Recent trends in cutaneous malignant melanoma in the Yorkshire region of England; incidence, mortality and survival in relation to stage of disease, 1993–2003

The aim of this study was to investigate recent trends in incidence, mortality and survival in patients diagnosed with malignant melanoma (MM) in relation to stage (Breslow thickness). Cases of primary invasive and in situ MM diagnosed between 1st January 1993 and 31st December 2003 in the former Yorkshire Health Authority were identified from cancer registry data. Over the study period, the incidence of invasive MM increased from 5.4 to 9.7 per 100 000 in male subjects and from 7.5 to 13.1 per 100 000 in female subjects. Most of this increase was seen in thin tumours (<1.5 mm). Thin tumours were more likely to be diagnosed in the younger age groups and be classified as superficial spreading melanoma. In situ melanoma rates increased only slightly. Over the same time period, mortality rates have been relatively constant in both male and female subjects. Five-year relative survival varied from 91.8% (95% CI 90.4–93.1) for patients with thin tumours to 41.5% (95% CI 36.7–46.3) for those with thick tumours. In multivariable analyses, Breslow thickness was the most important prognostic factor. Age, sex and level of deprivation were also identified as independent prognostic factors. The trends in incidence suggest that the increase is real, rather than an artefact of increased scrutiny, implying that primary prevention in the Yorkshire area of the UK has failed to control trends in incidence. Mortality, in contrast, appears to be levelling off, indicating that secondary prevention has been more effective

Factors associated with early menarche: results from the French Health Behaviour in School-aged Children (HBSC) study

<p>Abstract</p> <p>Background</p> <p>Puberty is a transition period making physiological development a challenge adolescents have to face. Early pubertal development could be associated with higher risks of poor health. Our objective was to examine risk behaviours, physical and psychological determinants associated with early menarche (<11 years).</p> <p>Methods</p> <p>Early menarche was assessed in the Health Behaviour in School-aged Children French cross-sectional survey. Data were collected in 2006 by anonymous self-reported standardized questionnaire from a nationally representative sample of 1072 15 years old girls in school classrooms. Family environment, school experience, physical and psychological factors, risk behaviours (substance use and sexual initiation) were recorded. Logistic regression models were applied (analysing for crude and adjusted relationships between early menarche and risk behaviours controlled for family context).</p> <p>Results</p> <p>Median age at menarche was 13.0 years; 57 girls (5.3%) were early-matured. Controlled for familial environment, early menarche was associated with having had more than two life-drunkenness episodes (adjusted OR = 2.5 [1.3-4.6]), early sexual initiation (adjusted OR = 2.8 [1.3-6.0]) and overweight (adjusted OR = 7.3 [3.6-14.9]).</p> <p>Conclusion</p> <p>Early-maturing girls may affiliate with older adolescents, hence engage in risk behaviours linked to their appearance rather than their maturity level. Factors associated with early menarche highlight the need to focus attention on early-matured girls to prevent further health problems linked to risk behaviours.</p

Individual and Situational Factors Related to Young Women’s Likelihood of Confronting Sexism in Their Everyday Lives

Factors related to young women’s reported likelihood of confronting sexism were investigated. Participants were 338 U.S. female undergraduates (M = 19 years) attending a California university. They were asked to complete questionnaire measures and to write a personal narrative about an experience with sexism. Approximately half (46%) the women reported confronting the perpetrator. Individual factors (prior experience with sexism, feminist identification, collective action) and situational factors (familiarity and status of perpetrator, type of sexism) were tested as predictors in a logistic regression. Women were less likely to report confronting sexism if (1) they did not identify as feminists, (2) the perpetrator was unfamiliar or high-status/familiar (vs. familiar/equal-status), or (3) the type of sexism involved unwanted sexual attention (vs. sexist comments)

Activation of Akt by the Bacterial Inositol Phosphatase, SopB, is Wortmannin Insensitive

Salmonella enterica uses effector proteins translocated by a Type III Secretion System to invade epithelial cells. One of the invasion-associated effectors, SopB, is an inositol phosphatase that mediates sustained activation of the pro-survival kinase Akt in infected cells. Canonical activation of Akt involves membrane translocation and phosphorylation and is dependent on phosphatidyl inositide 3 kinase (PI3K). Here we have investigated these two distinct processes in Salmonella infected HeLa cells. Firstly, we found that SopB-dependent membrane translocation and phosphorylation of Akt are insensitive to the PI3K inhibitor wortmannin. Similarly, depletion of the PI3K regulatory subunits p85α and p85ß by RNAi had no inhibitory effect on SopB-dependent Akt phosphorylation. Nevertheless, SopB-dependent phosphorylation does depend on the Akt kinases, PDK1 and rictor-mTOR. Membrane translocation assays revealed a dependence on SopB for Akt recruitment to Salmonella ruffles and suggest that this is mediated by phosphoinositide (3,4) P2 rather than phosphoinositide (3,4,5) P3. Altogether these data demonstrate that Salmonella activates Akt via a wortmannin insensitive mechanism that is likely a class I PI3K-independent process that incorporates some essential elements of the canonical pathway

Targeting the Wolbachia Cell Division Protein FtsZ as a New Approach for Antifilarial Therapy

Filarial nematode parasites are responsible for a number of devastating diseases in humans and animals. These include lymphatic filariasis and onchocerciasis that afflict 150 million people in the tropics and threaten the health of over one billion. The parasites possess intracellular bacteria, Wolbachia, which are needed for worm survival. Clearance of these bacteria with certain antibiotics leads to parasite death. These findings have pioneered the approach of using antibiotics to treat and control filarial infections. In the present study, we have investigated the cell division process in Wolbachia for new drug target discovery. We have identified the essential cell division protein FtsZ, which has a GTPase activity, as an attractive Wolbachia drug target. We describe the molecular characterization and catalytic properties of the enzyme and demonstrate that the GTPase activity is inhibited by the natural product, berberine, and small molecule inhibitors identified from a high-throughput screen. We also found that berberine was effective in reducing motility and reproduction in B. malayi parasites in vitro. Our results should facilitate the discovery of selective inhibitors of FtsZ as a novel antibiotic approach for controlling filarial infection

TGF-β1 Down-Regulation of NKG2D/DAP10 and 2B4/SAP Expression on Human NK Cells Contributes to HBV Persistence

The mechanism underlying persistent hepatitis B virus (HBV) infection remains unclear. We investigated the role of innate immune responses to persistent HBV infection in 154 HBV-infected patients and 95 healthy controls. The expression of NKG2D- and 2B4-activating receptors on NK cells was significantly decreased, and moreover, the expression of DAP10 and SAP, the intracellular adaptor proteins of NKG2D and 2B4 (respectively), were lower, which then impaired NK cell-mediated cytotoxic capacity and interferon-γ production. Higher concentrations of transforming growth factor-beta 1 (TGF-β1) were found in sera from persistently infected HBV patients. TGF-β1 down-regulated the expression of NKG2D and 2B4 on NK cells in our in vitro study, leading to an impairment of their effector functions. Anti-TGF-β1 antibodies could restore the expression of NKG2D and 2B4 on NK cells in vitro. Furthermore, TGF-β1 induced cell-cycle arrest in NK cells by up-regulating the expression of p15 and p21 in NK cells from immunotolerant (IT) patients. We conclude that TGF-β1 may reduce the expression of NKG2D/DAP10 and 2B4/SAP, and those IT patients who are deficient in these double-activating signals have impaired NK cell function, which is correlated with persistent HBV infection

Improving PBL in Empowering Meta cognitive Skill of Students

Abstract Objective: Problem-Based Learning (PBL) is a potential constructivist learning strategy that empowers students’ Meta cognitive skill. PBL focuses on problem, involves thinking activity to solve problems, and correlates to cognitive function of students. Methods: The implementation of PBL reveals various benefits, but there are also some weaknesses in this learning strategy. Thus, it is necessary to implement a certain learning strategy that can cover the PBL weaknesses, such as Reading, Questioning, and Answering (RQA) learning strategy. RQA is a new learning strategy developed based on a fact that almost all students do not read the next lecture materials, causing failure of learning strategy planned and finally the students’ comprehension becomes low. RQA is also potential to empower students’ Meta cognitive skill. Findings: The integration of RQA and PBL learning strategy is called PBL-RQA learning strategy. This study was a quasi-experimental study designed to compare the effect of PBL, RQA, and PBL-RQA learning strategies on the students’ Meta cognitive skill of Faculty of Mathematics and Science, State University of Makassar. Application: The results of the study showed that the potency of PBL learning strategy in empowering the students’ Meta cognitive skill has been increased by integrating it to RQA learning strategy. The meta cognitive skill mean score of the students taught by PBL-RQA learning strategy was 21% higher than that of the students taught by PBL and 26.9% higher than that of the students taught by RQA learning strategy. Keywords: Answering, Meta Cognitive Skill, Problem-Based Learning, Questioning, Reading, PBL-RQ

Systematic review: Effects, design choices, and context of pay-for-performance in health care

<p>Abstract</p> <p>Background</p> <p>Pay-for-performance (P4P) is one of the primary tools used to support healthcare delivery reform. Substantial heterogeneity exists in the development and implementation of P4P in health care and its effects. This paper summarizes evidence, obtained from studies published between January 1990 and July 2009, concerning P4P effects, as well as evidence on the impact of design choices and contextual mediators on these effects. Effect domains include clinical effectiveness, access and equity, coordination and continuity, patient-centeredness, and cost-effectiveness.</p> <p>Methods</p> <p>The systematic review made use of electronic database searching, reference screening, forward citation tracking and expert consultation. The following databases were searched: Cochrane Library, EconLit, Embase, Medline, PsychINFO, and Web of Science. Studies that evaluate P4P effects in primary care or acute hospital care medicine were included. Papers concerning other target groups or settings, having no empirical evaluation design or not complying with the P4P definition were excluded. According to study design nine validated quality appraisal tools and reporting statements were applied. Data were extracted and summarized into evidence tables independently by two reviewers.</p> <p>Results</p> <p>One hundred twenty-eight evaluation studies provide a large body of evidence -to be interpreted with caution- concerning the effects of P4P on clinical effectiveness and equity of care. However, less evidence on the impact on coordination, continuity, patient-centeredness and cost-effectiveness was found. P4P effects can be judged to be encouraging or disappointing, depending on the primary mission of the P4P program: supporting minimal quality standards and/or boosting quality improvement. Moreover, the effects of P4P interventions varied according to design choices and characteristics of the context in which it was introduced.</p> <p>Future P4P programs should (1) select and define P4P targets on the basis of baseline room for improvement, (2) make use of process and (intermediary) outcome indicators as target measures, (3) involve stakeholders and communicate information about the programs thoroughly and directly, (4) implement a uniform P4P design across payers, (5) focus on both quality improvement and achievement, and (6) distribute incentives to the individual and/or team level.</p> <p>Conclusions</p> <p>P4P programs result in the full spectrum of possible effects for specific targets, from absent or negligible to strongly beneficial. Based on the evidence the review has provided further indications on how effect findings are likely to relate to P4P design choices and context. The provided best practice hypotheses should be tested in future research.</p

Biocontrol Potential of Forest Tree Endophytes

Peer reviewe

Iron Behaving Badly: Inappropriate Iron Chelation as a Major Contributor to the Aetiology of Vascular and Other Progressive Inflammatory and Degenerative Diseases

The production of peroxide and superoxide is an inevitable consequence of aerobic metabolism, and while these particular "reactive oxygen species" (ROSs) can exhibit a number of biological effects, they are not of themselves excessively reactive and thus they are not especially damaging at physiological concentrations. However, their reactions with poorly liganded iron species can lead to the catalytic production of the very reactive and dangerous hydroxyl radical, which is exceptionally damaging, and a major cause of chronic inflammation. We review the considerable and wide-ranging evidence for the involvement of this combination of (su)peroxide and poorly liganded iron in a large number of physiological and indeed pathological processes and inflammatory disorders, especially those involving the progressive degradation of cellular and organismal performance. These diseases share a great many similarities and thus might be considered to have a common cause (i.e. iron-catalysed free radical and especially hydroxyl radical generation). The studies reviewed include those focused on a series of cardiovascular, metabolic and neurological diseases, where iron can be found at the sites of plaques and lesions, as well as studies showing the significance of iron to aging and longevity. The effective chelation of iron by natural or synthetic ligands is thus of major physiological (and potentially therapeutic) importance. As systems properties, we need to recognise that physiological observables have multiple molecular causes, and studying them in isolation leads to inconsistent patterns of apparent causality when it is the simultaneous combination of multiple factors that is responsible. This explains, for instance, the decidedly mixed effects of antioxidants that have been observed, etc...Comment: 159 pages, including 9 Figs and 2184 reference