Sub-Typing of Rheumatic Diseases Based on a Systems Diagnosis Questionnaire

The future of personalized medicine depends on advanced diagnostic tools to characterize responders and non-responders to treatment. Systems diagnosis is a new approach which aims to capture a large amount of symptom information from patients to characterize relevant sub-groups.49 patients with a rheumatic disease were characterized using a systems diagnosis questionnaire containing 106 questions based on Chinese and Western medicine symptoms. Categorical principal component analysis (CATPCA) was used to discover differences in symptom patterns between the patients. Two Chinese medicine experts where subsequently asked to rank the Cold and Heat status of all the patients based on the questionnaires. These rankings were used to study the Cold and Heat symptoms used by these practitioners.The CATPCA analysis results in three dimensions. The first dimension is a general factor (40.2% explained variance). In the second dimension (12.5% explained variance) 'anxious', 'worrying', 'uneasy feeling' and 'distressed' were interpreted as the Internal disease stage, and 'aggravate in wind', 'fear of wind' and 'aversion to cold' as the External disease stage. In the third dimension (10.4% explained variance) 'panting s', 'superficial breathing', 'shortness of breath s', 'shortness of breath f' and 'aversion to cold' were interpreted as Cold and 'restless', 'nervous', 'warm feeling', 'dry mouth s' and 'thirst' as Heat related. 'Aversion to cold', 'fear of wind' and 'pain aggravates with cold' are most related to the experts Cold rankings and 'aversion to heat', 'fullness of chest' and 'dry mouth' to the Heat rankings.This study shows that the presented systems diagnosis questionnaire is able to identify groups of symptoms that are relevant for sub-typing patients with a rheumatic disease

Sparse System Identification of Leptin Dynamics in Women With Obesity

The prevalence of obesity is increasing around the world at an alarming rate. The interplay of the hormone leptin with the hypothalamus-pituitary-adrenal axis plays an important role in regulating energy balance, thereby contributing to obesity. This study presents a mathematical model, which describes hormonal behavior leading to an energy abnormal equilibrium that contributes to obesity. To this end, we analyze the behavior of two neuroendocrine hormones, leptin and cortisol, in a cohort of women with obesity, with simplified minimal state-space modeling. Using a system theoretic approach, coordinate descent method, and sparse recovery, we deconvolved the serum leptin-cortisol levels. Accordingly, we estimate the secretion patterns, timings, amplitudes, number of underlying pulses, infusion, and clearance rates of hormones in eighteen premenopausal women with obesity. Our results show that minimal state-space model was able to successfully capture the leptin and cortisol sparse dynamics with the multiple correlation coefficients greater than 0.83 and 0.87, respectively. Furthermore, the Granger causality test demonstrated a negative prospective predictive relationship between leptin and cortisol, 14 of 18 women. These results indicate that increases in cortisol are prospectively associated with reductions in leptin and vice versa, suggesting a bidirectional negative inhibitory relationship. As dysregulation of leptin may result in an abnormality in satiety and thereby associated to obesity, the investigation of leptin-cortisol sparse dynamics may offer a better diagnostic methodology to improve better treatments plans for individuals with obesity

Extensive Nuclear Reprogramming Underlies Lineage Conversion into Functional Trophoblast Stem-like Cells

SummaryInduced pluripotent stem cells (iPSCs) undergo extensive nuclear reprogramming and are generally indistinguishable from embryonic stem cells (ESCs) in their functional capacity and transcriptome and DNA methylation profiles. However, direct conversion of cells from one lineage to another often yields incompletely reprogrammed, functionally compromised cells, raising the question of whether pluripotency is required to achieve a high degree of nuclear reprogramming. Here, we show that transient expression of Gata3, Eomes, and Tfap2c in mouse fibroblasts induces stable, transgene-independent trophoblast stem-like cells (iTSCs). iTSCs possess transcriptional profiles highly similar to blastocyst-derived TSCs, with comparable methylation and H3K27ac patterns and genome-wide H2A.X deposition. iTSCs generate trophoectodermal lineages upon differentiation, form hemorrhagic lesions, and contribute to developing placentas in chimera assays, indicating a high degree of nuclear reprogramming, with no evidence of passage through a transient pluripotent state. Together, these data demonstrate that extensive nuclear reprogramming can be achieved independently of pluripotency

Digital technologies to generate health awareness

Background: It is well known that most chronic diseases are the result of an unhealthy life-style. Nevertheless, it appears to be very difficult to motivate people to adopt more healthy habits. Even after receiving a diagnosis of a chronic disease, these habits seem to be too strong to overcome by most people. This mechanism of strong, stable patterns of behavior can be very well described and explored by using complexity science. This field has come up with concepts and tools to study the dynamical behavior of such patterns. An important example is the critical transition, and the methods to predict the occurrence of such critical transitions. Even more important will be developing methods to generate awareness about these transitions and the trigger points involved, that can be used by patients and consumers to improve their health and prevent chronic diseases from occurring. Awareness about the complexity of interactions between biological, psychological, social and environmental health determinants is also crucial for implementing health promotion programs. This presentation will discuss several tools that we designed to generate health awareness, based on a complexity science approach. Furthermore, the implementation of these tools in three use cases is presented: an integrated overweight treatment program, a systems dynamics model of employer health, and HealthCafé for empowerment and inspiring health. Description: A first step in improving health awareness is to connect the bits and pieces of health information that are out there in the literature. A shift is needed from considering all the separate health determinants towards considering the relationships and dynamics between the determinants. An enriched causal loop diagram was developed related to health and overweight using a TNO tool called MARVEL. MARVEL is specifically designed for group model building purposes with an easy to use interface and the possibility to construct models on the fly. A group of scientists from various disciplines (nutrition, systems biology, mathematical modelling, social psychology, cognitive psychology, physiology, movement sciences) came together in several sessions to construct a biopsychosocial model which could be used to explore the cross-domain interactions, feedback and feed forward loops. This model was presented to a rehabilitation center and used to develop a multidisciplinary program for the treatment of overweight. A team consisting of a psychologist, physician, movement expert, nutritionist and Chinese medicine practitioner prepare a personalized program for each individual, aiming for an optimal motivation of the person to change life-style habits. A pilot study was started in April 2015 with 10 participants. A systems perspective on health in which physiological, mental, psychological, social, and spiritual aspects that are important for the individual are combined into a treatment plan is essential. The first results of the pilot study are now available. A similar approach was taken for addressing workplace health. A groups of companies came to TNO to work on methods to improve the health of personnel. To gain insights into the mechanisms of workplace related health a systems dynamics model was constructed centered around vitality. Vitality consists of three key determinants: motivation, energy and resilience. The resulting model illustrated several important mechanisms. One of these mechanisms is the interaction between conditions and demands and how the balance between the conditions and demands can lead to either to an experience of challenge or stress. The model also shows interactions between physical, mental, emotional and social components of health. These mechanisms were then incorporated into a workshop conducted with one of the companies. This workshop is another tool in which a dynamic set of interactions between several experts and stakeholders is organized with the aim to develop new business cases. In this case the new business cases are designed to improve the health of employers. A third use case for improving health awareness is the launch of a HealthCafé. The aim is to inspire people to measure their own health and measure the effects of interventions on their health, using all sorts of do-it-your-self technologies. The current version of the HealthCafé offers first of all a physical location where people can interact. It also offers devices such as activity trackers, glucose and cholesterol measurement devices, questionnaires, and a personal internet portal to store and analyse the data. The goal is to empower people and give people more control over their own health. Conclusions: Complexity science offers new opportunities to create health awareness. We have shown how a systems dynamics software tool can be used in group model building sessions to generate a shared understanding of a health problem among stakeholders. The resulted in a successful integrative overweight treatment program at a rehabilitation centre in the Netherlands. The HealthCafé was launched as a living lab which can be used by people to explore their own health and conduct studies on themselves. These activities are aiming for a transition in health care towards more awareness as the personal level, empowerment and thereby increasing the chances for successful life-style changes towards more health and happiness

Complementary Medicine and Self-Care Strategies in Women with (Recurrent) Urinary Tract and Vaginal Infections: A Cross-Sectional Study on Use and Perceived Effectiveness in The Netherlands

Due to the excessive use of antibiotic and antimycotic treatments, the risk of resistant microbes and fungi is rapidly emerging. Previous studies have demonstrated that many women with (recurrent) urinary tract infection (UTI) and/or vaginal infections (VIs) welcome alternative management approaches to reduce the use of antibiotics and antifungals and avoid short- and long-term adverse effects. This study aims to determine which complementary medicine (CM) and self-care strategies are being used by women suffering from (recurrent) UTI and VI in The Netherlands and how they perceive their effectiveness in order to define directions for future research on safety, cost-effectiveness, and implementation of best practices. A cross-sectional online survey was performed among women, ≥18 years old, with a history of UTIs; 162 respondents were included in the data analysis, with most participants aged between 50 and 64 years (36.4%). The women reported having consulted a CM practitioner for UTI-specific symptoms (23.5%) and VI-specific symptoms (13.6%). Consultations of homeopaths, acupuncturists, and herbal physicians are most often reported. Overall, 81.7% of the women suffering from UTI used complementary or self-care strategies besides regular treatment, and 68.7% reported using CM/self-care strategies to treat vaginal symptoms. UTI- related use of cranberries (51.9%), vitamin C (43.8%), and D-mannose (32.7%) were most reported. Perceived effectiveness was mostly reported for homeopathic remedies and D-mannose. The results showed a substantial burden of UTI and VI on daily and sexual activities. Besides the frequency of use, the indication of perceived effectiveness seems to be an important parameter for further and rigorously designed research to encourage nonantibiotic/antifungal treatment implementation into daily clinical practice

Complementary Medicine and Self-Care Strategies in Women with (Recurrent) Urinary Tract and Vaginal Infections: A Cross-Sectional Study on Use and Perceived Effectiveness in The Netherlands

Due to the excessive use of antibiotic and antimycotic treatments, the risk of resistant microbes and fungi is rapidly emerging. Previous studies have demonstrated that many women with (recurrent) urinary tract infection (UTI) and/or vaginal infections (VIs) welcome alternative management approaches to reduce the use of antibiotics and antifungals and avoid short- and long-term adverse effects. This study aims to determine which complementary medicine (CM) and self-care strategies are being used by women suffering from (recurrent) UTI and VI in The Netherlands and how they perceive their effectiveness in order to define directions for future research on safety, cost-effectiveness, and implementation of best practices. A cross-sectional online survey was performed among women, ≥18 years old, with a history of UTIs; 162 respondents were included in the data analysis, with most participants aged between 50 and 64 years (36.4%). The women reported having consulted a CM practitioner for UTI-specific symptoms (23.5%) and VI-specific symptoms (13.6%). Consultations of homeopaths, acupuncturists, and herbal physicians are most often reported. Overall, 81.7% of the women suffering from UTI used complementary or self-care strategies besides regular treatment, and 68.7% reported using CM/self-care strategies to treat vaginal symptoms. UTI- related use of cranberries (51.9%), vitamin C (43.8%), and D-mannose (32.7%) were most reported. Perceived effectiveness was mostly reported for homeopathic remedies and D-mannose. The results showed a substantial burden of UTI and VI on daily and sexual activities. Besides the frequency of use, the indication of perceived effectiveness seems to be an important parameter for further and rigorously designed research to encourage nonantibiotic/antifungal treatment implementation into daily clinical practice

The Use of the Bolk Model for Positive Health and Living Environment in the Development of an Integrated Health Promotion Approach: A Case Study in a Socioeconomically Deprived Neighborhood in The Netherlands

Background. Despite considerable efforts, health disparities between people with high and low socioeconomic status (SES) have not changed over the past decades in The Netherlands. To create a culture of health and an environment in which all people can flourish, a shift in focus is needed from disease management towards health promotion. The Bolk model for Positive Health and Living Environment was used as a tool to guide this shift. This study aimed to describe how this model was used and perceived by stakeholders in a case study on an integrated health promotion approach for residents with low SES. Methods. An instrumental case study was undertaken in Venserpolder, a neighborhood in Amsterdam South East of approximately 8500 residents. A participatory action approach was used that allowed continuous interaction between the residents, health care professionals, researchers, and other stakeholders. The Bolk model is a tool, based on the conceptual framework of positive health, that was developed to guide health promotion practice. Its use in the case study was evaluated by means of semistructured interviews with stakeholders, using qualitative directed content analyses. Results. The Bolk model was found to be a useful tool to identify and map the needs and strengths of residents with low SES. The model facilitated the development and implementation of eight health promotion pilots by transforming the needs and strengths of residents into concrete actions carried out by responsible actors in the neighborhood. Although the Bolk model seemed to be accepted by all stakeholders, the shift towards positive health thinking appeared to be more embodied by local professionals than by residents. Adjustments were proposed to enhance the applicability of the model in a multicultural setting, to increase its cultural sensitivity and to use language more familiar to residents. Conclusions. The Bolk model for positive health and living environment seems to be promising in the guidance of health promotion practices in Amsterdam South East. Further research and development are needed to improve its cultural sensitivity and to investigate its applicability in a broader range of public health settings

Effects of mindfulness training on perceived stress, self-compassion, and self-reflection of primary care physicians : a mixed-methods study

Background Primary care physicians are subjected to a high workload, which can lead to stress and a high incidence of burnout. A mindfulness training course was developed and implemented for primary care physicians to better cope with stress and improve job functioning. Aim To gain insight into the effects of the mindfulness training on perceived stress, self-compassion, and self-reflection of primary care physicians. Design & setting A pragmatic mixed-methods pre–post design in which physicians received 8 weeks of mindfulness training. Method Participants completed validated questionnaires on perceived stress (Perceived Stress Scale [PSS]), self-compassion (Self-Compassion Scale [SCS]), and self-reflection (Groningen Reflection Ability Scale [GRAS]) before the training, directly after, and 6 months later. Semi-structured interviews were conducted with six participants after the training and a content analysis was performed to gain in depth understanding of experiences. Results A total of 54 physicians participated in the study. PSS was reduced (mean difference [MD] -4.5, P<0.001), SCS improved (MD = 0.5, P<0.001), and GRAS improved (MD = 3.3, P<0.001), directly after the 8-week training compared with before training. Six months later, PSS was still reduced (MD = -2.9, P = 0.025) and SCS improved (MD = 0.7, P<0.001). GRAS did not remain significant (MD = 2.5, P = 0.120). Qualitative analysis revealed four themes: being more aware of their own feelings and thoughts; being better able to accept situations; experiencing more peacefulness; and having more openness to the self and others. Conclusion Mindfulness training might be an effective approach for improving stress resilience, self-compassion, and self-reflection in primary care physicians