Analysis of tissue lipidomics and computed tomography pulmonary fat attenuation volume (CTPFAV ) in idiopathic pulmonary fibrosis.

BACKGROUND AND OBJECTIVE: There is increasing interest in the role of lipids in processes that modulate lung fibrosis with evidence of lipid deposition in idiopathic pulmonary fibrosis (IPF) histological specimens. The aim of this study was to identify measurable markers of pulmonary lipid that may have utility as IPF biomarkers. STUDY DESIGN AND METHODS: IPF and control lung biopsy specimens were analysed using a unbiased lipidomic approach. Pulmonary fat attenuation volume (PFAV) was assessed on chest CT images (CTPFAV ) with 3D semi-automated lung density software. Aerated lung was semi-automatically segmented and CTPFAV calculated using a Hounsfield-unit (-40 to -200HU) threshold range expressed as a percentage of total lung volume. CTPFAV was compared to pulmonary function, serum lipids and qualitative CT fibrosis scores. RESULTS: There was a significant increase in total lipid content on histological analysis of IPF lung tissue (23.16 nmol/mg) compared to controls (18.66 mol/mg, p = 0.0317). The median CTPFAV in IPF was higher than controls (1.34% vs. 0.72%, p < 0.001) and CTPFAV correlated significantly with DLCO% predicted (R2 = 0.356, p < 0.0001) and FVC% predicted (R2 = 0.407, p < 0.0001) in patients with IPF. CTPFAV correlated with CT features of fibrosis; higher CTPFAV was associated with >10% reticulation (1.6% vs. 0.94%, p = 0.0017) and >10% honeycombing (1.87% vs. 1.12%, p = 0.0003). CTPFAV showed no correlation with serum lipids. CONCLUSION: CTPFAV is an easily quantifiable non-invasive measure of pulmonary lipids. In this pilot study, CTPFAV correlates with pulmonary function and radiological features of IPF and could function as a potential biomarker for IPF disease severity assessment.

Chemical signals act as the main reproductive barrier between sister and mimetic Heliconius butterflies.

Colour pattern is the main trait that drives mate recognition between Heliconius species that are phylogenetically close. However, when this cue is compromised such as in cases of mimetic, sympatric and closely related species, alternative mating signals must evolve to ensure reproductive isolation and species integrity. The closely related species Heliconius melpomene malleti and H. timareta florencia occur in the same geographical region, and despite being co-mimics, they display strong reproductive isolation. In order to test which cues differ between species, and potentially contribute to reproductive isolation, we quantified differences in the wing phenotype and the male chemical profile. As expected, the wing colour pattern was indistinguishable between the two species, while the chemical profile of the androconial and genital males' extracts showed marked differences. We then conducted behavioural experiments to study the importance of these signals in mate recognition by females. In agreement with our previous results, we found that chemical blends and not wing colour pattern drive the preference of females for conspecific males. Also, experiments with hybrid males and females suggested an important genetic component for both chemical production and preference. Altogether, these results suggest that chemicals are the major reproductive barrier opposing gene flow between these two sister and co-mimic species.

DISC1 complexes with TRAK1 and Miro1 to modulate anterograde axonal mitochondrial trafficking.

Disrupted-In-Schizophrenia 1 (DISC1) is a candidate risk factor for schizophrenia, bipolar disorder and severe recurrent depression. Here, we demonstrate that DISC1 associates robustly with trafficking-protein-Kinesin-binding-1 which is, in turn, known to interact with the outer mitochondrial membrane proteins Miro1/2, linking mitochondria to the kinesin motor for microtubule-based subcellular trafficking. DISC1 also associates with Miro1 and is thus a component of functional mitochondrial transport complexes. Consistent with these observations, in neuronal axons DISC1 promotes specifically anterograde mitochondrial transport. DISC1 thus participates directly in mitochondrial trafficking, which is essential for neural development and neurotransmission. Any factor affecting mitochondrial DISC1 function is hence likely to have deleterious consequences for the brain, potentially contributing to increased risk of psychiatric illness. Intriguingly, therefore, a rare putatively causal human DISC1 sequence variant, 37W, impairs the ability of DISC1 to promote anterograde mitochondrial transport. This is likely related to a number of mitochondrial abnormalities induced by expression of DISC1-37W, which redistributes mitochondrial DISC1 and enhances kinesin mitochondrial association, while also altering protein interactions within the mitochondrial transport complex.

A national survey of prevention of infection in obstetric central neuraxial blockade in the UK.

We conducted a postal survey of all consultant-led UK obstetric anaesthetic units in August 2009, to assess the standard of aseptic technique used for neuraxial blocks. One hundred and sixty-four units responded giving a response rate of 76%; 93% of units (149/160) follow recommended precautions and attach a bacterial micropore filter to the epidural catheter. Epidural top-ups are provided by 72% (116/162) of units, with about two thirds using premixed solutions (of local anaesthetic with opioid) in a variety of ways: 51% (57/111) via a continuous infusion pump; 47% (52/111) by a prefilled syringe; and 23% (25/111) by multiple use of a premixed bag of solution. For spinals, 91% of units (149/164) add diamorphine: of these 85% (126/149) draw the diamorphine from non-sterile-wrapped ampoules. If required to draw opioid from a non-sterile-wrapped ampoule, 86% (119/138) of units use a micropore filter and 21% (29/138) wipe the ampoule neck with an alcohol swab. Although sepsis secondary to neuraxial block in obstetric practice is uncommon (declared by 8.5% of units over an unspecified period of time), there is scope for further improvement.

Personality, cardiovascular, and cortisol reactions to acute psychological stress in the Midlife in the United States (MIDUS) study.

Recent research has suggested that diminished, as well as elevated reactivity to acute psychological stress is maladaptive. These differences in stress reactions have been hypothesized to relate to the Big Five personality traits, which are said to be biologically-based and stable across adulthood; however, findings have been inconclusive. This study sought to replicate the findings of the largest study conducted to date (Bibbey et al., 2013), with a sample of participants from the Midlife in the United States Study (MIDUS), aged between 35 and 84 years (M = 56.33, SD = 10.87). Participants (N = 817) undertook a standardized, laboratory-based procedure during which their cardiovascular and neuroendocrine reactivity to acute stress was measured. In contrast to Bibbey et al. (2013), associations between neuroticism and blunted reactivity did not withstand adjustment for confounding variables. Further, following adjustment for multiple tests, no significant positive association between agreeableness and HR reactivity was observed. Methodological differences between the studies, which may account in part for the contrasting findings, are discussed. Further conceptual replication research is needed to clarify associations between the Big Five personality traits and stress reactivity, across the lifespan.

High-grade chondrosarcoma of the larynx: a case report and literature review.

A 64-year-old male presented with a 2-month history of sudden onset dysphonia. Endoscopic evaluation of the larynx revealed a complete right vocal cord palsy. Computed tomography of the neck revealed a mass medial to the right thyroid associated with the cricoid cartilage. Histologic examination confirmed high-grade chondrosarcoma. The patient underwent right-sided hemicricoidectomy with tracheal flap reconstruction, right thyroid lobectomy and partial oesophagectomy with primary anastomosis followed by adjuvant radiation therapy. He is currently being followed as an outpatient with no evidence of disease. High-grade chondrosarcoma of the larynx is an exceedingly rare tumour, associated with a poor prognosis. Current best evidence suggests primary surgical resection with negative margins. There is a lack of evidence to guide post-operative management of high-grade chondrosarcoma. They have a poor prognosis following surgical resection and a 10-year survival rate of 29%.

The development and validation of the Virtual Tissue Matrix, a software application that facilitates the review of tissue microarrays on line.

BACKGROUND: The Tissue Microarray (TMA) facilitates high-throughput analysis of hundreds of tissue specimens simultaneously. However, bottlenecks in the storage and manipulation of the data generated from TMA reviews have become apparent. A number of software applications have been developed to assist in image and data management; however no solution currently facilitates the easy online review, scoring and subsequent storage of images and data associated with TMA experimentation. RESULTS: This paper describes the design, development and validation of the Virtual Tissue Matrix (VTM). Through an intuitive HTML driven user interface, the VTM provides digital/virtual slide based images of each TMA core and a means to record observations on each TMA spot. Data generated from a TMA review is stored in an associated relational database, which facilitates the use of flexible scoring forms. The system allows multiple users to record their interpretation of each TMA spot for any parameters assessed. Images generated for the VTM were captured using a standard background lighting intensity and corrective algorithms were applied to each image to eliminate any background lighting hue inconsistencies or vignetting. Validation of the VTM involved examination of inter-and intra-observer variability between microscope and digital TMA reviews. Six bladder TMAs were immunohistochemically stained for E-Cadherin, beta-Catenin and PhosphoMet and were assessed by two reviewers for the amount of core and tumour present, the amount and intensity of membrane, cytoplasmic and nuclear staining. CONCLUSION: Results show that digital VTM images are representative of the original tissue viewed with a microscope. There were equivalent levels of inter-and intra-observer agreement for five out of the eight parameters assessed. Results also suggest that digital reviews may correct potential problems experienced when reviewing TMAs using a microscope, for example, removal of background lighting variance and tint, and potential disorientation of the reviewer, which may have resulted in the discrepancies evident in the remaining three parameters.

A low tilt waveform in the transthoracic defibrillation of ventricular arrhythmias during cardiac arrest.

AIM: Most commercially available defibrillators utilise a high tilt waveform. Work in atrial fibrillation has shown improved defibrillation success using low tilt waveforms. We hypothesise that a novel low tilt biphasic waveform will be non-inferior to a standard tilt waveform whilst delivering lower energy for the defibrillation of ventricular arrhythmias. METHODS: Patients in cardiac arrest who experienced ventricular arrhythmias received shocks from a novel low tilt waveform defibrillator at 120J or a standard tilt waveform defibrillator at 150J. Resuscitation guidelines were followed as per Resuscitation Council UK, 2005. A shock was successful when the ventricular arrhythmia was terminated for ≥ 5s following shock delivery. RESULTS: A total of 113 cardiac arrest cases were included. The low tilt device was used for 56 cases and the standard tilt device for 57 cases. The presenting rhythm was ventricular fibrillation (VF) in 71.7% (81/113), pulseless electrical activity (PEA) in 15.9% (18/113), ventricular tachycardia (VT) in 9.7% (11/113), asystole in 1.8% (2/113) and narrow complex rhythm in 0.9% (1/113). The low tilt device resulted in first shock success in 86% (48/56 cases) vs. the standard tilt device first shock success of 77% (44/57 cases). There was no significant difference in first shock success between the two devices (p=0.36). CONCLUSION: The low tilt waveform used in this study demonstrated first shock success rates in keeping with a commercially available high tilt defibrillator which could result in less myocardial damage due to reduced energy requirements.