Bleached pigment activates transduction in salamander cones.

We have used suction electrode recording together with rapid steps into 0.5 mM IBMX solution to investigate changes in guanylyl cyclase velocity produced by pigment bleaching in isolated cones of the salamander Ambystoma tigrinum. Both backgrounds and bleaches accelerate the time course of current increase during steps into IBMX. We interpret this as evidence that the velocity of the guanylyl cyclase is increased in background light or after bleaching. Our results indicate that cyclase velocity increases nearly linearly with increasing percent pigment bleached but nonlinearly (and may saturate) with increasing back-ground intensity. In cones (as previously demonstrated for rods), light-activated pigment and bleached pigment appear to have somewhat different effects on the transduction cascade. The effect of bleaching on cyclase rate is maintained for at least 15-20 min after the light is removed, much longer than is required after a bleach for circulating current and sensitivity to stabilize in an isolated cone. The effect on the cyclase rate can be completely reversed by treatment with liposomes containing 11-cis retinal. The effects of bleaching can also be partially reversed by beta-ionone, an analogue of the chromophore 11-cis-retinal which does not form a covalent attachment to opsin. Perfusion of a bleached cone with beta-ionone produces a rapid increase in circulating current and sensitivity, which rapidly reverses when the beta-ionone is removed. Perfusion with beta-ionone also causes a partial reversal of the bleach-induced acceleration of cyclase velocity. We conclude that bleaching produces an "equivalent background" excitation of the transduction cascade in cones, perhaps by a mechanism similar to that in rods

Child Health Care in Ireland

The Irish health care system is based on a complex and costly mix of private, statutory, and voluntary provisions. The majority of health care expenditure comes from the state, with a significant proportion of acute hospital care funded from private insurance, but there are relatively high out-of-pocket costs for most service users. There is free access to acute hospital care, but not for primary care, for all children. About 40% of the population have free access to primary care. Universal preventive public health services, including vaccination and immunization, newborn blood spot screening, and universal neonatal hearing screening are free. Major health challenges include poverty, obesity, drug and alcohol use, and mental health. The health care system has been dominated for the last 5 years by the impact of the current recession, which has led to very sharp cuts in health care expenditure. It is unclear if the necessary substantial reform of the system will happen. Government policy calls for a move toward a patient-centered, primary care-led system, but without very substantial transfers of resources and investment in Information and Communication Technology, this is unlikely to occur

A randomised controlled trial and cost-effectiveness evaluation of "booster" interventions to sustain increases in physical activity in middle-aged adults in deprived urban neighbourhoods

Background: Systematic reviews have identified a range of brief interventions which increase physical activity in previously sedentary people. There is an absence of evidence about whether follow up beyond three months can maintain long term physical activity. This study assesses whether it is worth providing motivational interviews, three months after giving initial advice, to those who have become more active. Methods/Design: Study candidates (n = 1500) will initially be given an interactive DVD and receive two telephone follow ups at monthly intervals checking on receipt and use of the DVD. Only those that have increased their physical activity after three months (n = 600) will be randomised into the study. These participants will receive either a "mini booster" (n = 200), "full booster" (n = 200) or no booster (n = 200). The "mini booster" consists of two telephone calls one month apart to discuss physical activity and maintenance strategies. The "full booster" consists of a face-to-face meeting with the facilitator at the same intervals. The purpose of these booster sessions is to help the individual maintain their increase in physical activity. Differences in physical activity, quality of life and costs associated with the booster interventions, will be measured three and nine months from randomisation. The research will be conducted in 20 of the most deprived neighbourhoods in Sheffield, which have large, ethnically diverse populations, high levels of economic deprivation, low levels of physical activity, poorer health and shorter life expectancy. Participants will be recruited through general practices and community groups, as well as by postal invitation, to ensure the participation of minority ethnic groups and those with lower levels of literacy. Sheffield City Council and Primary Care Trust fund a range of facilities and activities to promote physical activity and variations in access to these between neighbourhoods will make it possible to examine whether the effectiveness of the intervention is modified by access to community facilities. A one-year integrated feasibility study will confirm that recruitment targets are achievable based on a 10% sample.Discussion: The choice of study population, study interventions, brief intervention preceding the study, and outcome measure are discussed

Flexible network reconstruction from relational databases with Cytoscape and CytoSQL

<p>Abstract</p> <p>Background</p> <p>Molecular interaction networks can be efficiently studied using network visualization software such as Cytoscape. The relevant nodes, edges and their attributes can be imported in Cytoscape in various file formats, or directly from external databases through specialized third party plugins. However, molecular data are often stored in relational databases with their own specific structure, for which dedicated plugins do not exist. Therefore, a more generic solution is presented.</p> <p>Results</p> <p>A new Cytoscape plugin 'CytoSQL' is developed to connect Cytoscape to any relational database. It allows to launch SQL ('Structured Query Language') queries from within Cytoscape, with the option to inject node or edge features of an existing network as SQL arguments, and to convert the retrieved data to Cytoscape network components. Supported by a set of case studies we demonstrate the flexibility and the power of the CytoSQL plugin in converting specific data subsets into meaningful network representations.</p> <p>Conclusions</p> <p>CytoSQL offers a unified approach to let Cytoscape interact with relational databases. Thanks to the power of the SQL syntax, this tool can rapidly generate and enrich networks according to very complex criteria. The plugin is available at <url>http://www.ptools.ua.ac.be/CytoSQL</url>.</p

French Pregnancy Physical Activity Questionnaire Compared with an Accelerometer Cut Point to Classify Physical Activity among Pregnant Obese Women

Given the high risk for inactivity during pregnancy in obese women, validated questionnaires for physical activity (PA) assessment in this specific population is required before evaluating the effect of PA on perinatal outcomes. No questionnaire was validated in pregnant obese women. The Pregnancy Physical Activity Questionnaire (PPAQ) has been designed based on activities reported during pregnancy and validated in pregnant women. We translated the PPAQ to French and assessed reliability and accuracy of this French version among pregnant obese women. In this cross-sectional study, pregnant obese women were evenly recruited at the end of each trimester of pregnancy. They completed the PPAQ twice, with an interval of 7 days in-between, to recall PA of the last three months. Between PPAQ assessments, participants wore an accelerometer (Actigraph GT1M) during 7 consecutive days. Fourty-nine (49) pregnant obese women (29.8±4.2 yrs, 34.7±5.1 kg.m−2) participated to the study. The intraclass correlation coefficients (ICCs) between the two PPAQ assessments were 0.90 for total activity, 0.86 for light and for moderate intensity, and 0.81 for vigorous intensity activities. It ranged from 0.59 for “Transportation” to 0.89 for “Household and Caregiving” activities. Spearman correlation coefficients (SCCs) between the PPAQ and the Matthews’ cut point used to classify an activity of moderate and above intensity were 0.50 for total activity, 0.25 for vigorous intensity and 0.40 for moderate intensity. The correlations between the PPAQ and the accelerometer counts were 0.58 for total activity, 0.39 for vigorous intensity and 0.49 for moderate intensity. The highest SCCs were for “Occupation” and “Household and Caregiving” activities. Comparisons with other standard cutpoints were presented in files S1, S2, S3, S4, S5, S6, S7. The PPAQ is reliable and moderately accurate for the measure of PA of various intensities and types among pregnant obese women

βα-Hairpin Clamps Brace βαβ Modules and Can Make Substantive Contributions to the Stability of TIM Barrel Proteins

Non-local hydrogen bonding interactions between main chain amide hydrogen atoms and polar side chain acceptors that bracket consecutive βα or αβ elements of secondary structure in αTS from E. coli, a TIM barrel protein, have previously been found to contribute 4–6 kcal mol−1 to the stability of the native conformation. Experimental analysis of similar βα-hairpin clamps in a homologous pair of TIM barrel proteins of low sequence identity, IGPS from S. solfataricus and E. coli, reveals that this dramatic enhancement of stability is not unique to αTS. A survey of 71 TIM barrel proteins demonstrates a 4-fold symmetry for the placement of βα-hairpin clamps, bracing the fundamental βαβ building block and defining its register in the (βα)8 motif. The preferred sequences and locations of βα-hairpin clamps will enhance structure prediction algorithms and provide a strategy for engineering stability in TIM barrel proteins

Observational and genetic associations between cardiorespiratory fitness and cancer: a UK Biobank and international consortia study

BACKGROUND: The association of fitness with cancer risk is not clear. METHODS: We used Cox proportional hazards models to estimate hazard ratios (HRs) and 95% confidence intervals (CIs) for risk of lung, colorectal, endometrial, breast, and prostate cancer in a subset of UK Biobank participants who completed a submaximal fitness test in 2009-12 (N = 72,572). We also investigated relationships using two-sample Mendelian randomisation (MR), odds ratios (ORs) were estimated using the inverse-variance weighted method. RESULTS: After a median of 11 years of follow-up, 4290 cancers of interest were diagnosed. A 3.5 ml O2⋅min-1⋅kg-1 total-body mass increase in fitness (equivalent to 1 metabolic equivalent of task (MET), approximately 0.5 standard deviation (SD)) was associated with lower risks of endometrial (HR = 0.81, 95% CI: 0.73-0.89), colorectal (0.94, 0.90-0.99), and breast cancer (0.96, 0.92-0.99). In MR analyses, a 0.5 SD increase in genetically predicted O2⋅min-1⋅kg-1 fat-free mass was associated with a lower risk of breast cancer (OR = 0.92, 95% CI: 0.86-0.98). After adjusting for adiposity, both the observational and genetic associations were attenuated. DISCUSSION: Higher fitness levels may reduce risks of endometrial, colorectal, and breast cancer, though relationships with adiposity are complex and may mediate these relationships. Increasing fitness, including via changes in body composition, may be an effective strategy for cancer prevention

Focal Cerebral Magnetic Resonance Changes Associated with Partial Status Epilepticus

We report 2 patients with transient abnormalities on magnetic resonance imaging (MRI) associated with partial status epilepticus (SE). A man with a 4-month history of partial seizures had complex partial SE for 9 days, with left temporal maximum on ictal EEG. Left temporal lobe T 2 signal was increased on MRI during SE, but cerebral MRI was normal 9 weeks later. A woman with “cryptogenic” temporal lobe epilepsy for 16 years had complex partial SE for 1 week, with right temporal maximum on ictal EEG. T 2 Signal was increased over the entire right temporal lobe, extending into the insula, without mass effect, on MRI 1 month after SE ended. Repeat MRI 1 month later showed marked decrease in volume of increased T 2 intensity, without gadolinium enhancement, but with mild mass effect over the right anteroinferomesial temporal areas. A gemistocytic astrocytoma was resected. Focal cerebral MRI abnormalities consistent with cerebral edema may be due to partial SE but also may indicate underlying glioma, even in long-standing partial epilepsy. Focal structural imaging changes consistent with neoplasm should be followed to full resolution after partial SE.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/65221/1/j.1528-1157.1994.tb02909.x.pd