In vitro augmentation of carcinoembryonic antigen expression in colorectal cancer cells

Introduction: Carcinoembryonic antigen (CEA) is an oncofoetal antigen heterogeneously expressed by colorectal cancer cells, which may provide a useful target for antibody guided tumour localisation and therapy. The efficacy of tumour localisation would be improved by increased, more homogeneous CEA expression. Colorectal cancer cell lines are known to show augmentation of CEA expression on exposure to various chemical agents or to changing physicochemical environments. Aim: The aim of this work was to find chemical or environmental factors which successfully induced increased CEA expression in 3 different colorectal cell lines, Lovo, Ht29 and Colo, which are respectively high, low and non-expressors of CEA. Studies of differentiation were also undertaken, by observing concomitant changes in cell proliferation and morphology. Methods: The three cell lines were cultured in medium containing differentiating agents (Butyric acid, gamma-Interferon and 5-Azacytidine and Theophylline), or a range of commonly used cytotoxic drugs at a set dose, or in conditions of altered environmental factors (pH, temperature, oxygen supply, radiation, and serum content of medium). According to the observed effects of these factors used singly, combinations of chemical and physicochemical factors were also tested for additive or synergistic reactions. The growth, differentiation characteristics and CEA expression parameters were measured by a combination of Electron Microscopy, Immunocytochemistry and Fluorescein Activated Cell Sorting. Membrane CEA expression and total CEA content were compared. In addition, the degree of release of CEA by the growing cells into their medium was measured by Radioimmunoassay. A limited investigation of the genetic events which accompanied observed differentiation and CEA expression was conducted by immunostaining for oncogene products known to be associated with proliferation, apoptosis or tumour progression, e.g.,p53, Bcl-2, K-ras, and c-myc. Results: The differentiating agents were found to induce different effects in the three cell lines, with only the Ht29 cells showing increased CEA levels with each agent. It was noted that CEA expression was seen to rise in the Colo cells with two agents, using the more sensitive FACS analysis (Wilcoxon Rank Sum test). 5-Fluorouracil, hypoxia, serum-depletion and radiation induced increased CEA in some cells and not in others; Chloroquine, Methotrexate and Taxol were universally successful CEA-inducers. Of the combinations. Butyric Acid plus Interferon was particularly effective, causing potentiated augmentation of CEA in Lovo and Ht29 cells. Increases in CEA were frequently accompanied by significant growth inhibition (T-test, Correlation co-efficients -0.4, -0.54 & -0.57 for Lovo, Ht29 and Colo respectively); but were not associated with significant increases in CEA release into the supernatant, as measured by Radio-immunoassay. Electron Microscopy studies showed mixed responses to the various agents, with signs both of cell damage and of improved differentiation. No striking changes in oncogene expression by Ht29 cells exposed to successful CEA-inducers were observed; very slight changes in Bcl-2 or c-myc with 3 of the agents were noted. Conclusions: Apparent non-CEA expressing cells may be induced to express CEA using various agents. Different colorectal cell lines respond to chemical and environmental changes to different extents, via different mechanisms. Potentially useful CEA-inducing agents include Butyric Acid, Interferon, Theophylline, 5-Azacytidine, Chloroquine, 5-Fluorouracil, Methotrexate and Taxol. The combination of Butyric Acid and Interferon is particularly powerful in CEA augmentation. Increases in CEA expression are often accompanied by decreases in cell proliferation, but not by increases in CEA release. Augmentation of CEA expression may be accompanied by morphological features of cell damage or of improved differentiation

Keratinous Materials as Novel Absorbent Systems for Toxic Pollutants

A range of hazardous organic and inorganic compounds, and metal ions generated by human and industrialactivities leads to serious concerns for environments. Adsorption technologies based on polymeric materials are beingused to remove toxic substances from air and wastewater streams. Keratin protein, found abundantly in sheep’s wool,human hair and bird feathers, is an interesting and potentially useful renewable biopolymer. It contains a variety offunctional groups on the backbone and side chains of the proteins, and is an ideal component to fabricate a rangeof novel adsorbent systems for separation of toxic pollutants via physisorption or chemisorption mechanisms. Inthis review article, the key activities on keratin research and development with respect to the novel properties ofkeratin proteins and their utilization as absorbents or filtration systems are summarized. It is apparent that keratinsin the form of loose fibers, non-woven fabrics, short fibers or particles, membranes and colloids can be used as absorbents for air filtration and wastewater treatment. Keratin materials have potential to be applied in biological and chemical defence applications, and also in protection against radioactive elements.Defence Science Journal, Vol. 64, No. 3, May 2014, pp. 209-221, DOI:http://dx.doi.org/10.14429/dsj.64.731

Marine Biodegradation Behavior of Wool and Other Textile Fibers

Microplastic pollution is a growing concern for the earth’s terrestrial and marine environments. Synthetic fibers from textiles are one source of microplastic pollution as fibers may be released from garments during use and especially during laundering, whereby they may enter the aquatic environment via wastewater systems. Wool is a natural fiber, but it is often given treatments to enhance its performance, such as to make it resistant to shrinkage caused by machine washing. Treatments of this type might influence the fiber’s inherent biodegradability. We sought to understand the aquatic biodegradation behavior of wool (in its unmodified form, and chlorine-Hercosett shrink-resist treated) and a range of synthetic fibers that are used in similar clothing applications. The biodegradation test was carried out in a simulated marine environment using a natural seawater inoculant according to the ASTM D6691 method with some modifications. Biodegraded wool residues were characterized by Fourier transform infrared and energy dispersive X-ray spectroscopies. The extent of fiber damage was observed by scanning electron microscopy. Both types of wool biodegraded readily under these conditions and machine-washable wool biodegraded to a greater extent than untreated wool. Regenerated cellulosic fiber (viscose rayon) also degraded readily, but all three synthetic fibers (polyester, nylon and polypropylene) showed virtually no biodegradation. Analysis of solid and liquid residues generated by the biodegraded wool showed no evidence that the chlorine-Hercosett-treated wool generated any non-degraded residues. Based on these findings we believe that, unlike synthetics, wool fibers are very unlikely to lead to microplastic pollution in the aquatic environment

Beyond ruminants: discussing opportunities for alternative pasture uses in New Zealand

peer-reviewedThe New Zealand government has set ambitious goals for primary sector growth and of zero net carbon emissions by 2050. This presents an opportunity and obligation to develop new ideas for grassland production systems to increase export value and generate new job opportunities, while reducing environmental impacts. The aim of this paper is to draw on recent research in Europe to investigate some of the alternative and complementary uses for pasture as a feedstock for a green biorefinery. A biorefinery is a facility, or a series of processes, that convert biomass into a spectrum of value-added products. For example, protein can be extracted mechanically from green biomass once harvested. The residual fibre fraction could be used as a low-nitrogen feed for ruminants to reduce urinary nitrogen, while the liquid protein fraction could be processed to make it suitable for mono-gastric or human consumption. Enzymes can promote protein extraction and controlled conversion of insoluble plant fibres and oligosaccharides to foster gut-health promoting prebiotic food ingredients. Anaerobic digestion of residues can then be used to create energy and soilimproving products. Research and demonstration of these approaches in practice, along with the results of feasibility studies, will be required to see which of these opportunities is a good fit for New Zealand pasture systems

Population normative data for the 10/66 Dementia Research Group cognitive test battery from Latin America, India and China: a cross-sectional survey

Background: 1) To report site-specific normative values by age, sex and educational level for four components of the 10/66 Dementia Research Group cognitive test battery; 2) to estimate the main and interactive effects of age, sex, and educational level by site; and 3) to investigate the effect of site by region and by rural or urban location. Methods: Population-based cross-sectional one phase catchment area surveys were conducted in Cuba, Dominican Republic, Venezuela, Peru, Mexico, China and India. The protocol included the administration of the Community Screening Instrument for Dementia (CSI 'D', generating the COGSCORE measure of global function), and the Consortium to Establish a Registry for Alzheimer's Disease (CERAD) verbal fluency (VF), word list memory (WLM, immediate recall) and recall (WLR, delayed recall) tests. Only those free of dementia were included in the analysis. Results: Older people, and those with less education performed worse on all four tests. The effect of sex was much smaller and less consistent. There was a considerable effect of site after accounting for compositional differences in age, education and sex. Much of this was accounted for by the effect of region with Chinese participants performing better, and Indian participants worse, than those from Latin America. The effect of region was more prominent for VF and WLM than for COGSCORE and WLR. Conclusion: Cognitive assessment is a basic element for dementia diagnosis. Age- and education-specific norms are required for this purpose, while the effect of gender can probably be ignored. The basis of cultural effects is poorly understood, but our findings serve to emphasise that normative data may not be safely generalised from one population to another with quite different characteristics. The minimal effects of region on COGSCORE and WLR are reassuring with respect to the cross-cultural validity of the 10/66 dementia diagnosis, which uses only these elements of the 10/66 battery.Clinical NeurologySCI(E)SSCI17ARTICLEnull

A statistical approach for classifying change in cognitive function in individuals following pharmacologic challenge: an example with alprazolam

The effects of any drug treatment on cognitive function are typically studied in groups of subjects. Observations made about the behavior of the drug, in the study sample, are then generalized to the population from which the sample was drawn. However, the magnitude and pharmacodynamic qualities of the response to many central nervous system-active drugs are known to vary in the population. Therefore, it is useful to consider statistical models for the detection of cognitive change in response to a drug treatment in individual subjects.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/46374/1/213_2006_Article_331.pd

Length of carotid stenosis predicts peri-procedural stroke or death and restenosis in patients randomized to endovascular treatment or endarterectomy.

BACKGROUND: The anatomy of carotid stenosis may influence the outcome of endovascular treatment or carotid endarterectomy. Whether anatomy favors one treatment over the other in terms of safety or efficacy has not been investigated in randomized trials. METHODS: In 414 patients with mostly symptomatic carotid stenosis randomized to endovascular treatment (angioplasty or stenting; n = 213) or carotid endarterectomy (n = 211) in the Carotid and Vertebral Artery Transluminal Angioplasty Study (CAVATAS), the degree and length of stenosis and plaque surface irregularity were assessed on baseline intraarterial angiography. Outcome measures were stroke or death occurring between randomization and 30 days after treatment, and ipsilateral stroke and restenosis ≥50% during follow-up. RESULTS: Carotid stenosis longer than 0.65 times the common carotid artery diameter was associated with increased risk of peri-procedural stroke or death after both endovascular treatment [odds ratio 2.79 (1.17-6.65), P = 0.02] and carotid endarterectomy [2.43 (1.03-5.73), P = 0.04], and with increased long-term risk of restenosis in endovascular treatment [hazard ratio 1.68 (1.12-2.53), P = 0.01]. The excess in restenosis after endovascular treatment compared with carotid endarterectomy was significantly greater in patients with long stenosis than with short stenosis at baseline (interaction P = 0.003). Results remained significant after multivariate adjustment. No associations were found for degree of stenosis and plaque surface. CONCLUSIONS: Increasing stenosis length is an independent risk factor for peri-procedural stroke or death in endovascular treatment and carotid endarterectomy, without favoring one treatment over the other. However, the excess restenosis rate after endovascular treatment compared with carotid endarterectomy increases with longer stenosis at baseline. Stenosis length merits further investigation in carotid revascularisation trials

Effects of ecosystem protection on scallop populations within a community-led temperate marine reserve

This study investigated the effects of a newly established, fully protected marine reserve on benthic habitats and two commercially valuable species of scallop in Lamlash Bay, Isle of Arran, United Kingdom. Annual dive surveys from 2010 to 2013 showed the abundance of juvenile scallops to be significantly greater within the marine reserve than outside. Generalised linear models revealed this trend to be significantly related to the greater presence of macroalgae and hydroids growing within the boundaries of the reserve. These results suggest that structurally complex habitats growing within the reserve have substantially increased spat settlement and/or survival. The density of adult king scallops declined threefold with increasing distance from the boundaries of the reserve, indicating possible evidence of spillover or reduced fishing effort directly outside and around the marine reserve. However, there was no difference in the mean density of adult scallops between the reserve and outside. Finally, the mean age, size, and reproductive and exploitable biomass of king scallops were all significantly greater within the reserve. In contrast to king scallops, the population dynamics of queen scallops (Aequipecten opercularis) fluctuated randomly over the survey period and showed little difference between the reserve and outside. Overall, this study is consistent with the hypothesis that marine reserves can encourage the recovery of seafloor habitats, which, in turn, can benefit populations of commercially exploited species, emphasising the importance of marine reserves in the ecosystem-based management of fisheries

General practitioners knowledge and management of whiplash associated disorders and post-traumatic stress disorder: Implications for patient care

© 2016 The Author(s). Background: In Australia, general practitioners (GPs) see around two-thirds of people injured in road traffic crashes. Road traffic crash injuries are commonly associated with diverse physical and psychological symptoms that may be difficult to diagnose and manage. Clinical guidelines have been developed to assist in delivering quality, consistent care, however the extent to which GPs knowledge and practice in diagnosing and managing road traffic crash injuries concords with the guidelines is unknown. This study aimed to explore Australian GPs knowledge, attitudes and practices regarding the diagnosis and management of road traffic crash injuries, specifically whiplash associated disorders (WAD) and post-traumatic stress disorder (PTSD). Method: A cross-sectional survey of 423 GPs across Australia conducted between July and December 2014. We developed a questionnaire to assess their knowledge of WAD and PTSD, confidence in diagnosing and managing WAD and PTSD, frequency of referral to health providers, barriers to referral, and attitudes towards further education and training. Factor analysis, Spearman's correlation, and multiple ordered logistic regressions were performed. Results: Overall, GPs have good level knowledge of WAD and PTSD; only 9.6 % (95 % CI: 7.1 %, 12.8 %) and 23.9 % (95 % CI: 20.8 %, 28.2 %) of them were deemed to have lower level knowledge of WAD and PTSD respectively. Key knowledge gaps included imaging indicators for WAD and indicators for psychological referral for PTSD. GPs who were male, with more years of experience, working in the urban area and with higher knowledge level of WAD were more confident in diagnosing and managing WAD. Only GPs PTSD knowledge level predicted confidence in diagnosing and managing PTSD. GPs most commonly referred to physiotherapists and least commonly to vocational rehabilitation providers. Barriers to referral included out-of-pocket costs incurred by patients and long waiting times. Most GPs felt positive towards further education on road traffic crash injury management. Conclusion: This study has enhanced understanding of the knowledge skills and attitudes of GPs towards road traffic crash injury care in Australia, and has identified areas for further education and training. If delivered, this training has the potential to reduce unnecessary imaging for WAD and optimise the early referral of patients at risk of delayed recovery following a road traffic crash

Para-infectious brain injury in COVID-19 persists at follow-up despite attenuated cytokine and autoantibody responses

To understand neurological complications of COVID-19 better both acutely and for recovery, we measured markers of brain injury, inflammatory mediators, and autoantibodies in 203 hospitalised participants; 111 with acute sera (1–11 days post-admission) and 92 convalescent sera (56 with COVID-19-associated neurological diagnoses). Here we show that compared to 60 uninfected controls, tTau, GFAP, NfL, and UCH-L1 are increased with COVID-19 infection at acute timepoints and NfL and GFAP are significantly higher in participants with neurological complications. Inflammatory mediators (IL-6, IL-12p40, HGF, M-CSF, CCL2, and IL-1RA) are associated with both altered consciousness and markers of brain injury. Autoantibodies are more common in COVID-19 than controls and some (including against MYL7, UCH-L1, and GRIN3B) are more frequent with altered consciousness. Additionally, convalescent participants with neurological complications show elevated GFAP and NfL, unrelated to attenuated systemic inflammatory mediators and to autoantibody responses. Overall, neurological complications of COVID-19 are associated with evidence of neuroglial injury in both acute and late disease and these correlate with dysregulated innate and adaptive immune responses acutely