Estrogen stimulates dimethylarginine dimethylaminohydrolase activity and the metabolism of asymmetric dimethylarginine.

Background— Experimental evidence suggests that estrogens stimulate the production of nitric oxide (NO) by vascular endothelial cells. This effect has been attributed to increased expression and enzymatic activity of both the constitutive and inducible isoforms of NO synthase. In this study, we have investigated whether estrogens regulate the metabolism or release of asymmetric dimethylarginine (ADMA), an endogenous inhibitor of NO synthase. Methods and Results— The concentration of ADMA in the plasma of 15 postmenopausal women was 0.722±0.04 μmol/L (mean±SEM). Two weeks after subcutaneous implantation with estradiol, there was an increase in plasma estradiol concentration from 0.693±0.075 to 0.81±87 nmol/L, which was accompanied by a significant fall in plasma ADMA concentration to 0.588±0.03 μmol/L (P=0.006). Human and murine endothelial cell lines previously cultured in estrogen-free medium and then exposed to 17β-estradiol showed a dose-dependent decrease in the release of ADMA. This reached statistical significance at 10−14 mol/L 17β-estradiol and was accompanied by a corresponding increase in the activity of dimethylarginine dimethylaminohydrolase (DDAH), an enzyme that catalyzes the metabolism of ADMA. Conclusions— We have demonstrated that estrogens can alter the catabolism and release of ADMA in vitro and reduce the circulating concentration in vivo. We therefore propose that increased DDAH activity and the subsequent fall in ADMA could contribute to the positive effect of estrogen on NO synthesis

On Component Forces in Physics: A Pragmatic View

Do component forces exist? I argue that the answer lies in the affirmative, on historical and operational grounds

Making it work for me: beliefs about making a personal health record relevant and useable.

BACKGROUND: A Personal Health Record (PHR) is an electronic record that individuals use to manage and share their health information, e.g. data from their medical records and data collected by apps. However, engagement with their record can be low if people do not find it beneficial to their health, wellbeing or interactions with health and other services. We have explored the beliefs potential users have about a PHR, how it could be made personally relevant, and barriers to its use. METHODS: A qualitative design comprising eight focus groups, each with 6-8 participants. Groups included adults with long-term health conditions, young people, physically active adults, data experts, and members of the voluntary sector. Each group lasted 60-90 min, was audio recorded and transcribed verbatim. We analysed the data using thematic analysis to address the question "What are people's beliefs about making a Personal Health Record have relevance and impact?" RESULTS: We found four themes. Making it work for me is about how to encourage individuals to actively engage with their PHR. I control my information is about individuals deciding what to share and who to share it with. My concerns is about individuals' concerns about information security and if and how their information will be acted upon. Potential impact shows the potential benefits of a PHR such as increasing self-efficacy, uptake of health-protective behaviours, and professionals taking a more holistic approach to providing care and facilitating behaviour change. CONCLUSIONS: Our research shows the functionality that a PHR requires in order for people to engage with it. Interactive functions and integration with lifestyle and health apps are particularly important. A PHR could increase the effectiveness of behaviour change apps by specifying evidence-based behaviour change techniques that apps should incorporate. A PHR has the potential to increase health-protective behaviours and facilitate a more person-driven health and social care system. It could support patients to take responsibility for self-managing their health and treatment regimens, as well as helping patients to play a more active role when care transfers across boundaries of responsibility

First trimester placental endothelial cells from pregnancies with abnormal uterine artery Doppler are more sensitive to apoptotic stimuli.

Failure of the placental capillary network to develop normally is associated with early onset fetal growth restriction (FGR) and pre-eclampsia (PE). Although the symptoms are observed at term, the problem begins in the first trimester. However, investigations at this clinically relevant time are hindered by difficulties in identifying earlystage pregnancies that are at risk of developing FGR/PE. Using uterine artery Doppler ultrasound in the first trimester as a proxy measure of poor placentation, we have identified pregnancies at increased risk of developing early onset FGR/PE. Placental endothelial cells (PEC) isolated from pregnancies at increased risk of developing FGR/PE grew more slowly and their basal rate of apoptosis was significantly higher than that seen in the normal group. The pro-apoptotic stimulus, TNFα, induced apoptosis in cells from both groups but this was significantly greater in the high risk group. TNF receptor expression was unaffected. Inhibition of nitric oxide (NO) production significantly increased the sensitivity of cells from the normal pregnancies to TNFα but not in the high risk group establishing a functional role for NO in this system. In conclusion, first trimester PEC from pregnancies at increased risk of developing early onset FGR/PE were inherently more sensitive to apoptotic stimuli and this was functionally linked to the synthesis of NO. This may contribute to the poor placental vascular development seen in on going pregnancies

Implementing a quality improvement programme in palliative care in care homes: a qualitative study

<p>Abstract</p> <p>Background</p> <p>An increasing number of older people reach the end of life in care homes. The aim of this study is to explore the perceived benefits of, and barriers to, implementation of the Gold Standards Framework for Care Homes (GSFCH), a quality improvement programme in palliative care.</p> <p>Methods</p> <p>Nine care homes involved in the GSFCH took part. We conducted semi-structured interviews with nine care home managers, eight nurses, nine care assistants, eleven residents and seven of their family members. We used the Framework approach to qualitative analysis. The analysis was deductive based on the key tasks of the GSFCH, the 7Cs: communication, coordination, control of symptoms, continuity, continued learning, carer support, and care of the dying. This enabled us to consider benefits of, and barriers to, individual components of the programme, as well as of the programme as a whole.</p> <p>Results</p> <p>Perceived benefits of the GSFCH included: improved symptom control and team communication; finding helpful external support and expertise; increasing staff confidence; fostering residents' choice; and boosting the reputation of the home. Perceived barriers included: increased paperwork; lack of knowledge and understanding of end of life care; costs; and gaining the cooperation of GPs. Many of the tools and tasks in the GSFCH focus on improving communication. Participants described effective communication within the homes, and with external providers such as general practitioners and specialists in palliative care. However, many had experienced problems with general practitioners. Although staff described the benefits of supportive care registers, coding predicted stage of illness and advance care planning, which included improved communication, some felt the need for more experience of using these, and there were concerns about discussing death.</p> <p>Conclusions</p> <p>Most of the barriers described by participants are relevant to other interventions to improve end of life care in care homes. There is a need to investigate the impact of quality improvement programmes in care homes, such as the GSFCH, on a wider range of outcomes for residents and their families, and to monitor the sustainability of any resulting improvements. It is also important to explore the impact of the different components of these complex interventions.</p

Dental general anaesthetic receipt among Australians aged 15+ years, 1998–1999 to 2004–2005

Background Adults receive dental general anaesthetic (DGA) care when standard dental treatment is not possible. Receipt of DGA care is resource-intensive and not without risk. This study explores DGA receipt among 15+-year-old Australians by a range of risk indicators. Methods DGA data were obtained from Australia's Hospital Morbidity Database from 1998–1999 to 2004–2005. Poisson regression modeling was used to examine DGA rates in relation to age, sex, Indigenous status, location and procedure. Results The overall DGA rate was 472.79 per 100,000 (95% CI 471.50–474.09). Treatment of impacted teeth (63.7%) was the most common reason for DGA receipt, followed by dental caries treatment (12.4%), although marked variations were seen by age-group. After adjusting for other covariates, DGA rates among 15–19-year-olds were 13.20 (95% CI 12.65–13.78) times higher than their 85+-year-old counterparts. Females had 1.46 (95% CI 1.45–1.47) times the rate of their male counterparts, while those living in rural/remote areas had 2.70 (95% CI 2.68–2.72) times the rate of metropolitan-dwellers. DGA rates for non-Indigenous persons were 4.88 (95% CI 4.73–5.03) times those of Indigenous persons. The DGA rate for 1+ extractions was 461.9 per 100,000 (95% CI 460.6–463.2), compared with a rate of 23.6 per 100,000 (95% CI 23.3–23.9) for 1+ restorations. Conclusion Nearly two-thirds of DGAs were for treatment of impacted teeth. Persons aged 15–19 years were disproportionately represented among those receiving DGA care, along with females, rural/remote-dwellers and those identifying as non-Indigenous. More research is required to better understand the public health implications of DGA care among 15+-year-olds, and how the demand for receipt of such care might be reduced.Lisa M Jamieson and Kaye F Roberts-Thomso

Tobacco and the risk of acute leukaemia in adults

Self-reported smoking histories were collected during face-to-face interviews with 807 patients with acute leukaemia and 1593 age- and sex-matched controls. Individuals who had smoked regularly at some time during their lives were more likely to develop acute leukaemia than those who had never smoked (odds ratio (OR) = 1.2, 95% confidence interval (CI) 1.0–1.4). The association was strongest for current smokers, defined here as smoking 2 years before diagnosis (OR = 1.4, 95% CI 1.1–1.7). With respect to the numbers of years smoked, risk estimates were raised in all groups except those who had smoked for fewer than 10 years. Similarly, the odds ratio decreased as the number of years ‘stopped smoking’ increased, falling to one amongst those who had given up smoking for more than 10 years. No significant linear trends were found, however, with either the numbers of years smoked or the numbers of years stopped smoking, and no significant differences were found between AML and ALL. © 1999 Cancer Research Campaig

Following a foraging fish-finder : diel habitat use of Blainville's beaked whales revealed by echolocation

© The Author(s), 2011. This article is distributed under the terms of the Creative Commons Attribution License. The definitive version was published in PLoS One 6 (2011): e28353, doi:10.1371/journal.pone.0028353.Simultaneous high resolution sampling of predator behavior and habitat characteristics is often difficult to achieve despite its importance in understanding the foraging decisions and habitat use of predators. Here we tap into the biosonar system of Blainville's beaked whales, Mesoplodon densirostris, using sound and orientation recording tags to uncover prey-finding cues available to echolocating predators in the deep-sea. Echolocation sounds indicate where whales search and encounter prey, as well as the altitude of whales above the sea-floor and the density of organisms around them, providing a link between foraging activity and the bio-physical environment. Tagged whales (n = 9) hunted exclusively at depth, investing most of their search time either in the lower part of the deep scattering layer (DSL) or near the sea-floor with little diel change. At least 43% (420/974) of recorded prey-capture attempts were performed within the benthic boundary layer despite a wide range of dive depths, and many dives included both meso- and bentho-pelagic foraging. Blainville's beaked whales only initiate searching when already deep in the descent and encounter prey suitable for capture within 2 min of the start of echolocation, suggesting that these whales are accessing prey in reliable vertical strata. Moreover, these prey resources are sufficiently dense to feed the animals in what is effectively four hours of hunting per day enabling a strategy in which long dives to exploit numerous deep-prey with low nutritional value require protracted recovery periods (average 1.5 h) between dives. This apparent searching efficiency maybe aided by inhabiting steep undersea slopes with access to both the DSL and the sea-floor over small spatial scales. Aggregations of prey in these biotopes are located using biosonar-derived landmarks and represent stable and abundant resources for Blainville's beaked whales in the otherwise food-limited deep-ocean.The work was funded by the Office of Naval Research and the National Ocean Partnership Program (US), by a consortium consisting of the Canary Islands Government, the Spanish Ministry of Environment and the Spanish Ministry of Defense, and by the European environmental funding LIFE-INDEMARES program for the inventory and designation of the Natura 2000 network in marine areas of the Spanish territory, headed by Fundacion Biodiversidad, with additional support from the Cabildo Insular of El Hierro. PA is currently supported by the National Research Project: Cetacean, Oceanography and Biodiversity from La Palma and El Hierro (CGL2009-13112) of the Spanish Ministry of Science and NAS by a Marie Curie fellowship from the 7th European Frame Program. MJ was supported by grants from the Strategic Environmental Research Development Program and from the National Ocean Partnership Program. PTM was supported by frame grants from the National Danish Science Foundation