Impact of Close Margins on Oral Cancer Outcomes According to the Oral Subsite.

Background: The prognostic significance of close margins in oral squamous cell carcinoma (OSCC) is controversial. We wished to investigate the impact of close margins on the risk of local recurrence (LR) in OSCC according to the oral subsite.

Methods: A retrospective cohort study of 342 OSCC patients undergoing primary surgical treatment was conducted.

Does breast cancer policy meet the needs of Aboriginal and Torres Strait Islander women in Australia? a review.

Objective: To evaluate if existing Australian public policy related to screening, diagnosis, treatment and follow up care for breast cancer addresses the needs of and outcomes for Indigenous women?

Methods: This review of policy employed a modified Delphi method via an online panel of experts (n = 13), who were purposively recruited according to experience and expertise. A series of online meetings and online surveys were used for data collection. The aims of the study were to: Identify all existing and current breast cancer policy in Australia;  Analyse the extent to which consideration of Indigenous peoples is included in the development, design and implementation of the policy; and Identify policy gaps and make recommendations as to how they could be addressed.

"Everyone needs a Deb": what Australian indigenous women say about breast cancer screening and treatment services.

Background: Breast cancer continues to be the second most diagnosed cancer overall and the most diagnosed cancer for women in Australia. While mortality rates overall have declined in recent years, Indigenous women continue to be diagnosed at more marginal rates (0.9 times) and are more likely to die (1.

Comparison of royal college of pathologists and college of american pathologists definition for positive margins in oral cavity squamous cell carcinoma.

Background: Pathological margin assessment is an essential component of surgical management of oral cavity squamous cell carcinoma (OCSCC), however, in many studies, variable definitions of involved margins have been used. The purpose of the present study was to compare the prognostic ability of involved margins according to Royal College of Pathologists (RCPath) and College of American Pathologists (CAP) guidance.

Methods: Retrospective study of 300 patients with previously untreated OCSCC undergoing definitive surgical management.

Laryngopharyngeal reflux induced sleep-related laryngospasm.

Background: Sleep-related laryngospasm (SRL) has been defined as the sustained closure of the vocal cords during sleep. Studies have suggested that it is a rare manifestation of laryngopharyngeal reflux (LPR). Difficulties in diagnosing SRL and LPR have led to the condition being under-recognised in the clinical setting.

Astrocyte Control of Zika Infection Is Independent of Interferon Type I and Type III Expression.

Zika virus (ZIKV) is a pathogenic neurotropic virus that infects the central nervous system (CNS) and results in various neurological complications. Astrocytes are the dominant CNS cell producer of the antiviral cytokine IFN-β, however little is known about the factors involved in their ability to mediate viral infection control. Recent studies have displayed differential responses in astrocytes to ZIKV infection, and this study sought to elucidate astrocyte cell-specific responses to ZIKV using a variety of cell models infected with either the African (MR766) or Asian (PRVABC59) ZIKV strains.

Prognostic performance of TNM8 staging rules in oral cavity squamous cell carcinoma.

Background: Two major changes to the staging of oral cavity squamous cell carcinoma (OCSCC) were adopted in TNM8: (1) depth of invasion is now used for T staging and (2) extranodal extension for N staging. The aim of this study was to evaluate if TNM8 stratifies OCSCC patients more accurately than TNM7 based on overall survival (OS) statistics and hazard discrimination.

Methods: Retrospective study of 297 patients with OCSCC who underwent surgery at our institution.

Impact of 3 mm margin on risk of recurrence and survival in oral cancer.

Introduction: While positive surgical margins in oral squamous cell carcinoma (OSCC) is generally considered an adverse prognosticator, the significance of close (≤5 mm) margins is more debatable, and has not been widely adopted as an indicator for radiotherapy.

Materials And Methods: Retrospective study of 244 patients undergoing primary surgical resection of OSCC. The impact on local control (LC), disease-specific survival (DSS) and overall survival (OS) of margins at 1 mm intervals was studied.

Evolution of Cochlear implant mapping and vestibular function in a pediatric case of Labyrinthitis.

Background: Vestibular symptoms such as vertigo and imbalance are known to occur in some cochlear implant patients during the immediate postoperative period; however, acute vertigo in implanted children occurring remotely from the postoperative period has not been previously well-described.

Case Presentation: A three-year-old girl with a history of bilateral sequential cochlear implantation presented with acute labyrinthitis associated with sudden onset of vertigo, balance impairment, and decline in right cochlear implant function 2 years after her most recent implant surgery. We describe her audiological and vestibular testing results during both the acute phase and following medical management and recovery.

Mild Closed-Head Injury in Conscious Rats Causes Transient Neurobehavioral and Glial Disturbances: A Novel Experimental Model of Concussion.

Rodent models can provide insights into the most pertinent issues surrounding concussion. Nonetheless, the relevance of some existing models to clinical concussion can be questioned, particularly with regard to the use of surgery and anesthesia and the mechanism and severity of injury. Accordingly, we have co-developed an awake closed-head injury (ACHI) model in rats.

SOD1 Mutations Causing Familial Amyotrophic Lateral Sclerosis Induce Toxicity in Astrocytes: Evidence for Bystander Effects in a Continuum of Astrogliosis.

Astrocytes contribute to the death of motor neurons via non-cell autonomous mechanisms of injury in amyotrophic lateral sclerosis (ALS). Since mutations in the gene encoding Cu/Zn superoxide dismutase (SOD1) underlie the neuropathology of some forms of familial ALS, we explored how expression of mutant SOD1 protein A4V SOD1-EGFP affected the biology of secondary murine astrocytes. A4V SOD1-EGFP expressing astrocytes (72 h after transfection) displayed decreased mitochondrial activity (~45%) and L-glutamate transport (~25%), relative to cells expressing wild-type SOD1-EGFP.

Turbulent tackle: a novel surgical approach to a rugby-related jejunal perforation.

Viscus perforation in the context of blunt-force abdominal trauma is a rarity. Within a sporting context, it is especially rare. However, the increasing physicality observed in rugby union, both in the amateur and professional setting, has resulted in a higher rate of serious injury.

Galactose-functionalised PCL nanofibre scaffolds to attenuate inflammatory action of astrocytes in vitro and in vivo.

Astrocytes represent an attractive therapeutic target for the treatment of traumatic brain injury in the glial scar, which inhibits functional repair and recovery if persistent. Many biomaterial systems have been investigated for neural tissue engineering applications, including electrospun nanofibres, which are a favourable biomaterial as they can mimic the fibrous architecture of the extracellular matrix, and are conveniently modified to present biologically relevant cues to aid in regeneration. Here, we synthesised a novel galactose-presenting polymer, poly(l-lysine)-lactobionic acid (PLL-LBA), for use in layer-by-layer (LbL) functionalisation of poly(ε-caprolactone) (PCL) nanofibres, to covalently attach galactose moieties to the nanofibre scaffold surface.

Impact of current smoking and alcohol consumption on gastrostomy duration in patients with head and neck cancer undergoing definitive chemoradiotherapy.

Importance: Prophylactic gastrostomy tube (GT) insertion prior to chemoradiotherapy is a valuable nutritional adjunct in patients with head and neck cancer undergoing nonsurgical treatment. However, concerns have been expressed regarding high rates of GT dependence. There is little information in the literature regarding the impact of modifiable risk factors such as smoking and alcohol consumption on duration of GT use and dependence rates.

Transcriptomic analysis and 3D bioengineering of astrocytes indicate ROCK inhibition produces cytotrophic astrogliosis.

Astrocytes provide trophic, structural and metabolic support to neurons, and are considered genuine targets in regenerative neurobiology, as their phenotype arbitrates brain integrity during injury. Inhibitors of Rho kinase (ROCK) cause stellation of cultured 2D astrocytes, increased L-glutamate transport, augmented G-actin, and elevated expression of BDNF and anti-oxidant genes. Here we further explored the signposts of a cytotrophic, "healthy" phenotype by data-mining of our astrocytic transcriptome in the presence of Fasudil.

Combined excitotoxic-oxidative stress and the concept of non-cell autonomous pathology of ALS: insights into motoneuron axonopathy and astrogliosis.

Non-cell autonomous pathology is widely accepted to determine the demise of motoneurons (MNs) in amyotrophic lateral sclerosis (ALS) with astrocytes, GFAP and glutamate transport suggested to play roles in reactive astrogliosis. Previously we described actions of excitotoxicity and oxidative stress to produce differential injury of motoneurons and astrocytes, respectively, and our goal here was to define patterns of MN injury and astrogliosis during a combined excitotoxic-oxidative injury since such a paradigm more closely models disease pathology. Using an in vitro neuronal-glial culture of embryonic mouse spinal cord, we demonstrate that glutamate transport activity was maintained or increased initially, despite a loss of cellular viability, induced by exposure to combinations of excitotoxic [(S)-5-fluorowillardiine (FW)] and oxidative [3-morpholinosydnonimine (SIN-1)] insults over 48 h.

Transcriptomic profiling of astrocytes treated with the Rho kinase inhibitor fasudil reveals cytoskeletal and pro-survival responses.

Inhibitors of Rho kinase (ROCK) have potential for management of neurological disorders by inhibition of glial scarring. Since astrocytes play key roles in brain physiology and pathology, we determined changes in the astrocytic transcriptome produced by the ROCK inhibitor Fasudil to obtain mechanistic insights into its beneficial action during brain injury. Cultured murine astrocytes were treated with Fasudil (100 µM) and morphological analyses revealed rapid stellation by 1 h and time-dependent (2-24 h) dissipation of F-actin-labelled stress fibres.

Transportable and non-transportable inhibitors of L-glutamate uptake produce astrocytic stellation and increase EAAT2 cell surface expression.

Astrocytic excitatory amino acid transporters (EAATs) regulate excitatory transmission and limit excitotoxicity. Evidence for a functional interface between EAATs and glial fibrillary acidic protein (GFAP) relevant to astrocytic morphology led to investigations of actions of transportable (D-Aspartate (D-Asp) and (2S,3S,4R)-2-(carboxycyclopropyl)glycine (L-CCG-III)) and non-transportable (DL-threo-beta-benzyloxyaspartate (DL-TBOA)) inhibitors of Glu uptake in murine astrocytes. D-Asp (1 mM), L-CCG-III (0.

Evidence group I mGluR drugs modulate the activation profile of lipopolysaccharide-exposed microglia in culture.

Metabotropic glutamate receptors (mGluRs) may play a role in modulating microglial activation, but group I mGluRs have received little attention. This study aimed to investigate the effects of group I mGluR selective ligands, (S)-3,5-dihydroxyphenylglycine ((S)-3,5-DHPG) and (RS)-1-aminoindan-1,5-dicarboxylic acid (AIDA), in lipopolysaccharide (LPS; 50 ng/ml)-activated rat microglial cultures. (S)-3,5-DHPG (150 microM) significantly reduced (approximately 20-60%) the LPS-mediated production of nitrite (NO2(-)), tumour necrosis factor alpha (TNF-alpha), and L-glutamate (Glu) at 24 and 72 h.

Oxidative and excitotoxic insults exert differential effects on spinal motoneurons and astrocytic glutamate transporters: Implications for the role of astrogliosis in amyotrophic lateral sclerosis.

In amyotrophic lateral sclerosis (ALS) non-neuronal cells play key roles in disease etiology and loss of motoneurons via noncell-autonomous mechanisms. Reactive astrogliosis and dysfunctional transporters for L-glutamate [excitatory amino acid transporters, (EAATs)] are hallmarks of ALS pathology. Here, we describe mechanistic insights into ALS pathology involving EAAT-associated homeostasis in response to a destructive milieu, in which oxidative stress and excitotoxicity induce respectively astrogliosis and motoneuron injury.

The effects of estradiol on estrogen receptor and glutamate transporter expression in organotypic hippocampal cultures exposed to oxygen--glucose deprivation.

The molecular basis of estrogen-mediated neuroprotection against brain ischemia remains unclear. In the present study, we investigated changes in expression of estrogen receptors (ERs) alpha and beta and excitatory amino acid transporters (EAAT) 1 and 2 in rat organotypic hippocampal slice cultures treated with estradiol and subsequently exposed to oxygen--glucose deprivation (OGD). Pretreatment with 17beta-estradiol (10 nM) for 7 days protected the CA1 area of hippocampus against OGD (60 min), reducing cellular injury by 46% compared to the vehicle control group.

Effects of lipopolysaccharide on glial phenotype and activity of glutamate transporters: Evidence for delayed up-regulation and redistribution of GLT-1.

Excitatory amino acid transporters (EAATs) are responsible for homeostasis of extracellular L-glutamate, and the glial transporters are functionally dominant. EAAT expression or function is altered in acute and chronic neurological conditions, but little is known about the regulation of EAATs in reactive astroglia found in such neuropathologies. These studies examined the effects of the bacterial endotoxin lipopolysaccharide (LPS) on glial EAATs in vitro.

Hypoxic preconditioning in neonatal rat brain involves regulation of excitatory amino acid transporter 2 and estrogen receptor alpha.

Exposure of the brain to a sublethal insult can protect against a subsequent brain injury. Hypoxic preconditioning induces tolerance to hypoxic--ischemic injury in neonatal rat brain and is associated with changes in gene and protein expression. To study the involvement of excitatory amino acid transporters (EAAT1 and EAAT2) and estrogen receptors (ERalpha and ERbeta) in neonatal hypoxia--induced ischemic tolerance, we examined changes in expression of these proteins in the cortex, hippocampus and striatum of newborn rats at different time points after exposure to sublethal hypoxia (8% O(2), 3h).

Regulation of glutamate transporters in astrocytes: evidence for a relationship between transporter expression and astrocytic phenotype.

The astrocytic glutamate transporters, EAAT1 and EAAT2, remove released L-glutamate from the synaptic milieu thereby maintaining normal excitatory transmission. EAAT dysfunction during the excitotoxicity and oxidative stress of neurological insults may involve homoeostatic mechanisms associated with astrocytic function. We investigated aspects of EAAT function and expression in concert with astrocytic phenotype in primary cultures of cortical astrocytes and mixed cells of the spinal cord.

Binding and transport of [3H](2S,4R)- 4-methylglutamate, a new ligand for glutamate transporters, demonstrate labeling of EAAT1 in cultured murine astrocytes.

Transporters for L-glutamate (excitatory amino acid transporters; EAATs), localized to astrocytes, are involved intimately in intermediary metabolism within the brain. Because (2S,4R)-4-methylglutamate (4MG) has affinity for glial EAATs, we employed [(3)H]4MG to define the characteristics of EAATs in cultured murine astrocytes and describe new approaches to analyze EAAT function. Specific binding of [(3)H]4MG in astrocytic membranes at 4 degrees C represented 90% of total binding.