Phospholipase D signaling: orchestration by PIP2 and small GTPases

Hydrolysis of phosphatidylcholine by phospholipase D (PLD) leads to the generation of the versatile lipid second messenger, phosphatidic acid (PA), which is involved in fundamental cellular processes, including membrane trafficking, actin cytoskeleton remodeling, cell proliferation and cell survival. PLD activity can be dramatically stimulated by a large number of cell surface receptors and is elaborately regulated by intracellular factors, including protein kinase C isoforms, small GTPases of the ARF, Rho and Ras families and, particularly, by the phosphoinositide, phosphatidylinositol 4,5-bisphosphate (PIP2). PIP2 is well known as substrate for the generation of second messengers by phospholipase C, but is now also understood to recruit and/or activate a variety of actin regulatory proteins, ion channels and other signaling proteins, including PLD, by direct interaction. The synthesis of PIP2 by phosphoinositide 5-kinase (PIP5K) isoforms is tightly regulated by small GTPases and, interestingly, by PA as well, and the concerted formation of PIP2 and PA has been shown to mediate receptor-regulated cellular events. This review highlights the regulation of PLD by membrane receptors, and describes how the close encounter of PLD and PIP5K isoforms with small GTPases permits the execution of specific cellular functions

Understanding how adherence goals promote adherence behaviours: a repeated measure observational study with HIV seropositive patients

Background The extent to which patients follow treatments as prescribed is pivotal to treatment success. An exceptionally high level (> 95 %) of HIV medication adherence is required to suppress viral replication and protect the immune system and a similarly high level (> 80 %) of adherence has also been suggested in order to benefit from prescribed exercise programmes. However, in clinical practice, adherence to both often falls below the desirable level. This project aims to investigate a wide range of psychological and personality factors that may lead to adherence/non-adherence to medical treatment and exercise programmes. Methods HIV positive patients who are referred to the physiotherapist-led 10-week exercise programme as part of the standard care are continuously recruited. Data on social cognitive variables (attitude, intention, subjective norms, self-efficacy, and outcome beliefs) about the goal and specific behaviours, selected personality factors, perceived quality of life, physical activity, self-reported adherence and physical assessment are collected at baseline, at the end of the exercise programme and again 3 months later. The project incorporates objective measures of both exercise (attendance log and improvement in physical measures such as improved fitness level, weight loss, improved circumferential anthropometric measures) and medication adherence (verified by non-invasive hair analysis). Discussion The novelty of this project comes from two key aspects, complemented with objective information on exercise and medication adherence. The project assesses beliefs about both the underlying goal such as following prescribed treatment; and about the specific behaviours such as undertaking the exercise or taking the medication, using both implicit and explicit assessments of patients' beliefs and attitudes. We predict that i) the way people think about the underlying goal of their treatments explains medication and exercise behaviours over and above the effects of the behaviour-specific thinking and ii) the relationship between adherence to exercise and to medical treatment is stronger among those with more favourable views about the goal. Results from this study should identify the key contributing factors to inform subsequent adherence research and afford a more streamlined assessment matrix. The project also aims to inform patient care practices. UK Clinical Research Network registration number: UKCRN 7842

Health Literacy and Parental Oral Health Knowledge, Beliefs, Behavior, and Status Among Parents of American Indian Newborns

ObjectiveTo examine the relationship between health literacy (HL) and parental oral health knowledge, beliefs, behavior, and self-reported oral health status (OHS) among parents of American Indian (AI) children.MethodsThis analysis used baseline data from a randomized controlled trial that tested an oral health intervention with parents of AI newborns. Participants were recruited in parent-child dyads (N = 579). Parents completed items assessing sociodemographic characteristics, HL, and parental oral health knowledge, beliefs, behavior, and self-reported OHS. We examined the correlation of HL with each oral health construct, controlling for parent age and income.ResultsOn average, parents felt quite confident in their HL skills, performed well on questions assessing parental oral health knowledge, and endorsed beliefs likely to encourage positive parental oral health behaviors (e.g., confidence that one can successfully engage in such behaviors). Parents with more limited HL had significantly less knowledge, perceived cavities to be less severe, perceived more barriers and fewer benefits to recommended oral health behaviors, were less confident they could engage in these behaviors, and were more likely to believe their children's oral health was under the control of the dentist or a matter of chance (P values < 0.001). Limited HL was not associated with behavior (P > 0.05) but was linked to worse self-reported OHS (P = 0.040).ConclusionsHL was associated with parental oral health knowledge, beliefs, and self-reported OHS. Oral health education interventions targeting AI families should facilitate development of knowledge and positive oral health beliefs among parents with more limited HL skills