A mouse peritonitis model for the study of glycopeptide efficacy in GISA infections

In recent years, the emergence of Staphylococcus aureus strains with reduced susceptibility to glycopeptides has raised considerable concern. We studied the efficacy of vancomycin and teicoplanin, as well as cloxacillin and cefotaxime, against the infection caused by four S. aureus strains with different glycopeptide and β-lactam susceptibilities (strains A, B, C, and D; MICs for vancomycin of 1, 2, 4, and 8 µg/ml respectively), using a modified model of mouse peritonitis. This optimized model appeared to be straightforward and reproducible, and was able to detect low differences in bacterial killing between antibiotics and also between different S. aureus strains. Bactericidal activities in peritoneal fluid for vancomycin, teicoplanin, cloxacillin, and cefotaxime decreased from -2.98, -2.36, -3.22, and -3.57 log10 cfu/ml, respectively, in infection by strain A (MICs for vancomycin and cloxacillin of 1 and 0.38 µg/ml, respectively) to -1.22, -0.65, -1.04, and +0.24 in peritonitis due to strain D (MICs for vancomycin and cloxacillin of 8 and 1,024 µg/ml). Our data confirm the superiority of β-lactams against methicillin-susceptible S. aureus and show that bactericidal activity of glycopeptides decreases significantly with slight increases in MICs; this finding suggests a reduced efficacy of glycopeptides in the treatment of serious glycopeptide-intermediate S. aureus infections

Perspectives for the treatment of brucellosis in the 21st century: the Ioannina recommendations.

Brucellosis is probably the commonest anthropozoonotic infection worldwide [1-3], but remains in various aspects an enigma in the 21st century [4]. Brucella melitensis remains the major cause of human disease worldwide, followed by B. abortus and B. suis, while rare but persisting cases of B. canis human infection and disease by novel Brucella pathogens of marine mammals have also emerged. The disease is re-emerging as a significant cause of travel-related disease [5] and represents an index of poor socioeconomic status (Figure 1). Its treatment is largely based even today on the principles applied half a century ago by pioneer researchers [6] and few modifications have been made in the following years, despite the emergence of new antibiotic classes and different therapeutic approaches [7].

Trace me if you can: the use of intrinsic biogeochemical markers in marine top predators

Human activities have serious impacts on marine apex predators. Inadequate knowledge of the spatial and trophic ecology of these marine animals ultimately compromises the viability of their populations and impedes our ability to use them as environmental biomonitors. Intrinsic biogeochemical markers, such as stable isotopes, fatty acids, trace elements, and chemical pollutants, are increasingly being used to trace the spatial and trophic ecology of marine top predators. Notable advances include the emergence of the first oceanographic"isoscapes" (isotopic geographic gradients), the advent of compound-specific isotopic analyses, improvements in diet reconstruction through Bayesian statistics, and tissue analysis of tracked animals to ground-truth biogeochemical profiles. However, most researchers still focus on only a few tracers. Moreover, insufficient knowledge of the biogeochemical integration in tissues, fractionation and routing processes, and geographic and temporal variability in baseline levels continue to hamper the resolution and potential of these markers in studying the spatial and feeding ecology of top predators.

The effect of dynamic capabilities on operational-level innovation – Empirical study in magazine publishing industry

This master’s thesis aims to examine the relationship between dynamic capabilities and operational-level innovations. In addition, measures for the concept of dynamic capabilities are developed. The study was executed in the magazine publishing industry which is considered favourable for examining dynamic capabilities, since the sector is characterized by rapid change. As a basis for the study and the measure development, a literary review was conducted. Data for the empirical section was gathered by a survey targeted to chief-editors of Finnish consumer magazines. The relationship between dynamic capabilities and innovation was examined by multiple linear regression. The results indicate that dynamic capabilities have effect on the emergence of radical innovations. Environmental dynamism’s effect on radical innovations was not detected. Also, dynamic capabilities’ effect on innovation was not greater in turbulent operating environment.

Different pathways in the larval development of the crab Ucides cordatus (Decapoda, Ocypodidae) and their relation with high mortality rates by the end of massive larvicultures

One of the most limiting factors affecting the larval rearing of Ucides cordatus in the laboratory is a period of high mortality, which usually occurs late in the course of the larviculture during the metamorphosis from the zoeal to the megalopal phase. The objective of the present research was to analyze the post-embryonic development of U. cordatus on an individual basis and, in particular, to search for patterns linking disturbances in the molting process to the high larval death rates observed in massive larvicultures. A total of 50 larvae were individually reared from hatching to metamorphosis into the megalopal phase under controlled conditions, fed a combination of microalgae and rotifers. The survivorship rate was 70% until zoea V. The 35 surviving zoea V larvae followed two different pathways. Eleven underwent metamorphosis directly to megalopa, eighteen molted to zoea VI and six died as zoea V. In the last molting event, only two zoea VI larvae reached the megalopal stage, while the remaining sixteen died. In further observation under microscope, 13 of the dead zoea VI showed characteristics of the pre-molt stage and pereiopods disproportionably large in relation to the carapace. The observed pattern resembles the Molt Death Syndrome (MDS) described for other decapod species, in which larvae die in the late pre-molt phase of the molting cycle. We suggest that U. cordatus larvae develop disturbances in the molting process similar to the MDS described for other species and that these disturbances are related to a more complex pathway involving the emergence of larval stage zoea VI.

The role of IL-12 in experimental Trypanosoma cruzi infection

Host resistance to Trypanosoma cruzi infection is dependent on both natural and acquired immune responses. During the early acute phase of infection in mice, natural killer (NK) cell-derived IFN-g is involved in controlling intracellular parasite replication, mainly through the induction of nitric oxide biosynthesis by activated macrophages. We have shown that IL-12, a powerful inducer of IFN-g production by NK cells, is synthesized soon after trypomastigote-macrophage interaction. The role of IL-12 in the control of T. cruzi infection in vivo was determined by treating infected mice with anti-IL-12 monoclonal antibody (mAb) and analyzing both parasitemia and mortality during the acute phase of infection. The anti-IL-12 mAb-treated mice had higher levels of parasitemia and mortality compared to control mice. Also, treatment of infected mice with mAb specific for IFN-g or TNF-a inhibited the protective effect of exogenous IL-12. On the other hand, TGF-ß and IL-10 produced by infected macrophages inhibited the induction and effects of IL-12. Therefore, while IL-12, TNF-a and IFN-g correlate with resistance to T. cruzi infection, TGF-ß and IL-10 promote susceptibility. These results provide support for a role of innate immunity in the control of T. cruzi infection. In addition to its protective role, IL-12 may also be involved in the modulation of T. cruzi-induced myocarditis, since treatment of infected mice with IL-12 or anti-IL-12 mAb leads to an enhanced or decreased inflammatory infiltrate in the heart, respectively. Understanding the role of the cytokines produced during the acute phase of T. cruzi infection and their involvement in protection and pathogenesis would be essential to devise new vaccines or therapies.

The multicultural moment : the history of the idea and politics of multiculturalism in Sweden in comparative, transnational and biographical context, 1964–1975

The emergence of the idea of multiculturalism in Swedish public discourse and social science in the latter half of the 1960s and introduction of official multiculturalism in 1975 constituted a major intellectual and political shift in the post-war history of Sweden. The ambition of the 1975 immigrant and minority policy to enable the preservation of ethno-cultural minorities and to create a positive attitude towards the new multicultural society among the majority population was also incorporated into Swedish cultural, educational and media policies. The rejection of assimilationism and the new commitment to ethno-cultural diversity, the multicultural moment, has earned Sweden a place on the list of the early adopters of official multiculturalism, together with Canada and Australia. This compilation thesis examines the origins and early post-war history of the idea of multiculturalism as well as the interplay between idea and politics in the shift from a public ideal of homogeneity to an ideal of multiculturalism in Sweden. It does so from a range of conceptual, comparative, transnational, and biographical perspectives. The thesis consists of an introduction (Part I) and four previously published studies (Part II). The primary research result of the thesis concerns the agency involved in the break-through and formal establishment of the idea of multiculturalism in Sweden. Actors such as ethnic activists, experts and officials were instrumental in the introduction and establishment of multiculturalism in Sweden, as they also had been in Canada and in Australia. These actors have, however, not previously been recognized and analysed as significant idea-makers and political agents in the case of Sweden. The intertwined connections between activists, social scientists, linguists, and officials facilitated the transfer of the idea of multiculturalism from a publically contested idea to public policy via the way of The Swedish Trade Union Confederation, academia and the Royal Commission of Immigration. The thesis furthermore shows that the political success of the idea of multiculturalism, such as it was within the limits of the universalist social democratic welfare state, was dependent on whom the claims-makers were, the status and positions they held, and the way the idea of multiculturalism was conceptualised and used. It was also dependent on the migratory context of labour immigration in the 1960s and 1970s and on whose behalf the advocates of multiculturalism made their claims. The majority of the labour immigrants were Finnish citizens from the former eastern half of the kingdom of Sweden who were net contributors to the Swedish welfare state. This facilitated the recognition of their ethno-cultural difference, and, following the logic of universalism, the ethno-cultural difference of other minority groups in Sweden. The historical significance of the multicultural moment is still evident in the contemporary immigration and integration policies of Sweden. The affirmation of diversity continues to set Sweden apart from the rest of Europe, now more so than in the 1970s, even though the migratory context has changed radically in the last 40 years.

Photophysical studies of zinc phthalocyanine and chloroaluminum phthalocyanine incorporated into liposomes in the presence of additives

The photophysical properties of zinc phthalocyanine (ZnPC) and chloroaluminum phthalocyanine (AlPHCl) incorporated into liposomes of dimyristoyl phosphatidylcholine in the presence and absence of additives such as cholesterol or cardiolipin were studied by time-resolved fluorescence, laser flash photolysis and steady-state techniques. The absorbance of the drugs changed linearly with drug concentration, at least up to 5.0 µM in homogeneous and heterogeneous media, indicating that aggregation did not occur in these media within this concentration range. The incorporation of the drugs into liposomes increases the dimerization constant by one order of magnitude (for ZnPC, 3.6 x 10(4) to 1.0 x 10(5) M-1 and for AlPHCl, 3.7 x 10(4) to 1.5 x 10(5) M-1), but this feature dose does not rule out the use of this carrier, since the incorporation of these hydrophobic drugs into liposomes permits their systemic administration. Probe location in biological membranes and predominant positions of the phthalocyanines in liposomes were inferred on the basis of their fluorescence and triplet state properties. Both phthalocyanines are preferentially distributed in the internal regions of the liposome bilayer. The additives affect the distribution of these drugs within the liposomes, a fact that controls their delivery when both are used in a biological medium, retarding their release. The addition of the additives to the liposomes increases the internalization of phthalocyanines. The interaction of the drugs with a plasma protein, bovine serum albumin, was examined quantitatively by the fluorescence technique. The results show that when the drugs were incorporated into small unilamellar liposomes, the association with albumin was enhanced when compared with organic media, a fact that should increase the selectivity of tumor targeting by these phthalocyanines (for ZnPC, 0.71 x 10(6) to 1.30 x 10(7) M-1 and for AlPHCl, 4.86 x 10(7) to 3.10 x 10(8) M-1).

Genetic variability of hepatitis A virus isolates in Rio de Janeiro: implications for the vaccination of school children

The epidemiology of hepatitis A virus (HAV) infection is shifting from high to intermediate endemicity in Brazil, resulting in increased numbers of susceptible individuals and a greater potential for the emergence of outbreaks. Universal vaccination against HAV has been recommended for children, but updated sero-epidemiological data are necessary to analyze the level of natural immunity and to identify candidates for preventive measures. In addition, more molecular studies are necessary to characterize the genotypes involved in HAV infections and outbreaks. Sera from 299 school children (5-15 years old) and 25 school staff members, collected during an outbreak of HAV at a rural public school in June 2000, were tested for IgM and total anti-HAV antibodies (ELISA). Viral RNA was amplified by RT-PCR from anti-HAV IgM-positive sera and from 19 fecal samples. Direct nucleotide sequencing of the VP1/2A region was carried out on 18 PCR-positive samples. Acute HAV infection was detected by anti-HAV IgM in 93/299 children and in 3/25 adult staff members. The prevalence of total anti-HAV antibodies in IgM-negative children under 5 years of age was only 10.5%. HAV-RNA was detected in 46% IgM-positive serum samples and in 16% stool samples. Sequence analysis showed that half the isolates belonged to subgenotype IA and the other half to IB. On the basis of these data, mass vaccination against HAV is recommended without prevaccination screening, especially for children before they enter school, since nearly 90% of the children under 5 years were susceptible. Molecular characterization indicated the endemic circulation of specific HAV strains belonging to subgenotypes IA and IB.

Emergence of clonal complex 5 (CC5) methicillin-resistant Staphylococcus aureus (MRSA) isolates susceptible to trimethoprim-sulfamethoxazole in a Brazilian hospital

In this study, genotyping techniques including staphylococcal chromosomal cassette mec (SCCmec) typing, pulsed-field gel electrophoresis (PFGE), multilocus sequence typing (MLST) and restriction-modification tests were used to compare the molecular characteristics of methicillin-resistant Staphylococcus aureus (MRSA) isolates recovered at two times within a 10-year interval (1998 and 2008) from a tertiary Brazilian hospital. In addition, the antimicrobial susceptibility profiles were analyzed. All 48 MRSA isolates from 1998 and 85.7% from 2008 (48/56 isolates) displayed multidrug-resistance phenotypes and SCCmec III. All but one of the 13 representative SCCmec III isolates belonged to CC8 and had PFGE patterns similar to that of the BMB9393 strain (Brazilian epidemic clone of MRSA; BEC). In 2008, we found an increased susceptibility to rifampicin and chloramphenicol among the SCCmec III isolates. In addition, we detected the entrance of diverse international MRSA lineages susceptible to trimethoprim-sulfamethoxazole (SXT), almost all belonging to CC5. These non-SCCmec III isolates were related to the USA 300 (ST8-SCCmec IV; PFGE-type B), USA 800 (ST5-SCCmec IV; subtype D1), USA 100 (ST5-SCCmec II; subtype D2), and EMRSA-3/Cordobes (ST5-SCCmec I, type C) clones. To the best of our knowledge, this is the first report of the emergence of isolates genetically related to the EMRSA-3/Cordobes clone in southeast Brazil. In this regard, these isolates were the most common non-SCCmec III MRSA in our institution, accounting for 8.9% of all isolates recovered in 2008. Thus, despite the supremacy of BEC isolates in our country, significant changes may occur in local MRSA epidemiology, with possible consequences for the rationality of MRSA empiric therapy.

Developments in the use of nanocapsules in oncology

The application of nanotechnology to medicine can provide important benefits, especially in oncology, a fact that has resulted in the emergence of a new field called Nanooncology. Nanoparticles can be engineered to incorporate a wide variety of chemotherapeutic or diagnostic agents. A nanocapsule is a vesicular system that exhibits a typical core-shell structure in which active molecules are confined to a reservoir or within a cavity that is surrounded by a polymer membrane or coating. Delivery systems based on nanocapsules are usually transported to a targeted tumor site and then release their contents upon change in environmental conditions. An effective delivery of the therapeutic agent to the tumor site and to the infiltrating tumor cells is difficult to achieve in many cancer treatments. Therefore, new devices are being developed to facilitate intratumoral distribution, to protect the active agent from premature degradation and to allow its sustained and controlled release. This review focuses on recent studies on the use of nanocapsules for cancer therapy and diagnosis.

Late emergence of A594V and L595W mutations related to ganciclovir resistance in a patient with HCMV retinitis and long-term HIV progression

The emergence of ganciclovir (GCV) resistance during the treatment of human cytomegalovirus (HCMV) infection is a serious clinical challenge, and is associated with high morbidity and mortality. In this case report, we describe the emergence of two consecutive mutations (A594V and L595W) related to GCV resistance in a patient with HCMV retinitis and long-term HIV progression after approximately 240 days of GCV use. Following the diagnosis of retinitis, the introduction of GCV did not result in viral load reduction. The detected mutations appeared late in the treatment, and we propose that other factors (high initial HCMV load, previous GCV exposure, low CD4+ cell count), in addition to the presence of resistance mutations, may have contributed to the treatment failure of HCMV infection in this patient.

Changing roles of nurse educators employed in acute and chronic care settings : the impact of professional and statutory mandates in Ontario at four sites of one hospital corporation /

The role of the hospital-employed nurse educator is evolving. Factors influencing this change include the introduction of standards for nurse educators by the College of Nurses of Ontario (CNO), a change in the way nurses are educated, the emergence of nursing as a profession, and hospital restructuring as a result of budgetary constraints. Two of these influencing factors: the introduction of the updated Standards of Practice for Registered Nurses and Registered Practical Nurses (1996) and hospital restructuring occurred over the last 7 years at several hospitals in southern Ontario. Current literature as well as the Standards of Practice (1996) were utilized to examine the current roles and responsibilities of nurse educators and subsequently develop a questionnaire to study the impact of these influencing factors on the role of the nurse educator. This questionnaire was piloted and revised before its distribution at 4 hospitals in southern Ontario. Twenty-five of the 41 surveys (61%) distributed were returned for analysis. The data reflected that the Standards of Practice had a positive influence on the role of the nurse educator, while hospital restructuring had a negative impact. In addition, many of the roles and responsibilities identified in the literature were indeed part of the current role of nurse educators, as well as several responsibilities not captured in the literature. The predictions for the future of this role in its current state were not positive given the financial status of the health care system as well as the lack of clarity for the role and the current level ofjob satisfaction among practicing nurse educators. However, a list of recommendations were generated which, if implemented, could add clarity to the role and improve job satisfaction. This could enhance the retention of current nurse educators and the possibility of recruiting competent nurse educators to the role in the future.

Exploring the effects of change on nursing practice in acute ambulatory care settings : a qualitative study

As a result of the current changes taking place in the delivery of acute care services, the emergence of acute ambulatory care (AAC) settings is expanding. According to a literature review, the volume, acuity, and complexity of patient care in these settings is increasing while the time the patients spend under the care of nurses is decreasing. Two forces, hospital downsizing and advancing technology, are identified as the major contributors to the shift in acute care delivery. The effects that these changes are having on the clinical nursing practice of registered nurses working in AAC settings are not known. Given that AAC settings are rapidly expanding, it can be anticipated that the delivery of nursing care will continue to be compressed into a shorter time frame. Therefore, the following qualitative research question was formulated: What are the problems and issues related to clinical nursing practice in acute ambulatory settings? The purpose of this study was to explore the problems and issues associated with change and clinical nursing practice including the educational needs of nurses working in MC settings. Specific objectives of the study included the following: (a) to explore the problems and issues related to nursing practice in select AAC settings; (b) to explore the similarities and differences in perspectives related to role expectation between nurse managers, nurse educators, and staff nurses; and (c) to develop a conceptual framework that will guide the construction of an instrument needed for further research. This study used semistructured individual interviews and focus group sessions to collect data from the three categories of registered nurses. More specifically, data were collected from one nurse manager, two charge nurses, two nurse educators and fifteen staff nurses, working in three different MC settings of a major teaching hospital. Collected data were separately analyzed by the researcher and an external rater following grounded theory methodology. By using open and axial coding, the problems and issues identified by nurses were grouped into several major and minor themes. In final analysis, by using selective coding, the four core themes (intensification, moderation, frustration, and adaptation) were extracted. Each core theme was presented and discussed in relation to hospital downsizing and advancing technology. The relationships among the four core themes were discussed and depicted in a model termed the "Impact and Consequence Model on Nursing Practice in MC Settings." Implications for further research are discussed and research hypotheses, based on the research findings, are presented.

Emergence of conscious awareness of underlying verbal and visual rules over time in moderate closed-head trauma patients

Please consult the paper edition of this thesis to read. It is available on the 5th Floor of the Library at Call Number: Z 9999.5 E38 L64 2008