Donor bone marrow cells play a role in the prevention of accelerated graft rejection induced by semi-allogeneic spleen cells in transplantation

Spleen or spleen plus bone marrow cells from (BALB/c x C57Bl/6)F1 donors were transferred into BALB/c recipients 21 days before skin or cardiac transplantation. Prolonged graft survival was observed on recipients treated with the mixture of donor-derived cells as compared to those treated with spleen cells alone. We evaluated the expression of CD45RB and CD44 by splenic CD4(+) and CD8(+) T cells 7 and 21 days after donor cell transfer. The populations of CD8(+)CD45RB(low) and CD8(+)CD44(high) cells were significantly decreased in mice pre-treated with donor spleen and bone marrow cells as compared to animals treated with spleen cells only, although these cells expanded in both groups when compared to an earlier time-point. No differences were observed regarding CD4+ T cell population when recipients of donor-derived cells were compared. An enhanced production of IL-10 was observed seven days after transplantation in the supernatants of spleen cell cultures of mice treated with spleen and bone marrow cells. Taken together these data suggest that donor-derived bone marrow cells modulate the sensitization of the recipient by semi-allogeneic spleen cells in part by delaying the generation of activated/memory CD8(+) T cells leading to enhanced graft survival. (c) 2007 Elsevier B.V. All rights reserved.

PAS-1, an Ascaris suum Protein, Modulates Allergic Airway Inflammation via CD8(+) gamma delta TCR(+) and CD4(+) CD25(+) FoxP3(+) T Cells

We have previously demonstrated that PAS-1, a 200 kDa protein from Ascaris suum, has a potent immunomodulatory effect on humoral and cell-mediated responses induced by APAS-3 (an allergenic protein from A. suum) or unrelated antigens. In this study, we investigated the mechanisms by which PAS-1 is able to induce this effect on an allergic airway inflammation induced by OVA in mice. C57BL/6 mice were adoptively transferred on day 0 with seven different PAS-1-primed cell populations: PAS-1-primed CD19(+) or B220(+) or CD3(+) or CD4(+) or CD8(+) or CD4(+) CD25) or CD4(+) CD25(+) lymphocytes. These mice were immunized twice with OVA and alum by intraperitoneal route (days 0 and 7) and challenged twice by intranasal route (days 14 and 21). Two days after the last challenge, the airway inflammation was evaluated by antibody levels, cellular migration, eosinophil peroxidase levels, cytokine and eotaxin production, and pulmonary mechanical parameters. Among the adoptively transferred primed lymphocytes, only CD4(+) CD25(+), CD8(+) or the combination of both T cells impaired the production of total IgE and OVA-specific IgE and IgG1 antibodies, eosinophilic airway inflammation, Th2-type cytokines (IL-4, IL-5 and IL-13), eotaxin release and airway hyperreactivity. Moreover, airway recruited cells from CD4(+) CD25(+) and CD8(+) T-cell recipient secreted more IL-10/TGF-beta and IFN-gamma, respectively. Moreover, we found that PAS-1 expands significantly the number of CD4(+) CD25(+) FoxP3(+) and CD8(+) gamma delta TCR(+) cells. In conclusion, these findings demonstrate that the immunomodulatory effect of PAS-1 is mediated by these T-cell subsets.

Deficiency of thrombospondin-1 reduces Th17 differentiation and attenuates experimental autoimmune encephalomyelitis

Transforming growth factor beta (TGF-beta) plays a role both in the induction of Treg and in the differentiation of the IL-17-secreting T cells (Th17) which drive inflammation in experimental autoimmune encephalomyelitis (EAE). We investigated the role that thrombospondin-1 (TSP-1) dependent activation of TGF-beta played in the generation of an encephalitic Th17 response in EAE. Upon immunization with myelin oligodendrocyte glycoprotein peptide (MOG(35-55)), TSP-1 deficient (TSP-1(null)) mice and MOG(35-55) TCR transgenic mice that lack of TSP-1 (2D2.TSP-1(null)) exhibited an attenuated form of EAE, and secreted lower levels of IL-17. Adoptive transfer of in vitro-activated 2D2.TSP-1(null) T cells induced a milder form of EAE, independent of TSP-1 expression in the recipient mice. Furthermore, in vitro studies demonstrated that anti-CD3/anti-CD28 pre-activated CD4+ T cells transiently upregulated latent TGF-beta in a TSP-1 dependent way, and such activation of latent TGF-beta was required for the differentiation of Th17 cells. These results demonstrate that TSP-1 participates in the differentiation of Th17 cells through its ability to activate latent TGF-beta, and enhances the inflammatory response in EAE. (C) 2009 Elsevier Ltd. All rights reserved.

Autofluorescence spectroscopy in liver transplantation: Preliminary results from a pilot clinical study

The evaluation of graft function at various stages after transplantation is relevant, particularly at the moment of organ harvest, when a decision must be made whether to use the organ. Autofluorescence spectroscopy is noninvasive technique to monitor the metabolic condition of a liver graft throughout its course, from an initial evaluation in the donor, through cold ischemia transportation, to reperfusion and reoxygenation in the recipient. Preliminary results are presented in six liver transplantations spanning the periods from liver harvest to implant. The laser-induced fluorescence spectrum at 532-mn excitation was investigated before cold perfusion (autofluorescence), during cold ischemia, at the back table procedure, as well as 5 and 60 minutes after reperfusion. The results showed that the fluorescence analysis was sensitive to changes during the transplantation procedure. Fluorescence spectroscopy potentially provides a real-time, noninvasive technique to monitor liver graft function. The information could potentially be valuable for surgical decisions and transplant success.

Personalized Communications : A Cross Media tool for the future

Personalized communication is when the marketing message is adapted to each individual by using information from a databaseand utilizing it in the various, different media channels available today. That gives the marketer the possibility to create a campaign that cuts through today’s clutter of marketing messages and gets the recipients attention. PODi is a non-profit organization that was started with the aim of contributing knowledge in the field of digital printingtechnologies. They have created a database of case studies showing companies that have successfully implemented personalizedcommunication in their marketing campaigns. The purpose of the project was therefore to analyze PODi case studies with the main objective of finding out if/how successfully the PODi-cases have been and what made them so successful. To collect the data found in the PODi cases the authors did a content analysis with a sample size of 140 PODi cases from the year 2008 to 2010. The study was carried out by analyzing the cases' measurable ways of success: response rate, conversion rate, visited PURL (personalized URL:s) and ROI (Return On Investment). In order to find out if there were any relationships to be found between the measurable result and what type of industry, campaign objective and media vehicle that was used in the campaign, the authors put up different research uestions to explore that. After clustering and merging the collected data the results were found to be quite spread but shows that the averages of response rates, visited PURL and conversion rates were consistently very high. In the study the authors also collected and summarized what the companies themselves claim to be the reasons for success with their marketing campaigns. The resultshows that the creation of a personalized campaign is complex and dependent on many different variables. It is for instance ofgreat importance to have a well thought-out plan with the campaign and to have good data and insights about the customer in order to perform creative personalization. It is also important to make it easy for the recipient to reply, to use several media vehicles for multiple touch points and to have an attractive and clever design.

Gerillakampanjer – karakteristika och reklambyråns arbetssätt : En djupintervjuundersökning med särskilt fokus på visuella gerillakampanjer

Syftet med denna studie var att genom semistrukturerade djupintervjuer, med särskild fokus på visuella gerillakampanjer, kartlägga de av byråerna benämnda karaktärsdragen för gerillakampanjer samt byråernas arbetssätt för dessa kampanjer.Fem semistrukturerade djupintervjuer genomfördes på respektive respondents arbetsplats utvalda genom ett kombinerat strategiskt och bekvämlighetsurval.Resultaten visade tydliga karaktärsdrag för en gerillakampanj. Utifrån dessa har följande definition tagits fram: en gerillakampanj kännetecknas av att den saknar köpt medieexponering och ofta karaktäriseras av en kreativ, ofta situations- och miljöanpassad, utformning som på egen hand väcker stort intresse eller uppmärksamhet relativt mot den nyttjade budgeten i syfte att skapa djupare relationer med mottagaren.Arbetssätten för en visuell gerillakampanj och vanliga gerillakampanjer skiljer sig inte nämnvärt mot arbetssätten för en traditionell reklamkampanj. Vid framtagandet av en gerillakampanj görs juridiska överväganden om huruvida lagöverträdelser kan komma att krävas. Det framkom även att spridningen i efterhand av en gerillakampanj var viktig för att få så stort genomslag som möjligt genom nyttjandet av traditionell media.

Older people's experience of utilisation and administration of medicines in a health- and social care context

BACKGROUND: People living at home who lack ability to manage their medicine are entitled to assistance to improve adherence provided by a home care assistant employed by social care. AIM: The aim was to describe how older people with chronic diseases, living at home, experience the use and assistance of administration of medicines in the context of social care. DESIGN: A qualitative descriptive study. METHODS: Ten participants (age 65+) living at home were interviewed in the participants' own homes. Latent content analysis was used. FINDINGS: The assistance eases daily life with regard to practical matters and increases adherence to a medicine regimen. There were mixed feelings about being dependent on assistance; it interferes with self-sufficiency at a time of health transition. Participants were balancing empowerment and a dubious perception of the home care assistants' knowledge of medicine and safety. Physicians' and district nurses' professional knowledge was a safety guarantee for the medicine process. CONCLUSIONS: Assistance eases daily life and medicine regimen adherence. Dependence on assistance may affect self-sufficiency. Perceived safety varied relating to home care assistants' knowledge of medicine. RELEVANCE TO CLINICAL PRACTICE: A well-functioning medicine assistance is crucial to enable older people to remain at home. A person-centred approach to health- and social care delivery is efficient and improve outcome for the recipient of care.

The subjective well-being of people caring for a family member with a severe disability at home: a review

This review concerns the life quality of people caring for a relative with a severe disability within their family. It involves the balance between the advantages such care brings to the care recipient and the costs borne by the family. A brief history indicates that the forces that encourage family care are minimally concerned with family welfare. Moreover, an analysis of both qualitative and quantitative data indicates that primary caregivers are at considerable risk of high stress, clinical depression, and abnormally low subjective quality of life. It is concluded that increased public expenditure directed to the care of people with severe disability is urgently required.

Promoting the health and well being of older carers : a proactive strategy

Research has indicated that carers are concerned about their ageing status, their deteriorating health and their ability to continue to care for their dependants. Given that the health care system will become increasingly reliant on carers the health care needs of carers should be a concern for all health care professionals. This paper describes the first stage of a project designed to enhance older carers health promotion knowledge and skills and improve their health promoting behaviours. This stage investigated the mental and physical health status of older carers. It also sought information on older carers' levels of participation in health related and social activities and identification of barriers to participation in these types of activities. The results highlighted that carers responding to the survey experienced compromised physical and mental health. Many carers reported being unable to participate in social and health-type activities as they were unable to leave the care recipient. Of note, is that carers identified their own mental fragility and felt they needed further emotional support.

The impact of caring on caregivers' mental health : a review of the literature

This paper provides a brief overview of the literature on the impact of caring on the mental health of informal caregivers in the areas of aged care, disability and mental health. Factors discussed that may impact on caregivers' mental health include the relationship between the caregiver and care recipient, the nature of the care recipient's disability and the stage of the caregiving process. Several moderators of the impact of caring on mental health are described, including socio-economic factors, social support and coping strategies. This information provides a context within which to examine the type of interventions appropriate to assist caregivers in various situations.

Testosterone replacement therapy-perceptions of recipients and partners

Background. The androgenic hormones are important determinants of sexual behaviour in men. Testosterone replacement is important treatment for pituitary disease to maintain normal functioning. Although the physical effects of testosterone replacement have been well documented, little is known about the effects on relationships, particularly from the point of view of the sexual partners of men receiving testosterone replacement.

Aims. This paper reports a study exploring the perceptions of testosterone replacement on well-being and sexual functioning.

Methods. Semi-structured interviews were conducted with five men receiving testosterone implants (recipients), their permanent partners, and five recipients without partners. Recipient serum testosterone concentration was measured at 0, 1 and 4 months after testosterone implantation.

Results. The three groups reported similar effects of testosterone on well-being and sexual functioning. Recipient and partner ratings were also similar. Strength was less affected by decreasing testosterone concentration than energy in men with partners, but both strength and energy declined in men without partners. Decreased testosterone levels had a statistically significantly different effect on libido at time zero between men with and without partners (P < 0·015) and on ability to sustain an erection, but the ability to achieve an erection persisted over the 6 months in both male groups. Intercourse frequency increased from once per week at time 0 to ≥3 per week between 1 and 4 months after implant in men with partners. There were important effects of testosterone deficiency on general and sexual relationships, and these differed between men with partners and those without.

Conclusions. Testosterone has important physical and psychological benefits that may be related to the age at which testosterone replacement commences and the indications for its use. The small sample size may limit the ability to generalize the findings outside the study.

Patients' decision-making strategies for managing postoperative pain

Despite technological advances, many postoperative patients continue to suffer unrelieved pain. The aim of this study was to identify the strategies used by postoperative patients to bring about pain management decisions. A single-group noncomparative study design was chosen using observations as the means of examining pain activities in 2 surgical units of a metropolitan teaching hospital in Melbourne, Australia. A total of 52 nurses and 312 patients participated in the study, and 316 pain activities were observed. The most common strategy used was patients acting as a passive recipient for pain relief (60%), whereas problem solving (23%) and active negotiation (17%) were less commonly used. Patients in this study were admitted for surgical treatment of a particular condition, and their subsequent pain was specifically related to this acute event. Therefore, the lack of familiarity of the situation and the severity of pain experienced may have encouraged passivity. Patients may have also felt uncertain about how to approach the pain decision, preferring to defer to nurses. Because increased pain levels can be associated with fear, patients could have been unwilling to speak with nurses to discuss their need for pain relief.

Liver cell transplantation leads to repopulation and functional correction in a mouse model of Wilson's disease

Background and Aim: The toxic milk (tx) mouse is a non-fatal animal model for the metabolic liver disorder, Wilson's disease. The tx mouse has a mutated gene for a copper-transporting protein, causing early copper accumulation in the liver and late accumulation in other tissues. The present study investigated the efficacy of liver cell transplantation (LCT) to correct the tx mouse phenotype.

Methods: Congenic hepatocytes were isolated and intrasplenically transplanted into 3–4-month-old tx mice, which were then placed on various copper-loaded diets to examine its influence on repopulation by transplanted cells. The control animals were age-matched untransplanted tx mice. Liver repopulation was determined by comparisons of restriction fragment length polymorphism ratios (DNA and mRNA), and copper levels were measured by atomic absorption spectroscopy.

Results: Repopulation in recipient tx mice was detected in 11 of 25 animals (44%) at 4 months after LCT. Dietary copper loading (whether given before or after LCT, or both) provided no growth advantage for donor cells, with similar repopulation incidences in all copper treatment groups. Overall, liver copper levels were significantly lower in repopulated animals (538 ± 68 µg/g, n = 11) compared to non-repopulated animals (866 ± 62 µg/g, n = 14) and untreated controls (910 ± 103 µg/g, n = 6; P < 0.05). This effect was also seen in the kidney and spleen. Brain copper levels remained unchanged.

Conclusion: Transplanted liver cells can proliferate and correct a non-fatal metabolic liver disease, with some restoration of hepatic copper homeostasis after 4 months leading to reduced copper levels in the liver and extrahepatic tissues, but not in the brain.

The Isolation and Characterization of Multiply Antibiotic Resistant Strains of Fish Pathogenic Flavobacterium Species

Since the development of the first antibiotics in the 1940’s, there has been widespread overuse in both clinical and agricultural applications. Antibiotic resistance has become a significant problem as a result of subsequent dissemination of antibiotics into the environment, and multiply-resistant strains of bacteria are now a major pathogenic threat. In this study eight separate strains of Flavobacterium responsible for recent disease outbreaks in fish hatcheries throughout Maine were collected and analyzed. All eight strains were found to be resistant to high levels of a number of different antibiotics, including those used for aquaculture as well as human chemotherapeutic applications. Flavobacterium isolates were also shown phenotypically to transfer antibiotic resistance determinants using a conjugation mating system in which Flavobacterium was the donor and Escherichia coli DH5- alpha was the recipient. This experiment suggests that it may be possible for Flavobacterium strains to transfer their multiple antibiotic resistance determinants to human pathogenic bacterial strains. Importantly, none of the hatcheries from which the Flavobacterium isolates were obtained had ever used antibiotics to treat their fish stock. It is possible that there is another selective agent responsible for the development of antibiotic resistance in the absence of antibiotic pressure. Mercury is one possible candidate, as all of the strains tested were resistant to mercuric chloride and it is known that genes encoding antibiotic resistance can be carried on the same mobile genetic elements that encode for mercury resistance. Preliminary data also suggest that the majority of the Flavobacterium isolates contain genes for mercuric ion reduction, which would confirm the mercury resistance genotype.

The importance of informal investing to New Zealand's new and growing firms

As part of the Global Entrepreneurship Monitor project, we asked 2,000 adult New Zealanders if they have made a personal investment in a new firm in the past three years as well as the magnitude of their supPort, the nature of the businesses they sponsored, and their relationship with
the recipient. We compared these data on informal investment to data on venture capital obtained from national sources. We are thus able to compare New Zealand's performance to cross-national measures. We also surveyed 20 key informants/experts on questions on financing.
In New Zealand, venture capital accounts for only 0.80/o of total investment in new and growing start-ups. Yet New Zealand is world-ranked in terms of informal investment. In New Zealand, informal investment activity is 3.5olo of the national GDP amount. New Zealand is also a world leader in the prevalence of informal investors (percentage in the adult population). Seventy-three percent of informal investors put their money into a relative's or a friend's business. Fifty-eight Percent of New Zealand's informal investors are female, quite the reverse of the world pattern.

When we compare Australia and New Zealandlo the rest of the GEM world, Australia ranks favourably with the GEM globat measures in terms of venture capital as a percentage of GDp, while New Zealand does poorly. Australia also does about 40olo better than New Zealand in terms
of the amount of VC invested in individual companies. But New Zealand is clearly higher in the measures of informal investment.

We conclude with implications for entrepreneurs, policy makers, educators, researchers, and journalists. In a nutshell, they should pay more attention to the critical role of the four F's - family friends, founders, and "foolish" investors - in start-up ventures. Informal investment is a critical component of New Zealand's entrepreneurial process and thus to its economic growth. Perhaps fifty superstars with extraordinary opportunities will receive financing from the New Zealand Venture Investment Fund to launch their businesses. Meanwhile, the vast majority of firms rely on the 4Fs - friends, family founders, and "foolish" lnvestors.