Tumor budding cells, cancer stem cells and epithelial-mesenchymal transition-type cells in pancreatic cancer

Pancreatic ductal adenocarcinoma (PDAC) is one of the most lethal cancers with a 5-year survival rate of less than 5%. Moreover, PDAC escapes early detection and resists treatment. Multiple combinations of genetic alterations are known to occur in PDAC including mutational activation of KRAS, inactivation of p16/CDKN2A and SMAD4 (DPC4) and dysregulation of PTEN/PI3K/AKT signaling. Through their interaction with Wingless-INT pathway, the downstream molecules of these pathways have been implicated in the promotion of epithelial-mesenchymal transition (EMT). Emerging evidence has demonstrated that cancer stem cells (CSCs), small populations of which have been identified in PDAC, and EMT-type cells play critical roles in drug resistance, invasion, and metastasis in pancreatic cancer. EMT may be histologically represented by the presence of tumor budding which is described as the occurrence of single tumor cells or small clusters (<5) of dedifferentiated cells at the invasive front of gastrointestinal (including colorectal, oesophageal, gastric, and ampullary) carcinomas and is linked to poor prognosis. Tumor budding has recently been shown to occur frequently in PDAC and to be associated with adverse clinicopathological features and decreased disease-free and overall survival. The aim of this review is to present a short overview on the morphological and molecular aspects that underline the relationship between tumor budding cells, CSCs, and EMT-type cells in PDAC.

Study protocol: Transition from localized low back pain to chronic widespread pain in general practice: identification of risk factors, preventive factors and key elements for treatment--a cohort study

Background Chronic localized pain syndromes, especially chronic low back pain (CLBP), are common reasons for consultation in general practice. In some cases chronic localized pain syndromes can appear in combination with chronic widespread pain (CWP). Numerous studies have shown a strong association between CWP and several physical and psychological factors. These studies are population-based cross-sectional and do not allow for assessing chronology. There are very few prospective studies that explore the predictors for the onset of CWP, where the main focus is identifying risk factors for the CWP incidence. Until now there have been no studies focusing on preventive factors keeping patients from developing CWP. Our aim is to perform a cross sectional study on the epidemiology of CLBP and CWP in general practice and to look for distinctive features regarding resources like resilience, self-efficacy and coping strategies. A subsequent cohort study is designed to identify the risk and protective factors of pain generalization (development of CWP) in primary care for CLBP patients. Methods/Design Fifty-nine general practitioners recruit consecutively, during a 5 month period, all patients who are consulting their family doctor because of chronic low back pain (where the pain is lasted for 3 months). Patients are asked to fill out a questionnaire on pain anamnesis, pain-perception, co-morbidities, therapy course, medication, socio demographic data and psychosomatic symptoms. We assess resilience, coping resources, stress management and self-efficacy as potential protective factors for pain generalization. Furthermore, we raise risk factors for pain generalization like anxiety, depression, trauma and critical life events. During a twelve months follow up period a cohort of CLBP patients without CWP will be screened on a regular basis (3 monthly) for pain generalization (outcome: incident CWP). Discussion This cohort study will be the largest study which prospectively analyzes predictors for transition from CLBP to CWP in primary care setting. In contrast to the typically researched risk factors, which increase the probability of pain generalization, this study also focus intensively on protective factors, which decrease the probability of pain generalization.

A field study on characteristics and diversity of gene expression in the liver of dairy cows during the transition period

Metabolic and endocrine adaptations to support milk production during the transition period vary between individual cows. This variation between cows to adapt to lactation may have a genetic basis. The present field study was carried out to determine hepatic adaptations occurring from late pregnancy through early lactation by measuring mRNA abundance of candidate genes in dairy cows on-farm. Additionally, the objective was to observe the diversity in inter-individual variation for the candidate genes that may give indications where individual adaptations at a molecular level can be found. This study was carried out on-farm including 232 dairy cows (parity >3) from 64 farms in Switzerland. Blood and liver samples were collected on d 20+/-7 before parturition, on d 24+/-2, and on d 89+/-4 after parturition. Blood plasma was assayed for concentrations of glucose, nonesterified fatty acids, beta-hydroxybutyrate, cholesterol, triglycerides, urea, albumin, protein, insulin, insulin-like growth factor-1, leptin, 3,5,3'-triiodothyronine, and thyroxine. Liver samples were obtained at the same time points and were measured for mRNA abundance of 26 candidate genes encoding enzymes and nuclear receptors involved in gluconeogenesis, fatty acid beta-oxidation, fatty acid and triglyceride synthesis, ketogenesis, citric acid cycle, cholesterol synthesis, and the urea cycle. The cows in the present study experienced a marked metabolic load in early lactation, as presented by changes in plasma metabolites and hormones, and responded accordingly with upregulation and downregulation of almost all candidate genes involved in metabolic processes in the liver. The observed inter-individual variation for the candidate genes, which was highest for acetyl-CoA-carboxylase and glycerol-3-phosphate dehydrogenase 2, should be further investigated to unravel the regulation at molecular level for optimal adaptive performance in dairy cows.

Axis I diagnoses and transition to psychosis in clinical high-risk patients EPOS project: prospective follow-up of 245 clinical high-risk outpatients in four countries

In selected samples, a considerable number of patients at clinical high risk of psychosis (CHR) are found to meet criteria for co-morbid clinical psychiatric disorders. It is not known how clinical diagnoses correspond to or even predict transitions to psychosis (TTP). Our aim was to examine distributions of life-time and current Axis I diagnoses, and their association with TTP in CHR patients.

The Role of Monetary Policy in Pursuing Economic Activity in Selected Transition Countries

The process of transition has brought an urgent need to develop many new market-oriented institutions or in some cases to reconstruct existing ones. One of the most important institutions of western-type economies is a central bank. It fulfils several "public good" functions, the most important of which are the achievement of stable price levels and assuring the financial stability of the economy. Nevertheless, even in economies with a long-standing market tradition, the question of whether a central bank is able to stimulate economic activity or whether all its cyclical actions lead only to changes in price levels remains open. The main purpose of this analysis was to empirically prove or disprove the relation between monetary policy and economic activity in more advanced transition countries. Basing his findings on commonly used econometric methods (causality tests, VAR modelling and simulations, simultaneous equations models), Delakorda concludes that the relation between money and economic activity is a mutual one, as there are significant differences between different countries in the conduct of monetary policy and in the environment of central banks. It is the latter which determines the relation between money and economic activity.

From Elitism through Corporatism to Pluralism? The Role of Elites in the Political Transition of Ukraine

The group set out to analyse the dynamics of elite groups in Ukraine today, both internal and inter-group, and their ideas on major socio-economic, political and foreign policies, in order to identify the degree of competitiveness between groups, methods of elite recruitment and the degree of elite response, which influence both the political agenda and the results of political activity. Having observed the contemporary debate and identified the pre-eminence of various elite groups in the decision-making process at the regional and state levels, they also sought to determine the type and degree of elite consensus which might be achieved in contemporary Ukraine. They also considered the extent of concealed power, in terms of covert interaction more characteristic of corporate societies, which might allow for the abuse of authority within a technically democratic system. The group then went on to consider the stages of counter-elite transformation and the continuing importance of the communist elite, as well as the issue of rivalry versus consensus. They see their findings as relevant not only to the Central and Eastern European context but also to the situation in Latin America today.

Changes in Psychological Characteristics of Working Adults in Different Stages of Economic Transition in Lithuania

Global economic changes have psychological consequences and Mr. Lepeska set out to assess these changes in working adults in Lithuania between 1993 and 1997. He surveyed two groups of working adults, with a total of 200 people, randomly selected and representing different organisations and professions. In both groups around 30% of participants were managers, with the remainder working in non-managerial positions. The participants were surveyed twice, once in 1993 and the second time in 1997,using various psychodiagnostic tools to measure their psychological characteristics. The results showed that strategies for coping with stress have changed, with problem solving strategies being used more often, and avoidance behaviour or seeking social support less. Men tended to have rejected these strategy more radically than women. Attitudes towards work had become more positive, with managers' attitudes having changed more significantly than those of employees from lower levels of organisations. Younger people were more positive towards work-related changes, while situational anxiety tended to increase with age, although overall it remained low. Mr. Lepeska found that while there were some indications of an increasing individualist in relation to peers, the traditional collective orientation of Lithuanian adults had if anything increased. People have become more accepting of an unequal distribution of power, making it difficult to increase the participation of subordinates in decision making. He also noted a tendency for Lithuanians to see their organisations as traditional families, expecting them to take care of them physically and economically in return for loyalty. The strong feminine orientation with its stress on interpersonal relations and overall quality of life has also strengthened, but the ability of Lithuanians to take initiative and control their environment was relatively low. Mr. Lepeska concludes that organisations should seek to recruit people who are able to adjust more easily to changes and consider measuring dominance, individualism, and attitudes to work-related change and situational anxiety in the process of professional selection. There should also be more emphasis on team building and on training managers to maintain closer relationships with their subordinates so as to increase the latter's participation in decision making. Good interpersonal relations can be a strong work motivator, as may be special attention to the security needs of older employees.

Civil Society and Political Parties in the Period of Transition

The major aim of Mr. Marada's project was to investigate the role of political parties on the one hand, and various institutional forms of civil society on the other, in the process of establishing mechanisms of political decision-making and policy-formation in Czechoslovakia and the Czech Republic, after November 1989. Mr. Marada wanted to examine what consequences the interplay and tensions between political parties and institutions of civil society had on the status and practical understanding of citizenship and civil society. At the beginning of his research Mr. Marada found that, while the sphere of the political was relatively clearly defined, the phenomenon of civil society required a conceptual clarification. He devoted a great deal of time to analysing the emergence, development, and disintegration of Civic Forum as the major agent of the regime change and subsequent political reforms. Alongside this analysis is a commentary on Czech society in general, drawing on established research to show how, as yet, a kind of civic incompetence reigns within the country, and how this situation has its roots in the belief, promoted by politicians themselves, that politics is an activity for experts only. The final outcome of his research took the form of a series of articles, in English, totalling 40 pages.

Separation of Ownership from Control and Discretionary Managerial Behaviour in a Transition Economy

This study was the final stage of a four-year study of managerial behaviour and company performance in Bulgaria and examined the influence of changing ownership and control structures of companies on managerial behaviour and initiative. It provides a theoretical summary of the specific types of ownership, control, governance structures and managerial strategies in the Bulgarian transitional economy during 1992-1996. It combines two theoretical approaches, the property-rights approach to show concentrated property-rights structure and private and majority types of control as determinants of efficient enterprise risk bearing and constrained managerial discretion, and the agency theory approach to reveal the efficient role of direct non-market governance mechanisms over managers. Mr. Peev also used empirical information collected from the Central Statistical office in Bulgaria, three different enterprise investigations of corporatised state-owned enterprises between 1992 and 1994, and his own data base of privatised and private de novo industrial companies in 1996-1996. The project gives a detailed description of the main property-rights structures in Bulgaria at the present time and of the various control structures related to these. It found that there is a strong owner type of control in private and privatised firms, although, contrary to expectations, 100% state -owned enterprises tended to be characterised by a separation of ownership from control, leaving scope for managerial discretion. Mr. Peev predicts that after the forthcoming mass privatisation, many companies will acquire a dispersed ownership structure and there will be a greater separation of ownership from control and potential or inefficient managerial behaviour. The next aspect considered in detail was governance structures and the influence of the generally unstable macroeconomic environment in the country during the period in question. In examining managerial strategies, Mr. Peev divided the years since 1990 into 3 periods. Even in the first period (1990-1992) there were some signs of a more efficient role for managers and between 1992 and 1994 the picture of control structures and different managerial behaviour in state-owned companies became more diversified. Managerial strategies identified included managerial initiatives for privatisation, where managers took initiative in resolving problems of property rights and introducing restructuring measures and privatisation proposals, managerial initiatives for restructuring without privatisation, and passive adjustment and passive management, where managers seek outside services for marketing, finance management, etc. in order to adjust to the new environment. During 1995-1996 some similarities and differences between the managerial behaviour of privatised and state-owned firms emerged. Firstly, the former have undergone many changes in investment and technology, while managers of state-owned companies have changed little in this field, indicating that the private property-rights structure is more efficient for the long-term adaptation of enterprises. In the area of strategies relating to product quality, marketing, and pricing policy there was little difference between managers of private, privatised and state-owned firms. The most passive managerial behaviour was found in non-incorporated state-owned firms, although these have only an insignificant stake in the economy.