Mesenchymal stem cells from patients with chronic myeloid leukemia do not express BCR-ABL and have absence of chimerism after allogeneic bone marrow transplant

Bone marrow is a heterogeneous cell population which includes hematopoietic and mesenchymal progenitor cells. Dysregulated hematopoiesis occurs in chronic myelogenous leukemia (CML), being caused at least in part by abnormalities in the hematopoietic progenitors. However, the role of mesenchymal stem cells (MSCs) in CML has not been well characterized. The objectives of the present study were to observe the biological characteristics of MSCs from CML patients and to determine if MSCs originate in part from donors in CML patients after bone marrow transplantation (BMT). We analyzed MSCs from 5 untreated patients and from 3 CML patients after sex-mismatched allogeneic BMT. Flow cytometry analysis revealed the typical MSC phenotype and in vitro assays showed ability to differentiate into adipocytes and osteoblasts. Moreover, although some RT-PCR data were contradictory, combined fluorescence in situ hybridization analysis showed that MSCs from CML patients do not express the bcr-abl gene. Regarding MSCs of donor origin, although it is possible to detect Y target sequence by nested PCR, the low frequency (0.14 and 0.34%) of XY cells in 2 MSC CML patients by fluorescence in situ hybridization analysis suggests the presence of contaminant hematopoietic cells and the absence of host-derived MSCs in CML patients. Therefore, we conclude that MSCs from CML patients express the typical MSC phenotype, can differentiate into osteogenic and adipogenic lineages and do not express the bcr-abl gene. MSCs cannot be found in recipients 12 to 20 months after BMT. The influence of MSCs on the dysregulation of hematopoiesis in CML patients deserves further investigation.

Effects of isoflavone on the learning and memory of women in menopause: a double-blind placebo-controlled study

Hormone decline is common to all women during aging and, associated with other factors, leads to cognitive impairment. Its replacement enhances cognitive performance, but not all women present a clinical and family or personal history that justifies its use, mainly women with a history of cancer. The aim of this study was to determine whether a daily oral dose of 80 mg of isoflavone extract for 4 months can produce benefits in women with low hormone levels, contributing to improvement in cognitive aspects. The sample comprised 50- to 65-year-old women whose menstruation had ceased at least 1 year before and who had not undergone hormone replacement. The volunteers were allocated to two groups of 19 individuals each, i.e., isoflavone and placebo. There was a weak correlation between menopause duration and low performance in the capacity to manipulate information (central executive). We observed an increase in the capacity to integrate information in the group treated with isoflavone, but no improvement in the capacity to form new memories. We did not observe differences between groups in terms of signs and symptoms suggestive of depression according to the Geriatric Depression Scale. Our results point to a possible beneficial effect of isoflavone on some abilities of the central executive. These effects could also contribute to minimizing the impact of memory impairment. Further research based on controlled clinical trials is necessary to reach consistent conclusions.

An animal experimental study of porous magnesium scaffold degradation and osteogenesis

Our objective was to observe the biodegradable and osteogenic properties of magnesium scaffolding under in vivo conditions. Twelve 6-month-old male New Zealand white rabbits were randomly divided into two groups. The chosen operation site was the femoral condyle on the right side. The experimental group was implanted with porous magnesium scaffolds, while the control group was implanted with hydroxyapatite scaffolds. X-ray and blood tests, which included serum magnesium, alanine aminotransferase (ALT), creatinine (CREA), and blood urea nitrogen (BUN) were performed serially at 1, 2, and 3 weeks, and 1, 2, and 3 months. All rabbits were killed 3 months postoperatively, and the heart, kidney, spleen, and liver were analyzed with hematoxylin and eosin (HE) staining. The bone samples were subjected to microcomputed tomography scanning (micro-CT) and hard tissue biopsy. SPSS 13.0 (USA) was used for data analysis, and values of P<0.05 were considered to be significant. Bubbles appeared in the X-ray of the experimental group after 2 weeks, whereas there was no gas in the control group. There were no statistical differences for the serum magnesium concentrations, ALT, BUN, and CREA between the two groups (P>0.05). All HE-stained slices were normal, which suggested good biocompatibility of the scaffold. Micro-CT showed that magnesium scaffolds degraded mainly from the outside to inside, and new bone was ingrown following the degradation of magnesium scaffolds. The hydroxyapatite scaffold was not degraded and had fewer osteoblasts scattered on its surface. There was a significant difference in the new bone formation and scaffold bioabsorption between the two groups (9.29±1.27 vs 1.40±0.49 and 7.80±0.50 vs 0.00±0.00 mm3, respectively; P<0.05). The magnesium scaffold performed well in degradation and osteogenesis, and is a promising material for orthopedics.

Low serum concentrations of 25-hydroxyvitamin D in children and adolescents with systemic lupus erythematosus

We evaluated the concentrations of 25-hydroxyvitamin D [25(OH)D] in children and adolescents with juvenile systemic lupus erythematosus (JSLE) and associated them with disease duration and activity, use of medication (chloroquine and glucocorticoids), vitamin D intake, calcium and alkaline phosphatase levels, and bone mineral density. Thirty patients with JSLE were evaluated and compared to 30 healthy individuals, who were age and gender matched. Assessment was performed of clinical status, disease activity, anthropometry, laboratory markers, and bone mineral density. The 30 patients included 25 (83.3%) females and 16 (53.3%) Caucasians, with a mean age of 13.7 years. The mean age at diagnosis was 10.5 years and mean disease duration was 3.4 years. Mean levels of calcium, albumin, and alkaline phosphatase were significantly lower in patients with JSLE compared with controls (P<0.001, P=0.006, and P<0.001, respectively). Twenty-nine patients (97%) and 23 controls (77%) had 25(OH)D concentrations lower than 32 ng/mL, with significant differences between them (P<0.001). Fifteen patients (50%) had vitamin D levels <20 ng/mL and 14 had vitamin D levels between 20 and 32 ng/mL. However, these values were not associated with greater disease activity, higher levels of parathormone, medication intake, or bone mineral density. Vitamin D concentrations were similar with regard to ethnic group, body mass index, height for age, and pubertal stage. Significantly more frequently than in controls, we observed insufficient serum concentrations of 25(OH)D in patients with JSLE; however, we did not observe any association with disease activity, higher levels of parathormone, lower levels of alkaline phosphatase, use of medications, or bone mineral density alterations.

Protective effects of tumor necrosis factor-α blockade by adalimumab on articular cartilage and subchondral bone in a rat model of osteoarthritis

We aimed to investigate the effects of an anti-tumor necrosis factor-α antibody (ATNF) on cartilage and subchondral bone in a rat model of osteoarthritis. Twenty-four rats were randomly divided into three groups: sham-operated group (n=8); anterior cruciate ligament transection (ACLT)+normal saline (NS) group (n=8); and ACLT+ATNF group (n=8). The rats in the ACLT+ATNF group received subcutaneous injections of ATNF (20 μg/kg) for 12 weeks, while those in the ACLT+NS group received NS at the same dose for 12 weeks. All rats were euthanized at 12 weeks after surgery and specimens from the affected knees were harvested. Hematoxylin and eosin staining, Masson's trichrome staining, and Mankin score assessment were carried out to evaluate the cartilage status and cartilage matrix degradation. Matrix metalloproteinase (MMP)-13 immunohistochemistry was performed to assess the cartilage molecular metabolism. Bone histomorphometry was used to observe the subchondral trabecular microstructure. Compared with the rats in the ACLT+NS group, histological and Mankin score analyses showed that ATNF treatment reduced the severity of the cartilage lesions and led to a lower Mankin score. Immunohistochemical and histomorphometric analyses revealed that ATNF treatment reduced the ACLT-induced destruction of the subchondral trabecular microstructure, and decreased MMP-13 expression. ATNF treatment may delay degradation of the extracellular matrix via a decrease in MMP-13 expression. ATNF treatment probably protects articular cartilage by improving the structure of the subchondral bone and reducing the degradation of the cartilage matrix.

Influence of carbon source and the fermentation process on levan production by Zymomonas mobilis analyzed by the surface response method

The aim of this study is to assess sugar cane juice and sucrose as substrates, the batch and fed batch processes and their interaction in the levan production using a complete factorial design. Zymomonas mobilis was cultivated in different sugar cane juice and sucrose concentrations in two fermentation processes at 25 °C for 20 h. A complete factorial design (2³) was used to analyze the effects of the type and concentration of the substrate, as well as the batch and fed batch processes. A complete second factorial design (2²) was used to observe the importance of sugar cane juice. The results indicated that the batch process improved the levan production reaching 40.14 g/L. The addition of sugar cane juice was not statistically significant for levan formation, however sugar cane juice stimulated biomass, sorbitol and ethanol production. The best medium for levan production was 150 g/L sucrose in batch.

Fiscal reform and federal relations: Brazilian deadlocks

Brazilian fiscal reform got to deadlocks because proposals tried to avoid considering federal relations. There are two main types of federal relations: the competitive and the cooperative. In both types is possible to observe coordination mechanisms. Brazilian federalism is a mixture of both types what leads to difficulties finding solutions. We argue that is more important to find mechanisms to facilitate cooperation than to discuss the qualities of any alternative fiscal structure. Fiscal reforms brings along a great deal of uncertainty. So it is important to discuss the reform timing and the compensation mechanisms before hand.

In search of the interrelatedness of innovation and internationalisation processes in entrepreneurial life science companies

This study is motivated by the question how resource scarce innovative entrepreneurial companies seek and leverage global resources. This study takes a resource-seeking perspective a step forward and suggests that resources that enable the entrepreneurial internationalisation are largely accrued from the early stages of entrepreneurial life; that is from the innovation development. Consequently, this study seeks to explain how innovation and internationalisation processes are interrelated in the entrepreneurial internationalisation. This main objective is approached through three research questions, (1) What role do inter-organisational relationships in innovation have in the entrepreneurial internationalisation process? (2) What kind of inward–outward links do inter-organisational relationships create in the resource-seeking-based entrepreneurial internationalisation process? (3) What kind of capability to collaborate forms in the interaction of inter-organisational relationship deployment? The research design is a mixed methods design that consists of quantitative pilot study and qualitative multiple case study of five entrepreneurial life science companies from Finland and Austria. The findings show that innovation and internationalisation processes are tightly interwoven in pre-internationalisation state. The findings also reveal that the more experienced companies are able to take advantage of complexcross-border inter-organisational relationship structures better than the starting companies. However, very minor evidence was found on inward links translating into outward links in the entrepreneurial internationalisation process, despite the expectation to observe more of these links in the data. Combined intangible-tangible resource-seeking was the most preferred to build links between inward–outward internationalisation but also to develop competence to collaborate. By adopting a resource- instead of market-seeking approach, this study illustrated that internationalisation extends to early stages of innovative companies, and that in high-technology companies’ potentially significant cross-border relationships have started to form long before incorporation. Therefore, these observations justified the firmer inclusion of pre-company history in innovative entrepreneurship studies. The study offers a conceptualisation of entrepreneurial internationalisation that is perceived as a process. The main theoretical contributions are in the areas of international entrepreneurship and in the behavioural process studies of entrepreneurial internationalisation and resource-based internationalisation. The inclusion of the innovation-based discussion, namely the innovation process, in the internationalisation process theories has clearly contributed to the understanding of entrepreneurial internationalisation in the context of international entrepreneurship. Innovation development is a central act of entrepreneurial companies, and neglecting innovation process investigation from entrepreneurial internationalisation leaves potentially influential mechanisms unexplored.

The role of molecular, clinical and socioeconomic factors in the long-term survival of axillary node negative breast cancer patients

The overall objective of this study was to investigate factors associated with long-term survival in axillary node negative (ANN) breast cancer patients. Clinical and biological factors included stage, histopathologic grade, p53 mutation, Her-2/neu amplification, estrogen receptor status (ER), progesterone receptor status (PR) and vascular invasion. Census derived socioeconomic (SES) indicators included median individual and household income, proportions of university educated individuals, housing type, "incidence" of low income and an indicator of living in an affluent neighbourhood. The effects of these measures on breast cancer-specific survival and competing cause survival were investigated. A cohort study examining survival among axillary node negative (ANN) breast cancer patients in the greater Toronto area commenced in 1 989. Patients were followed up until death, lost-to-follow up or study termination in 2004. Data were collected from several sources measuring patient demographics, clinical factors, treatment, recurrence of disease and survival. Census level SES data were collected using census geo-coding of patient addresses' at the time of diagnosis. Additional survival data were acquired from the Ontario Cancer Registry to enhance and extend the observation period of the study. Survival patterns were examined using KaplanMeier and life table procedures. Associations were examined using log-rank and Wilcoxon tests of univariate significance. Multivariate survival analyses were perfonned using Cox proportional hazards models. Analyses were stratified into less than and greater than 5 year survival periods to observe whether known markers of short-tenn survival were also associated with reductions in long-tenn survival among breast cancer patients. The 15 year survival probabilities in this cohort were: for breast cancerspecific survival 0.88, competing causes survival 0.89 and for overall survival 0.78. Estrogen receptor (ER) and progesterone receptor (PR) status (Hazard Ratio (HR) ERIPR- versus ER+/PR+, 8.15,95% CI, 4.74, 14.00), p53 mutation (HR, 3.88, 95% CI, 2.00, 7.53) and Her-2 amplification (HR, 2.66, 95% CI, 1.36, 5.19) were associated with significant reductions in short-tenn breast cancer-specific survival «5 years following diagnosis), however, not with long-term survival in univariate analyses. Stage, histopathologic grade and ERiPR status were the clinicallbiologieal factors that were associated with short-term breast cancer specific survival in multivariate results. Living in an affluent neighbourhood (top quintile of median household income compared to the rest of the population) was associated with the largest significant increase in long-tenn breast cancer-specific survival after adjustment for stage, histopathologic grade and treatment (HR, 0.36, 95% CI, 0.12, 0.89).

An analysis of the photoelectron and Rydberg states of formaldehyde /|nby Carol R. Lessard. -- 260 St. Catharines [Ont.] : Dept. of Chemistry, Brock University,

Although it is generally accepted that Rydberg orbitals are very large and diffuse, and that electron promotion to a Rydberg orbital is not too different from ionization of the molecule, analysis of the two types of transitions proves otherwise. The photoelectron spectrum of the 2B2 (n) ion has very little vibrational structure attached to the origin band; on the other hand, several of the Rydberg transitions which involve the promotion of the n(bZ) electron exhibit a great deal of vibrational activity. In particular, the members of the n=3 Rydberg\ series interact with and perturb each other through pseudo-Jahn-Teller vibronic coupling. The vacuum ultraviolet spectrum contains a number of features which are difficult to explain, and two unusually sharp bands can only be identified as representing some form of electron promotion in formaldehyde.

An investigation into fungal metabolism of halogenated and related steroids

Fungal metabolism of halogenated and related steroids was investigated. The fungi Aspergillus niger ATCC 9142, Curvularia lunata NRRL 2380 and Rhizopus stolonifer ATCC6227b were studied in this regard. 2l-Fluoro-, 2l-chloro, 2l-bromo- and 2l-methyl-pregn-4-ene-3,20diones were prepared and incubated with ~ niger (a C-2l-hydroxylator) in order to observe the effect of the C-2l substituent on the metabolism of these substrates. In all four cases, the C-2l substituent prevented any significant metabolism of these substrates. llB-Fluoropregn-4-ene-3,20-dione was prepared and incubated with C. lunata (an llB-hydroxylator) and ~ stolonifer (an lla-hydroxylator). With ~ lunata, the ll-fluoro- substituent prevent hydroxylation at the 11 position, but diverted it to a site remote from the fluorine atom. In contrast, with ~ stolonifer the llB-fluoro- substituent, although slowing the apparent rate of hydroxylation, did not prevent its occurrence at the 11a- position. llB-Hydroxypregn-4-ene-3,20-dione was also incubated with R. stolonifer. The llB-hydroxy-;group did not appear to have any significant effect on hydroxylation at the lla- position. The incubation of a substrate, unsaturated at a favoured site of hydroxylation with Rhizopus arrhizus ATCC 11145 provided a complex mixture of products; among them were both the a and S epoxides. The formation of these products is rationalized as arising because of the lack of regio- and stereospecificity of the hydroxylase enzyme(s) involved.

The impact of the Canadian Standardized Test of Fitness and of health counselling on health attitudes and behaviour

The purpose of this research study was to determine whether or not the use of a single day of Personal Wellness Evaluations would be meaningful enough to change the attitudes of participants toward adopting a healthier lifestyle, or if it was necessary to include regular planned health counselling alon-g with the Personal Wellness Evaluations in order to'observe changes in beliefs, attitudes and behaviours toward active living and the adoption of a healthier lifestyle. Attitudes and behaviours toward physical fitness and healthy lifestyle choices were assessed through a questionnaire composed of the following instruments: Fishbein and Ajzen Attitude and Behaviour Questionnaire, Leisure Behaviour Questionnaire, Ten Centimeter Bipolar Health Continuum, Neugarten Life Satisfaction Assessment, Job Description Index, Selected questions from the Ontario Health Survey, and the Symptom Reporting Questionnaire. Physical fitness evaluation consisted of the Canadian Standardized Test of Fitness, measures of blood pressure, and total cholesterol. The participants were divided into three groups: Group 1- CSTF & health counselling, Group 2- CSTF only, and Group 3- a control group. All three groups received the questionnaire both at the beginning and at the end of the study. Group 1 and Group 2 also participated in fitness testing at these same times, with a three-month time interval between test times. Group 1 also received weekly one-hour health education sessions during the three months between fitness testing. While there were some differences found between the three groups in this study, the results of this study suggested that this three-month workplace wellness program had no impact on the participants' attitudes and behaviours toward health and physical activity. There were no significant differences in the physical fitness measures between Group 1 and Group 2 , nor in the participants' questionnaire responses. These results may be due to the participants' lack of compliance to this wellness program. Employees who 11 participate in a workplace weIlness program must be self-motivated to comply with the program in order to receive the full benefits the program has to offer. Some participants in this study did not have the internal motivation necessary to remain in the study for the three-month period. Future research may consider implementing a workplace wellness program for a longer duration as well as incorporating a specific physical fitness program for the participants to follow. An exercise program could improve the participants' physical fitness, while the health counselling would give the individuals the health education necessary to lead a healthy lifestyle.

Examination of students' ability to observe domains of client behaviour in therapeutic recreation

When observing client behaviours, a therapeutic recreation specialist must have a base understanding of typical client behaviours to provide an informed analysis (burlingame & Blaschko, 2010). Providing students with the necessary tools for client observation is significant to the success of this process. The purpose of this study was to assess the relationships amongst the TR student demographic characteristics on acquiring the observation competency necessary to conduct a TR assessment. One hundred seventy-two TR college and university students, enrolled in post-secondary undergraduate TR programs across Ontario, observed a client assessment via video, and recorded their observations using the Tracking Behavioural Assessment (TBA) (Passmore, 2002). Independent samples t-tests and analysis of variance were calculated for the different student characteristics on the domains of the TBA. Significant findings indicated that university students scored more accurately than college students, and advanced students more accurately than novice students, on the emotional and socialization domains.

The Impact of a Corporate Name Change on Stock Price and Trading Volume of Canadian Companies

This thesis examines the impact of a corporate name change on stock price and trading volume of Canadian companies around the announcement date, the approval date, and the adoption date over the time period from 1997 to 2011. Name changes are classified into six categories: major and minor, structural and pure, diversified and focused, accompanied with a change in ticker symbol and without a change in ticker symbol, “Gold” name addition and deletion, and different reasons for name changes (e.g., merger and acquisition, change of structure, change of strategy, and better image). The thesis uses the standard event study methodology to perform abnormal return and trading volume analyses. In addition, regression analysis is employed to examine which type of a name change has the largest impact on cumulative abnormal returns. Sample stocks exhibit a significant positive abnormal return one-day prior to the approval day and one day after the adoption date. Around the approval date we observe significant abnormal returns for stocks with a structural name change. On the day after the adoption date we document abnormal returns for stocks with major, minor, structural, pure, focused, and ticker symbol name changes. If a merger or acquisition is the reason for a name change, companies tend to experience a significant positive abnormal return one-day before the approval date and on the adoption date. If a change of structure is the reason for a name change, companies exhibit a significant positive abnormal return on the approval date and a significant negative abnormal return on the adoption date. In case of a change of strategy as the reason for a name change, companies show a significant negative abnormal return around the approval date and a significant positive abnormal return around the adoption date.

A DYNAMIC FRAMEWORK FOR THE RELATIONS BETWEEN FOREIGN EXCHANGE RATES, SAVINGS AND INVESTMENTS

The Meese-Rogoff forecasting puzzle states that foreign exchange (FX) rates are unpredictable. Since one country’s macroeconomic conditions could affect the price of its national currency, we study the dynamic relations between the FX rates and some macroeconomic accounts. Our research tests whether the predictability of the FX rates could be improved through the advanced econometrics. Improving the predictability of the FX rates has important implications for various groups including investors, business entities and the government. The present thesis examines the dynamic relations between the FX rates, savings and investments for a sample of 25 countries from the Organization for Economic Cooperation and Development. We apply quarterly data of FX rates, macroeconomic indices and accounts including the savings and the investments over three decades. Through preliminary Augmented Dickey-Fuller unit root tests and Johansen cointegration tests, we found that the savings rate and the investment rate are cointegrated with the vector (1,-1). This result is consistent with many previous studies on the savings-investment relations and therefore confirms the validity of the Feldstein-Horioka puzzle. Because of the special cointegrating relation between the savings rate and investment rate, we introduce the savings-investment rate differential (SID). Investigating each country through a vector autoregression (VAR) model, we observe extremely insignificant coefficient estimates of the historical SIDs upon the present FX rates. We also report similar findings through the panel VAR approach. We thus conclude that the historical SIDs are useless in forecasting the FX rate. Nonetheless, the coefficients of the past FX rates upon the current SIDs for both the country-specific and the panel VAR models are statistically significant. Therefore, we conclude that the historical FX rates can conversely predict the SID to some degree. Specifically, depreciation in the domestic currency would cause the increase in the SID.