The genomic road to invasion-examining the similarities and differences in the genomes of associated oral pre-cancer and cancer samples.

Background: It is frequently assumed that pre-invasive lesions are simpler precursors of cancer and will contain a limited subset of the genomic changes seen in their associated invasive disease. Driver mutations are thought to occur early, but it is not known how many of these are present in pre-invasive lesions. These assumptions need to be tested with the increasing focus on both personalised cancer treatments and early detection methodologies.

Numerical Simulation of Stent Angioplasty with Predilation: An Investigation into Lesion Constitutive Representation and Calcification Influence.

It is acceptable clinical practice to predilate a severely occluded vessel to allow better positioning of endovascular stents, and while the impact of this intervention has been examined for aggregate response in animals there has been no means to examine whether there are specific vessels that might benefit. Finite element methods offer the singular ability to explore the mechanical response of arteries with specific pathologic alterations in mechanics to stenting and predilation. We examined varying representations of atherosclerotic tissue including homogeneous and heterogeneous dispersion of calcified particles, and elastic, pseudo-elastic, and elastic-plastic constitutive representations of bulk atherosclerotic tissue.

Asymmetric Synthesis of the Major Metabolite of a Calcitonin Gene-Related Peptide Receptor Antagonist and Mechanism of Epoxide Hydrogenolysis.

An asymmetric synthesis of the major metabolite of the calcitonin gene-related peptide recepotor antagonist BMS-846372 is presented. The variously substituted cyclohepta[b]pyridine ring system represents an underexplored ring system and showed some unexpected chemistry. Reactivities of epoxide and ketone functional groups on the cycloheptane ring were extensively controlled by a remote bulky TIPS group.

Pufferfish mortality associated with novel polar marine toxins in Hawaii.

Fish die-offs are important signals in tropical marine ecosystems. In 2010, a mass mortality of pufferfish in Hawaii (USA) was dominated by Arothron hispidus showing aberrant neurological behaviors. Using pathology, toxinology, and field surveys, we implicated a series of novel, polar, marine toxins as a likely cause of this mass mortality.

Core dimensions of anxiety and depression change independently during adolescence.

The developmental trajectories of emotional disorder symptoms during adolescence remain elusive, owing in part to a shortage of intensive longitudinal data. In the present study, we charted the temporal course of the tripartite model of anxiety and depression-which posits an overarching negative affect dimension and specific anhedonia and anxious arousal dimensions-over adolescence and emerging adulthood to construct a developmental map of the core dimensions of emotional disorders. We recruited 604 high school juniors, overselecting those at high risk for emotional disorders, and assessed the tripartite symptom domains 5 times annually.

High-sensitivity Cardiac Troponin Elevation after Electroconvulsive Therapy: A Prospective, Observational Cohort Study.

Background: While electroconvulsive therapy is widely regarded as a lifesaving and safe procedure, evidence regarding its effects on myocardial cell injury is sparse. The objective of this investigation was to determine the incidence and magnitude of new cardiac troponin elevation after electroconvulsive therapy using a novel high-sensitivity cardiac troponin I assay.

Methods: This was a prospective cohort study in adult patients undergoing electroconvulsive therapy in a single academic center (up to three electroconvulsive therapy treatments per patient).

Stents: Biomechanics, Biomaterials, and Insights from Computational Modeling.

Coronary stents have revolutionized the treatment of coronary artery disease. Improvement in clinical outcomes requires detailed evaluation of the performance of stent biomechanics and the effectiveness as well as safety of biomaterials aiming at optimization of endovascular devices. Stents need to harmonize the hemodynamic environment and promote beneficial vessel healing processes with decreased thrombogenicity.

Inhibition Mediated by Glycinergic and GABAergic Receptors on Excitatory Neurons in Mouse Superficial Dorsal Horn Is Location-Specific but Modified by Inflammation.

The superficial dorsal horn is the synaptic termination site for many peripheral sensory fibers of the somatosensory system. A wide range of sensory modalities are represented by these fibers, including pain, itch, and temperature. Because the involvement of local inhibition in the dorsal horn, specifically that mediated by the inhibitory amino acids GABA and glycine, is so important in signal processing, we investigated regional inhibitory control of excitatory interneurons under control conditions and peripheral inflammation-induced mechanical allodynia.

Emergence of mania in two middle-aged patients with a history of unipolar treatment-refractory depression receiving vagus nerve stimulation.

Objectives: We report on two patients who experienced emergence of full manic symptoms while receiving vagal nerve stimulation (VNS).

Methods: Two patients, both with a well-documented and verified history of longstanding unipolar depression, were initiated on VNS for treatment of their severe major depressive episodes.

Results: The two patients had emergence of full manic symptoms after 8 and 9 months of VNS, respectively.

Molecular characterization of a novel orthomyxovirus from rainbow and steelhead trout (Oncorhynchus mykiss).

A novel virus, rainbow trout orthomyxovirus (RbtOV), was isolated in 1997 and again in 2000 from commercially-reared rainbow trout (Oncorhynchus mykiss) in Idaho, USA. The virus grew optimally in the CHSE-214 cell line at 15°C producing a diffuse cytopathic effect; however, juvenile rainbow trout exposed to cell culture-grown virus showed no mortality or gross pathology. Electron microscopy of preparations from infected cell cultures revealed the presence of typical orthomyxovirus particles.

Visual statistical learning is related to natural language ability in adults: An ERP study.

Statistical learning (SL) is believed to enable language acquisition by allowing individuals to learn regularities within linguistic input. However, neural evidence supporting a direct relationship between SL and language ability is scarce. We investigated whether there are associations between event-related potential (ERP) correlates of SL and language abilities while controlling for the general level of selective attention.

Stress responsivity and the structure of common mental disorders: Transdiagnostic internalizing and externalizing dimensions are associated with contrasting stress appraisal biases.

Biased stress appraisals critically relate to the origins and temporal course of many-perhaps most-forms of psychopathology. We hypothesized that aberrant stress appraisals are linked directly to latent internalizing and externalizing traits that, in turn, predispose to multiple disorders. A high-risk community sample of 815 adolescents underwent semistructured interviews to assess clinical disorders and naturalistic stressors at ages 15 and 20.

Towards Stratified Medicine in Plasma Cell Myeloma.

Plasma cell myeloma is a clinically heterogeneous malignancy accounting for approximately one to 2% of newly diagnosed cases of cancer worldwide. Treatment options, in addition to long-established cytotoxic drugs, include autologous stem cell transplant, immune modulators, proteasome inhibitors and monoclonal antibodies, plus further targeted therapies currently in clinical trials. Whilst treatment decisions are mostly based on a patient's age, fitness, including the presence of co-morbidities, and tumour burden, significant scope exists for better risk stratification, sub-classification of disease, and predictors of response to specific therapies.

A growing role for 'smart' sensors.

Dr. Ghasson Shabha, senior lecturer at the integrated Design and Construction Centre at the School of Engineering and the Built Environment at Birmingham City University (BCU), and associate professor, Chris Conway, associate professor and the Centre's acting head, explain their recent work to investigate 'the latest development' of incorporating smart sensor technology (SST) to monitor and detect airborne infection in British hospitals. Here they set out why they believe effective incorporation of such technology in healthcare facilities in this digital age is the sine qua non for an effective infection control strategy to mitigate against this 'endemic problem', and ask whether such smart sensors can indeed be the 'panacea for hospitals' ills'.

Inhibition of AAK1 Kinase as a Novel Therapeutic Approach to Treat Neuropathic Pain.

To identify novel targets for neuropathic pain, 3097 mouse knockout lines were tested in acute and persistent pain behavior assays. One of the lines from this screen, which contained a null allele of the adapter protein-2 associated kinase 1 (AAK1) gene, had a normal response in acute pain assays (hot plate, phase I formalin), but a markedly reduced response to persistent pain in phase II formalin. AAK1 knockout mice also failed to develop tactile allodynia following the Chung procedure of spinal nerve ligation (SNL).

Alteration of immune markers in a group of melancholic depressed patients and their response to electroconvulsive therapy.

Background: Immune system dysfunction is implicated in the pathophysiology of major depression, and is hypothesized to normalize with successful treatment. We aimed to investigate immune dysfunction in melancholic depression and its response to ECT.

Methods: 55 melancholic depressed patients and 26 controls participated.

The Application of Digital Pathology to Improve Accuracy in Glomerular Enumeration in Renal Biopsies.

Background: In renal biopsy reporting, quantitative measurements, such as glomerular number and percentage of globally sclerotic glomeruli, is central to diagnostic accuracy and prognosis. The aim of this study is to determine the number of glomeruli and percent globally sclerotic in renal biopsies by means of registration of serial tissue sections and manual enumeration, compared to the numbers in pathology reports from routine light microscopic assessment.

Design: We reviewed 277 biopsies from the Nephrotic Syndrome Study Network (NEPTUNE) digital pathology repository, enumerating 9,379 glomeruli by means of whole slide imaging.

Morphometry Predicts Early GFR Change in Primary Proteinuric Glomerulopathies: A Longitudinal Cohort Study Using Generalized Estimating Equations.

Objective: Most predictive models of kidney disease progression have not incorporated structural data. If structural variables have been used in models, they have generally been only semi-quantitative.

Methods: We examined the predictive utility of quantitative structural parameters measured on the digital images of baseline kidney biopsies from the NEPTUNE study of primary proteinuric glomerulopathies.

Learning and Memory Processes Following Cochlear Implantation: The Missing Piece of the Puzzle.

At the present time, there is no question that cochlear implants (CIs) work and often work very well in quiet listening conditions for many profoundly deaf children and adults. The speech and language outcomes data published over the last two decades document quite extensively the clinically significant benefits of CIs. Although there now is a large body of evidence supporting the "efficacy" of CIs as a medical intervention for profound hearing loss in both children and adults, there still remain a number of challenging unresolved clinical and theoretical issues that deal with the "effectiveness" of CIs in individual patients that have not yet been successfully resolved.

Dysfunctional Attitudes and Affective Responses to Daily Stressors: Separating Cognitive, Genetic, and Clinical Influences on Stress Reactivity.

Despite decades of research examining diathesis-stress models of emotional disorders, it remains unclear whether dysfunctional attitudes interact with stressful experiences to shape affect on a daily basis and, if so, how clinical and genetic factors influence these associations. To address these issues, we conducted a multi-level daily diary study that examined how dysfunctional attitudes and stressful events relate to daily fluctuations in negative and positive affect in 104 young adults. Given evidence that clinical and genetic factors underlie stress sensitivity, we also examined how daily affect is influenced by internalizing and externalizing symptoms and brain-derived neurotrophic factor (BDNF) genotype, which have been shown to influence neural, endocrine, and affective responses to stress.

Finding Your Way™: a collaborative approach to increase awareness of missing person events among persons with dementia.

Aim: To describe an innovative community-wide program aimed at increasing awareness of risks of missing person events among persons with dementia targeting various cultural groups and to present preliminary evaluation findings.

Methods: Review of program records to describe program implementation and a community partner survey.

Results: Over 23 months, 386 partnerships were established to implement the program; 941 awareness-raising sessions were conducted reaching 23,495 individuals.