement: case report and discussion of the literature.

Background: Lichen myxedematosus (LM) is a rare idiopathic disorder characterized by papules, plaques, and/or nodules in the skin secondary to mucin deposition and variable dermal fibrosis in the absence of thyroid disease. Case reports are the predominant literature on LM due to its rarity, and the data are limited regarding the disease. No standard treatment regimen exists, and the response to treatment varies.

Visualizing movement in the tumor microenvironment landscape.

The local microenvironment influences tumor progression in several important ways. A recent study by Nguyen-Ngoc and colleagues used explants of primary human and mouse mammary tumors to examine how the composition of the extracellular matrix modulates tumor cell invasion. Culture in the presence of a three-dimensional laminin-rich basement membrane, similar to the mammary basement membrane in vivo, resulted in minimal invasion.

Inflation of correlation in the pursuit of drug-likeness.

Drug-likeness is a frequently invoked, although not always precisely defined, concept in drug discovery. Opinions on drug-likeness are to a large extent shaped by the relationships that are observed between surrogate measures of drug-likeness (e.g.

The effect of inclement weather on ankle fracture management in an Irish trauma unit.

Introduction: Ireland is unfamiliar with extreme weather conditions. Such conditions occurred in winter 2009-2010 and 2010-2011, with much of the country being affected by snow and ice. We reviewed the effect that these conditions had on the treatment of ankle fractures in our trauma unit.

Molecular mechanisms underlying behaviors related to nicotine addiction.

Tobacco smoking results in more than 5 million deaths each year and accounts for almost 90% of all deaths from lung cancer. Nicotine, the major reinforcing component of tobacco smoke, acts in the brain through the neuronal nicotinic acetylcholine receptors (nAChRs). The nAChRs are allosterically regulated, ligand-gated ion channels consisting of five membrane-spanning subunits.

Selective gene-expression profiling of migratory tumor cells in vivo predicts clinical outcome in breast cancer patients.

Introduction: Metastasis of breast cancer is the main cause of death in patients. Previous genome-wide studies have identified gene-expression patterns correlated with cancer patient outcome. However, these were derived mostly from whole tissue without respect to cell heterogeneity.

Neck narrowing in resurfacing hip arthroplasty: a vascular insult?

Introduction: Recent reports show increased failure rates in hip resurfacings that display >10 % neck narrowing. The etiology of neck narrowing remains unknown.

Methods: We assessed 80 hip resurfacings at mean 3.

Development of novel pharmacotherapeutics for tobacco dependence: progress and future directions.

Introduction: The vast majority of tobacco smokers seeking to quit will relapse within the first month of abstinence. Currently available smoking cessation agents have limited utility in increasing rates of smoking cessation and in some cases there are notable safety concerns related to their use. Hence, there is a pressing need to develop safer and more efficacious smoking cessation medications.

The triple reuptake inhibitor DOV 216,303 induces long-lasting enhancement of brain reward activity as measured by intracranial self-stimulation in rats.

Triple reuptake inhibitors (TRIs) are potential new antidepressants, which not only enhance brain serotonin and norepinephrine concentrations but also increase dopamine levels. Therefore TRIs are believed to have faster therapeutic onset than SSRIs, and may be particularly useful for the treatment of anhedonia (i.e.

Pharmacokinetic benefits of 3,4-dimethoxy substitution of a phenyl ring and design of isosteres yielding orally available cathepsin K inhibitors.

Rational structure-based design has yielded highly potent inhibitors of cathepsin K (Cat K) with excellent physical properties, selectivity profiles, and pharmacokinetics. Compounds with a 3,4-(CH₃O)₂Ph motif, such as 31, were found to have excellent metabolic stability and absorption profiles. Through metabolite identification studies, a reactive metabolite risk was identified with this motif.