Does gamma-aminobutyric acid (GABA) influence the development of chronic inflammation in rheumatoid arthritis?

<p>Abstract</p> <p>Background</p> <p>Recent studies have demonstrated a role for spinal p38 MAP kinase (MAPK) in the development of chronic inflammation and peripheral arthritis and a role for GABA in the inhibition of p38 MAPK mediated effects. Integrating these data suggests that GABA may play a role in downregulating mechanisms that lead to the production of proinflammatory agents such as interleukin-1, interleukin-6, and matrix metalloproteinase 3 – agents implicated in the pathogenesis of rheumatoid arthritis (RA). Genetic studies have also associated RA with members of the p38 MAPK pathway.</p> <p>Hypothesis</p> <p>We propose a hypothesis for an inefficient GABA signaling system that results in unchecked proinflammatory cytokine production via the p38 MAPK pathway. This model also supports the need for increasing research in the integration of immunology and neuroscience.</p

GPER mediates the angiocrine actions induced by IGF1 through the HIF-1α/VEGF pathway in the breast tumor microenvironment

The G protein estrogen receptor GPER/GPR30 mediates estrogen action in breast cancer cells as well as in breast cancer-associated fibroblasts (CAFs), which are key components of microenvironment driving tumor progression. GPER is a transcriptional target of hypoxia inducible factor 1 alpha (HIF-1α) and activates VEGF expression and angiogenesis in hypoxic breast tumor microenvironment. Furthermore, IGF1/IGF1R signaling, which has angiogenic effects, has been shown to activate GPER in breast cancer cells. We analyzed gene expression data from published studies representing almost 5000 breast cancer patients to investigate whether GPER and IGF1 signaling establish an angiocrine gene signature in breast cancer patients. Next, we used GPER-positive but estrogen receptor (ER)-negative primary CAF cells derived from patient breast tumours and SKBR3 breast cancer cells to investigate the role of GPER in the regulation of VEGF expression and angiogenesis triggered by IGF1. We performed gene expression and promoter studies, western blotting and immunofluorescence analysis, gene silencing strategies and endothelial tube formation assays to evaluate the involvement of the HIF-1α/GPER/VEGF signaling in the biological responses to IGF1. We first determined that GPER is co-expressed with IGF1R and with the vessel marker CD34 in human breast tumors (n = 4972). Next, we determined that IGF1/IGF1R signaling engages the ERK1/2 and AKT transduction pathways to induce the expression of HIF-1α and its targets GPER and VEGF. We found that a functional cooperation between HIF-1α and GPER is essential for the transcriptional activation of VEGF induced by IGF1. Finally, using conditioned medium from CAFs and SKBR3 cells stimulated with IGF1, we established that HIF-1α and GPER are both required for VEGF-induced human vascular endothelial cell tube formation. These findings shed new light on the essential role played by GPER in IGF1/IGF1R signaling that induces breast tumor angiogenesis. Targeting the multifaceted interactions between cancer cells and tumor microenvironment involving both GPCRs and growth factor receptors has potential in future combination anticancer therapies

Changes in treatment and mortality of acute myocardial infarction in Estonian tertiary and secondary care hospitals in 2001 and 2007

<p>Abstract</p> <p>Background</p> <p>High quality care for acute myocardial infarction (AMI) improves patient outcomes. Still, AMI patients are treated in hospitals with unequal access to percutaneous coronary intervention. The study compares changes in treatment and 30-day and 3-year mortality of AMI patients hospitalized into tertiary and secondary care hospitals in Estonia in 2001 and 2007.</p> <p>Results</p> <p>Final analysis included 423 cases in 2001 (210 from tertiary and 213 from secondary care hospitals) and 687 cases in 2007 (327 from tertiary and 360 from secondary care hospitals). The study sample in 2007 was older and had twice more often diabetes mellitus. The patients in the tertiary care hospitals underwent reperfusion for ST-elevation myocardial infarction, cardiac catheterization and revascularisation up to twice as often in 2007 as in 2001. In the secondary care, patient transfer for further invasive treatment into tertiary care hospitals increased (<it>P </it>< 0.001). Prescription rates of evidence-based medications for in-hospital and for outpatient use were higher in 2007 in both types of hospitals. However, better treatment did not improve significantly the short- and long-term mortality within a hospital type in crude and baseline-adjusted analysis. Still, in 2007 a mortality gap between the two hospital types was observed (<it>P </it>< 0.010).</p> <p>Conclusions</p> <p>AMI treatment improved in both types of hospitals, while the improvement was more pronounced in tertiary care. Still, better treatment did not result in a significantly lower mortality. Higher age and cardiovascular risk are posing a challenge for AMI treatment.</p

The propensity to adopt evidence-based practice among physical therapists

<p>Abstract</p> <p>Background</p> <p>Many authors, as well as the American Physical Therapy Association, advocate that physical therapists adopt practice patterns based on research evidence, known as evidence-based practice (EBP). At the same time, physical therapists should be capable of integrating EBP within the day-to-day practice of physical therapy. The purpose of this study was to determine the extent to which personal characteristics and the characteristics of the social system in the workplace influence the propensity of physical therapists to adopt EBP.</p> <p>Methods</p> <p>The study used a 69 item mailed self-completion questionnaire. The questionnaire had four major sections. The first three sections were each drawn from a different theoretical framework and from different authors' work. The instrument was developed to capture the propensity of physical therapists to adopt EBP, characteristics of the social system in the workplace of physical therapists, personal characteristics of physical therapists, and selected demographic variables of physical therapists. The eligible population consisted of 3,897 physical therapists licensed by the state of Georgia in the United States of America. A random sample of 1320 potential participants was drawn.</p> <p>Results</p> <p>939 questionnaires were returned for a response rate of 73%. 831 of the participants' questionnaires were useable and became the basis for the study. There was a moderate association between desire for learning (<it>r </it>= .36, <it>r</it>²= .13), highest degree held (<it>r </it>= .29, <it>r</it>²= .08), practicality (<it>r </it>= .27, <it>r</it>²= .07) and nonconformity (<it>r </it>= .24, <it>r</it>²= .06) and the propensity to adopt EBP. A negative correlation was found between age, years licensed and percentage of time in direct patient care. The findings demonstrated that the best three variables for predicting the propensity to adopt EBP in physical therapy were: desire for learning, highest degree held, and practicality.</p> <p>Conclusion</p> <p>The study confirms there is no single factor to facilitate research evidence into day-to-day practice. Multiple practice change strategies will be needed to facilitate change in practice.</p

Functional assessment of older patients in the emergency department: comparison between standard instruments, medical records and physicians' perceptions

BACKGROUND: We evaluated the accuracy of physician recognition of functional status impairment in older emergency departments (ED) patients. In particular, we evaluated the accuracy of medical records (a comparison of the information in the medical record with the functional status based on proxy interviews), and the accuracy of physician knowledge (a comparison of the information obtained from the responsible physician with the functional status based on proxy interviews). METHODS: Cross-sectional study on 101 frail older patients selected at random from among those attending ED, their ED physicians, and respondents. The study was conducted at ED in four general university teaching hospitals in a city, from July through November 2003. Functional data shown on patients' medical records were compared against functional data obtained from respondents (family members), using Kendall's Tau-b statistic. In addition patients' Katz Indices (which assesses six basic activities of daily living – basic ADL) based on interviews with ED physicians were compared against those obtained from respondents, using the coefficient of concordance weighted kappa (κ). Each patient and his respondent were paired with a single physician. RESULTS: The correlation between information on dependence for basic ADL obtained from medical records and that furnished by respondents, was 0.41 (95% CI 0.27–0.55). Concordance between the respective Katz Indices obtained from physicians and respondents was 0.47 (95% CI 0.38–0.57). CONCLUSION: Older subjects' functional status is not properly assessed by emergency department physicians

The Co-Regulation of Emotions Between Mothers and their Children with Autism

Thirty-four toddlers with autism and their mothers participated in an early intervention targeting joint engagement. Across the 24 intervention sessions, any significant distress episode in the child was coded for emotion regulation outcomes including child negativity, child emotion self-regulation, and mother emotion co-regulation. Results revealed that emotion regulation strategies by both mother and child were employed during distress episodes. An effect of intervention was found such that children decreased their expression of negativity across the intervention and mothers increased their emotional and motivational scaffolding. The results of this study indicate a positive effect of an intervention targeting joint engagement on emotion co-regulation outcomes

Genetic architecture and evolution of the S locus supergene in Primula vulgaris

Darwin’s studies on heterostyly in Primula described two floral morphs, pin and thrum, with reciprocal anther and stigma heights that promote insect-mediated cross-pollination. This key innovation evolved independently in several angiosperm families. Subsequent studies on heterostyly in Primula contributed to the foundation of modern genetic theory and the neo-Darwinian synthesis. The established genetic model for Primula heterostyly involves a diallelic S locus comprising several genes, with rare recombination events that result in self-fertile homostyle flowers with anthers and stigma at the same height. Here we reveal the S locus supergene as a tightly-linked cluster of thrum-specific genes that are absent in pins. We show that thrums are hemizygous not heterozygous for the S locus, which suggests that homostyles do not arise by recombination between S locus haplotypes as previously proposed. Duplication of a floral homeotic gene 51.7 MYA, followed by its neofunctionalisation, created the current S locus assemblage which led to floral heteromorphy in Primula. Our findings provide new insights into the structure, function and evolution of this archetypal supergene