Enabling a robust scalable manufacturing process for therapeutic exosomes through oncogenic immortalization of human ESC-derived MSCs

Background  

Exosomes or secreted bi-lipid vesicles from human ESC-derived mesenchymal stem cells (hESC-MSCs) have been shown to reduce myocardial ischemia/reperfusion injury in animal models. However, as hESC-MSCs are not infinitely expansible, large scale production of these exosomes would require replenishment of hESC-MSC through derivation from hESCs and incur recurring costs for testing and validation of each new batch. Our aim was therefore to investigate if MYC immortalization of hESC-MSC would circumvent this constraint without compromising the production of therapeutically efficacious exosomes.     

Xenotropic Murine Leukemia Virus-Related Virus (XMRV) in Patients with Systemic Lupus Erythematosus

Objectives  

Xenotropic murine leukemia virus-related virus (XMRV)-specific proviral DNA has been recently detected in peripheral blood mononuclear cells of patients with chronic fatigue syndrome. Since chronic fatigue is commonly reported in patients with systemic lupus erythematosus (SLE) we aimed at testing the presence of this virus in these patients.     

Living with hope: developing a psychosocial supportive program for rural women caregivers of persons with advanced cancer

Background  

Hope is defined by caregivers as the inner strength to achieve future good and to continue care giving. Pilot test findings of a Living with Hope Program (LWHP) suggested it is an acceptable and feasible intervention for use by family caregivers. Although it shows promise in potentially increasing hope and quality of life, further testing and development is needed. Questions remain as to: a) what are the mechanisms through which the LWHP affects outcomes and b) how long it is effective? The overall purpose of this time series mixed method study is the further development and testing of the LWHP by :

Design and methods for testing a simple dietary message to improve weight loss and dietary quality

Background  

It can be challenging for patients and clinicians to properly interpret a change in the clinical condition after a treatment has been given. It is not known to which extent spontaneous improvement, effect of placebo and effect of active interventions contribute to the observed change from baseline, and we aimed at quantifying these contributions.     

Variable selection under multiple imputation using the bootstrap in a prognostic study

Background  

Missing data is a challenging problem in many prognostic studies. Multiple imputation (MI) accounts for imputation uncertainty that allows for adequate statistical testing. We developed and tested a methodology combining MI with bootstrapping techniques for studying prognostic variable selection.     

Electronic voting to encourage interactive lectures: a randomised trial

Background  

Electronic Voting Systems have been used for education in a variety of disciplines. Outcomes from these studies have been mixed. Because results from these studies have been mixed, we examined whether an EVS system could enhance a lecture's effect on educational outcomes.     

Primary cultured fibroblasts derived from patients with chronic wounds: a methodology to produce human cell lines and test putative growth factor therapy such as GMCSF

Background  

Multiple physiologic impairments are responsible for chronic wounds. A cell line grown which retains its phenotype from patient wounds would provide means of testing new therapies. Clinical information on patients from whom cells were grown can provide insights into mechanisms of specific disease such as diabetes or biological processes such as aging.     

Procrastination and health: A longitudinal test of the roles of stress and health behaviours

Objectives

Procrastination is a common form of self-regulation failure that a growing evidence base suggests can confer risk for poor health outcomes, especially when it becomes habitual. However, the proposed linkages of chronic procrastination to health outcomes have not been tested over time or accounted for the contributions of higher-order personality factors linked to both chronic procrastination and health-related outcomes. We addressed these issues by examining the role of chronic procrastination in health outcomes over time in which the hypothesized links of procrastination to health problems operate via stress and health behaviours.

Design

Three-wave longitudinal study with 1-month intervals.

Methods

Participants (N = 379) completed measures of trait procrastination at Time 1, and measures of health behaviours, stress and health problems at each time point, in a lab setting.

Results

Procrastination and the health variables were inter-related in the expected directions across the three assessments. Chronic procrastination was positively associated with stress and negatively with health behaviours at each time point. Path analysis testing a cross-lagged longitudinal mediation model found an indirect relationship operating between procrastination and health problems via stress, after accounting for the contributions of conscientiousness and neuroticism.

Conclusions

This research extends previous work by demonstrating that the links between chronic procrastination and poor health are accounted for mainly by higher stress, after accounting for other key traits, and that these associations are robust over time. The findings are discussed in terms of the importance of addressing habitual self-regulation failure for improving health.     

Methods for the synthesis of qualitative research: a critical review

Background  

In recent years, a growing number of methods for synthesising qualitative research have emerged, particularly in relation to health-related research. There is a need for both researchers and commissioners to be able to distinguish between these methods and to select which method is the most appropriate to their situation.     

Validation of human papillomavirus genotyping by signature DNA sequence analysis

Background  

Screening with combined cytologic and HPV testing has led to the highest number of excessive colposcopic referrals due to high false positive rates of the current HPV testing in the USA. How best to capitalize on the enhanced sensitivity of HPV DNA testing while minimizing false-positive results from its lower specificity is an important task for the clinical pathologists.     

Best practice guidelines for the molecular genetic diagnosis of Type 1 (HFE-related) hereditary haemochromatosis

Background  

Hereditary haemochromatosis (HH) is a recessively-inherited disorder of iron over-absorption prevalent in Caucasian populations. Affected individuals for Type 1 HH are usually either homozygous for a cysteine to tyrosine amino acid substitution at position 282 (C282Y) of the HFE gene, or compound heterozygotes for C282Y and for a histidine to aspartic acid change at position 63 (H63D). Molecular genetic testing for these two mutations has become widespread in recent years. With diverse testing methods and reporting practices in use, there was a clear need for agreed guidelines for haemochromatosis genetic testing. The UK Clinical Molecular Genetics Society has elaborated a consensus process for the development of disease-specific best practice guidelines for genetic testing.     

Segregation analysis identifies specific alpha-defensin (DEFA1A3) SNP–CNV haplotypes in predisposition to IgA nephropathy

Background

Immunoglobulin A (IgA) nephropathy is a disorder of the immune system affecting kidney function, and genome-wide association studies (GWAS) have defined numerous loci with associated variation, all implicating components of innate or adaptive immunity. Among these, single nucleotide polymorphisms (SNPs) in a region including the multiallelic copy number variation (CNV) of DEFA1A3 are associated with IgA nephropathy in both European and Asian populations. At present, the precise factors underlying the observed associations at DEFA1A3 have not been defined, although the key alleles differ between Asian and European populations, and multiple independent factors may be involved even within a single population.

Methods

In this study, we measured DEFA1A3 copy number in UK family trios with an offspring affected by IgA nephropathy, used the population distributions of joint SNP–CNV haplotypes to infer the likely segregation in trios, and applied transmission disequilibrium tests (TDT) to examine joint SNP–CNV haplotypes for over- or undertransmission into affected offspring from heterozygous parents.

Results and Conclusions

We observed overtransmission of 3-copy class 2 haplotypes (raw p = 0.029) and some evidence for under-transmission of 3-copy class 1 haplotypes (raw p = 0.051), although these apparent effects were not statistically significant after correction for testing of multiple haplotypes.     

Association and interaction of <Emphasis Type="Italic">PPAR</Emphasis>-complex gene variants with latent traits of left ventricular diastolic function

Background  

Abnormalities in myocardial metabolism and/or regulatory genes have been implicated in left ventricular systolic dysfunction. However, the extent to which these modulate left ventricular diastolic function (LVDF) is uncertain.     

FTY720 mediates activation suppression and G<Subscript>0</Subscript>/G<Subscript>1</Subscript> cell cycle arrest in a concanavalin A-induced mouse lymphocyte pan-activation model

Objective  

FTY720 is a potent drug for multiple sclerosis treatment. To biologically address its possible applications to more generalized diseases with aberrant inflammation, we are testing whether FTY720 can function as a lymphocyte cell cycle blocker and activation suppressor via a concanavalin A (ConA)-mediated mouse lymphocyte pan-activation model.     

Disease surveillance using a hidden Markov model

Background  

Routine surveillance of disease notification data can enable the early detection of localised disease outbreaks. Although hidden Markov models (HMMs) have been recognised as an appropriate method to model disease surveillance data, they have been rarely applied in public health practice. We aimed to develop and evaluate a simple flexible HMM for disease surveillance which is suitable for use with sparse small area count data and requires little baseline data.     

Evaluating the effectiveness of a radiation safety training intervention for oncology nurses: a pretest – intervention – posttest study

Background  

Radiation, for either diagnosis or treatment, is used extensively in the field of oncology. An understanding of oncology radiation safety principles and how to apply them in practice is critical for nursing practice. Misconceptions about radiation are common, resulting in undue fears and concerns that may negatively impact patient care. Effectively educating nurses to help overcome these misconceptions is a challenge. Historically, radiation safety training programs for oncology nurses have been compliance-based and behavioral in philosophy.     

A knowledge-based taxonomy of critical factors for adopting electronic health record systems by physicians: a systematic literature review

Background  

The health care sector is an area of social and economic interest in several countries; therefore, there have been lots of efforts in the use of electronic health records. Nevertheless, there is evidence suggesting that these systems have not been adopted as it was expected, and although there are some proposals to support their adoption, the proposed support is not by means of information and communication technology which can provide automatic tools of support. The aim of this study is to identify the critical adoption factors for electronic health records by physicians and to use them as a guide to support their adoption process automatically.     

Exploring consumer and pharmacist views on the professional role of the pharmacist with respect to natural health products: a study of focus groups

Background  

Natural health products (NHPs) such as herbs, vitamins and homeopathic medicines, are currently available for sale in most Canadian pharmacies. However, most pharmacists report that they have limited knowledge about these products which have been regulated in Canada as a specific sub-category of drugs. In this paper, consumers' and practicing pharmacists' perceptions of pharmacists' professional responsibilities with respect to NHPs are examined.     

The attitudes of brain cancer patients and their caregivers towards death and dying: a qualitative study

Background  

Much money and energy has been spent on the study of the molecular biology of malignant brain tumours. However, little attention has been paid to the wishes of patients afflicted with these incurable tumours, and how this might influence treatment considerations.