Developing an In Vitro Model to Screen Drugs for Nerve Regeneration

Peripheral nerve injuries (PNI) have a high prevalence and can be debilitating, resulting in life-long loss or disturbance in end-organ function, which compromises quality of life for patients. Current therapies use microsurgical approaches but there is the potential for enhancing recovery through other therapeutic modalities such as; cell-based conduits, gene therapy and small molecules. A number of molecular targets and drugs which have the potential to improve nerve regeneration have been identified, however, there are challenges associated with moving therapies toward clinical translation. Due to the lack of detailed knowledge about the pro-regenerative effect of potential drug treatments, there is a need for effective in vitro models to screen compounds to inform future pre-clinical and clinical studies. The interaction between regenerating neurites and supporting Schwann cells is a key feature of the nerve environment, therefore, in vitro models that mimic this cellular association are useful tools. In this study, we have investigated various cell culture models, including simple monolayer systems and more complex 3D-engineered co-cultures, as models for use in PNI drug development. Anat Rec, 2018. © 2018 The Authors. The Anatomical Record: Advances in Integrative Anatomy and Evolutionary Biology published by Wiley Periodicals, Inc. on behalf of Wiley-Liss, Inc

High-speed camera characterization of voluntary eye blinking kinematics.

Blinking is vital to maintain the integrity of the ocular surface and its characteristics such as blink duration and speed can vary significantly, depending on the health of the eyes. The blink is so rapid that special techniques are required to characterize it. In this study, a high-speed camera was used to record and characterize voluntary blinking. The blinking motion of 25 healthy volunteers was recorded at 600 frames per second. Master curves for the palpebral aperture and blinking speed were constructed using palpebral aperture versus time data taken from the high-speed camera recordings, which show that one blink can be divided into four phases; closing, closed, early opening and late opening. Analysis of data from the high-speed camera images was used to calculate the palpebral aperture, peak blinking speed, average blinking speed and duration of voluntary blinking and compare it with data generated by other methods previously used to evaluate voluntary blinking. The advantages of the high-speed camera method over the others are discussed, thereby supporting the high potential usefulness of the method in clinical research

Discovery of anti-cancer activity for benzo[1,2,4]triazin-7-ones : very strong correlation to pleurotin and thioredoxin reductase inhibition

The thioredoxin (Trx)-thioredoxin reductase (TrxR) system plays a key role in maintaining the cellular redox balance with Trx being over-expressed in a number of cancers. Inhibition of TrxR is an important strategy for anti-cancer drug discovery. The natural product pleurotin is a well-known irreversible inhibitor of TrxR. The cytotoxicity data for benzo[1,2,4]triazin-7-ones showed very strong correlation (Pearson correlation coefficients ~0.8) to pleurotin using National Cancer Institute COMPARE analysis. A new 3-CF3 substituted benzo[1,2,4]triazin-7-one gave submicromolar inhibition of TrxR, although the parent compound 1,3-diphenylbenzo[1,2,4]triazin-7-one was more cytotoxic against cancer cell lines. Benzo[1,2,4]triazin-7-ones exhibited different types of reversible inhibition of TrxR, and cyclic voltammetry showed characteristic quasi-reversible redox processes. Cell viability studies indicated strong dependence of cytotoxicity on substitution at the 6-position of the 1,3-diphenylbenzo[1,2,4]triazin-7-one ring.F.A. thanks the Irish Research Council (IRC) for a Government of Ireland Postgraduate Scholarship for Martin Sweeney and College of Science, National University of Ireland Galway (NUI Galway) for a postgraduate scholarship for Robert Coyle. We thank the National Cancer Institute (USA), Development Therapeutic Program for providing us with a small quantity of pleurotin. P.A.K. thanks the Cyprus Research Promotion Foundation [Grants: NEAYPODOMH/NEKYP/0308/02 and YGEIA/BIOS/0308(BIE)/13], the University of Cyprus (Medium Sized Grant), and the following organizations in Cyprus for generous donations of chemicals and glassware: the State General Laboratory, the Agricultural Research Institute, the Ministry of Agriculture, Medochemie Ltd and Biotronics Ltd. Furthermore, P.A.K. thanks the A. G. Leventis Foundation for helping to establish the NMR facility in the University of Cyprus.2018-05-3

The impact of personality factors on delay in seeking treatment of acute myocardial infarction

<p>Abstract</p> <p>Background</p> <p>Early hospital arrival and rapid intervention for acute myocardial infarction is essential for a successful outcome. Several studies have been unable to identify explanatory factors that slowed decision time. The present study examines whether personality, psychosocial factors, and coping strategies might explain differences in time delay from onset of symptoms of acute myocardial infarction to arrival at a hospital emergency room.</p> <p>Methods</p> <p>Questionnaires on coping strategies, personality dimensions, and depression were completed by 323 patients ages 26 to 70 who had suffered an acute myocardial infarction. Tests measuring stress adaptation were completed by 180 of them. The patients were then categorised into three groups, based on time from onset of symptoms until arrival at hospital, and compared using logistic regression analysis and general linear models.</p> <p>Results</p> <p>No correlation could be established between personality factors (i.e., extraversion, neuroticism, openness, agreeableness, conscientiousness) or depressive symptoms and time between onset of symptoms and arrival at hospital. Nor was there any significant relationship between self-reported patient coping strategies and time delay.</p> <p>Conclusions</p> <p>We found no significant relationship between personality factors, coping strategies, or depression and time delays in seeking hospital after an acute myocardial infraction.</p

Distribution of Alarin Immunoreactivity in the Mouse Brain

Alarin is a 25 amino acid peptide that belongs to the galanin peptide family. It is derived from the galanin-like peptide gene by a splice variant, which excludes exon 3. Alarin was first identified in gangliocytes of neuroblastic tumors and later shown to have a vasoactive function in the skin. Recently, alarin was demonstrated to stimulate food intake as well as the hypothalamic–pituitary–gonadal axis in rodents, suggesting that it might be a neuromodulatory peptide in the brain. However, the individual neurons in the central nervous system that express alarin have not been identified. Here, we determined the distribution of alarin-like immunoreactivity (alarin-LI) in the adult murine brain. The specificity of the antibody against alarin was demonstrated by the absence of labeling after pre-absorption of the antiserum with synthetic alarin peptide and in transgenic mouse brains lacking neurons expressing the GALP gene. Alarin-LI was observed in different areas of the murine brain. A high intensity of alarin-LI was detected in the accessory olfactory bulb, the medial preoptic area, the amygdala, different nuclei of the hypothalamus such as the arcuate nucleus and the ventromedial hypothalamic nucleus, the trigeminal complex, the locus coeruleus, the ventral chochlear nucleus, the facial nucleus, and the epithelial layer of the plexus choroideus. The distinct expression pattern of alarin in the adult mouse brain suggests potential functions in reproduction and metabolism

Cognitive and psychological science insights to improve climate change data visualization

Visualization of climate data plays an integral role in the communication of climate change findings to both expert and non-expert audiences. The cognitive and psychological sciences can provide valuable insights into how to improve visualization of climate data based on knowledge of how the human brain processes visual and linguistic information. We review four key research areas to demonstrate their potential to make data more accessible to diverse audiences: directing visual attention, visual complexity, making inferences from visuals, and the mapping between visuals and language. We present evidence-informed guidelines to help climate scientists increase the accessibility of graphics to non-experts, and illustrate how the guidelines can work in practice in the context of Intergovernmental Panel on Climate Change graphics

TRY plant trait database - enhanced coverage and open access

Plant traits-the morphological, anatomical, physiological, biochemical and phenological characteristics of plants-determine how plants respond to environmental factors, affect other trophic levels, and influence ecosystem properties and their benefits and detriments to people. Plant trait data thus represent the basis for a vast area of research spanning from evolutionary biology, community and functional ecology, to biodiversity conservation, ecosystem and landscape management, restoration, biogeography and earth system modelling. Since its foundation in 2007, the TRY database of plant traits has grown continuously. It now provides unprecedented data coverage under an open access data policy and is the main plant trait database used by the research community worldwide. Increasingly, the TRY database also supports new frontiers of trait-based plant research, including the identification of data gaps and the subsequent mobilization or measurement of new data. To support this development, in this article we evaluate the extent of the trait data compiled in TRY and analyse emerging patterns of data coverage and representativeness. Best species coverage is achieved for categorical traits-almost complete coverage for 'plant growth form'. However, most traits relevant for ecology and vegetation modelling are characterized by continuous intraspecific variation and trait-environmental relationships. These traits have to be measured on individual plants in their respective environment. Despite unprecedented data coverage, we observe a humbling lack of completeness and representativeness of these continuous traits in many aspects. We, therefore, conclude that reducing data gaps and biases in the TRY database remains a key challenge and requires a coordinated approach to data mobilization and trait measurements. This can only be achieved in collaboration with other initiatives

PRISM (Program of Resources, Information and Support for Mothers) Protocol for a community-randomised trial [ISRCTN03464021]

BACKGROUND: In the year after birth one in six women has a depressive illness, and 30% are still depressed, or depressed again, when their child is 2 years old, 94% experience at least one major health problem (e.g. back pain, perineal pain, mastitis, urinary or faecal incontinence), 26% experience sexual problems and almost 20% have relationship problems with partners. Women with depression report less practical and emotional support from partners, less social support overall, more negative life events, and poorer physical health. Their perceptions of factors contributing to depression are lack of support, isolation, exhaustion and physical health problems. Fewer than one in three affected women seek help in primary care despite frequent contacts. METHODS/DESIGN: PRISM aims to reduce depression and physical health problems of recent mothers through primary care strategies to increase practitioners' response to these issues, and through community-based strategies to develop broader family and community supports for recent mothers. Eligible local governments will be recruited and randomised to intervention or comparison arms, after stratification (urban/rural, size, birth numbers, extent of community activity), avoiding contiguous boundaries. Maternal depression and physical health will be measured six months after birth, in a one year cohort of mothers, in intervention and comparison communities. The sample size to detect a 20% relative reduction in depression, adjusting for cluster sampling, and estimating a population response fraction of 67% is 5740 × 2. Analysis of the physical and mental health outcomes, by intention to treat, will adjust for the correlated structure of the data

Interactions Between Estrogen- and Ah-Receptor Signalling Pathways in Primary Culture of Salmon Hepatocytes Exposed to Nonylphenol and 3,3',4,4'-Tetrachlorobiphenyl (Congener 77)

BACKGROUND: The estrogenic and xenobiotic biotransformation gene expressions are receptor-mediated processes that are ligand structure-dependent interactions with estrogen-receptor (ER) and aryl hydrocarbon receptor (AhR), probably involving all subtypes and other co-factors. The anti-estrogenic activities of AhR agonists have been reported. In teleost fish, exposure to AhR agonists has been associated with reduced Vtg synthesis or impaired gonadal development in both in vivo- and in vitro studies. Inhibitory AhR and ER cross-talk have also been demonstrated in breast cancer cells, rodent uterus and mammary tumors. Previous studies have shown that AhR-agonists potentiate xenoestrogen-induced responses in fish in vivo system. Recently, several studies have shown that AhR-agonists directly activate ERα and induce estrogenic responses in mammalian in vitro systems. In this study, two separate experiments were performed to study the molecular interactions between ER and AhR signalling pathways using different concentration of PCB-77 (an AhR-agonist) and time factor, respectively. Firstly, primary Atlantic salmon hepatocytes were exposed to nonylphenol (NP: 5 μM – an ER agonist) singly or in combination with 0.001, 0.01 and 1 μM PCB-77 and sampled at 48 h post-exposure. Secondly, hepatocytes were exposed to NP (5 μM) or PCB-77 (1 μM) singly or in combination for 12, 24, 48 and 72 h. Samples were analyzed using a validated real-time PCR for genes in the ER pathway or known to be NP-responsive and AhR pathway or known to be PCB-77 responsive. RESULTS: Our data showed a reciprocal inhibitory interaction between NP and PCB-77. PCB-77 produced anti-NP-mediated effect by decreasing the mRNA expression of ER-responsive genes. NP produced anti-AhR mediated effect or as inhibitor of AhRα, AhRR, ARNT, CYP1A1 and UDPGT expression. A novel aspect of the present study is that low (0.001 μM) and medium (0.01 μM) PCB-77 concentrations increased ERα mRNA expression above control and NP exposed levels, and at 12 h post-exposure, PCB-77 exposure alone produced significant elevation of ERα, ERβ and Zr-protein expressions above control levels. CONCLUSION: The findings in the present study demonstrate a complex mode of ER-AhR interactions that were dependent on time of exposure and concentration of individual chemicals (NP and PCB-77). This complex mode of interaction is further supported by the effect of PCB-77 on ERα and ERβ (shown as increase in transcription) with no concurrent activation of Vtg (but Zr-protein) response. These complex interactions between two different classes of ligand-activated receptors provide novel mechanistic insights on signalling pathways. Therefore, the degree of simultaneous interactions between the ER and AhR gene transcripts demonstrated in this study supports the concept of cross-talk between these signalling pathways

Smoking behaviour predicts tobacco control attitudes in a high smoking prevalence hospital: A cross-sectional study in a Portuguese teaching hospital prior to the national smoking ban

<p>Abstract</p> <p>Background</p> <p>Several studies have investigated attitudes to and compliance with smoking bans, but few have been conducted in healthcare settings and none in such a setting in Portugal. Portugal is of particular interest because the current ban is not in line with World Health Organization recommendations for a "100% smoke-free" policy. In November 2007, a Portuguese teaching-hospital surveyed smoking behaviour and tobacco control (TC) attitudes before the national ban came into force in January 2008.</p> <p>Methods</p> <p>Questionnaire-based cross-sectional study, including all eligible staff. Sample: 52.9% of the 1, 112 staff; mean age 38.3 ± 9.9 years; 65.9% females. Smoking behaviour and TC attitudes and beliefs were the main outcomes. Bivariable analyses were conducted using chi-squared and MacNemar tests to compare categorical variables and Mann-Whitney tests to compare medians. Multilogistic regression (MLR) was performed to identify factors associated with smoking status and TC attitudes.</p> <p>Results</p> <p>Smoking prevalence was 40.5% (95% CI: 33.6-47.4) in males, 23.5% (95% CI: 19.2-27.8) in females (p < 0.001); 43.2% in auxiliaries, 26.1% in nurses, 18.9% among physicians, and 34.7% among other non-health professionals (p = 0.024). The findings showed a very high level of agreement with smoking bans, even among smokers, despite the fact that 70.3% of the smokers smoked on the premises and 76% of staff reported being frequently exposed to second-hand smoke (SHS). In addition 42.8% reported that SHS was unpleasant and 28.3% admitted complaining. MLR showed that smoking behaviour was the most important predictor of TC attitudes.</p> <p>Conclusions</p> <p>Smoking prevalence was high, especially among the lower socio-economic groups. The findings showed a very high level of support for smoking bans, despite the pro-smoking environment. Most staff reported passive behaviour, despite high SHS exposure. This and the high smoking prevalence may contribute to low compliance with the ban and low participation on smoking cessation activities. Smoking behaviour had greater influence in TC attitudes than health professionals' education. Our study is the first in Portugal to identify potential predictors of non-compliance with the partial smoking ban, further emphasising the need for a 100% smoke-free policy, effective enforcement and public health education to ensure compliance and promote social norm change.</p