Coarse-grained simulations suggest potential competing roles of phosphoinositides and amphipathic helix structures in membrane curvature sensing of the AP180 N-terminal homology domain

The generation and sensing of membrane curvature by proteins has become of increasing interest to researchers with multiple mechanisms, from hydrophobic insertion to protein crowding, being identified. However, the role of charged lipids in the membrane curvature-sensing process is still far from understood. Many proteins involved in endocytosis bind phosphatidylinositol 4,5-bisphosphate (PIP2) lipids, allowing these proteins to accumulate at regions of local curvature. Here, using coarse-grained molecular dynamics simulations, we study the curvature-sensing behavior of the ANTH domain, a protein crucial for endocytosis. We selected three ANTH crystal structures containing either an intact, split, or truncated terminal amphipathic helix. On neutral membranes, the ANTH domain has innate curvature-sensing ability. In the presence of PIP2, however, only the domain with an intact helix senses curvature. Our work sheds light on the role of PIP2 and its modulation of membrane curvature sensing by proteins

Relationship Between Non-Hodgkin's Lymphoma and Blood Levels of Epstein-Barr Virus in Children in North-Western Tanzania: A Case Control Study.

Non-Hodgkin's Lymphomas (NHL) are common in African children, with endemic Burkitt's lymphoma (BL) being the most common subtype. While the role of Epstein-Barr Virus (EBV) in endemic BL is known, no data are available about clinical presentations of NHL subtypes and their relationship to Human Immunodeficiency Virus (HIV) infection and Epstein Barr Virus (EBV) load in peripheral blood of children in north-western, Tanzania. A matched case control study of NHL subtypes was performed in children under 15 years of age and their respective controls admitted to Bugando Medical Centre, Sengerema and Shirati district designated hospitals in north-western, Tanzania, between September 2010 and April 2011. Peripheral blood samples were collected on Whatman 903 filter papers and EBV DNA levels were estimated by multiplex real-time PCR. Clinical and laboratory data were collected using a structured data collection tool and analysed using chi-square, Fisher and Wilcoxon rank sum tests where appropriate. The association between NHL and detection of EBV in peripheral blood was assessed using conditional logistic regression model and presented as odds ratios (OR) and 95% confidence intervals (CI). A total of 35 NHL cases and 70 controls matched for age and sex were enrolled. Of NHLs, 32 had BL with equal distribution between jaw and abdominal tumour, 2 had large B cell lymphoma (DLBCL) and 1 had NHL-not otherwise specified (NHL-NOS). Central nervous system (CNS) presentation occurred only in 1 BL patient; 19 NHLs had stage I and II of disease. Only 1 NHL was found to be HIV-seropositive. Twenty-one of 35 (60%) NHL and 21 of 70 (30%) controls had detectable EBV in peripheral blood (OR = 4.77, 95% CI 1.71 - 13.33, p = 0.003). In addition, levels of EBV in blood were significantly higher in NHL cases than in controls (p = 0.024). BL is the most common childhood NHL subtype in north-western Tanzania. NHLs are not associated with HIV infection, but are strongly associated with EBV load in peripheral blood. The findings suggest that high levels of EBV in blood might have diagnostic and prognostic relevance in African children

Early Respiratory Management of Respiratory Distress Syndrome in Very Preterm Infants and Bronchopulmonary Dysplasia: A Case-Control Study

BACKGROUND: In the period immediately after birth, preterm infants are highly susceptible to lung injury. Early nasal continuous positive airway pressure (ENCPAP) is an attempt to avoid intubation and may minimize lung injury. In contrast, ENCPAP can fail, and at that time surfactant rescue can be less effective. OBJECTIVE: To compare the pulmonary clinical course and outcome of very preterm infants (gestational age 25–32 weeks) with respiratory distress syndrome (RDS) who started with ENCPAP and failed (ECF group), with a control group of infants matched for gestational age, who were directly intubated in the delivery room (DRI group). Primary outcome consisted of death during admission or bronchopulmonary dysplasia (BPD). RESULTS: 25 infants were included in the ECF group and 50 control infants matched for gestational age were included in the DRI group. Mean gestational age and birth weight in the ECF group were 29.7 weeks and 1,393 g and in the DRI group 29.1 weeks and 1,261 g (p = NS). The incidence of BPD was significantly lower in the ECF group than in the DRI group (4% vs. 35%; P<0.004; OR 12.6 (95% CI 1.6–101)). Neonatal mortality was similar in both groups (4%). The incidence of neonatal morbidities such as severe cerebral injury, patent ductus arteriosus, necrotizing enterocolitis and retinopathy of prematurity, was not significantly different between the two groups. CONCLUSION: A trial of ENCPAP at birth may reduce the incidence of BPD and does not seem to be detrimental in very preterm infants. Randomized controlled trials are needed to test whether early respiratory management of preterm infants with RDS plays an important role in the development of BPD

Revision and Update of the Consensus Definitions of Invasive Fungal Disease From the European Organization for Research and Treatment of Cancer and the Mycoses Study Group Education and Research Consortium.

BACKGROUND: Invasive fungal diseases (IFDs) remain important causes of morbidity and mortality. The consensus definitions of the Infectious Diseases Group of the European Organization for Research and Treatment of Cancer and the Mycoses Study Group have been of immense value to researchers who conduct clinical trials of antifungals, assess diagnostic tests, and undertake epidemiologic studies. However, their utility has not extended beyond patients with cancer or recipients of stem cell or solid organ transplants. With newer diagnostic techniques available, it was clear that an update of these definitions was essential. METHODS: To achieve this, 10 working groups looked closely at imaging, laboratory diagnosis, and special populations at risk of IFD. A final version of the manuscript was agreed upon after the groups' findings were presented at a scientific symposium and after a 3-month period for public comment. There were several rounds of discussion before a final version of the manuscript was approved. RESULTS: There is no change in the classifications of "proven," "probable," and "possible" IFD, although the definition of "probable" has been expanded and the scope of the category "possible" has been diminished. The category of proven IFD can apply to any patient, regardless of whether the patient is immunocompromised. The probable and possible categories are proposed for immunocompromised patients only, except for endemic mycoses. CONCLUSIONS: These updated definitions of IFDs should prove applicable in clinical, diagnostic, and epidemiologic research of a broader range of patients at high-risk

'This is what democracy looks like' : New Labour's blind spot and peripheral vision

New Labour in government since 1997 has been roundly criticized for not possessing a clear, coherent and consistent democratic vision. The absence of such a grand vision has resulted, from this critical perspective, in an absence of 'joined-up' thinking about democracy in an evolving multi-level state. Tensions have been all too apparent between the government's desire to exert central direction - manifested in its most pathological form as 'control freakery' - and its democratising initiatives derived from 'third-way' obsessions with 'decentralising', 'empowering' and 'enabling'. The purpose of this article is to examine why New Labour displayed such apparently impaired democratic vision and why it appeared incapable of conceiving of democratic reform 'in the round'. This article seeks to explain these apparent paradoxes, however, through utilising the notion of 'macular degeneration'. In this analysis, the perceived democratic blind spot of New Labour at Westminster is connected to a democratic peripheral vision, which has envisaged innovative participatory and decentred initiatives in governance beyond Westminster

Accuracy and usefulness of BMI measures based on self-reported weight and height: findings from the NHANES & NHIS 2001-2006

<p>Abstract</p> <p>Background</p> <p>The Body Mass Index (BMI) based on self-reported height and weight ("self-reported BMI") in epidemiologic studies is subject to measurement error. However, because of the ease and efficiency in gathering height and weight information through interviews, it remains important to assess the extent of error present in self-reported BMI measures and to explore possible adjustment factors as well as valid uses of such self-reported measures.</p> <p>Methods</p> <p>Using the combined 2001-2006 data from the continuous National Health and Nutrition Examination Survey, discrepancies between BMI measures based on self-reported and physical height and weight measures are estimated and socio-demographic predictors of such discrepancies are identified. Employing adjustments derived from the socio-demographic predictors, the self-reported measures of height and weight in the 2001-2006 National Health Interview Survey are used for population estimates of overweight & obesity as well as the prediction of health risks associated with large BMI values. The analysis relies on two-way frequency tables as well as linear and logistic regression models. All point and variance estimates take into account the complex survey design of the studies involved.</p> <p>Results</p> <p>Self-reported BMI values tend to overestimate measured BMI values at the low end of the BMI scale (< 22) and underestimate BMI values at the high end, particularly at values > 28. The discrepancies also vary systematically with age (younger and older respondents underestimate their BMI more than respondents aged 42-55), gender and the ethnic/racial background of the respondents. BMI scores, adjusted for socio-demographic characteristics of the respondents, tend to narrow, but do not eliminate misclassification of obese people as merely overweight, but health risk estimates associated with variations in BMI values are virtually the same, whether based on self-report or measured BMI values.</p> <p>Conclusion</p> <p>BMI values based on self-reported height and weight, if corrected for biases associated with socio-demographic characteristics of the survey respondents, can be used to estimate health risks associated with variations in BMI, particularly when using parametric prediction models.</p

Diabetic autonomic neuropathy: evidence for apoptosis in situ in the rat

Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/75065/1/j.1365-2982.2004.00524.x.pd