Single-Cell Analysis of Contractile Forces in iPSC-Derived Cardiomyocytes: Paving the Way for Precision Medicine in Cardiovascular Disease.

Induced pluripotent stem cell-derived cardiomyocytes (iPSC-CMs) hold enormous potential in cardiac disease modeling, drug screening, and regenerative medicine. Furthermore, patient-specific iPSC-CMS can be tested for personalized medicine. To provide a deeper understanding of the contractile force dynamics of iPSC-CMs, we employed Atomic Force Microscopy (AFM) as an advanced detection tool to distinguish the characteristics of force dynamics at a single cell level. We measured normal (vertical) and lateral (axial) force at different pacing frequencies. We found a significant correlation between normal and lateral force. We also observed a significant force-frequency relationship for both types of forces. This work represents the first demonstration of the correlation of normal and lateral force from individual iPSC-CMs. The identification of this correlation is relevant because it validates the comparison across systems and models that can only account for either normal or lateral force. These findings enhance our understanding of iPSC-CM properties, thereby paving the way for the development of therapeutic strategies in cardiovascular medicine.

Pharmacological Inhibition of Epac1 Protects against Pulmonary Fibrosis by Blocking FoxO3a Neddylation.

Background: Idiopathic Pulmonary fibrosis (IPF) is characterized by progressive scarring and fibrosis within the lungs. There is currently no cure for IPF; therefore, there is an urgent need to identify novel therapeutic targets that can prevent the progression of IPF. Compelling evidence indicates that the second messenger, cyclic adenosine monophosphate (cAMP), inhibits lung fibroblast proliferation and differentiation through the classical PKA pathway. However, the contribution of the e xchange p rotein directly a ctivated by c AMP 1 (Epac1) to IPF pathophysiological processes is yet to be investigated. Objective: To determine the role of the cAMP-binding protein Epac1 in the progression of IPF. Methods: We used lung samples from IPF patients or healthy controls, mouse lung samples, or lung fibroblast isolated from a preclinical mouse model of PF induced by bleomycin intratracheal injection. The effect of bleomycin (BLM) treatment was determined in Epac1 knock-out mice or wild-type littermates. Epac1 expression was modulated in vitro by using lentiviral vectors or adenoviruses. The therapeutic potential of the Epac1-selective pharmacological inhibitor, AM-001, was tested in vivo and in vitro, using a bleomycin mouse model of PF and an ex vivo precision-cut lung slices (PCLs) model of human lung fibrosis. Results: Epac1 expression was increased in the lung tissue of IPF patients, in IPF-diseased fibroblasts and in BLM-challenged mice. Furthermore, Epac1 genetic or pharmacological inhibition with AM-001 decreased normal and IPF fibroblast proliferation and the expression of profibrotic markers, αSMA, TGF-ß/SMAD2/3, and interleukin-6 (IL-6)/STAT3 signaling pathways. Consistently, blocking Epac1 protected against BLM-induced lung injury and fibrosis, suggesting a therapeutic effect of Epac1 inhibition on PF pathogenesis and progression. Global gene expression profiling revealed a decrease in the key components of the profibrotic gene signature and neddylation pathway in Epac1-deficient lung fibroblasts and IPF human-derived PLCs. Mechanistically, the protective effect of Epac1 inhibition against PF development involves the inhibition of FoxO3a neddylation and its subsequent degradation by NEDD8, and in part, by limiting the proliferative capacity of lung-infiltrating monocytes. Conclusions: We demonstrated that Epac1 is an important regulator of the pathological state of fibroblasts in PF and that small molecules targeting Epac1 can serve as novel therapeutic drugs against PF.

Switch-Independent 3A: An Epigenetic Regulator in Cancer with New Implications for Pulmonary Arterial Hypertension.

Epigenetic mechanisms, including DNA methylation, histone modifications, and non-coding RNA, play a crucial role in the regulation of gene expression and are pivotal in biological processes like apoptosis, cell proliferation, and differentiation. SIN3a serves as a scaffold protein and facilitates interactions with transcriptional epigenetic partners and specific DNA-binding transcription factors to modulate gene expression by adding or removing epigenetic marks. However, the activation or repression of gene expression depends on the factors that interact with SIN3a, as it can recruit both transcriptional activators and repressors. The role of SIN3a has been extensively investigated in the context of cancer, including melanoma, lung, and breast cancer. Our group is interested in defining the roles of SIN3a and its partners in pulmonary vascular disease. Pulmonary arterial hypertension (PAH) is a multifactorial disease often described as a cancer-like disease and characterized by disrupted cellular metabolism, sustained vascular cell proliferation, and resistance to apoptosis. Molecularly, PAH shares many common signaling pathways with cancer cells, offering the opportunity to further consider therapeutic strategies used for cancer. As a result, many signaling pathways observed in cancer were studied in PAH and have encouraged new research studying SIN3a's role in PAH due to its impact on cancer growth. This comparison offers new therapeutic options. In this review, we delineate the SIN3a-associated epigenetic mechanisms in cancer and PAH cells and highlight their impact on cell survival and proliferation. Furthermore, we explore in detail the role of SIN3a in cancer to provide new insights into its emerging role in PAH pathogenesis.

2009 Spiritual Care Collaborative survey results on continuing education.

Continuing education for chaplains, pastoral counselors and clinical pastoral educators is important for maintaining and advancing professional competency. Pastoral professionals who visited the Spiritual Care Collaborative (SCC) website to register for a conference were asked to complete a questionnaire on continuing education. Results of the survey show that continuing education, both in-person and through electronic means, were clearly ranked as the most important activities the SCC partner organizations could provide in the future. Additionally, continuing education preferences vary depending upon constituent groups. These findings have implications for the design of future educational programs.

Threats to the Internal Validity of Experimental and Quasi-Experimental Research in Healthcare.

The article defines, describes, and discusses the seven threats to the internal validity of experiments discussed by Donald T. Campbell in his classic 1957 article: history, maturation, testing, instrument decay, statistical regression, selection, and mortality. These concepts are said to be threats to the internal validity of experiments because they pose alternate explanations for the apparent causal relationship between the independent variable and dependent variable of an experiment if they are not adequately controlled. A series of simple diagrams illustrate three pre-experimental designs and three true experimental designs discussed by Campbell in 1957 and several quasi-experimental designs described in his book written with Julian C. Stanley in 1966. The current article explains why each design controls for or fails to control for these seven threats to internal validity.

The t-test: An Influential Inferential Tool in Chaplaincy and Other Healthcare Research.

The t-test developed by William S. Gosset (also known as Student's t-test and the two-sample t-test) is commonly used to compare one sample mean on a measure with another sample mean on the same measure. The outcome of the t-test is used to draw inferences about how different the samples are from each other. It is probably one of the most frequently relied upon statistics in inferential research. It is easy to use: a researcher can calculate the statistic with three simple tools: paper, pen, and a calculator. A computer program can quickly calculate the t-test for large samples. The ease of use can result in the misuse of the t-test. This article discusses the development of the original t-test, basic principles of the t-test, two additional types of t-tests (the one-sample t-test and the paired t-test), and recommendations about what to consider when using the t-test to draw inferences in research.

Studying Associations in Health Care Research.

This article discusses some of the types of relationships observed in healthcare research and depicts them in graphic form. The article begins by explaining two basic associations observed in chemistry and physics (Boyles' Law and Charles' Law), and illustrates how these associations are similar to curvilinear and linear associations, respectively, found in healthcare. Graphs of curvilinear associations include morbidity curves and survival and mortality curves. Several examples of linear relationships are given and methods of testing linear relationships with interval and ratio data are introduced (i.e., correlation and ordinary least-squares regression). In addition, 2 × 2 contingency tables for testing the association between categorical (or nominal) data are described. Finally, Sir Austin Bradford Hill's eight criteria for assessing causality from research on associations between variables are presented and explained. Three appendices provide interested readers with opportunities to practice interpreting selected curvilinear and linear relationships.

Measures of central tendency in chaplaincy, health care, and related research.

The three measures of central tendency are discussed in this article: the mode, the median, and the mean. These measures of central tendency describe data in different and important ways, in relation to the level of measurement (nominal, ordinal, interval, or ratio) used to obtain the data. The results of published research studies, thought experiments, and graphs of frequency and percentage distributions of data are used as examples to demonstrate and explain the similarities and differences among these summary measures of data. The examples include the application of nominal, ordinal, interval, and ratios scales to measure pain, anxiety, chaplaincy services, religious behaviors, and treatment-related preferences, and their respective measures of central tendency. Examples of unimodal and bimodal distributions, and differences in the relative locations of the median and mean in symmetrical and skewed distributions are also presented and discussed.

Measures of variability in chaplaincy, health care, and related research.

This article discusses statistical measures of variability in relation to measures of central tendency and levels of measurement. Three measures of variability used in healthcare research (the range, the interquartile range, and the standard deviation) are described and compared, including their uses and limitations. The article describes how each of the three measures is calculated, and it provides a step-by-step example of calculating the sums of squares, variance, and standard deviation. Graphs of frequency and percentage distributions are used to show how the interquartile range and the standard deviation represent the variability observed within distributions. The article discusses the properties of the normal curve regarding the distribution of scores around the mean in relation to the standard deviation, and illustrates differences in the shapes of normal curves with the same mean but different standard deviations.

Depression and negative life events among pregnant African-American and Hispanic women.

Depression, social support, and life events were assessed in a sample of African-American and Hispanic women (N = 148) with uncomplicated pregnancies. Over half (51%) showed elevated depressive symptoms. Overall, women had fewer social supports and more negative life events than found in previous studies. African-Americans had more practical social support and persons in their support networks than Hispanics. Over a third of the sample (37%) had lost an important person in the past year. Depressed women reported more negative events than nondepressed women. Many negative life events and few social supports place minority women at risk for prenatal depression.

Research designs and making causal inferences from health care studies.

This article summarizes the major types of research designs used in healthcare research, including experimental, quasi-experimental, and observational studies. Observational studies are divided into survey studies (descriptive and correlational studies), case-studies and analytic studies, the last of which are commonly used in epidemiology: case-control, retrospective cohort, and prospective cohort studies. Similarities and differences among the research designs are described and the relative strength of evidence they provide is discussed. Emphasis is placed on five criteria for drawing causal inferences that are derived from the writings of the philosopher John Stuart Mill, especially his methods or canons. The application of the criteria to experimentation is explained. Particular attention is given to the degree to which different designs meet the five criteria for making causal inferences. Examples of specific studies that have used various designs in chaplaincy research are provided.

Fundamentals of measurement in health care research.

This article discusses levels of measurement and their application to research and practice in health care. The concept of levels of measurement was codified in a seminal article by S. S. Stevens in 1946 that defined four levels of measurement: nominal scales, which label and classify cases (objects and individuals) and assign them to categories; ordinal scales, which rank cases on some attribute; interval scales, which have equal intervals for measuring attributes; and ratio scales, which have equal intervals and a natural zero point. The rules that apply to each level of measurement are presented and the mathematical operations that can be performed on them are explained. The similarities and differences among the four types of scales are discussed and examples of their use in health care and other contexts are described.

Operational definitions in research on religion and health.

This article summarizes the historical development of operational definitions and discusses their application to research on religion and health, and their importance for research, in general. The diversity of religious concepts that have been operationalized is described, as well as the development of multi-dimensional self-report measures of religion specifically designed for use in health research. The operational definitions of a variety of health concepts are also described, including the development of multi-dimensional self-report measures of health. Some of the most consistently observed salutary relationships between religion and health are mentioned. The rising interest in spirituality in health research is discussed, along with problems with the current operational definitions of spirituality in healthcare research. The levels of measurement used in various, operationally defined religious and healthcare concepts are highlighted.

Independent, dependent, and other variables in healthcare and chaplaincy research.

This article begins by defining the term variable and the terms independent variable and dependent variable, providing examples of each. It then proceeds to describe and discuss synonyms for the terms independent variable and dependent variable, including treatment, intervention, predictor, and risk factor, and synonyms for dependent variable, such as response variables and outcomes. The article explains that the terms extraneous, nuisance, and confounding variables refer to any variable that can interfere with the ability to establish relationships between independent variables and dependent variables, and it describes ways to control for such confounds. It further explains that even though intervening, mediating, and moderating variables explicitly alter the relationship between independent variables and dependent variables, they help to explain the causal relationship between them. In addition, the article links terminology about variables with the concept of levels of measurement in research.

Spiritual coping and anxiety in palliative care patients: a pilot study.

Patients often rely on spirituality to cope with anxiety, yet it is not known if spiritual coping actually helps patients deal with anxiety. The present study was designed, therefore, to examine this relationship. A series of patients who were referred to the palliative care team at New York University, Langone Medical Center (N = 44) were interviewed about their spiritual coping and anxiety. Anxiety was measured using the first three items of the GAD-7. Fourteen items, which were adapted from existing scales, were used to create the "Beliefs and Activities Spirituality Scale" (BASS), having two subscales: Activities (α = .79) and Beliefs (α = .82). Anxiety had a significant negative correlations with the total BASS (r = -.56), and the Activities (r = -.52) and Beliefs (r = -.42) subscales. The salubrious association of spiritual coping and anxiety remained for the BASS and the Activities subscale, after controlling for demographic variables.

Testing the efficacy of chaplaincy care.

The current article reviews the research conducted in the United States on the clinical practice of chaplains with patients and family members, referrals to chaplains, patient satisfaction with chaplaincy services, and the limited literature on the efficacy of chaplain interventions. It also discusses the methodological limitations of studies conducted on these topics and makes suggestions for improving future chaplaincy research. The authors conclude that past studies have not adequately defined chaplain interventions, nor sufficiently documented the clinical practice of chaplains, and that more and better designed studies are needed to test the efficacy of chaplaincy interventions. The authors recommend that chaplains generate research-based definitions of spirituality, spiritual care, and chaplaincy practice; and that more research be conducted to describe the unique contributions of chaplains to spiritual care, identify best chaplaincy practices to optimize patient and family health outcomes, and test the efficacy of chaplaincy care.

A methodological analysis of chaplaincy research: 2000-2009.

The present article presents a comprehensive review and analysis of quantitative research conducted in the United States on chaplaincy and closely related topics published between 2000 and 2009. A combined search strategy identified 49 quantitative studies in 13 journals. The analysis focuses on the methodological sophistication of the studies, compared to earlier research on chaplaincy and pastoral care. Cross-sectional surveys of convenience samples still dominate the field, but sample sizes have increased somewhat over the past three decades. Reporting of the validity and reliability of measures continues to be low, although reporting of response rates has improved. Improvements in the use of inferential statistics and statistical controls were also observed, compared to previous research. The authors conclude that more experimental research is needed on chaplaincy, along with an increased use of hypothesis testing, regardless of the research designs that are used.

Complementary alternative medicine practices used by religious professionals.

Religious professionals completed an online survey of their use of health related practices currently known as complementary and alternative medicine (CAM). They indicated how often they engaged in these practices and how often they had used these practices when helping other people. The majority of religious professionals used at least one of the practices when alone and when helping other people. The most frequently used practices were meditation and deep breathing exercises used both when alone and when helping others. Female respondents were more likely to use these practices on their own and when helping others than were males, and older respondents were more likely to use multiple CAM practices than their younger counterparts. Other Faith/Humanists used the most CAM practices when alone and Jewish respondents used the fewest. In general, religious professionals used fewer practices when helping others than they used for themselves. Limitations of this study and suggestions for future studies for examining CAM practices among religious professionals are discussed.

Change in pastoral skills, emotional intelligence, self-reflection, and social desirability across a unit of CPE.

Clinical Pastoral Education (CPE) is experiential learning of the art and science of pastoral care. CPE students increase capacities in psychological strengths such as self-awareness and empathy, and improve skills in interpersonal and inter-professional relationships. Previous research has documented different kinds of change and experiences for students depending on the length of the CPE unit (short/intensive vs. long/extended). The current study involves CPE students who have taken either an intensive unit or an extended unit and compares the average amount of change in pastoral skills, emotional intelligence, self-reflection, and insight while controlling for the influence of social desirability. Intensive and extended unit students were different from each other in terms of age and experience, beginning level of pastoral skill, and amount of change in the measured abilities. Limitations and strengths of this study and the need for future research are discussed.