Reducing recurrent stroke: methodology of the motivational interviewing in stroke (MIST) randomized clinical trial

Recurrent stroke is prevalent in both developed and developing countries, contributing significantly to disability and death. Recurrent stroke rates can be reduced by adequate risk factor management. However, adherence to prescribed medications and lifestyle changes recommended by physicians at discharge after stroke is poor, leading to a large number of preventable recurrent strokes. Using behavior change methods such as Motivational Interviewing early after stroke occurrence has the potential to prevent recurrent stroke

Moving out of the shadows: accomplishing bisexual motherhood

Our qualitative study explored the ways in which bisexual mothers came to identify as such and how they structured their relationships and parenting within hetero-patriarchal society. The experiences of seven self-identified White bisexual women (aged from 28 to 56-years-old) from across England and the Republic of Ireland were investigated through semi-structured interviews. Participants’ children were aged 8 months to 28 years old at the time of their interviews. A thematic narrative analysis highlighted the following issues that participants had encountered in constructing their self-identity: prioritizing children; connecting and disconnecting with others and finessing self-definition; questioning societal relationship expectations. Nevertheless, participants varied considerably in how each of the themes identified were reflected in their lives, in particular depending upon each participant’s interpretation of her local social context. Both motherhood and self-identifying as bisexual gave a sense of meaning and purpose to participants’ life stories, although participants sometimes foregrounded their commitment to their children even at a personal cost to their bisexual identity. Using three different theoretical perspectives from feminist theory, queer theory and life course theory, the narratives analysed revealed ways in which bisexual motherhood not only had been influenced both intentionally and unintentionally by heteronormative expectations but also had directly and indirectly challenged these expectations

Modulation of the surface proteome through multiple ubiquitylation pathways in African Trypanosomes

Recently we identified multiple suramin-sensitivity genes with a genome wide screen in Trypanosoma brucei that includes the invariant surface glycoprotein ISG75, the adaptin-1 (AP-1) complex and two deubiquitylating enzymes (DUBs) orthologous to ScUbp15/HsHAUSP1 and pVHL-interacting DUB1 (type I), designated TbUsp7 and TbVdu1, respectively. Here we have examined the roles of these genes in trafficking of ISG75, which appears key to suramin uptake. We found that, while AP-1 does not influence ISG75 abundance, knockdown of TbUsp7 or TbVdu1 leads to reduced ISG75 abundance. Silencing TbVdu1 also reduced ISG65 abundance. TbVdu1 is a component of an evolutionarily conserved ubiquitylation switch and responsible for rapid receptor modulation, suggesting similar regulation of ISGs in T. brucei. Unexpectedly, TbUsp7 knockdown also blocked endocytosis. To integrate these observations we analysed the impact of TbUsp7 and TbVdu1 knockdown on the global proteome using SILAC. For TbVdu1, ISG65 and ISG75 are the only significantly modulated proteins, but for TbUsp7 a cohort of integral membrane proteins, including the acid phosphatase MBAP1, that is required for endocytosis, and additional ISG-related proteins are down-regulated. Furthermore, we find increased expression of the ESAG6/7 transferrin receptor and ESAG5, likely resulting from decreased endocytic activity. Therefore, multiple ubiquitylation pathways, with a complex interplay with trafficking pathways, control surface proteome expression in trypanosomes

Establishment of a murine epidermal cell line suitable for in vitro and in vivo skin modelling

<p>Abstract</p> <p>Background</p> <p>Skin diseases are a major health problem. Some of the most severe conditions involve genetic disorders, including cancer. Several of these human diseases have been modelled in genetically modified mice, thus becoming a highly valuable preclinical tool for the treatment of these pathologies. However, development of three-dimensional models of skin using keratinocytes from normal and/or genetically modified mice has been hindered by the difficulty to subculture murine epidermal keratinocytes.</p> <p>Methods</p> <p>We have generated a murine epidermal cell line by serially passaging keratinocytes isolated from the back skin of adult mice. We have termed this cell line COCA. Cell culture is done in fully defined media and does not require feeder cells or any other coating methods.</p> <p>Results</p> <p>COCA retained its capacity to differentiate and stratify in response to increased calcium concentration in the cell culture medium for more than 75 passages. These cells, including late passage, can form epidermis-like structures in three-dimensional <it>in vitro </it>models with a well-preserved pattern of proliferation and differentiation. Furthermore, these cells form epidermis in grafting assays <it>in vivo</it>, and do not develop tumorigenic ability.</p> <p>Conclusions</p> <p>We propose that COCA constitutes a good experimental system for <it>in vitro </it>and <it>in vivo </it>skin modelling. Also, cell lines from genetically modified mice of interest in skin biology could be established using the method we have developed. COCA keratinocytes would be a suitable control, within a similar background, when studying the biological implications of these alterations.</p

Cardio-metabolic risk in 5-year-old children prenatally exposed to maternal psychosocial stress: the ABCD study

<p>Abstract</p> <p>Background</p> <p>Recent evidence, both animal and human, suggests that modifiable factors during fetal and infant development predispose for cardiovascular disease in adult life and that they may become possible future targets for prevention. One of these factors is maternal psychosocial stress, but so far, few prospective studies have been able to investigate the longer-term effects of stress in detail, i.e. effects in childhood. Therefore, our general aim is to study whether prenatal maternal psychosocial stress is associated with an adverse cardio-metabolic risk profile in the child at age five.</p> <p>Methods/design</p> <p>Data are available from the Amsterdam Born Children and their Development (ABCD) study, a prospective birth cohort in the Netherlands. Between 2003-2004, 8,266 pregnant women filled out a questionnaire including instruments to determine anxiety (STAI), pregnancy related anxiety (PRAQ), depressive symptoms (CES-D), parenting stress (PDH scale) and work stress (Job Content Questionnaire).</p> <p>Outcome measures in the offspring (age 5-7) are currently collected. These include lipid profile, blood glucose, insulin sensitivity, body composition (body mass index, waist circumference and bioelectrical impedance analysis), autonomic nervous system activity (parasympathetic and sympathetic measures) and blood pressure.</p> <p>Potential mediators are maternal serum cortisol, gestational age and birth weight for gestational age (intrauterine growth restriction). Possible gender differences in programming are also studied.</p> <p>Discussion</p> <p>Main strengths of the proposed study are the longitudinal measurements during three important periods (pregnancy, infancy and childhood), the extensive measurement of maternal psychosocial stress with validated questionnaires and the thorough measurement of the children's cardio-metabolic profile. The availability of several confounding factors will give us the opportunity to quantify the independent contribution of maternal stress during pregnancy to the cardio-metabolic risk profile of her offspring. Moreover, the mediating role of maternal cortisol, intrauterine growth, gestational age and potential gender differences can be explored extensively. If prenatal psychosocial stress is indeed found to be associated with the offspring's cardio-metabolic risk, these results support the statement that primary prevention of cardiovascular disease may start even before birth by reducing maternal stress during pregnancy.</p