Defibrotide for the management of sinusoidal obstruction syndrome in patients who undergo haemopoietic stem cell transplantation.

Sinusoidal obstruction syndrome, previously known as veno-occlusive disease (VOD/SOS), is a complication in patients undergoing haemopoietic stem cell transplantation (HSCT). Severe VOD/SOS, including progression to multi-organ failure, has resulted in a mortality of greater than 80%. Defibrotide's varying pharmacological actions, particularly on endothelial cells, make it is a useful agent to consider for prophylaxis and treatment of VOD/SOS.

Detection of cellular senescence within human invasive breast carcinomas distinguishes different breast tumor subtypes.

Oncogene-induced senescence is thought to act as a barrier to tumorigenesis by arresting cells at risk of malignant transformation. Nevertheless, numerous findings suggest that senescent cells may conversely promote tumor progression through the development of the senescence-associated secretome they produce. It is likely that the composition and the physiological consequences mediated by the senescence secretome are dependent on the oncogenes that trigger the senescence program.

New Landmark for Localizing the Site of the Subdental Synchondrosis Remnant: Application to Discerning Pathology from Normal on Imaging.

Objective: We hypothesized that the entry site of the basivertebral vein into the basivertebral foramen of C2 might localize the subdental synchondrosis between the odontoid process and body of C2, which may be helpful for odontoid fracture classification.

Methods: Twenty-five dry adult C2 specimens underwent thin-cut computed tomography and were sectioned sagittally. The basivertebral foramen was then correlated to internal bony anatomy.

Growth control switch by a DNA-damage-inducible toxin-antitoxin system in Caulobacter crescentus.

Bacterial toxin-antitoxin systems (TASs) are thought to respond to various stresses, often inducing growth-arrested (persistent) sub-populations of cells whose housekeeping functions are inhibited. Many such TASs induce this effect through the translation-dependent RNA cleavage (RNase) activity of their toxins, which are held in check by their cognate antitoxins in the absence of stress. However, it is not always clear whether specific mRNA targets of orthologous RNase toxins are responsible for their phenotypic effect, which has made it difficult to accurately place the multitude of TASs within cellular and adaptive regulatory networks.

Comparative Plasma and Cerebrospinal Fluid Pharmacokinetics of Paracetamol After Intravenous and Oral Administration.

Background: We compared plasma and cerebrospinal fluid (CSF) pharmacokinetics of paracetamol after intravenous (IV) and oral administration to determine dosing regimens that optimize CSF concentrations.

Methods: Twenty-one adult patients were assigned randomly to 1 g IV, 1 g oral or 1.5 g oral paracetamol.

CD8+ T cells produce a dialyzable antigen-specific activator of dendritic cells.

Cellular lysates from PPD donors have been reported to transfer tuberculin reactivity to naïve recipients, but not diphtheria reactivity, and vice versa. A historically controversial topic, the terms "transfer factor" and "DLE" were used to characterize the reactivity-transferring properties of lysates. Intrigued by these reported phenomena, we found that the cellular extract derived from antigen-specific memory CD8 T cells induces IL-6 from antigen-matched APCs.

"Race for the Surface": Eukaryotic Cells Can Win.

With an aging population and the consequent increasing use of medical implants, managing the possible infections arising from implant surgery remains a global challenge. Here, we demonstrate for the first time that a precise nanotopology provides an effective intervention in bacterial cocolonization enabling the proliferation of eukaryotic cells on a substratum surface, preinfected by both live Gram-negative, Pseudomonas aeruginosa, and Gram-positive, Staphylococcus aureus, pathogenic bacteria. The topology of the model black silicon (bSi) substratum not only favors the proliferation of eukaryotic cells but is biocompatible, not triggering an inflammatory response in the host.

Impact of polymer-modified gold nanoparticles on brain endothelial cells: exclusion of endoplasmic reticulum stress as a potential risk factor.

A library of polymer-coated gold nanoparticles (AuNPs) differing in size and surface modifications was examined for uptake and induction of cellular stress responses in the endoplasmic reticulum (ER stress) in human brain endothelial cells (hCMEC/D3). ER stress is known to affect the physiology of endothelial cells (ECs) and may lead to inflammation or apoptosis. Thus, even if applied at non-cytotoxic concentrations ER stress caused by nanoparticles should be prevented to reduce the risk of vascular diseases and negative effects on the integrity of barriers (e.

Lithium in Paediatric Patients with Bipolar Disorder: Implications for Selection of Dosage Regimens via Population Pharmacokinetics/Pharmacodynamics.

Background: Lithium is a well-established treatment for bipolar I disorder in adults. However, there is a paucity of information on its pharmacokinetics/pharmacodynamics in children and adolescents. We aimed to develop the first lithium dosage regimens based on population pharmacokinetics/pharmacodynamics for paediatric patients.

Prioritizing interventions to manage polypharmacy in Australian aged care facilities.

Background: Polypharmacy is highly prevalent in residential aged care facilities (RACFs). Although polypharmacy is sometimes unavoidable, polypharmacy has been associated with increased morbidity and mortality.

Objective: To identify and prioritize a range of potential interventions to manage polypharmacy in RACFs from the perspectives of health care professionals, health policy and consumer representatives.

Expansion of the peri-implant attached gingiva with a three-dimensional collagen matrix in head and neck cancer patients-results from a prospective clinical and histological study.

Objectives: Attached peri-implant gingiva has proven to have an influence on the long-term stability of dental implants. In patients with head and neck cancer, a functional peri-implant gingiva is even more of critical importance. The aim of the presented prospective study was to investigate a three-dimensional xenogeneic collagen matrix for augmentation around dental implants in patients with former head and neck cancer.

Honeybees Produce Millimolar Concentrations of Non-Neuronal Acetylcholine for Breeding: Possible Adverse Effects of Neonicotinoids.

The worldwide use of neonicotinoid pesticides has caused concern on account of their involvement in the decline of bee populations, which are key pollinators in most ecosystems. Here we describe a role of non-neuronal acetylcholine (ACh) for breeding of Apis mellifera carnica and a so far unknown effect of neonicotinoids on non-target insects. Royal jelly or larval food are produced by the hypopharyngeal gland of nursing bees and contain unusually high ACh concentrations (4-8 mM).

Disruptive innovation in community pharmacy - Impact of automation on the pharmacist workforce.

Pharmacy workforce planning has been relatively static for many decades. However, like all industries, health care is exposed to potentially disruptive technological changes. Automated dispensing systems have been available to pharmacy for over a decade and have been applied to a range of repetitive technical processes which are at risk of error, including record keeping, item selection, labeling and dose packing.

Effect of different renal function on antibacterial effects of piperacillin against Pseudomonas aeruginosa evaluated via the hollow-fibre infection model and mechanism-based modelling.

Background: Pathophysiological changes in critically ill patients can cause severely altered pharmacokinetics and widely varying antibiotic exposures. The impact of altered pharmacokinetics on bacterial killing and resistance has not been characterized in the dynamic hollow-fibre in vitro infection model (HFIM).

Methods: A clinical Pseudomonas aeruginosa isolate (piperacillin MIC 4 mg/L) was studied in the HFIM (inoculum ∼10(7) cfu/mL).

Clinically relevant concentrations of fosfomycin combined with polymyxin B, tobramycin or ciprofloxacin enhance bacterial killing of Pseudomonas aeruginosa, but do not suppress the emergence of fosfomycin resistance.

Objectives: Fosfomycin resistance occurs rapidly with monotherapy. This study systematically investigated bacterial killing and emergence of fosfomycin resistance with fosfomycin combinations against Pseudomonas aeruginosa.

Methods: Four clinical isolates and a reference strain of P.

The development of a tissue-engineered tracheobronchial epithelial model using a bilayered collagen-hyaluronate scaffold.

Today, chronic respiratory disease is one of the leading causes of mortality globally. Epithelial dysfunction can play a central role in its pathophysiology. The development of physiologically-representative in vitro model systems using tissue-engineered constructs might improve our understanding of epithelial tissue and disease.

Spontaneously reported haemorrhagic adverse events associated with rivaroxaban and dabigatran in Australia.

Objectives: The objective of our study was to describe spontaneously reported haemorrhagic adverse events associated with rivaroxaban and dabigatran in Australia.

Methods: Data were sourced from the Australian Therapeutic Goods Administration (TGA) Database of Adverse Event Notifications between June 2009 and May 2014. Records of haemorrhagic adverse events in which rivaroxaban or dabigatran was considered as a potential cause were analysed.

Foreign Body Giant Cell-Related Encapsulation of a Synthetic Material Three Years After Augmentation.

Bone substitute materials of different origin and chemical compositions are frequently used in augmentation procedures to enlarge the local bone amount. However, relatively little data exist on the long-term tissue reactions. The presented case reports for the first time histological and histomorphometrical analyses of a nanocrystaline hydroxyapatite-based bone substitute material implanted in the human sinus cavity after an integration period of 3 years.

Modelling the regenerative niche: a major challenge in biomaterials research.

By definition, biomaterials are developed for clinical application. In the field of regenerative medicine their principal function is to play a significant, and, if possible, an instructive role in tissue healing. In the last analysis the latter involves targeting the 'regenerative niche'.

Why is polypharmacy increasing in aged care facilities? The views of Australian health care professionals.

Rationale, Aims And Objectives: The prevalence of polypharmacy in residential aged care facilities (RACFs) is high and increasing. Although not necessarily inappropriate, polypharmacy has been associated with drug interactions, adverse drug events, geriatric syndromes and hospital admissions. The aim of this study was to identify and prioritize factors contributing to the increasing prevalence of polypharmacy in RACFs.

Effects of Changes in Number of Medications and Drug Burden Index Exposure on Transitions Between Frailty States and Death: The Concord Health and Ageing in Men Project Cohort Study.

Objectives: To investigate the effects of number of medications and Drug Burden Index (DBI) on transitions between frailty stages and death in community-dwelling older men.

Design: Cohort study.

Setting: Sydney, Australia.

Do the cerebellar tonsils move during flexion and extension of the neck in patients with Chiari I malformation? A radiological study with clinical implications.

Background: In the past, diagnosis of the Chiari I malformation has primarily been made on midsagittal MRI. We hypothesized that based on the frequent presentation of opisthotonos in patients with hindbrain hernia (primarily Chiari II malformation but sometimes Chiari I malformation) that the hyperextension might be a compensatory technique used by such patients to bring the cerebellar tonsils up out of the cervical spine.

Patients And Methods: This prospective study reviewed imaging of patients with Chiari I malformation who underwent flexion/extension MRI for evaluation of their hindbrain herniation.

Influenza virus damages the alveolar barrier by disrupting epithelial cell tight junctions.

A major cause of respiratory failure during influenza A virus (IAV) infection is damage to the epithelial-endothelial barrier of the pulmonary alveolus. Damage to this barrier results in flooding of the alveolar lumen with proteinaceous oedema fluid, erythrocytes and inflammatory cells. To date, the exact roles of pulmonary epithelial and endothelial cells in this process remain unclear.