The sterol-binding activity of PATHOGENESIS-RELATED PROTEIN 1 reveals the mode of action of an antimicrobial protein

Pathogenesis-related proteins played a pioneering role 50 years ago in the discovery of plant innate immunity as a set of proteins that accumulated upon pathogen challenge. The most abundant of these proteins, PATHOGENESIS-RELATED 1 (PR-1) encodes a small antimicrobial protein that has become, as a marker of plant immune signaling, one of the most referred to plant proteins. The biochemical activity and mode of action of PR-1 proteins has remained elusive, however. Here, we provide genetic and biochemical evidence for the capacity of PR-1 proteins to bind sterols, and demonstrate that the inhibitory effect on pathogen growth is caused by the sequestration of sterol from pathogens. In support of our findings, sterol-auxotroph pathogens such as the oomycete Phytophthora are particularly sensitive to PR-1, whereas sterol-prototroph fungal pathogens become highly sensitive only when sterol biosynthesis is compromised. Our results are in line with previous findings showing that plants with enhanced PR-1 expression are particularly well protected against oomycete pathogens

The @RISK Study: Risk communication for patients with type 2 diabetes: design of a randomised controlled trial

<p>Abstract</p> <p>Background</p> <p>Patients with type 2 diabetes mellitus (T2DM) have an increased risk to develop severe diabetes related complications, especially cardiovascular disease (CVD). The risk to develop CVD can be estimated by means of risk formulas. However, patients have difficulties to understand the outcomes of these formulas. As a result, they may not recognize the importance of changing lifestyle and taking medication in time. Therefore, it is important to develop risk communication methods, that will improve the patients' understanding of risks associated with having diabetes, which enables them to make informed choices about their diabetes care.</p> <p>The aim of this study is to investigate the effects of an intervention focussed on the communication of the absolute 10-year risk to develop CVD on risk perception, attitude and intention to change lifestyle behaviour in patients with T2DM. The conceptual framework of the intervention is based on the Theory of Planned Behaviour and the Self-regulation Theory.</p> <p>Methods</p> <p>A randomised controlled trial will be performed in the Diabetes Care System West-Friesland (DCS), a managed care system. Newly referred T2DM patients of the DCS, younger than 75 years will be eligible for the study. The intervention group will be exposed to risk communication on CVD, on top of standard managed care of the DCS. This intervention consists of a simple explanation on the causes and consequences of CVD, and possibilities for prevention. The probabilities of CVD in 10 year will be explained in natural frequencies and visualised by a population diagram. The control group will receive standard managed care. The primary outcome is appropriateness of risk perception. Secondary outcomes are attitude and intention to change lifestyle behaviour and illness perception. Differences between baseline and follow-up (2 and 12 weeks) between groups will be analysed according to the intention-to-treat principle. The study was powered on 120 patients in each group.</p> <p>Discussion</p> <p>This innovative risk communication method based on two behavioural theories might improve patient's appropriateness of risk perception and attitude concerning lifestyle change. With a better understanding of their CVD risk, patients will be able to make informed choices concerning diabetes care.</p> <p>Trail registration</p> <p>The trial is registered as NTR1556 in the Dutch Trial Register.</p

A randomized, double blind, placebo and active comparator controlled pilot study of UP446, a novel dual pathway inhibitor anti-inflammatory agent of botanical origin

<p>Abstract</p> <p>Background</p> <p>Current use of prescribed or over the counter non-steroidal anti-inflammatory drugs (NSAIDs) for pain and osteoarthritis (OA) have untoward gastrointestinal and cardiovascular related side effects, as a result the need for a safe and effective alternative has become unequivocally crucial.</p> <p>Method</p> <p>A randomized, double blind, placebo and active controlled pilot study of a novel dual pathway, COX1/2 and LOX, inhibitor anti-inflammatory agent of botanical origin, UP446 was conducted. Sixty subjects (age 40-75) with symptomatic OA of the hip or knee were assigned to 4 treatment groups (n = 15); Group A0 (Placebo, CMC capsule), Group A1 (UP446 250 mg/day), Group A2 (UP446 500 mg/day) and Group A3 (Celecoxib, 200 mg/day). MOS-SF-36 and Western Ontario and McMaster University Osteoarthritis Index (WOMAC) data were collected at baseline and after 30, 60 and 90 days of treatment as a measure of efficacy. Erythrocyte sedimentation rate, C-reactive protein, plasma thrombin time (PTT), fructosamine, Hematology, clinical chemistry and fecal occult blood were monitored for safety.</p> <p>Results</p> <p>Statistically significant decrease in WOMAC pain score were observed for Group A1 at day 90, Group A2 at 30 and 90 days and Group A3 at 60 and 90 days. Statistically significant decrease in WOMAC stiffness score were observed for Group A1 and Group A2 at 30, 60 and 90 days; but not for Group A0 and Group A3. The mean change in WOMAC functional impairment scores were statistically significant for Group A1 and Group A2 respectively at 30 days (p = 0.006 and p = 0.006), at 60 days (p = 0.016 and p = 0.002) and at 90 days (p = 0.018 and p = 0.002), these changes were not significant for Group A0 and Group A3. Based on MOS -SF-36 questionnaires, statistically significant improvements in physical function, endurance and mental health scores were observed for all active treatment groups compared to placebo. No significant changes suggestive of toxicity in routine hematologies, serum chemistries, liver enzymes or PTT were noted in any of the treatment groups.</p> <p>Conclusion</p> <p>Based on current findings UP446 is safe and efficacious alternative to established anti-inflammatory medications for alleviating OA symptoms as measured by the WOMAC Index.</p

HIV Disease Impact on Mothers: What They Miss During Their Children’s Developmental Years

Adjusting to chronic illness is very complicated for families with children, as they are already faced with the challenge of development and childrearing. In this study, qualitative interviews were conducted with HIV positive mothers on a number of issues related to being an HIV positive mother raising young children. One topic of the interview was whether or not they felt that HIV had caused them to miss activities with their children while the children were growing up, what types of activities they had missed, the age of the child for each example, and how HIV had led to missing these activities. Interviews were conducted in 2008 with a random sample of 57 mothers being followed in a longitudinal assessment study. All study participants were English or Spanish speaking. Mean age was 44.1 (SD = 5.6) years; 47% were Latina; 35% African American; 11% White; and 7% other race. About 60% of the mothers disclosed that their HIV status had caused them to miss out on activities with their children while their children were growing up, ranging from daily care activities to major school and extra-curricular activities. Some mothers missed significant amounts of time with their children due to hospitalizations. In some cases mothers felt forced into a choice between mothering ability and their own health, including adherence to medications. Implications for the mothers and the children are discussed

Performance related factors are the main determinants of the von Willebrand factor response to exhaustive physical exercise

Background: Physical stress triggers the endothelium to release von Willebrand Factor (VWF) from the Weibel Palade bodies. Since VWF is a risk factor for arterial thrombosis, it is of great interest to discover determinants of VWF response to physical stress. We aimed to determine the main mediators of the VWF increase by exhaustive physical exercise. Methods: 105 healthy individuals (18-35 years) were included in this study. Each participant performed an incremental exhaustive exercise test on a cycle ergometer. Respiratory gas exchange measurements were obtained while cardiac function was continuously monitored. Blood was collected at baseline and directly after exhaustion. VWF antigen (VWF:Ag) levels, VWF collagen binding (VWF:CB) levels, ADAMTS13 activity and common variations in Syntaxin Binding Protein-5 (STXBP5, rs1039084 and rs9399599), Syntaxin-2 (STX2, rs7978987) and VWF (promoter, rs7965413) were determined. Results: The median VWF:Ag level at baseline was 0.94 IU/mL [IQR 0.8-1.1] and increased with 47% [IQR 25-73] after exhaustive exercise to a median maximum VWF:Ag of 1.38 IU/mL [IQR 1.1-1.8] (p<0.0001). VWF:CB levels and ADAMTS13 activity both also increased after exhaustive exercise (median increase 43% and 12%, both p<0.0001). The strongest determinants of the VWF:Ag level increase are performance related (p<0.0001). We observed a gender difference in VWF:Ag response to exercise (females 1.2 IU/mL; males 1.7 IU/mL, p = 0.001), which was associated by a difference in performance. Genetic variations in STXBP5, STX2 and the VWF promoter were not associated with VWF:Ag levels at baseline nor with the VWF:Ag increase. Conclusions: VWF:Ag levels strongly increase upon exhaustive exercise and this increase is strongly determined by physical fitness level and the intensity of the exercise, while there is no clear effect of genetic variation in STXBP5, STX2 and the VWF promoter

Improving patient adherence to lifestyle advice (IMPALA): a cluster-randomised controlled trial on the implementation of a nurse-led intervention for cardiovascular risk management in primary care (protocol)

Background Many patients at high risk of cardiovascular diseases are managed and monitored in general practice. Recommendations for cardiovascular risk management, including lifestyle change, are clearly described in the Dutch national guideline. Although lifestyle interventions, such as advice on diet, physical exercise, smoking and alcohol, have moderate, but potentially relevant effects in these patients, adherence to lifestyle advice in general practice is not optimal. The IMPALA study intends to improve adherence to lifestyle advice by involving patients in decision making on cardiovascular prevention by nurse-led clinics. The aim of this paper is to describe the design and methods of a study to evaluate an intervention aimed at involving patients in cardiovascular risk management. Methods A cluster-randomised controlled trial in 20 general practices, 10 practices in the intervention arm and 10 in the control arm, starting on October 2005. A total of 720 patients without existing cardiovascular diseases but eligible for cardiovascular risk assessment will be recruited. In both arms, the general practitioners and nurses will be trained to apply the national guideline for cardiovascular risk management. Nurses in the intervention arm will receive an extended training in risk assessment, risk communication, the use of a decision aid and adapted motivational interviewing. This communication technique will be used to support the shared decision-making process about risk reduction. The intervention comprises 2 consultations and 1 follow-up telephone call. The nurses in the control arm will give usual care after the risk estimation, according to the national guideline. Primary outcome measures are self-reported adherence to lifestyle advice and drug treatment. Secondary outcome measures are the patients' perception of risk and their motivation to change their behaviour. The measurements will take place at baseline and after 12 and 52 weeks. Clinical endpoints will not be measured, but the absolute 10-year risk of cardiovascular events will be estimated for each patient from medical records at baseline and after 1 year. Discussion The combined use of risk communication, a decision aid and motivational interviewing to enhance patient involvement in decision making is an innovative aspect of the intervention. Trial registration Current Controlled Trials ISRCTN5155672

The Oslo Health Study: The impact of self-selection in a large, population-based survey

BACKGROUND: Research on health equity which mainly utilises population-based surveys, may be hampered by serious selection bias due to a considerable number of invitees declining to participate. Sufficient information from all the non-responders is rarely available to quantify this bias. Predictors of attendance, magnitude and direction of non-response bias in prevalence estimates and association measures, are investigated based on information from all 40 888 invitees to the Oslo Health Study. METHODS: The analyses were based on linkage between public registers in Statistics Norway and the Oslo Health Study, a population-based survey conducted in 2000/2001 inviting all citizens aged 30, 40, 45, 59–60 and 75–76 years. Attendance was 46%. Weighted analyses, logistic regression and sensitivity analyses are performed to evaluate possible selection bias. RESULTS: The response rate was positively associated with age, educational attendance, total income, female gender, married, born in a Western county, living in the outer city residential regions and not receiving disability benefit. However, self-rated health, smoking, BMI and mental health (HCSL) in the attendees differed only slightly from estimated prevalence values in the target population when weighted by the inverse of the probability of attendance. Observed values differed only moderately provided that the non-attending individuals differed from those attending by no more than 50%. Even though persons receiving disability benefit had lower attendance, the associations between disability and education, residential region and marital status were found to be unbiased. The association between country of birth and disability benefit was somewhat more evident among attendees. CONCLUSIONS: Self-selection according to sociodemographic variables had little impact on prevalence estimates. As indicated by disability benefit, unhealthy persons attended to a lesser degree than healthy individuals, but social inequality in health by different sociodemographic variables seemed unbiased. If anything we would expect an overestimation of the odds ratio of chronic disease among persons born in non-western countries

Spatial clustering in the spatio-temporal dynamics of endemic cholera

<p>Abstract</p> <p>Background</p> <p>The spatio-temporal patterns of infectious diseases that are environmentally driven reflect the combined effects of transmission dynamics and environmental heterogeneity. They contain important information on different routes of transmission, including the role of environmental reservoirs. Consideration of the spatial component in infectious disease dynamics has led to insights on the propagation of fronts at the level of counties in rabies in the US, and the metapopulation behavior at the level of cities in childhood diseases such as measles in the UK, both at relatively coarse scales. As epidemiological data on individual infections become available, spatio-temporal patterns can be examined at higher resolutions.</p> <p>Methods</p> <p>The extensive spatio-temporal data set for cholera in Matlab, Bangladesh, maps the individual location of cases from 1983 to 2003. This unique record allows us to examine the spatial structure of cholera outbreaks, to address the role of primary transmission, occurring from an aquatic reservoir to the human host, and that of secondary transmission, involving a feedback between current and past levels of infection. We use Ripley's K and L indices and bootstrapping methods to evaluate the occurrence of spatial clustering in the cases during outbreaks using different temporal windows. The spatial location of cases was also confronted against the spatial location of water sources.</p> <p>Results</p> <p>Spatial clustering of cholera cases was detected at different temporal and spatial scales. Cases relative to water sources also exhibit spatial clustering.</p> <p>Conclusions</p> <p>The clustering of cases supports an important role of secondary transmission in the dynamics of cholera epidemics in Matlab, Bangladesh. The spatial clustering of cases relative to water sources, and its timing, suggests an effective role of water reservoirs during the onset of cholera outbreaks. Once primary transmission has initiated an outbreak, secondary transmission takes over and plays a fundamental role in shaping the epidemics in this endemic area.</p

Exercise therapy in Type 2 diabetes

Structured exercise is considered an important cornerstone to achieve good glycemic control and improve cardiovascular risk profile in Type 2 diabetes. Current clinical guidelines acknowledge the therapeutic strength of exercise intervention. This paper reviews the wide pathophysiological problems associated with Type 2 diabetes and discusses the benefits of exercise therapy on phenotype characteristics, glycemic control and cardiovascular risk profile in Type 2 diabetes patients. Based on the currently available literature, it is concluded that Type 2 diabetes patients should be stimulated to participate in specifically designed exercise intervention programs. More attention should be paid to cardiovascular and musculoskeletal deconditioning as well as motivational factors to improve long-term treatment adherence and clinical efficacy. More clinical research is warranted to establish the efficacy of exercise intervention in a more differentiated approach for Type 2 diabetes subpopulations within different stages of the disease and various levels of co-morbidity