Symptom changes in multiple sclerosis following psychological interventions: a systematic review

Background: Multiple Sclerosis is a disease of the central nervous system involving a variety of debilitating physical, sensory, cognitive and emotional symptoms. This literature review evaluated the impact of psychological interventions on the physiological symptoms associated with the illness. Methods: A systematic literature search was conducted using Medline, PsycINFO, Scopus, and the Cochrane Library databases, as well as reference lists. Relevant studies were selected and assessed according to a preset protocol. Results: The search produced 220 articles, with 22 meeting inclusion criteria for the review. A total of 5,705 subjects with Multiple Sclerosis were analyzed. Results from the included studies indicate a general improvement in both psychological and physiological outcomes following psychological treatment. The most highly influenced physical symptoms include fatigue, sleep disturbances, pain, and physical vitality. Conclusions: Findings from the review suggest a positive relationship between psychological interventions and physiological Multiple Sclerosis symptoms. Implications for future research are discussed

Snail promotes the cell-autonomous generation of Flk1 + endothelial cells through the repression of the microRNA-200 family

Expression of the transcription factor Snail is required for normal vasculogenesis in the developing mouse embryo. In addition, tumors expressing Snail have been associated with a more malignant phenotype, with both increased invasive properties and angiogenesis. Although the relationship between Snail and vasculogenesis has been noted, no mechanistic analysis has been elucidated. Here, we show that in addition to inducing an epithelial mesenchymal transition, Snail promotes the cell-autonomous induction of Flk1(+) endothelial cells in an early subset of differentiating mouse embryonic stem (ES) cells. Cells that become Flk1+ in response to Snail have a transcriptional profile specific to Gata6+primitive endoderm, but not the early Nanog+epiblast. We further show that Snail's ability to promote Flk1(+) endothelium depends on fibroblast growth factor signaling as well as the repression of the microRNA-200 (miR-200) family, which directly targets the 3′ UTRs of Flk1 and Ets1. Together, our results show that Snail is capable of inducing Flk1+ lineage commitment in a subset of differentiating ES cells through the down-regulation of the miR-200 family. We hypothesize that this mechanism of Snail-induced vasculogenesis may be conserved in both the early developing embryo and malignant cancers

Forecasting the onset and course of mental illness with Twitter data

We developed computational models to predict the emergence of depression and Post-Traumatic Stress Disorder in Twitter users. Twitter data and details of depression history were collected from 204 individuals (105 depressed, 99 healthy). We extracted predictive features measuring affect, linguistic style, and context from participant tweets (N = 279,951) and built models using these features with supervised learning algorithms. Resulting models successfully discriminated between depressed and healthy content, and compared favorably to general practitioners\u27 average success rates in diagnosing depression, albeit in a separate population. Results held even when the analysis was restricted to content posted before first depression diagnosis. State-space temporal analysis suggests that onset of depression may be detectable from Twitter data several months prior to diagnosis. Predictive results were replicated with a separate sample of individuals diagnosed with PTSD (Nusers = 174, Ntweets = 243,775). A state-space time series model revealed indicators of PTSD almost immediately post-trauma, often many months prior to clinical diagnosis. These methods suggest a data-driven, predictive approach for early screening and detection of mental illness

Pleasure and meaningful discourse: an overview of research issues

The concept of pleasure has emerged as a multi-faceted social and cultural phenomenon in studies of media audiences since the 1980s. In these studies different forms of pleasure have been identified as explaining audience activity and commitment. In the diverse studies pleasure has emerged as a multi-faceted social and cultural concept that needs to be contextualized carefully. Genre and genre variations, class, gender, (sub-)cultural identity and generation all seem to be instrumental in determining the kind and variety of pleasures experienced in the act of viewing. This body of research has undoubtedly contributed to a better understanding of the complexity of audience activities, but it is exactly the diversity of the concept that is puzzling and poses a challenge to its further use. If pleasure is maintained as a key concept in audience analysis that holds much explanatory power, it needs a stronger theoretical foundation. The article maps the ways in which the concept of pleasure has been used by cultural theorists, who have paved the way for its application in reception analysis, and it goes on to explore the ways in which the concept has been used in empirical studies. Central to our discussion is the division between the ‘public knowledge’ and the ‘popular culture’ projects in reception analysis which, we argue, have major implications for the way in which pleasure has come to be understood as divorced from politics, power and ideology. Finally, we suggest ways of bridging the gap between these two projects in an effort to link pleasure to the concepts of hegemony and ideology

Bcl-xL Deamidation Is a Critical Switch in the Regulation of the Response to DNA Damage

AbstractThe therapeutic value of DNA-damaging antineoplastic agents is dependent upon their ability to induce tumor cell apoptosis while sparing most normal tissues. Here, we show that a component of the apoptotic response to these agents in several different types of tumor cells is the deamidation of two asparagines in the unstructured loop of Bcl-xL, and we demonstrate that deamidation of these asparagines imports susceptibility to apoptosis by disrupting the ability of Bcl-xL to block the proapoptotic activity of BH3 domain-only proteins. Conversely, Bcl-xL deamidation is actively suppressed in fibroblasts, and suppression of deamidation is an essential component of their resistance to DNA damage-induced apoptosis. Our results suggest that the regulation of Bcl-xL deamidation has a critical role in the tumor-specific activity of DNA-damaging antineoplastic agents

Imagining transitions in old age through the visual matrix method: thinking about what is hard to bear

Dominant discourses of ageing are often confined to what is less painful to think about and therefore idealise or denigrate ageing and later life. We present findings from an exploratory psychosocial study, in a Nordic context into three later-life transitions: from working life to retirement, from mental health to dementia, and from life to death. Because, for some, these topics are hard to bear, and therefore defended against and routinely excluded from everyday awareness, we used a method led by imagery and affect - the Visual Matrix - to elicit participants’ free associative personal and collective imagination. Through analysis of data extracts, on the three transitions, we illustrate oscillations between defending against the challenges of ageing and realism in facing the anxieties it can provoke. A recurring theme includes the finality of individual life and the inter-generational continuity, which together link life and death, hope and despair, separation and connectedness

Switching Multiple Sclerosis Patients with Breakthrough Disease to Second-Line Therapy

BACKGROUND: Multiple sclerosis (MS) patients with breakthrough disease on immunomodulatory drugs are frequently offered to switch to natalizumab or immunosuppressants. The effect of natalizumab monotherapy in patients with breakthrough disease is unknown. METHODS: This is an open-label retrospective cohort study of 993 patients seen at least four times at the University of California San Francisco MS Center, 95 had breakthrough disease on first-line therapy (60 patients switched to natalizumab, 22 to immunosuppressants and 13 declined the switch [non-switchers]). We used Poisson regression adjusted for potential confounders to compare the relapse rate within and across groups before and after the switch. RESULTS: In the within-group analyses, the relapse rate decreased by 70% (95% CI 50,82%; p<0.001) in switchers to natalizumab and by 77% (95% CI 59,87%; p<0.001) in switchers to immunosuppressants; relapse rate in non-switchers did not decrease (6%, p =  0.87). Relative to the reduction among non-switchers, the relapse rate was reduced by 68% among natalizumab switchers (95% CI 19,87%; p = 0.017) and by 76% among the immunosuppressant switchers (95% CI 36,91%; p = 0.004). CONCLUSIONS: Switching to natalizumab or immunosuppressants in patients with breakthrough disease is effective in reducing clinical activity of relapsing MS. The magnitude of the effect and the risk-benefit ratio should be evaluated in randomized clinical trials and prospective cohort studies