The Fourth International Symposium on the Intraductal Approach to Breast Cancer, Santa Barbara, California, 10–13 March 2005

Intraductal approaches encompass procedures and technologies that are designed to access and interrogate the ductal–alveolar systems of the human breast, and include nipple aspiration, ductal lavage, random periareolar fine needle aspiration, and ductoscopy. These approaches are being used to collect and analyze fluids and cells to develop methods for breast cancer detection and risk assessment; to introduce imaging technologies to explore the mammary tree for abnormalities; to administer therapeutic and/or preventive agents directly to the breast tissue; and to explore the biology of the normal mammary gland. The latest research findings in these areas, presented at The 4th International Symposium on the Intraductal Approach to Breast Cancer in 2005, are summarized in this report

Asiatic Acid Inhibits Liver Fibrosis by Blocking TGF-beta/Smad Signaling In Vivo and In Vitro

Liver fibrosis is a major cause of liver failure, but treatment remains ineffective. In the present study, we investigated the mechanisms and anti-hepatofibrotic activities of asiatic acid (AA) in a rat model of liver fibrosis induced by carbon tetrachloride (CCl4) and in vitro in TGF-beta1-stimulated rat hepatic stellate cell line (HSC-T6). Treatment with AA significantly attenuated CCl4-induced liver fibrosis and functional impairment in a dosage-dependent manner, including blockade of the activation of HSC as determined by inhibiting de novo alpha smooth muscle actin (a-SMA) and collagen matrix expression, and an increase in ALT and AST (all p<0.01). The hepatoprotective effects of AA on fibrosis were associated with upregulation of hepatic Smad7, an inhibitor of TGF-beta signaling, thereby blocking upregulation of TGF-beta1 and CTGF and the activation of TGF-beta/Smad signaling. The anti-fibrosis activity and mechanisms of AA were further detected in vitro in HSC-T6. Addition of AA significantly induced Smad7 expression by HSC-T6 cells, thereby inhibiting TGF-beta1-induced Smad2/3 activation, myofibroblast transformation, and collagen matrix expression in a dosage-dependent manner. In contrast, knockdown of Smad7 in HSC-T6 cells prevented AA-induced inhibition of HSC-T6 cell activation and fibrosis in response to TGF-beta1, revealing an essential role for Smad7 in AA-induced anti-fibrotic activities during liver fibrosis in vivo and in vitro. In conclusion, AA may be a novel therapeutic agent for liver fibrosis. Induction of Smad7-dependent inhibition of TGF-beta/Smad-mediated fibrogenesis may be a central mechanism by which AA protects liver from injury

The Promise and Challenge of Therapeutic MicroRNA Silencing in Diabetes and Metabolic Diseases

MicroRNAs (miRNAs) are small, non-coding, RNA molecules that regulate gene expression. They have a long evolutionary history and are found in plants, viruses, and animals. Although initially discovered in 1993 in Caenorhabditis elegans, they were not appreciated as widespread and abundant gene regulators until the early 2000s. Studies in the last decade have found that miRNAs confer phenotypic robustness in the face of environmental perturbation, may serve as diagnostic and prognostic indicators of disease, underlie the pathobiology of a wide array of complex disorders, and represent compelling therapeutic targets. Pre-clinical studies in animal models have demonstrated that pharmacologic manipulation of miRNAs, mostly in the liver, can modulate metabolic phenotypes and even reverse the course of insulin resistance and diabetes. There is cautious optimism in the field about miRNA-based therapies for diabetes, several of which are already in various stages of clinical trials. This review will highlight both the promise and the most pressing challenges of therapeutic miRNA silencing in diabetes and related conditions

Knowledge about complementary, alternative and integrative medicine (CAM) among registered health care providers in Swedish surgical care: a national survey among university hospitals

<p>Abstract</p> <p>Background</p> <p>Previous studies show an increased interest and usage of complementary and alternative medicine (CAM) in the general population and among health care workers both internationally and nationally. CAM usage is also reported to be common among surgical patients. Earlier international studies have reported that a large amount of surgical patients use it prior to and after surgery. Recent publications indicate a weak knowledge about CAM among health care workers. However the current situation in Sweden is unknown. The aim of this study was therefore to explore perceived knowledge about CAM among registered healthcare professions in surgical departments at Swedish university hospitals.</p> <p>Method</p> <p>A questionnaire was distributed to 1757 registered physicians, nurses and physiotherapists in surgical wards at the seven university hospitals in Sweden from spring 2010 to spring 2011. The questionnaire included classification of 21 therapies into conventional, complementary, alternative and integrative, and whether patients were recommended these therapies. Questions concerning knowledge, research, and patient communication about CAM were also included.</p> <p>Result</p> <p>A total of 737 (42.0%) questionnaires were returned. Therapies classified as complementary; were massage, manual therapies, yoga and acupuncture. Alternative therapies; were herbal medicine, dietary supplements, homeopathy and healing. Classification to integrative therapy was low, and unfamiliar therapies were Bowen therapy, iridology and Rosen method. Therapies recommended by > 40% off the participants were massage and acupuncture. Knowledge and research about CAM was valued as minor or none at all by 95.7% respectively 99.2%. Importance of possessing knowledge about it was valued as important by 80.9%. It was believed by 61.2% that more research funding should be addressed to CAM research, 72.8% were interested in reading CAM-research results, and 27.8% would consider taking part in such research. Half of the participants (55.8%) were positive to learning such therapy. Communication about CAM between patients and the health care professions was found to be rare.</p> <p>Conclusion</p> <p>There is a lack of knowledge about CAM and research about it among registered health care professions in Swedish surgical care. However, in contrast to previous studies the results revealed that the majority perceived it as important to gain knowledge in this field.</p

Land Law, Property Ideologies and the British-Irish relationship

English and Irish land law are deeply influenced by the historical context of the British-Irish relationship, yet property scholarship comparing the two jurisdictions is surprisingly rare. The current Brexit negotiations provide a timely reminder of the strategic importance of property and trade relations between the two countries; and of their related-but-different legal cultures. In this article we examine how the property cultures of England and Ireland were shaped by the politics and practices of land tenure, by competing economic and property ideologies, and by the influence of both on national identity and statehood in both jurisdictions. The article reveals the role of local contexts and events in shaping land reform, and demonstrates the fertile potential of the comparative frame to contextualise each jurisdiction’s doctrines and practices. As domestic land law systems are drawn together in the context of emerging EU jurisdiction over areas like mortgage credit, each jurisdiction’s underpinning ideological commitments have important implications for the ease – or not – of attempts to harmonize member state practices. We explain the alignments and divergences between domestic underpinnings of Irish and English law, and reflect on the implications of our findings for contemporary property problems in the context of evolving economic and political relationships between the UK and Ireland

Analysis of differential gene expression in human melanocytic tumour lesions by custom made oligonucleotide arrays

Melanoma is one of the most aggressive types of cancer and resection of the tumour prior to dissemination of tumour cells is still the most effective treatment. Therefore, early diagnosis of melanocytic lesions is important and identification of novel (molecular) markers would be helpful to improve diagnosis. Moreover, better understanding of molecular targets involved in melanocytic tumorigenesis could possibly lead to development of novel interventions. In this study, we used a custom made oligonucleotide array containing 298 genes that were previously found to be differentially expressed in human melanoma cell lines 1F6 (rarely metastasising) and Mel57 (frequently metastasising). We determined differential gene expression in human common nevocellular nevus and melanoma metastasis lesions. By performing nine dye-swap array experiments, using individual as well as pooled melanocytic lesions, a constant differential expression could be detected for 25 genes in eight out of nine or nine out of nine array analyses. For at least nine of these genes, namely THBD, FABP7, H2AFJ, RRAGD, MYADM, HR, CKS2, NCK2 and GDF15, the differential expression found by array analyses could be verified by semiquantitative and/or real-time quantitative RT–PCR. The genes that we identified to be differentially expressed during melanoma progression could be potent targets for diagnostic, prognostic and/or therapeutic interventions

Ocular accommodation and cognitive demand: An additional indicator besides pupil size and cardiovascular measures?

<p>Abstract</p> <p>Background</p> <p>The aim of the present study was to assess accommodation as a possible indicator of changes in the autonomic balance caused by altered cognitive demand. Accounting for accommodative responses from a human factors perspective may be motivated by the interest of designing virtual image displays or by establishing an autonomic indicator that allows for remote measurement at the human eye. Heart period, pulse transit time, and the pupillary response were considered as reference for possible closed-loop accommodative effects. Cognitive demand was varied by presenting monocularly numbers at a viewing distance of 5 D (20 cm) which had to be read, added or multiplied; further, letters were presented in a "n-back" task.</p> <p>Results</p> <p>Cardiovascular parameters and pupil size indicated a change in autonomic balance, while error rates and reaction time confirmed the increased cognitive demand during task processing. An observed decrease in accommodation could not be attributed to the cognitive demand itself for two reasons: (1) the cognitive demand induced a shift in gaze direction which, for methodological reasons, accounted for a substantial part of the observed accommodative changes. (2) Remaining effects disappeared when the correctness of task processing was taken into account.</p> <p>Conclusion</p> <p>Although the expectation of accommodation as possible autonomic indicator of cognitive demand was not confirmed, the present results are informative for the field of applied psychophysiology noting that it seems not to be worthwhile to include closed-loop accommodation in future studies. From a human factors perspective, expected changes of accommodation due to cognitive demand are of minor importance for design specifications – of, for example, complex visual displays.</p

Policy and prevention approaches for disordered and hazardous gaming and internet use: an international perspective

Problems related to high levels of gaming and Internet usage are increasingly recognized as a potential public health burden across the developed world. The aim of this review was to present an international perspective on prevention strategies for Internet gaming disorder and related health conditions (e.g., Internet addiction), as well as hazardous gaming and Internet use. A systematic review of quantitative research evidence was conducted, followed by a search of governmental reports, policy and position statements, and health guidelines in the last decade. The regional scope included the United States, United Kingdom, Australia, China, Germany, Japan, and South Korea. Prevention studies have mainly involved school-based programs to train healthier Internet use habits in adolescents. The efficacy of selective prevention is promising but warrants further empirical attention. On an international scale, the formal recognition of gaming or Internet use as a disorder or as having quantifiable harms at certain levels of usage has been foundational to developing structured prevention responses. The South Korean model, in particular, is an exemplar of a coordinated response to a public health threat, with extensive government initiatives and long-term strategic plans at all three levels of prevention (i.e., universal, selective, and indicated). Western regions, by comparison, are dominated by prevention approaches led by non-profit organizations and private enterprise. The future of prevention of gaming and Internet problems ultimately relies upon all stakeholders working collaboratively in the public interest, confronting the reality of the evidence base and developing practical, ethical, and sustainable countermeasures

Social Participation and Disaster Risk Reduction Behaviors in Tsunami Prone Areas

This paper examines the relationships between social participation and disaster risk reduction actions. A survey of 557 households in tsunami prone areas in Phang Nga, Thailand was conducted following the 2012 Indian Ocean earthquakes. We use a multivariate probit model to jointly estimate the likelihood of undertaking three responses to earthquake and tsunami hazards (namely, (1) following disaster-related news closely, (2) preparing emergency kits and/or having a family emergency plan, and (3) having an intention to migrate) and community participation.We find that those who experienced losses from the 2004 tsunami are more likely to participate in community activities and respond to earthquake hazards. Compared to men, women are more likely to prepare emergency kits and/or have an emergency plan and have a greater intention to migrate. Living in a community with a higher proportion of women with tertiary education increases the probability of engaging in community activities and carrying out disaster risk reduction measures. Individuals who participate in village-based activities are 5.2% more likely to undertake all three risk reduction actions compared to those not engaging in community activities. This implies that encouraging participation in community activities can have positive externalities in disaster mitigation