Segregation of myoblast fusion and muscle-specific gene expression by distinct ligand-dependent inactivation of GSK-3β

Myogenic differentiation involves myoblast fusion and induction of muscle-specific gene expression, which are both stimulated by pharmacological (LiCl), genetic, or IGF-I-mediated GSK-3β inactivation. To assess whether stimulation of myogenic differentiation is common to ligand-mediated GSK-3β inactivation, myoblast fusion and muscle-specific gene expression were investigated in response to Wnt-3a. Moreover, crosstalk between IGF-I/GSK-3β/NFATc3 and Wnt/GSK-3β/β-catenin signaling was assessed. While both Wnt-3a and LiCl promoted myoblast fusion, muscle-specific gene expression was increased by LiCl, but not by Wnt-3a or β-catenin over-expression. Furthermore, LiCl and IGF-I, but not Wnt-3a, increased NFATc3 transcriptional activity. In contrast, β-catenin-dependent transcriptional activity was increased by Wnt-3a and LiCl, but not IGF-I. These results for the first time reveal a segregated regulation of myoblast fusion and muscle-specific gene expression following stimulation of myogenic differentiation in response to distinct ligand-specific signaling routes of GSK-3β inactivation

Incipient Social Groups: An Analysis via In-Vivo Behavioral Tracking

Social psychology is fundamentally the study of individuals in groups, yet there remain basic unanswered questions about group formation, structure, and change. We argue that the problem is methodological. Until recently, there was no way to track who was interacting with whom with anything approximating valid resolution and scale. In the current study we describe a new method that applies recent advances in image-based tracking to study incipient group formation and evolution with experimental precision and control. In this method, which we term "in vivo behavioral tracking," we track individuals' movements with a high definition video camera mounted atop a large field laboratory. We report results of an initial study that quantifies the composition, structure, and size of the incipient groups. We also apply in-vivo spatial tracking to study participants' tendency to cooperate as a function of their embeddedness in those crowds. We find that participants form groups of seven on average, are more likely to approach others of similar attractiveness and (to a lesser extent) gender, and that participants' gender and attractiveness are both associated with their proximity to the spatial center of groups (such that women and attractive individuals are more likely than men and unattractive individuals to end up in the center of their groups). Furthermore, participants' proximity to others early in the study predicted the effort they exerted in a subsequent cooperative task, suggesting that submergence in a crowd may predict social loafing. We conclude that in vivo behavioral tracking is a uniquely powerful new tool for answering longstanding, fundamental questions about group dynamics

Motives and comprehension in a public goods game with induced emotions

This study analyses the sensitivity of public goods contributions through the lens of psychological motives. We report the results of a public goods experiment in which subjects were induced with the motives of care and anger through autobiographical recall. Subjects' preferences, beliefs, and perceptions under each motive are compared with those of subjects experiencing a neutral autobiographical recall control condition. We find, but only for those subjects with the highest comprehension of the game, that care elicits significantly higher contributions than anger, with the control treatment in between. This positive influence of the care motive on unconditional giving is accounted for partly by preferences for giving and partly by the beliefs concerning greater contributions by others. Anger also affects attention to own and other's payoffs (using mouse tracking) and perceptions of the game's incentive structure (cooperative or competitive)

Mouse models of breast cancer metastasis

Metastatic spread of cancer cells is the main cause of death of breast cancer patients, and elucidation of the molecular mechanisms underlying this process is a major focus in cancer research. The identification of appropriate therapeutic targets and proof-of-concept experimentation involves an increasing number of experimental mouse models, including spontaneous and chemically induced carcinogenesis, tumor transplantation, and transgenic and/or knockout mice. Here we give a progress report on how mouse models have contributed to our understanding of the molecular processes underlying breast cancer metastasis and on how such experimentation can open new avenues to the development of innovative cancer therapy

Supporting shared decision making for older people with multiple health and social care needs: a realist synthesis

Background: Health care systems are increasingly moving towards more integrated approaches. Shared decision making (SDM) is central to these models but may be complicated by the need to negotiate and communicate decisions between multiple providers, as well as patients and their family carers; particularly for older people with complex needs. The aim of this review was to provide a context relevant understanding of how interventions to facilitate SDM might work for older people with multiple health and care needs, and how they might be applied in integrated care models. Methods: Iterative, stakeholder driven, realist synthesis following RAMESES publication standards. It involved: 1) scoping literature and stakeholder interviews (n-13) to develop initial programme theory/ies, 2) systematic searches for evidence to test and develop the theories, and 3) validation of programme theory/ies with stakeholders (n=11). We searched PubMed, The Cochrane Library, Scopus, Google, Google Scholar, and undertook lateral searches. All types of evidence were included. Results: We included 88 papers; 29 focused on older people or people with complex needs. We identified four context-mechanism-outcome configurations that together provide an account of what needs to be in place for SDM to work for older people with complex needs. This includes: understanding and assessing patient and carer values and capacity to access and use care, organising systems to support and prioritise SDM, supporting and preparing patients and family carers to engage in SDM and a person-centred culture of which SDM is a part. Programmes likely to be successful in promoting SDM are those that allow older people to feel that they are respected and understood, and that engender confidence to engage in SDM. Conclusions: To embed SDM in practice requires a radical shift from a biomedical focus to a more person-centred ethos. Service providers will need support to change their professional behaviour and to better organise and deliver services. Face to face interactions, permission and space to discuss options, and continuity of patient-professional relationships are key in supporting older people with complex needs to engage in SDM. Future research needs to focus on inter-professional approaches to SDM and how families and carers are involved

Healthcare provider relational quality is associated with better self-management and less treatment burden in people with multiple chronic conditions

David T Eton,1,2 Jennifer L Ridgeway,1,2 Mark Linzer,3 Deborah H Boehm,4 Elizabeth A Rogers,5 Kathleen J Yost,1,2 Lila J Finney Rutten,1,2 Jennifer L St Sauver,1,2 Sara Poplau,4 Roger T Anderson6 1Department of Health Sciences Research, 2Robert D and Patricia E Kern Center for the Science of Health Care Delivery, Mayo Clinic, Rochester, MN, 3Division of General Internal Medicine, Hennepin County Medical Center, 4Minneapolis Medical Research Foundation, 5Division of General Internal Medicine, University of Minnesota Medical School, Minneapolis, MN, 6Department of Public Health Sciences, University of Virginia School of Medicine, Charlottesville, VA, USA Purpose: Having multiple chronic conditions (MCCs) can lead to appreciable treatment and self-management burden. Healthcare provider relational quality (HPRQ) – the communicative and interpersonal skill of the provider – may mitigate treatment burden and promote self-management. The objectives of this study were to 1) identify the associations between HPRQ, treatment burden, and psychosocial outcomes in adults with MCCs, and 2) determine if certain indicators of HPRQ are more strongly associated than others with these outcomes.Patients and methods: This is a cross-sectional survey study of 332 people with MCCs. Patients completed a 7-item measure of HPRQ and measures of treatment and self-management burden, chronic condition distress, self-efficacy, provider satisfaction, medication adherence, and physical and mental health. Associations between HPRQ, treatment burden, and psychosocial outcomes were determined using correlational analyses and independent samples t-tests, which were repeated in item-level analyses to explore which indicators of HPRQ were most strongly associated with the outcomes.Results: Most respondents (69%) were diagnosed with ≥3 chronic conditions. Better HPRQ was found to be associated with less treatment and self-management burden and better psychosocial outcomes (P<0.001), even after controlling for physical and mental health. Those reporting 100% adherence to prescribed medications had higher HPRQ scores than those reporting less than perfect adherence (P<0.001). HPRQ items showing the strongest associations with outcomes were “my healthcare provider spends enough time with me”, “my healthcare provider listens carefully to me”, and “I have trust in my healthcare provider”.Conclusion: Good communication and interpersonal skills of healthcare providers may lessen feelings of treatment burden and empower patients to feel confident in their self-management. Patient trust in the provider is an important element of HPRQ. Educating healthcare providers about the importance of interpersonal and relational skills could lead to more patient-centered care. Keywords: patient–provider relationship, multi-morbidity, adherence, patient-centered care, trust&nbsp

Building a measurement framework of burden of treatment in complex patients with chronic conditions: a qualitative study

David T Eton,1 Djenane Ramalho de Oliveira,2,3 Jason S Egginton,1 Jennifer L Ridgeway,1 Laura Odell,4 Carl R May,5 Victor M Montori1,61Division of Health Care Policy and Research, Department of Health Sciences Research, Mayo Clinic, Rochester, MN, USA; 2College of Pharmacy, Universidade Federal de Minas Gerais, Belo Horizonte, Brazil; 3Medication Therapy Management Program, Fairview Pharmacy Services LLC, Minneapolis, MN, USA; 4Pharmacy Services, Mayo Clinic, Rochester, MN, USA; 5Faculty of Health Sciences, University of Southampton, Southampton, UK; 6Knowledge and Evaluation Research Unit, Mayo Clinic, Rochester, MN, USABackground: Burden of treatment refers to the workload of health care as well as its impact on patient functioning and well-being. We set out to build a conceptual framework of issues descriptive of burden of treatment from the perspective of the complex patient, as a first step in the development of a new patient-reported measure.Methods: We conducted semistructured interviews with patients seeking medication therapy management services at a large, academic medical center. All patients had a complex regimen of self-care (including polypharmacy), and were coping with one or more chronic health conditions. We used framework analysis to identify and code themes and subthemes. A conceptual framework of burden of treatment was outlined from emergent themes and subthemes.Results: Thirty-two patients (20 female, 12 male, age 26–85 years) were interviewed. Three broad themes of burden of treatment emerged including: the work patients must do to care for their health; problem-focused strategies and tools to facilitate the work of self-care; and factors that exacerbate the burden felt. The latter theme encompasses six subthemes including challenges with taking medication, emotional problems with others, role and activity limitations, financial challenges, confusion about medical information, and health care delivery obstacles.Conclusion: We identified several key domains and issues of burden of treatment amenable to future measurement and organized them into a conceptual framework. Further development work on this conceptual framework will inform the derivation of a patient-reported measure of burden of treatment.Keywords: conceptual framework, patient-centered, medication therapy management, adherence, questionnaire, minimally disruptive medicin