Exosomal cancer immunotherapy is independent of MHC molecules on exosomes

Peptide-loaded exosomes are promising cancer treatment vehicles; however, moderate T cell responses in human clinical trials indicate a need to further understand exosome-induced immunity. We previously demonstrated that antigen-loaded exosomes carry whole protein antigens and require B cells for inducing antigen-specific T cells. Therefore, we investigated the relative importance of exosomal major histocompatibility complex (MHC) class I for the induction of antigen-specific T cell responses and tumour protection. We show that ovalbumin-loaded dendritic cell-derived exosomes from MHCI-/- mice induce antigen-specific T cells at the same magnitude as wild type exosomes. Furthermore, exosomes lacking MHC class I, as well as exosomes with both MHC class I and II mismatch, induced tumour infiltrating T cells and increased overall survival to the same extent as syngeneic exosomes in B16 melanoma. In conclusion, T cell responses are independent of exosomal MHC/peptide complexes if whole antigen is present. This establishes the prospective of using impersonalised exosomes, and will greatly increase the feasibility of designing exosome-based vaccines or therapeutic approaches in humans

Patient participation: A qualitative study of immigrant women and their experiences

Patient participation in healthcare is a neglected area of interest in the rather extensive amount of research on immigrant so-called Selma patients in Swedish health care as well as worldwide. The aim is to explore the phenomenon “patient participation” in the context of the Swedish health care from the perspective of immigrants non-fluent in Swedish. A phenomenological lifeworld approach was chosen. Data were collected from patients within a municipal home care setting in Sweden. Eight women agreed to participate. In seven interviews, an interpreter was necessary for the translation of the interview. Five authorized interpreters were used. Data were analysed in accordance to a descriptive phenomenological method for caring research. The analysis led to an essence of the phenomenon with three constituents, “to experience participation,” “to refrain from participation,” and “to be deprived of participation.” Patient participation from the perspective of immigrant women means that patients are involved and active in their own health and caring processes. For these women, it is particularly important to have the opportunity to express themselves. Patient participation presupposes professional caregivers who act in a way that increases the patients' opportunities to take part. A skilled interpreter is often necessary in order to enable the patient participation

Microparticle-mediated transfer of the viral receptors CAR and CD46, and the CFTR channel in a CHO cell model confers new functions to target cells

Cell microparticles (MPs) released in the extracellular milieu can embark plasma membrane and intracellular components which are specific of their cellular origin, and transfer them to target cells. The MP-mediated, cell-to-cell transfer of three human membrane glycoproteins of different degrees of complexity was investigated in the present study, using a CHO cell model system. We first tested the delivery of CAR and CD46, two monospanins which act as adenovirus receptors, to target CHO cells. CHO cells lack CAR and CD46, high affinity receptors for human adenovirus serotype 5 (HAdV5), and serotype 35 (HAdV35), respectively. We found that MPs derived from CHO cells (MP-donor cells) constitutively expressing CAR (MP-CAR) or CD46 (MP-CD46) were able to transfer CAR and CD46 to target CHO cells, and conferred selective permissiveness to HAdV5 and HAdV35. In addition, target CHO cells incubated with MP-CD46 acquired the CD46-associated function in complement regulation. We also explored the MP-mediated delivery of a dodecaspanin membrane glycoprotein, the CFTR to target CHO cells. CFTR functions as a chloride channel in human cells and is implicated in the genetic disease cystic fibrosis. Target CHO cells incubated with MPs produced by CHO cells constitutively expressing GFP-tagged CFTR (MP-GFP-CFTR) were found to gain a new cellular function, the chloride channel activity associated to CFTR. Time-course analysis of the appearance of GFP-CFTR in target cells suggested that MPs could achieve the delivery of CFTR to target cells via two mechanisms: the transfer of mature, membrane-inserted CFTR glycoprotein, and the transfer of CFTR-encoding mRNA. These results confirmed that cell-derived MPs represent a new class of promising therapeutic vehicles for the delivery of bioactive macromolecules, proteins or mRNAs, the latter exerting the desired therapeutic effect in target cells via de novo synthesis of their encoded proteins

FIRE (facilitating implementation of research evidence) : a study protocol

Research evidence underpins best practice, but is not always used in healthcare. The Promoting Action on Research Implementation in Health Services (PARIHS) framework suggests that the nature of evidence, the context in which it is used, and whether those trying to use evidence are helped (or facilitated) affect the use of evidence. Urinary incontinence has a major effect on quality of life of older people, has a high prevalence, and is a key priority within European health and social care policy. Improving continence care has the potential to improve the quality of life for older people and reduce the costs associated with providing incontinence aids

After colonic surgery: The lived experience of participating in a fast-track programme

Postoperative recovery can be accelerated and hospitalization reduced through fast-track programmes. However, documented knowledge is limited and primarily focusing on a medical perspective whereas the patients' perspective lacks documentation. This study describes the lived experience of participating in a fast-track programme after colonic surgery. Sixteen patients were interviewed twice. The interviews were analysed using a descriptive phenomenological approach. Participating in a fast-track programme is characterized by a process where patients experience how the daily regimen works both with them and against them. To succeed in the overall goal of recovering fast according to the evidence-based care plan involves facing dilemmas and mobilizing courage and will to follow the regimen. Support from the professionals is crucial. The participants had a strong desire to comply and regain health; but this role of being a good and cooperative patient had a built-in asymmetric power relationship favouring the professionals' expectations. The complexities of this power relationship were related to both patient factors and contextual factors, e.g. the daily regimen and hospital norms. Although patient participation in care is an accepted ideal, it is demanding and difficult to accomplish. More studies on fast-track programmes are needed, with special attention to patient autonomy and partnership

Long-Term Follow-Up of Transsexual Persons Undergoing Sex Reassignment Surgery: Cohort Study in Sweden

CONTEXT: The treatment for transsexualism is sex reassignment, including hormonal treatment and surgery aimed at making the person's body as congruent with the opposite sex as possible. There is a dearth of long term, follow-up studies after sex reassignment. OBJECTIVE: To estimate mortality, morbidity, and criminal rate after surgical sex reassignment of transsexual persons. DESIGN: A population-based matched cohort study. SETTING: Sweden, 1973-2003. PARTICIPANTS: All 324 sex-reassigned persons (191 male-to-females, 133 female-to-males) in Sweden, 1973-2003. Random population controls (10:1) were matched by birth year and birth sex or reassigned (final) sex, respectively. MAIN OUTCOME MEASURES: Hazard ratios (HR) with 95% confidence intervals (CI) for mortality and psychiatric morbidity were obtained with Cox regression models, which were adjusted for immigrant status and psychiatric morbidity prior to sex reassignment (adjusted HR [aHR]). RESULTS: The overall mortality for sex-reassigned persons was higher during follow-up (aHR 2.8; 95% CI 1.8-4.3) than for controls of the same birth sex, particularly death from suicide (aHR 19.1; 95% CI 5.8-62.9). Sex-reassigned persons also had an increased risk for suicide attempts (aHR 4.9; 95% CI 2.9-8.5) and psychiatric inpatient care (aHR 2.8; 95% CI 2.0-3.9). Comparisons with controls matched on reassigned sex yielded similar results. Female-to-males, but not male-to-females, had a higher risk for criminal convictions than their respective birth sex controls. CONCLUSIONS: Persons with transsexualism, after sex reassignment, have considerably higher risks for mortality, suicidal behaviour, and psychiatric morbidity than the general population. Our findings suggest that sex reassignment, although alleviating gender dysphoria, may not suffice as treatment for transsexualism, and should inspire improved psychiatric and somatic care after sex reassignment for this patient group

Patients' independence of a nurse for the administration of subcutaneous anti-TNF therapy: A phenomenographic study

Rheumatology nursing supports patients to manage their lives and live as independently as possible without pain, stiffness and functional restrictions. When conventional drugs fail to delay the development of the rheumatic disease, the patient may require biological treatment such as self-administered subcutaneous anti-tumour necrosis factor (TNF) therapy. It is therefore important that the patient perspective focuses on the life-changing situation caused by the administration of regular subcutaneous injections. The aim of this study was to describe variations in how patients with rheumatic diseases experience their independence of a nurse for administration of subcutaneous anti-TNF therapy. The study had a descriptive, qualitative design with a phenomenographic approach and was carried out by means of 20 interviews. Four ways of understanding the patients' experience of their subcutaneous anti-TNF therapy and independence of a nurse emerged: the struggling patient; the learning patient; the participating patient; the independent patient. Achieving independence of a nurse for subcutaneous anti-TNF injections can be understood by the patients in different ways. In their strive for independence, patients progress by learning about and participating in drug treatment, after which they experience that the injections make them independent

Hsp20 Functions as a Novel Cardiokine in Promoting Angiogenesis via Activation of VEGFR2

Heat shock proteins (Hsps) are well appreciated as intrinsic protectors of cardiomyocytes against numerous stresses. Recent studies have indicated that Hsp20 (HspB6), a small heat shock protein, was increased in blood from cardiomyopathic hamsters. However, the exact source of the increased circulating Hsp20 and its potential role remain obscure. In this study, we observed that the circulating Hsp20 was increased in a transgenic mouse model with cardiac-specific overexpression of Hsp20, compared with wild-type mice, suggesting its origin from cardiomyocytes. Consistently, culture media harvested from Hsp20-overexpressing cardiomyocytes by Ad.Hsp20 infection contained an increased amount of Hsp20, compared to control media. Furthermore, we identified that Hsp20 was secreted through exosomes, independent of the endoplasmic reticulum-Golgi pathway. To investigate whether extracellular Hsp20 promotes angiogenesis, we treated human umbilical vein endothelial cells (HUVECs) with recombinant human Hsp20 protein, and observed that Hsp20 dose-dependently promoted HUVEC proliferation, migration and tube formation. Moreover, a protein binding assay and immunostaining revealed an interaction between Hsp20 and VEGFR2. Accordingly, stimulatory effects of Hsp20 on HUVECs were blocked by a VEGFR2 neutralizing antibody and CBO-P11 (a VEGFR inhibitor). These in vitro data are consistent with the in vivo findings that capillary density was significantly enhanced in Hsp20-overexpressing hearts, compared to non-transgenic hearts. Collectively, our findings demonstrate that Hsp20 serves as a novel cardiokine in regulating myocardial angiogenesis through activation of the VEGFR signaling cascade

RNA extraction from self-assembling peptide hydrogels to allow qPCR analysis of encapsulated cells

Self-assembling peptide hydrogels offer a novel 3-dimensional platform for many applications in cell culture and tissue engineering but are not compatible with current methods of RNA isolation; owing to interactions between RNA and the biomaterial. This study investigates the use of two techniques based on two different basic extraction principles: solution-based extraction and direct solid-state binding of RNA respectively, to extract RNA from cells encapsulated in four β-sheet forming self-assembling peptide hydrogels with varying net positive charge. RNA-peptide fibril interactions, rather than RNA-peptide molecular complexing, were found to interfere with the extraction process resulting in low yields. A column-based approach relying on RNA-specific binding was shown to be more suited to extracting RNA with higher purity from these peptide hydrogels owing to its reliance on strong specific RNA binding interactions which compete directly with RNA-peptide fibril interactions. In order to reduce the amount of fibrils present and improve RNA yields a broad spectrum enzyme solution—pronase—was used to partially digest the hydrogels before RNA extraction. This pre-treatment was shown to significantly increase the yield of RNA extracted, allowing downstream RT-qPCR to be performed