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The trouble with cowboys
Eight years ago, Tyler Donnelly left Wishing River, Montana, after a terrible fight with his father and swore he'd never return. But when his father has a stroke, guilt and duty drive him home, and nothing is as he remembers---from the run-down ranch to Lainey Sullivan, who is all grown up now. And darn if he can't seem to stay away. Lainey's late grandma left her two things: the family diner and a deep-seated mistrust of cowboys. So when Tyler quietly rides back into town looking better than hot apple pie, she knows she's in trouble. But she owes his dad everything, and she's determined to show Ty what it means to be part of a small town...and part of a family. Lainey's courage pushes Ty to want to make Wishing River into a home again--together. But one of them is harboring a secret that could change everything.
Book
Therapeutic Application of Mesenchymal Stem Cells Derived Extracellular Vesicles for Immunomodulation
The immunosuppressive potential of mesenchymal stem cells has been extensively investigated in many studies
and
. In recent years, a variety preclinical and clinical studies have demonstrated that mesenchymal stem cells ameliorate immune-mediated disorders, including autoimmune diseases. However, to date mesenchymal stem cells have not become a widely used therapeutic agent due to safety challenges, high cost and difficulties in providing long term production. A key mechanism underpinning the immunomodulatory effect of MSCs is the production of paracrine factors including growth factors, cytokines, chemokines, and extracellular vesicles (EVs). MSCs derived EVs have become an attractive therapeutic agent for immunomodulation and treatment of immune-mediated disorders. In addition to many preclinical studies of MSCs derived EVs, their beneficial effects have been observed in patients with both acute graft-vs.-host disease and chronic kidney disease. In this review, we discuss the current findings in the field of MSCs derived EVs-based therapies in immune-mediated disorders and approaches to scale EV production for clinical use.
Journal Article
Effectiveness of community adolescent treatment supporters (CATS) interventions in improving linkage and retention in care, adherence to ART and psychosocial well-being: a randomised trial among adolescents living with HIV in rural Zimbabwe
Background
Engagement with community adolescent treatment supporters (CATS) improves adherence, psychosocial well-being, linkage and retention in care among adolescents living with HIV. However, there is an urgent need for empirical evidence of the effectiveness of this approach, in order to inform further programmatic development, national and international policy, guidelines and service delivery for adolescents living with HIV. This study set out to determine the effectiveness of CATS services on improving linkage to services and retention in care, adherence and psychosocial well-being among adolescents living with HIV in Zimbabwe.
Methods
A randomised trial was conducted in Gokwe South district, Zimbabwe over a period of 12 months. Ninety-four HIV-positive adolescents, 10–15 years old, on antiretroviral therapy were recruited to the study. 47 participants received standard of care from the Ministry of Health and Child Care and 47 received the same standard of care plus CATS services. Data collection involved a questionnaire which was administered at baseline then repeated at three, six, nine and twelve months for all participants. Survey questions on confidence, self-esteem and self-worth had a three-point Likert scale. Stigma, quality of life and the linkages to services and retention questions had a five-point Likert scale.
Results
Survey questionnaires were completed with response rates of 40 out of 47 (85%) for the intervention arm, and 28 out of 47 (60%) for the control arm, at end-line. The intervention group were 3.9 times more likely to adhere to treatment compared to the control group. Linkage to services and retention in care within the intervention group increased compared with a decrease in the control arm. The intervention group reported a statistically significant increase in confidence, self-esteem, self-worth (
p
< 0.001) and quality of life compared (
p
= 0.028) with a decrease in the control arm.
Conclusions
This study found that adolescents receiving the CATS service had improved linkage to services and retention in care, improved adherence and improved psychosocial well-being compared to adolescents who did not have access to such services.
Trial registration
PACTR201711002755428
. Registered 11 November 2017. Retrospectively registered.
Journal Article
Ancient Africa : archaeology unlocks the secrets of Africa's past
Discusses what archaeologists today know about prehistoric and ancient Africa, and how they have discovered it.
Book
Extracellular vesicles and chronic obstructive pulmonary disease (COPD): a systematic review
Background
Chronic Obstructive Pulmonary Disease (COPD) is a common inflammatory disease of the airways characterized by irreversible airflow limitation, ranking the third highest cause of death worldwide. Extracellular vesicles (EVs) are important intercellular communication mediators released by cells into their extracellular environment with the capacity to transfer biological signals. EVs involved in COPD hold great potential to understand disease pathogenesis and identify important biomarkers. This systematic review aims to examine all available research on EVs in the pathogenesis and diagnosis of COPD to identify existing knowledge and support further research within the field.
Methods
Publications were searched using PubMed and EMBASE with the search terms (Exosomes or extracellular vesicles or microvesicles or microparticles or ectosomes) AND (chronic obstructive pulmonary disease or COPD or emphysema or bronchitis).
Results
Initial search yielded 512 papers of which 142 were manually selected for review and 43 were eligible for analyses. The studies were divided into groups according to the role of EVs in pathogenesis, EV origin and cargo, their role in COPD exacerbations and their diagnostic utility. EVs were found to be involved in the mechanism of pathogenesis of COPD, derived from various cell types, as well as containing modified levels of miRNAs. EVs also varied according to the pathophysiological status of disease, therefore presenting a possible method for COPD diagnosis and progress monitoring.
Conclusion
The current findings show the limited but good quality research looking at the role of EVs in COPD, demonstrating the need for more studies to better define and provide further insight into the functional characteristics of EV in COPD pathogenesis.
Journal Article
The art of the illustrated book
Throughout history, images have been used to reflect the meaning of words and to enhance our understanding of texts. With the invention of mechanized printing in Germany in the 15th century, illustrated books were no longer the preserve of the elite and became a source of knowledge, instruction and pleasure for a wider audience. This title follows the story of the illustrated book, from the earliest printed books to the present day, told through the collections of the V&A's National Art Library.
Book
Therapeutic Prospects of Extracellular Vesicles in Cancer Treatment
Extracellular vesicles (EVs) are released by all cells within the tumor microenvironment, such as endothelial cells, tumor-associated fibroblasts, pericytes, and immune system cells. The EVs carry the cargo of parental cells formed of proteins and nucleic acids, which can convey cell-to-cell communication influencing the maintenance and spread of the malignant neoplasm, for example, promoting angiogenesis, tumor cell invasion, and immune escape. However, EVs can also suppress tumor progression, either by the direct influence of the protein and nucleic acid cargo of the EVs or
antigen presentation to immune cells as tumor-derived EVs carry on their surface some of the same antigens as the donor cells. Moreover, dendritic cell-derived EVs carry major histocompatibility complex class I and class II/peptide complexes and are able to prime other immune system cell types and activate an antitumor immune response. Given the relative longevity of vesicles within the circulation and their ability to cross blood-brain barriers, modification of these unique organelles offers the potential to create new biological-tools for cancer therapy. This review examines how modification of the EV cargo has the potential to target specific tumor mechanisms responsible for tumor formation and progression to develop new therapeutic strategies and to increase the efficacy of antitumor therapies.
Journal Article
Role of Mesenchymal Stem Cell-Derived Extracellular Vesicles in Epithelial–Mesenchymal Transition
Epithelial–mesenchymal transition (EMT) is a process that takes place during embryonic development, wound healing, and under some pathological processes, including fibrosis and tumor progression. The molecular changes occurring within epithelial cells during transformation to a mesenchymal phenotype have been well studied. However, to date, the mechanism of EMT induction remains to be fully elucidated. Recent findings in the field of intercellular communication have shed new light on this process and indicate the need for further studies into this important mechanism. New evidence supports the hypothesis that intercellular communication between mesenchymal stroma/stem cells (MSCs) and resident epithelial cells plays an important role in EMT induction. Besides direct interactions between cells, indirect paracrine interactions by soluble factors and extracellular vesicles also occur. Extracellular vesicles (EVs) are important mediators of intercellular communication, through the transfer of biologically active molecules, genetic material (mRNA, microRNA, siRNA, DNA), and EMT inducers to the target cells, which are capable of reprogramming recipient cells. In this review, we discuss the role of intercellular communication by EVs to induce EMT and the acquisition of stemness properties by normal and tumor epithelial cells.
Journal Article