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Atherosclerosis - the pathophysiological mechanism shared by most cardiovascular diseases - can be directly or indirectly assessed by a variety of clinical tests including measurement of carotid intima-media thickness, carotid plaque, ankle-brachial index, pulse wave velocity, and coronary artery calcium. the Prospective Studies of Atherosclerosis (Proof-ATHERO) consortium (https://clinicalepi.i-med.ac.at/research/proof-athero/) collates de-identified individual-participant data of studies with information on atherosclerosis measures, risk factors for cardiovascular disease, and incidence of cardiovascular diseases. It currently comprises 74 studies that involve 106,846 participants from 25 countries and over 40 cities. in summary, 21 studies recruited participants from the general population (n = 67,784), 16 from high-risk populations (n = 22,677), and 37 as part of clinical trials (n = 16,385). Baseline years of contributing studies range from April 1980 to July 2014; the latest follow-up was until June 2019. Mean age at baseline was 59 years (standard deviation: 10) and 50% were female. Over a total of 830,619 person-years of follow-up, 17,270 incident cardiovascular events (including coronary heart disease and stroke) and 13,270 deaths were recorded, corresponding to cumulative incidences of 2.1% and 1.6% per annum, respectively. the consortium is coordinated by the Clinical Epidemiology Team at the Medical University of Innsbruck, Austria. Contributing studies undergo a detailed data cleaning and harmonisation procedure before being incorporated in the Proof-ATHERO central database. Statistical analyses are being conducted according to pre-defined analysis plans and use established methods for individual-participant data meta-analysis. Capitalising on its large sample size, the multi-institutional collaborative Proof-ATHERO consortium aims to better characterise, understand, and predict the development of atherosclerosis and its clinical consequences. (c) 2020 S. Karger AG, Basel, Austrian Science Fund (FWF)Austrian Science Fund (FWF) [P 32488]; Dr.-Johannes-and-Hertha-Tuba Foundation, This work was funded by the Austrian Science Fund (FWF) (P 32488) and the Dr.-Johannes-and-Hertha-Tuba Foundation. Funders of individual studies contributing to the present analysis arelisted onthe Proof-ATHERO webpage(https://clinicalepi.i-med.ac.at/research/proof-athero/studies/).

Background and Purpose: Driven by the positive results of randomized, controlled trials of endovascular stroke therapies (EVT) in stroke patients with large vessel occlusion, different approaches to speed up the workflow for EVT candidates are currently being implemented worldwide. We aimed to assess the effect of a simple stroke network-wide workflow improvement project, primarily focusing on i.v. thrombolysis, on process times for patients undergoing EVT. Methods: In 2015, we conducted a network-wide, peer-to-peer acute stroke workflow improvement program for i.v. thrombolysis with the main components of implementing a binding team-based algorithm at every stroke unit of the regional network, educating all stroke teams about non-technical skills and providing a stroke-specific simulation training. Before and after the intervention we recorded periprocedural process times, including patients undergoing EVT at the 3 EVT-capable centers (January – June 2015, n = 80 vs. July 2015 – June 2016, n = 184). Results: In this multi-centric evaluation of 268 patients receiving EVT, we observed a relevant shortening of the median time from symptom onset to EVT specifically in patients requiring secondary transfer by almost an hour (300 min, 25–75% interquartile range [IQR] 231–381 min to 254 min, IQR 215.25–341 min; p = 0.117), including a reduction of the median door-to-groin time at the EVT-capable center in this patient group by 15.5 min (59 min, IQR 35–102 min to 43.5 min, IQR 27.75–81.25 min; p = 0.063). In patients directly admitted to an EVT-capable center, the median door-to-groin interval was reduced by 10.5 min (125 min, IQR 83.5–170.5 min to 114.5 min, IQR 66.5–151 min; p = 0.167), but a considerable heterogeneity between the centers was observed (p < 0.001). Conclusions: We show that a simple network-wide workflow improvement program primarily directed at fast i.v. thrombolysis also accelerates process times for EVT candidates and is a promising measure to improve the performance of an entire stroke network.

AimsAveraged measurements, but not the progression based on multiple assessments of carotid intima-media thickness, (cIMT) are predictive of cardiovascular disease (CVD) events in individuals. Whether this is true for conventional risk factors is unclear.Methods and resultsAn individual participant meta-analysis was used to associate the annualised progression of systolic blood pressure, total cholesterol, low-density lipoprotein cholesterol and high-density lipoprotein cholesterol with future cardiovascular disease risk in 13 prospective cohort studies of the PROG-IMT collaboration ( n = 34,072). Follow-up data included information on a combined cardiovascular disease endpoint of myocardial infarction, stroke, or vascular death. In secondary analyses, annualised progression was replaced with average. Log hazard ratios per standard deviation difference were pooled across studies by a random effects meta-analysis. In primary analysis, the annualised progression of total cholesterol was marginally related to a higher cardiovascular disease risk (hazard ratio (HR) 1.04, 95% confidence interval (CI) 1.00 to 1.07). The annualised progression of systolic blood pressure, low-density lipoprotein cholesterol and high-density lipoprotein cholesterol was not associated with future cardiovascular disease risk. In secondary analysis, average systolic blood pressure (HR 1.20 95% CI 1.11 to 1.29) and low-density lipoprotein cholesterol (HR 1.09, 95% CI 1.02 to 1.16) were related to a greater, while high-density lipoprotein cholesterol (HR 0.92, 95% CI 0.88 to 0.97) was related to a lower risk of future cardiovascular disease events.ConclusionAveraged measurements of systolic blood pressure, low-density lipoprotein cholesterol and high-density lipoprotein cholesterol displayed significant linear relationships with the risk of future cardiovascular disease events. However, there was no clear association between the annualised progression of these conventional risk factors in individuals with the risk of future clinical endpoints.

Background The clinical use of carotid intima media thickness (cIMT) requires normal values, which may be subject to variation of geographical factors, ethnicity or measurement details. The influence of these factors has rarely been studied. The aim of this study was to determine whether normative cIMT values and their association with event risk are generalizable across populations. Design Meta-analysis of individual participant data. Method From 22 general population cohorts from Europe, North America and Asia we selected subjects free of cardiovascular disease. Percentiles of cIMT and cIMT progression were assessed separately for every cohort. Cox proportional hazards models for vascular events were used to estimate hazard ratios for cIMT in each cohort. The estimates were pooled across Europe, North America and Asia, with random effects meta-analysis. The influence of geography, ethnicity and ultrasound protocols on cIMT values and on the hazard ratios was examined by meta-regression. Results Geographical factors, ethnicity and the ultrasound protocol had influence neither on the percentiles of cIMT and its progression, nor on the hazard ratios of cIMT for vascular events. Heterogeneity for percentiles of cIMT and cIMT progression was too large to create meaningful normative values. Conclusions The distribution of cIMT values is too heterogeneous to define universal or regional population reference values. CIMT values vary widely between different studies regardless of ethnicity, geographic location and ultrasound protocol. Prediction of vascular events with cIMT values was more consistent across all cohorts, ethnicities and regions.

AIMS: Carotid intima media thickness (CIMT) predicts cardiovascular (CVD) events, but the predictive value of CIMT change is debated. We assessed the relation between CIMT change and events in individuals at high cardiovascular risk. METHODS AND RESULTS: From 31 cohorts with two CIMT scans (total n = 89070) on average 3.6 years apart and clinical follow-up, subcohorts were drawn: (A) individuals with at least 3 cardiovascular risk factors without previous CVD events, (B) individuals with carotid plaques without previous CVD events, and (C) individuals with previous CVD events. Cox regression models were fit to estimate the hazard ratio (HR) of the combined endpoint (myocardial infarction, stroke or vascular death) per standard deviation (SD) of CIMT change, adjusted for CVD risk factors. These HRs were pooled across studies. In groups A, B and C we observed 3483, 2845 and 1165 endpoint events, respectively. Average common CIMT was 0.79mm (SD 0.16mm), and annual common CIMT change was 0.01mm (SD 0.07mm), both in group A. The pooled HR per SD of annual common CIMT change (0.02 to 0.43mm) was 0.99 (95% confidence interval: 0.95-1.02) in group A, 0.98 (0.93-1.04) in group B, and 0.95 (0.89-1.04) in group C. The HR per SD of common CIMT (average of the first and the second CIMT scan, 0.09 to 0.75mm) was 1.15 (1.07-1.23) in group A, 1.13 (1.05-1.22) in group B, and 1.12 (1.05-1.20) in group C. CONCLUSIONS: We confirm that common CIMT is associated with future CVD events in individuals at high risk. CIMT change does not relate to future event risk in high-risk individuals. The PROG-IMT project, which includes this publication, has been funded by the German Research Foundation (Deutsche Forschungsgemeinschaft, www.dfg.de) under the grants DFG Lo 1569/2-1 and DFG Lo 1569/2-3, received by MWL. The DFG had no role in the study design, data collection and analysis, decision to publish, or preparation of the manuscript. Simon Thompson is supported by the British heart Foundation (CH/12/2/29428). Some of the contributing studies were funded by different parties, as listed in the acknowledgement section. Here, too, the funders had no role in the study design, data collection and analysis, decision to publish, or preparation of the manuscript. Sí

Two ultrasound tests that can be used to assess increased intracranial pressure (ICP) at the bedside are described. In outpatients receiving lumbar puncture and in intensive care patients with invasive ICP monitoring, we measured the optic nerve sheath diameter (ONSD) with transbulbar B-mode sonography and septum pellucidum undulation (SPU) induced by repeated passive head rotation with transtemporal M-mode sonography. We assessed the sensitivity and specificity of ONSD and SPU in the prediction of ICP >20 cm H2O. For ONSD, sensitivity was 53% and specificity 100% (n = 35, p < 0.001). The sensitivity of the SPU test was 75% and the specificity 100% (n = 32, p < 0.001). Although the SPU test may not feasible in some patients, it has high sensitivity and specificity comparable to those of ONSD measurement. The SPU test and ONSD may be useful alternatives to fundoscopy in clinical routine, preferably in combination.

The honeydew composition and production of four aphid species feeding on Tanacetum vulgare, and mutualistic relationships with the ant Lasius niger were studied. In honeydew of Metopeurum fuscoviride and Brachycaudus cardui, xylose, glucose, fructose, sucrose, maltose, melezitose, and raffinose were detected. The proportion of trisaccharides (melezitose, raffinose) ranged between 20% and 35%. No trisaccharides were found in honeydew of Aphis fabae, and honeydew of Macrosiphoniella tanacetaria consisted of only xylose, glucose and sucrose. M. fuscoviride produced by far the largest amounts of honeydew per time unit (880 μg/aphid per hour), followed by B. cardui (223 μg/aphid per hour), A. fabae (133 μg/aphid per hour) and M. tanacetaria (46 μg/aphid per hour). The qualitative and quantitative honeydew production of the aphid species corresponded well with the observed attendance by L. niger. L. niger workers preferred trisaccharides over disaccharides and monosaccharides when these sugars were offered in choice tests. The results are consistent with the ants' preference for M. fuscoviride, which produced the largest amount of honeydew including a considerable proportion of the trisaccharides melezitose and raffinose. The preference of L. niger for B. cardui over A. fabae, both producing similar amounts of honeydew, may be explained by the presence of trisaccharides and the higher total sugar concentration in B. cardui honeydew. M. tanacetaria, which produced only low quantities of honeydew with no trisaccharides was not attended at all by L. niger.

Background The relation of a single risk factor with atherosclerosis is established. Clinically we know of risk factor clustering within individuals. Yet, studies into the magnitude of the relation of risk factor clusters with atherosclerosis are limited. Here, we assessed that relation. Methods Individual participant data from 14 cohorts, involving 59,025 individuals were used in this cross-sectional analysis. We made 15 clusters of four risk factors (current smoking, overweight, elevated blood pressure, elevated total cholesterol). Multilevel age and sex adjusted linear regression models were applied to estimate mean differences in common carotid intima-media thickness (CIMT) between clusters using those without any of the four risk factors as reference group. Results Compared to the reference, those with 1, 2, 3 or 4 risk factors had a significantly higher common CIMT: mean difference of 0.026 mm, 0.052 mm, 0.074 mm and 0.114 mm, respectively. These findings were the same in men and in women, and across ethnic groups. Within each risk factor cluster (1, 2, 3 risk factors), groups with elevated blood pressure had the largest CIMT and those with elevated cholesterol the lowest CIMT, a pattern similar for men and women. Conclusion Clusters of risk factors relate to increased common CIMT in a graded manner, similar in men, women and across race-ethnic groups. Some clusters seemed more atherogenic than others. Our findings support the notion that cardiovascular prevention should focus on sets of risk factors rather than individual levels alone, but may prioritize within clusters., published version, peerReviewed

Background and Purpose— Because of a low prevalence of severe carotid stenosis in the general population, screening for presence of asymptomatic carotid artery stenosis (ACAS) is not warranted. Possibly, for certain subgroups, screening is worthwhile. The present study aims to develop prediction rules for the presence of ACAS (>50% and >70%). Methods— Individual participant data from 4 population-based cohort studies (Malmö Diet and Cancer Study, Tromsø Study, Carotid Atherosclerosis Progression Study, and Cardiovascular Health Study; totaling 23 706 participants) were pooled. Multivariable logistic regression was performed to determine which variables predict presence of ACAS (>50% and >70%). Calibration and discrimination of the models were assessed, and bootstrapping was used to correct for overfitting. Results— Age, sex, history of vascular disease, systolic and diastolic blood pressure, total cholesterol/high-density lipoprotein ratio, diabetes mellitus, and current smoking were predictors of stenosis (>50% and >70%). The calibration of the model was good confirmed by a nonsignificant Hosmer and Lemeshow test for moderate ( P =0.59) and severe stenosis ( P =0.07). The models discriminated well between participants with and without stenosis, with an area under the receiver operating characteristic curve corrected for over optimism of 0.82 (95% confidence interval, 0.80–0.84) for moderate stenosis and of 0.87 (95% confidence interval, 0.85–0.90) for severe stenosis. The regression coefficients of the predictors were converted into a score chart to facilitate practical application. Conclusions— A clinical prediction rule was developed that allows identification of subgroups with high prevalence of moderate (>50%) and severe (>70%) ACAS. When confirmed in comparable cohorts, application of the prediction rule may lead to a reduction in the number needed to screen for ACAS.

Item does not contain fulltext Carotid intima-media thickness (CIMT) is a marker of cardiovascular risk. It is unclear whether measurement of mean common CIMT improves 10-year risk prediction of first-time myocardial infarction or stroke in individuals with elevated blood pressure. We performed an analysis among individuals with elevated blood pressure (i.e., a systolic blood pressure >/=140 mm Hg and a diastolic blood pressure >/= 90 mm Hg) in USE-IMT, a large ongoing individual participant data meta-analysis. We refitted the risk factors of the Framingham Risk Score on asymptomatic individuals (baseline model) and expanded this model with mean common CIMT (CIMT model) measurements. From both models, 10-year risks to develop a myocardial infarction or stroke were estimated. In individuals with elevated blood pressure, we compared discrimination and calibration of the 2 models and calculated the net reclassification improvement (NRI). We included 17 254 individuals with elevated blood pressure from 16 studies. During a median follow-up of 9.9 years, 2014 first-time myocardial infarctions or strokes occurred. The C-statistics of the baseline and CIMT models were similar (0.73). NRI with the addition of mean common CIMT was small and not significant (1.4%; 95% confidence intervals, -1.1 to 3.7). In those at intermediate risk (n=5008, 10-year absolute risk of 10% to 20%), the NRI was 5.6% (95% confidence intervals, 1.6-10.4). There is no added value of measurement of mean common CIMT in individuals with elevated blood pressure for improving cardiovascular risk prediction. For those at intermediate risk, the addition of mean common CIMT to an existing cardiovascular risk score is small but statistically significant.

In workers of the Western honeybee, Apis mellifera, juvenile hormone (JH) and ecdysteroids regulate many aspects of age polyphenism. Here we investigated whether these derived functions in workers have developed by an uncoupling of endocrine mechanisms in adult queens and workers, or whether parallels can be found between the roles of the two hormones in both castes. We looked at yolk protein metabolism as a process central to the physiology of both queens and workers, and at sperm storage as a feature of the queen alone. Queens of differing fertility status (virgin, virgin but CO2-treated, inseminated, freshly laying and 1-2 years-old) were compared regarding vitellogenin (Vg), JH and ecdysteroid-titers in their hemolymph, as well as ovarian yolk protein and spermathecal gland composition. Our results showed that hormone titres were unrelated to the composition of spermathecal glands. JH-concentrations in the hemolymph were low in the groups of queens characterized by yolk uptake into the ovaries, and high in pre-vitellogenic queens or animals that were forced to interrupt egg-laying by caging. Ecdysteroid-concentrations were higher in untreated virgins than after insemination or during egg-laying. They were not affected by the caging of queens. These patterns of hormone changes were parallel to those known from worker bees. Together, these findings suggest a conserved role for JH as repressor of vitellogenin uptake into tissues, and for ecdysteroids in preparing tissues for this process. An involvement of the two hormones in the regulation of sperm storage seems unlikely. Our results add to the view that JH and ecdysteroids act similarly on the yolk protein metabolism of both castes of A. mellifera. This may imply that it was the biochemical versatility of Vg rather than that of hormonal regulatory circuits that allowed for the functional separation of the two castes.

BACKGROUND: Large-scale epidemiological evidence on the role of inflammation in early atherosclerosis, assessed by carotid ultrasound, is lacking. We aimed to quantify cross-sectional and longitudinal associations of inflammatory markers with common-carotid-artery intima-media thickness (CCA-IMT) in the general population.METHODS: Information on high-sensitivity C-reactive protein, fibrinogen, leucocyte count and CCA-IMT was available in 20 prospective cohort studies of the PROG-IMT collaboration involving 49,097 participants free of pre-existing cardiovascular disease. Estimates of associations were calculated within each study and then combined using random-effects meta-analyses.RESULTS: Mean baseline CCA-IMT amounted to 0.74 mm (SD = 0.18) and mean CCA-IMT progression over a mean of 3.9 years to 0.011 mm/year (SD = 0.039). Cross-sectional analyses showed positive linear associations between inflammatory markers and baseline CCA-IMT. After adjustment for traditional cardiovascular risk factors, mean differences in baseline CCA-IMT per one-SD higher inflammatory marker were: 0.0082 mm for high-sensitivity C-reactive protein (p CONCLUSION: Inflammation was independently associated with CCA-IMT cross-sectionally. The lack of clear associations with CCA-IMT progression may be explained by imprecision in its assessment within a limited time period. Our findings for 'inflammatory load' suggest important combined effects of the three inflammatory markers on early atherosclerosis.

Context The evidence that measurement of the common carotid intima-media thickness (CIMT) improves the risk scores in prediction of the absolute risk of cardiovascular events is inconsistent. Objective To determine whether common CIMT has added value in 10-year risk prediction of first-time myocardial infarctions or strokes, above that of the Framingham Risk Score. Data Sources Relevant studies were identified through literature searches of databases (PubMed from 1950 to June 2012 and EMBASE from 1980 to June 2012) and expert opinion. Study Selection Studies were included if participants were drawn from the general population, common CIMT was measured at baseline, and individuals were followed up for first-time myocardial infarction or stroke. Data Extraction Individual data were combined into 1 data set and an individual participant data meta-analysis was performed on individuals without existing cardiovascular disease. Results We included 14 population-based cohorts contributing data for 45 828 individuals. During a median follow-up of 11 years, 4007 first-time myocardial infarctions or strokes occurred. We first refitted the risk factors of the Framingham Risk Score and then extended the model with common CIMT measurements to estimate the absolute 10-year risks to develop a first-time myocardial infarction or stroke in both models. The C statistic of both models was similar (0.757; 95% CI, 0.749-0.764; and 0.759; 95% CI, 0.752-0.766). The net reclassification improvement with the addition of common CIMT was small (0.8%; 95% CI, 0.1%-1.6%). In those at intermediate risk, the net reclassification improvement was 3.6% in all individuals (95% CI, 2.7%-4.6%) and no differences between men and women. Conclusion The addition of common CIMT measurements to the Framingham Risk Score was associated with small improvement in 10-year risk prediction of first-time myocardial infarction or stroke, but this improvement is unlikely to be of clinical importance. JAMA. 2012;308(8):796-803 www.jama.com

The aim of this paper is to review and discuss current methods of risk stratification for cardiovascular disease (CVD) prevention, emerging biomarkers, and imaging techniques, and their relative merits and limitations. This report is based on discussions that took place among experts in the area during a special CardioVascular Clinical Trialists workshop organized by the European Society of Cardiology Working Group on Cardiovascular Pharmacology and Drug Therapy in September 2009. Classical risk factors such as blood pressure and low-density lipoprotein cholesterol levels remain the cornerstone of risk estimation in primary prevention but their use as a guide to management is limited by several factors: (i) thresholds for drug treatment vary with the available evidence for cost-effectiveness and benefit-to-risk ratios; (ii) assessment may be imprecise; (iii) residual risk may remain, even with effective control of dyslipidemia and hypertension. Novel measures include C-reactive protein, lipoprotein-associated phospholipase A2, genetic markers, and markers of subclinical organ damage, for which there are varying levels of evidence. High-resolution ultrasound and magnetic resonance imaging to assess carotid atherosclerotic lesions have potential but require further validation, standardization, and proof of clinical usefulness in the general population. In conclusion, classical risk scoring systems are available and inexpensive but have a number of limitations. Novel risk markers and imaging techniques may have a place in drug development and clinical trial design. However, their additional value above and beyond classical risk factors has yet to be determined for risk-guided therapy in CVD prevention.

Background and Purpose— The adipocytokines adiponectin and leptin have been suggested as risk factors for cardiovascular disease, including stroke, acting through atherosclerosis. However, studies have provided conflicting results in underpowered cohorts with some suggesting that the leptin:adiponectin ratio is a better predictor of risk. We examined these associations with carotid intima-media thickness (IMT), a marker of early atherosclerosis and arterial remodeling and an independent predictor of stroke. We also examined association between genetic variants in the leptin and adiponectin genes and IMT. Methods— Adiponectin and leptin levels were determined in 990 individuals from the community Carotid Atherosclerosis Progression Study. Five variants in the gene encoding adiponectin and 7 in the gene encoding leptin were genotyped and their effects on circulating levels assessed. Both were then correlated with IMT. Results— Adiponectin levels negatively correlated with IMT (−0.079, P =0.013). There was no correlation between leptin levels or leptin:adiponectin ratio and IMT. Two variants in the ADIPOQ gene encoding adiponectin were associated with altered adiponectin levels, 1 of which (rs266729) was associated with IMT. There was also an interaction with body mass index ( P =0.019) with the association being present in obese subjects ( P =0.02). Conclusions— Our results support a causal role for adiponectin in early carotid IMT and suggest it may act through interaction with obesity. In contrast, we found no evidence of a role for leptin and no evidence that leptin:adiponectin ratio is a better predictor of risk that adiponectin levels alone.

Background Multiple sclerosis (MS) is a chronic, inflammatory demyelinating disease of the central nervous system, believed to be triggered by an autoimmune reaction to myelin. Recently, a fundamentally different pathomechanism termed ‘chronic cerebrospinal venous insufficiency’ (CCSVI) was proposed, provoking significant attention in the media and scientific community. Methods Twenty MS patients (mean age 42.2±13.3 years; median Extended Disability Status Scale 3.0, range 0–6.5) were compared with 20 healthy controls. Extra- and intracranial venous flow direction was assessed by colour-coded duplex sonography, and extracranial venous cross-sectional area (VCSA) of the internal jugular and vertebral veins (IJV/VV) was measured in B-mode to assess the five previously proposed CCSVI criteria. IJV-VCSA≤0.3 cm 2 indicated ‘stenosis,’ and IJV-VCSA decrease from supine to upright position ‘reverted postural control.’ The sonographer, data analyser and statistician were blinded to the patient/control status of the participants. Results No participant showed retrograde flow of cervical or intracranial veins. IJV-VCSA≤0.3 cm 2 was found in 13 MS patients versus 16 controls (p=0.48). A decrease in IJV-VCSA from supine to upright position was observed in all participants, but this denotes a physiological finding. No MS patient and one control had undetectable IJV flow despite deep inspiration (p=0.49). Only one healthy control and no MS patients fulfilled at least two criteria for CCSVI. Conclusions This triple-blinded extra- and transcranial duplex sonographic assessment of cervical and cerebral veins does not provide supportive evidence for the presence of CCSVI in MS patients. The findings cast serious doubt on the concept of CCSVI in MS.

Carotid intima media thickness (cIMT) is an intermediate phenotype of early atherosclerosis that independently pre- dicts vascular events. It is often suggested that cIMT be used as a screening tool to select subjects with an elevated event risk. Whether cIMT adds information to traditional risk models has so far received little investigation. Methods and results The 10-year follow-up of 4904 subjects from the Carotid Atherosclerosis Progression Study (CAPS) without pre- existing vascular disease included cardiovascular events and total mortality. Using Cox models and reclassification statistics, we investigated the usefulness of cIMT in individual risk prediction beyond the Framingham and the SCORE models, using risk strata of 0-5, 5-10, 10-20, and ≥20% over 10 years. Carotid intima media thickness was significantly and independently predictive for cardiovascular events. Compared with a model using the Framing- ham risk factors, a second model that included the common carotid-IMT led to the reclassification of 357 subjects (8.1%). In 107 subjects (30.0%), this reclassification was correct as confirmed with the actual outcome over 10 years. Net reclassification improvement was 21.41% (P ¼ NS); integrated discrimination improvement was 0.04% (P ¼ NS). More subjects were shifted to lower than to higher risk categories by the inclusion of cIMT. Analyses including other endpoint definitions, other carotid segments, and the SCORE risk model for baseline prediction did not result in consistently better risk prediction with cIMT. Conclusion Despite cIMT being predictive for cardiovascular endpoints, it did not consistently improve the risk classification of individuals. Carotid intima media thickness may not be useful for the risk stratification of individuals in the general population.

Excitability and locomotor activity of male and female last instar larvae and adults of the two-spotted cricket are measured under crowded conditions, allowing the animals to interact with conspecifics during observations. Male and female last instar larvae display age-dependent cyclic patterns of activity with maxima during early to mid scotophase and minima during early photophase. A period of low locomotor activity without time of day-dependent cyclic changes starts 1 day before the final moult and lasts until 1 day after the moult. Then, both excitability and locomotor activity increase and become cyclic again within 2 or 3 days. The cyclic changes gradually dampen in adult females older than 6 days and finally cease. When injected into photophase larvae and adults, adipokinetic hormone (AKH) increases excitability and locomotor activity in a dose-dependent manner, whereas it has no such effect when injected into scotophase animals. Other behaviours (jumping, hind wing trembling) that mostly occur in scotophase crickets are also increased by injecting AKH into photophase crickets. We argue that AKH could be responsible for linking the endogenous clock output with the cyclic changes in locomotor activity. Furthermore, AKH may serve to synchronise metabolism and behaviour to optimise larval development and reproduction.

Background Ischemia/reperfusion injury is an unavoidable complication in liver surgery and transplantation. Hemodilution with colloids can reduce postischemic injury but limits oxygen transport. Hemoglobin-based oxygen carriers have been evaluated as blood substitute and provide a plasma-derived oxygen transport. It was the aim of our study to evaluate the combined benefits of hemodilution with a better oxygen supply to reperfused liver tissue by the use of HBOC-201 (Hemopure ® ). Material and methods A model of partial warm liver ischemia in the rat was used. One group served as untreated control, the other groups were hemodiluted either with Ringer’s lactate, Dextran-70, HBOC-201 or a mixture of Dextran and HBOC-201. After reperfusion, intravital microscopy studies were done and tissue pO 2 levels and transaminases measured. Statistical analysis was done by one- and two-way ANOVA, followed by pairwise comparison. Results Hemodilution with Ringer’s lactate did not show any improvement compared to the control group. Dextran and HBOC group were superior to the Ringer and control animals in all parameters studied. Leucocyte adherence in postsinusoidal venules improved from 569.03 ± 171.87 and 364.52 ± 167.32 in control and Ringer group to 131.68 ± 58.34 and 68.44 ± 20.31/mm 2 endothelium in Dextran and HBOC group ( p 2 levels, HBOC (23.4 ± 5.0 mmHg) proved to be superior to Dextran (7.9 ± 4.4 mmHg; p = 0.007). Conclusion HBOC was equivalent to Dextran in reducing I/R injury in the liver, but improved oxygenation of postreperfusion liver tissue.

In this study, we investigated whether differences in the reproductive biology of honey bee (Apis mellifera) queens and laying workers are reflected in their eggs. We first tested the capacity of queen- and worker-laid male eggs to withstand dry conditions, by incubating samples at 30.0, 74.9, and 98.7% relative humidity. We found that worker-laid eggs were more sensitive to desiccation. Secondly, we measured the weight and quantities of vitellin, total protein, lipid, glycogen, and free carbohydrate in queen- and workerlaid eggs. Although worker-laid eggs were found to be heavier than queen-laid eggs in two of the four replicates, no systematic differences were found regarding nutrient content. Finally, we compared the duration of embryo development in the two egg types. Worker-laid eggs developed more slowly than queen-laid eggs in two out of three replicates, suggesting that they may only be partly mature at the moment they are laid. Possible causes and consequences of the observed differences are discussed.

Background and Purpose— Pretreatment lesion size on diffusion-weighted imaging (DWI) is a risk factor for symptomatic intracerebral hemorrhage (sICH) associated with thrombolytic treatment. Here, we investigated whether the Alberta Stroke Programme Early CT Score (ASPECTS) applied to DWI images (DWI-ASPECTS) predicts sICH risk accurately. Methods— In this retrospective multicenter study, prospectively collected data of 217 patients with anterior circulation stroke treated with intravenous or intraarterial thrombolysis within 6 hours after symptom onset were analyzed. Pretreatment DWI-ASPECTS scores were assessed by 2 independent investigators. For bleeding risk analysis, DWI-ASPECTS scores were either categorized into 0 to 7 (n=105) or 8 to 10 (n=112) or in 3 groups of similar sample size (DWI-ASPECTS 0 to 5 [n=69], 6 to 7 [n=70], and 8 to 10 [n=78]). Results— DWI-ASPECTS scores correlated well with the DWI lesion volume ( r =0.77, P P =0.004). sICH risk was 20.3%, 10%, and 2.6% in the 0 to 5, 6 to 7, and 8 to 10 DWI-ASPECTS groups, respectively. DWI-ASPECTS remained an independent prognostic factor for sICH after adjustment for clinical baseline variables (age, NIHSS, time to thrombolysis). Conclusions— DWI-ASPECTS predicts sICH risk after thrombolysis and may be helpful to contributing to quick sICH risk assessment before thrombolytic therapy.

Since all life processes depend on energy, the endocrine control of energy metabolism is one of the driving forces for the performance of an individual. Here, we review the literature on the key players in the endocrine regulation of energy homeostasis in insects, the adipokinetic hormones. These pleiotropic peptides not only control dynamic performance traits (flight, swimming, walking) but also regulatory performance traits (egg production, larval growth, and molting). Adipokinetic hormone is released into the hemolymph during intense muscular activity (flight) and also during apparently less energy-demanding locomotory activities, such as swimming and even walking, and, finally, activates the catabolic enzymes phosphorylase and/or triacylglycerol lipase that mobilize carbohydrates and/or lipids and proline, respectively. At the same time, anabolic processes such as the synthesis of protein, lipid, and glycogen are inhibited. Furthermore, adipokinetic hormones affect locomotory activity via neuromodulatory mechanisms that apparently employ biogenic amines. During oogenesis, it is thought that adipokinetic hormone performs similar tasks, because energetic substrates have to be mobilized and transported from the fat body to the ovaries in order to support oocyte growth. Inhibition of anabolic processes by exogenous adipokinetic hormone results in females that lay fewer and smaller eggs. Much less is known about the role of adipokinetic hormones during larval development and during molting but in this case energy homeostasis has to be tightly regulated as well: in general, during the early phase of a larval instar intake of food prevails and the energy stores of the fat body are established, whereas, prior to the molt, insects stop feeding and mobilize energy stores in the fat body, thereby fueling energy-demanding processes such as the formation of the new cuticle and the emergence from the old one. From the few data available to date, it is clear that adipokinetic hormones are involved in the regulation of these events in larvae.

The adipokinetic hormone (AKH) of the large milkweed bug Oncopeltus fasciatus is isolated from an acidified methanolic extract of 200 corpora cardiaca, purified by single step reversed phase high-performance liquid chromatography (HPLC) and N-terminally deblocked using pyroglutamate aminopeptidase. The sequence is identified by Edman degradation and matrix assisted laser desorption/ionization-time of flight mass spectroscopy as pGlu-Leu-Asn-Phe-Ser-Pro-Asn-Trp amide. This structure is confirmed by chemical synthesis and coelution of native and synthetic peptide on HPLC. The AKH of O. fasciatus is identical to Tenmo-HrTH, a member of the adipokinetic/red pigment-concentrating hormone peptide family that had been isolated earlier from several tenebrionid beetles. Tenmo-HrTH causes a significant rise in the concentration of haemolymph lipids when injected into adult male and female O. fasciatus, but displays no hyperglycaemic activity. There is no indication of the presence of other AKHs in O. fasciatus. The large milkweed bug represents the first member of the seed bugs (Lygaeidae) for which the endogenous AKH has been identified.

African desert locusts (Schistocerca gregaria) crossed the Atlantic from West Africa to the Caribbean in 1988, a non-stop flight of about 5000 km. Although this migration was assisted by winds, the locusts had to actively maintain altitude and to fly for 4–6 days. Locusts are known to be outstanding flyers that migrate for thousands of kilometres over land, but this trans-Atlantic flight seems to be beyond their capacity. A phenomenon called phase polymorphism, inherent to all locusts sensu stricto, helps them to perfectly adapt to their ephemeral habitat and assists the formation of giant locust swarms with incredible flight performance. The present review briefly summarises the locust ecology, behaviour, physiology and morphology that are associated with the phase polymorphism and outlines the climatic conditions that may lead to such long-range displacements.

Background and Purpose— The recent finding that genetic variation in the leukotriene biosynthesis pathway may confer an increased risk of ischemic stroke and atherosclerosis has implicated the leukotriene family as potential mediators of cardiovascular disease. Using a 2-stage replication design, we have examined whether polymorphisms in 8 genes related to this pathway are associated with early atherosclerosis and remodeling as measured by carotid artery intima-media thickness. Methods— We assessed 969 individuals from the Carotid Atherosclerosis Progression Study (CAPS), a community based study of normal subjects, for 39 variants in the leukotriene pathway. Significant associations and gene–environment interactions were found for 21 variants in the initial cohort and were examined in the next 1905 consecutive cases from the same CAPS population. Results— No replicable association between any individual polymorphism and carotid intima-media thickness itself was present after correction for multiple testing. A single gene–environment interaction was replicated between rs17222814 on bifurcation intima-media thickness and alcohol consumption exceeding 30 grams per day. Conclusion— The genetic variants we examined in the leukotriene biosynthesis pathway have little effect on early atherosclerosis and remodeling risk as determined by carotid intima-media thickness. Our study cannot exclude them as being risk factors for more advanced stages in the atherosclerotic process.

The ammonia monooxygenase (AMO) ofNitrosomonas europaeais a metalloenzyme that catalyses the oxidation of ammonia to hydroxylamine. We have identified histidine 191 of AmoA as the binding site for the oxidized mechanism-based inactivator acetylene. Binding of acetylene changed the molecular mass of His-191 from 155.15 to 197.2 Da (+42.05), providing evidence that acetylene was oxidized to ketene (CH2CO; 42.04 Da) which binds specifically to His-191. It must be assumed that His-191 is part of the acetylene-activating site in AMO or at least directly neighbours this site.

Honey bee workers normally produce brood food at an age of 5 to 15 days. However, natural events like swarming or brood diseases may lead to the occurrence of over-aged nurses. Here we investigated the physiological consequences of prolonged nursing for both the nurses and the brood they rear, and tried to separate the effects of chronological age and of task affiliation on some important physiological parameters. Brood was reared in groups of colonies with either a normal age structure or with moderately over-aged workers.The haemolymph concentrations of total protein and vitellogenin, the development of mandibular and hypopharyngeal glands, and the activity of α-glucosidase in the hypopharyngeal glands of nurses from these groups of colonies were compared. Moreover, we used the fertility of young workers reared by normal- and overaged nurses as a bioindicator for the quality of the brood care they had received. It showed that parameters linked to the production of brood food proteins remained stable in over-aged nurses, whereas the development of mandibular glands regressed. Workers reared by over-aged nurses had more ovarioles and showed stronger ovary development under queenless conditions. Our results indicate that while over-aged nurses remain capable of producing brood food, they are not functionally equivalent to young nurses. The partial degeneration of the mandibular glands normally occurring at the end of the nursing period cannot be prevented by prolonged nursing. The distinct phenotype of workers reared by old nurses raises the question of possible age-related specialisations among nurses in colonies with a normal age structure.

Most studies of insect reproductive allocation concentrate on propagule size and number and very few consider egg composition, which is likely to be equally important. In the present study, data are provided on changes in egg lipid, glycogen, free carbohydrate and protein during embryonic development of the aphidophagous ladybird Adalia bipunctata (L.) and the compositions of A. bipunctata, Adalia decempunctata and Anisosticta novemdecimpunctata eggs are compared. In A. bipunctata, egg mass, lipid and glycogen decline strongly during development and egg protein declines more weakly. Free carbohydrate declines early in egg development and increases at egg hatching. Lipid is energetically the most important developmental fuel, although approximately half of the initial egg lipid remains in the neonate larva. Across the three species, energy per unit egg mass is lowest in the least specialized species, A. bipunctata, which also has the largest eggs, and is highest in the most specialized, An. novemdecimpunctata, which has the smallest eggs. Two possible explanations for the observed pattern are discussed: (i) species laying smaller eggs may incur higher developmental costs per unit mass than species laying larger eggs and (ii) more specialized species, which reproduce at lower aphid densities, may provision neonate larvae better to facilitate location and capture of aphids.

The perioperative use of a single course adjuvant portal vein infusion chemotherapy in patients with potentially curable colorectal cancer has been shown to significantly improve overall survival but did not reduce the occurrence of liver metastases (SAKK 40/81) [Swiss Group for Clinical Cancer Research (SAKK) Lancet 345(8946):349-353, 1995]. The objective of the present prospective, three-arm randomized multicenter trial was to assess whether peripheral venous administration of adjuvant chemotherapy regimen based on 5-fluorouracil (5-FU) and mitomycin C decreases the occurrence of liver metastases as well as prolongs disease-free and overall survival.Stages I-III colorectal cancer patients (n = 753) were randomized to receive either surgery alone (control arm), surgery plus postoperative portal venous infusion of 5-FU 500 mg/m(2) plus heparin given for 24 hours for seven consecutive days plus mitomycin C 10 mg/m(2) given on the first day (arm 2), or surgery and the same chemotherapy regimen administered by peripheral venous route (arm 3).The 5-year disease-free survival for the three treatment groups were 65% (control group), 60% (portal vein infusion, hazard ratio 1.18, p = 0.23), and 64% (intravenous infusion, hazard ratio 1.04, p = 0.76); the 5-year overall survival was 72% (control group), 69% (portal vein infusion, hazard ratio 1.21, p = 0.2), and 74% (intravenous infusion, hazard ratio 1.03, p = 0.86), respectively. A significant accumulation of early deaths were observed in the portal vein infusion group (p = 0.015).The present prospective randomized multicenter trial provides compelling evidence that short-term perioperative chemotherapy does not improve disease-free and overall survival in patients with potentially curative colorectal cancer. In contrary, the chemotherapy regimen administered in the present investigation seems to have potentially harmful effects, a finding which should be carefully considered in the planning of future trials. Postoperative short-term administration of 5-FU plus mitomycin C either through portal infusion or a central venous catheter is not recommended for routine use in patients with potentially curable colorectal cancer.

Environmentally induced phenotypic plasticity is common in nature. Hormones, affecting multiple traits and signaling to a variety of distant target tissues, provide a mechanistic link between environments, genes and trait expression, and may therefore well be involved in the regulation phenotypic plasticity. Here, we investigate whether in the tropical butterfly Bicyclus anynana temperature-mediated plasticity in egg size and number, with fewer but larger eggs produced at lower temperatures and vice versa, is under control of juvenile hormone, and whether different temperatures cause differences in egg composition. Female B. anynana butterflies showed the expected response to temperature, however, we found no evidence for an involvement of juvenile hormone. Neither haemolymph JH II and JH III titres nor vitellogenin levels differed across temperatures. The smaller eggs produced at the higher temperature contained relatively higher amounts of water, free carbohydrates and proteins, but relatively lower amounts of lipids. While these smaller eggs had a lower absolute energy content, total reproductive investment was higher at the higher temperature (due to a higher fecundity). Overall, our study indicates that temperature-mediated plasticity in reproduction in B. anynana is mechanistically related to a biophysical model, with oocyte production (differentiation) and oocyte growth (vitellogenesis) having differential temperature sensitivities.

Phenotypic plasticity may allow an organism to adjust its phenotype to environmental needs. However, little is known about environmental effects on offspring biochemical composition and turnover rates, including energy budgets and developmental costs. Using the tropical butterfly Bicyclus anynana and employing a full-factorial design with two oviposition and two developmental temperatures, we explore the consequences of temperature variation on egg and hatchling composition, and the associated use and turnover of energy and egg compounds. At the lower temperature, larger but fewer eggs were produced. Larger egg sizes were achieved by provisioning these eggs with larger quantities of all compounds investigated (and thus more energy), whilst relative egg composition was rather similar to that of smaller eggs laid at the higher temperature. Turnover rates during embryonic development differed across developmental temperatures, suggesting an emphasis on hatchling quality (i.e. protein content) at the more stressful lower temperature, but on storage reserves (i.e. lipids) at the higher temperature. These differences may represent adaptive maternal effects. Embryonic development was much more efficient at the lower temperature, providing a possible mechanism underlying the temperature-size rule.

Cerebral autoregulation is an important pathophysiological and prognostic parameter for a variety of neurologic conditions. It can be assessed quickly and safely using transcranial Doppler sonography (TCD). In elderly patients, poor insonation conditions decrease the number of examinable patients and can cause a systematic bias in autoregulation parameters. The aim of this study was to investigate whether a constant infusion of an ultrasound contrast agent (Levovist((R))) can counteract these effects. We examined two cohorts of unselected neurologic patients. In 45 patients with good insonation windows (cohort 1), we used a thin aluminium foil between the skin and the TCD probe to artificially decrease the insonation quality. We determined two parameters of cerebral autoregulation (phase difference [PD] and a cross-correlation coefficient [Mx]) in native patients, with aluminium foil and with aluminium foil and a constant infusion of Levovist. In 30 patients with poor insonation windows (cohort 2), we measured the autoregulation twice, with and without an infusion of Levovist, to assess the reproducibility of the autoregulation parameters. In cohort 1, the foil model significantly decreased the Doppler signal quality, i.e., the mean spectrum energy decreased from 33.9 +/- 2.7 dB to 26.3 +/- 2.4 dB (p0.001). This introduced a significant bias to all autoregulation parameters (PD: decreased from 38.2 +/- 10.0 degrees to 27.9 +/- 12.5 degrees (p0.001); Mx: decreased from 0.308 +/- 0.170 to 0.254 +/- 0.162 (p0.01)). Both effects were compensated largely by a constant infusion of Levovist (300 mg/min). In cohort 2, infusion of the contrast agent at the same rate increased insonation quality, too, but to a lesser degree (27.4 +/- 2.4 dB to 32.0 +/- 3.7 dB, p0.001). This smaller increase did not cause a significant change in the autoregulation parameters, but the reproducibility of the PD was significantly improved (intraclass coefficient coefficient [ICC] 0.76, 95% confidence interval [0.59-0.87] in native poor bone window compared with ICC 0.90, 95% confidence interval [0.81-0.95] with infusion of the contrast agent). Our data show that constant infusion of an ultrasound contrast agent during the assessment of cerebral autoregulation can avoid potential bias introduced by poor insonation conditions. Furthermore, infusion of the contrast agent can improve reproducibility and contribute to the credibility of autoregulation assessment in the elderly. (E-mail: matthias.lorenz@em.uni-frankfurt.de).

There is controversy over whether or not chronic HIV infection contributes to atherosclerosis. We investigated the relationship between HIV infection, antiretroviral medication and ultrasound evidence of early atherosclerosis in the context of vascular risk factors.A case-control design with 292 HIV-positive subjects and 1168 age- and sex-matched controls.We assessed vascular risk factors, blood pressure, serum lipids and carotid intima media thickness (IMT) in cases and controls. With multivariate regression models, we investigated the effects of HIV status and antiretroviral medication on IMT.The common carotid artery (CCA) IMT value was 5.70% (95% confidence interval [3.08-8.38%], p0.0001) or 0.044 mm [0.021-0.066 mm] (p=0.0001) higher in HIV-positives, adjusted for multiple risk factors. In the carotid bifurcation (BIF), the IMT values were 24.4% [19.5-29.4%] or 0.250 mm [0.198-0.303 mm] higher in HIV patients (p0.0001). An investigation of antiretroviral substances revealed higher CCA- and BIF-IMT values in patients receiving combination antiretroviral therapy (HAART).HIV infection and HAART are independent risk factors for early carotid atherosclerosis. Assuming a risk ratio similar to that in large population-based cohorts, the observed IMT elevation suggests that vascular risk is 4-14% greater and the "vascular age" 4-5 years higher in HIV-positive subjects. The underlying mechanisms remain to be clarified.

The giant milkweed bug, Oncopeltus fasciatus , is an intermittent feeder, spending most of its time in compact groups away from the food, with feeding bouts lasting 30 - 60 min. They macerate a small area of the seed with their stylets, secreting large amounts of saliva (which suspends and emulsifies the seed tissue), and quickly suck the emulsion into the gut. Therefore, little digestive activity occurs in the seed tissue. Freshly ingested food in the first gut region (V1) con- sists of 50% water, 46% lipid, 5% protein, and 1% soluble carbohydrates. The junction of the midgut and hindgut lacks a lumen in the larvae stages, and a 3 L large oil drop (> 85% triacylglycerides) accumulates in the third gut region (V3). Approximately 24 h after the imaginal moult, this large volume of oil and faeces is defecated, and thereafter an oily faeces is defecated several times daily. It is postulated that the delayed egestion in larvae protects them against suffocation due to self-soiling with oily faeces. Serine proteases are absent in the gut and, instead, a cystein proteinase, inhibited by E64, is present (gut pH 6.0). High lipase activity was found throughout the gut, but only limited amylase activities. Basal levels of all three enzymes occurred throughout the gut, but at lower levels in starved bugs. Salivary gland extracts contain a cysteine proteinase and a lipase, but no amylase.

Cerebral autoregulation can be assessed quickly and noninvasively using transcranial Doppler sonography (TCD). A poor transtemporal insonation window is a common limitation in TCD examinations. The effects of insonation quality on TCD autoregulation measurements have never been investigated. We developed two methods to quantitatively measure insonation quality. We also validated a model to artificially worsen the insonation window. This involves inserting a thin aluminium foil between the TCD probe and the skin. Forty-six healthy volunteers underwent TCD examination before and after artificial reduction of the transtemporal insonation quality. Two autoregulation parameters, the phase difference (PD) and a cross-correlation coefficient (Mx), were calculated from the recordings. The aluminium foil model realistically simulates poor insonation conditions, producing a decrease in the signal power from 36.4 +/- 2.8 dB to 32.0 +/- 1.5 dB. In corrupted insonation windows, the PD is artificially low (native: 34.2 +/- 9.3 degrees , corrupted: 29.9 +/- 9.7 degrees , p = 0.002), but the Mx is not significantly different. Insonation quality may introduce a systematic bias of clinically relevant magnitude into TCD-based cerebral autoregulation studies. This must be considered when studies of elderly patients are planned. This article discusses strategies to account for this bias.

Using lines artificially selected on egg size and being subjected to a restricted and an unrestricted feeding treatment, we examined the relationships between egg size, egg number, egg composition, and reproductive investment in the butterfly Bicyclus anynana. Despite a successful manipulation of egg size, correlated responses to selection in larval time, pupal mass, pupal time, longevity, fecundity, or the amount of energy allocated to reproduction were virtually absent. Thus, there was no indication for an evolutionary link between offspring size and reproductive investment. Egg composition, in contrast, was affected by selection, with larger eggs containing relatively more lipid and water, but less protein and energy compared to smaller eggs. Hence, females producing large eggs did not have to sacrifice fecundity due to adjustments in egg composition. Food limitation per se caused only minor changes in egg composition, and there was no general reduction in egg provisioning with female age. The latter was restricted to food-limited females, whereas egg quality remained remarkably similar throughout the females’ life in control groups. We conclude that neglecting changes in biochemical egg composition, depending on genetic background, food availability, and female age, may introduce substantial error when estimating reproductive effort, and may ultimately lead to invalid conclusions. © 2007 The Linnean Society of London, Biological Journal of the Linnean Society, 2007, 91, 403–418.

In the cricket Gryllus bimaculatus , proventricular pressure forces a nutri- ent fluid from the ground food-brei through a sieve at the base of the caecae, and the combination of secreted enzymes and water causes a rapid inflation of the caecae on the first day after imaginal ecdysis. The ceacal region of the midgut is the pri- mary site for the secretion of digestive enzymes. Proteases and amylase flow from the caecae into the mostly empty crop on day 1, and carbohydrate and protein diges- tion starts as soon as food is present (6 h). Thereafter, much of the amylase activity (but not protease) in the crop is synthesized and released by the crop tissues them- selves. Regurgitating proteases and amylases from the caecae into the crop after day 1 is most likely accomplished by temporarily halting proventricular peristalsis and allowing the caecal muscles to contract, forcing caecal contents, including enzymes, forward. The total activity of digestive enzymes in the caecae is virtually identical in 2-day-old fed and unfed females, indicating little or no secretagogue (prandial) regulation of enzyme secretion. Most of the digestive enzymes in the ventricular endoperitrophic space may originate from the mucus dragged from the caecae. Lipase activity is low in all gut regions in both starved and fed females. Head liga- tion or injection of trypsin modulating oostatic factor, allatostatin A or B fails to indicate any involvement of nerves or hormones in the release of digestive enzymes in the caecae. Gryllus bimaculatus appears to secrete digestive enzymes continuously, and a considerable loss of enzymes may occur at certain times through egestion.

The flow of nutrients through the digestive tract of Gryllus bimaculatus is regulated by the proventriculus, which effectively triturates the partially digested food coming from the crop and shoves the mushy nutrient mass into the space between the paired caeca. The many folds at the base of the caeca form a sieve, and only fine food particles (4-10 microm) and fluids in the mush are filtered under pressure (produced by proventricular peristalsis) into the caeca. Combined with the release of enzymes in the caeca and the influx of water, the caeca are rapidly inflated on day 1 after the terminal molt. The remaining, mostly undigested food is shoved into a tube formed by the peritrophic membrane, which is first formed at the anterior end of the ventriculus. A mucous membrane (peritrophic gel) covers the caecal epithelium, and seems to merge with the true peritrophic membrane at the beginning of the ventriculus. The Type I peritrophic membrane is dragged posteriorly through the entire ventriculus and ileum by the posterior movement of the food bolus, which is shoved posteriorly at a rate of 6 mm/h by proventricular pressure. The growth rate of the peritrophic membrane is about 3 mm/h. Peristalsis does not occur in the midgut or ileum; the muscles in these regions function solely to counteract the internal pressure produced by the proventriculus. The exo- and endoperitrophic space in newly molted animals is open and fluids can flow in both directions. The endoperitrophic space becomes filled on day 1, and leads to a great reduction of the exoperitrophic space. In the ileal pouch (exoperitrophic space) the peritrophic membrane separates the mass of bacteria from the waste bolus within the endoperitrophic space. Feathery bristles arising from the cuticular covering of the finger-like invaginations of the ileal wall hold most of the bacterial mass in place. The crop weight decreases from day 1 to day 3 as the weight of caeca, ventriculus, and ileum increases. After day 3, food uptake and the weight of the entire gut system decrease in female crickets, partly in response to space restrictions in the abdomen caused by rapid ovarial growth.

A series of mono- and polyenehomobenzenes was synthesised by a highly regioselective palladium-catalysed allylic alkylation of substituted and unsubstituted benzylic Grignard reagents employing catalytic amounts of catalyst and tested for juvenile hormone activity on the fruit fly Drosophila virilis Sturtevant (Diptera: Drosophilidae), on an important agricultural pest species, the fall armyworm Spodoptera frugiperda JE Smith (Lepidoptera: Noctuidae), and on the map butterfly Araschnia levana L. (Lepidoptera: Nymphalidae). In D. virilis only polyenehomobenzenes with a geranyl chain and a methyl, methoxy or isopropyl group at the para position of the aromatic ring displayed significant juvenile hormonal activity at low doses. A monoenehomobenzene and polyenehomobenzenes with longer allylic chains or without a substituted aromatic ring were not active. In S. frugiperda and in A. levana, a mono-, a di- and a tetraene displayed juvenile hormonal activity. In the lepidopteran species, a trend for the necessity of a substitution at position 4 of the phenyl group for high juvenile hormonal activity was also found.

Background and Purpose— In acute ischemic stroke, time from onset to tissue-type plasminogen activator treatment (OTT) is a major determinant of outcome. To reduce OTT, clinical trials have been undertaken evaluating prehospital cerebral imaging with mobile computed tomographic scanners. Furthermore, blood biomarkers may allow rapid differentiation between ischemic stroke and intracerebral hemorrhage before hospital admission. How such treatment strategies translate into clinical benefit has not been specifically evaluated. Methods— We constructed decision models to estimate the net clinical benefit yielded by shorter OTT. In different scenarios, we estimated the proportion of patients with favorable outcome and the average quality of life. Results— An OTT reduction of 60 minutes increases the probability of favorable outcome by 6.6% in a mixed stroke population. For comparison, the average effect of tissue-type plasminogen activator itself is 7.0%. Prehospital mobile computed tomography gaining 25 to 40 minutes increases the probability of favorable outcome by 3.0% to 4.6%. The additional benefit of prehospital computed tomography to deliver patients with large vessel occlusion directly to endovascular treatment centers increases the probability of favorable outcome by another 0.2% to 1.0%. A blood test discriminating ischemic stroke and intracerebral hemorrhage may beneficially substitute brain scan before tissue-type plasminogen activator if >32 to 40 minutes are gained and if sensitivity for intracerebral hemorrhage is >75% to 80%. Conclusions— Reducing the OTT has robust beneficial effects for acute stroke patients. Prehospital tissue-type plasminogen activator treatment without brain imaging may become conceivable under several preconditions, including a point-of-care test with >75% to 80% sensitivity to detect intracerebral hemorrhage and a time gain of >32 to 40 minutes. Ethical implications remain to be addressed.

Contains fulltext : 153797.PDF (Publisher’s version ) (Open Access) BACKGROUND: Clinical manifestations and outcomes of atherosclerotic disease differ between ethnic groups. In addition, the prevalence of risk factors is substantially different. Primary prevention programs are based on data derived from almost exclusively White people. We investigated how race/ethnic differences modify the associations of established risk factors with atherosclerosis and cardiovascular events. METHODS: We used data from an ongoing individual participant meta-analysis involving 17 population-based cohorts worldwide. We selected 60,211 participants without cardiovascular disease at baseline with available data on ethnicity (White, Black, Asian or Hispanic). We generated a multivariable linear regression model containing risk factors and ethnicity predicting mean common carotid intima-media thickness (CIMT) and a multivariable Cox regression model predicting myocardial infarction or stroke. For each risk factor we assessed how the association with the preclinical and clinical measures of cardiovascular atherosclerotic disease was affected by ethnicity. RESULTS: Ethnicity appeared to significantly modify the associations between risk factors and CIMT and cardiovascular events. The association between age and CIMT was weaker in Blacks and Hispanics. Systolic blood pressure associated more strongly with CIMT in Asians. HDL cholesterol and smoking associated less with CIMT in Blacks. Furthermore, the association of age and total cholesterol levels with the occurrence of cardiovascular events differed between Blacks and Whites. CONCLUSION: The magnitude of associations between risk factors and the presence of atherosclerotic disease differs between race/ethnic groups. These subtle, yet significant differences provide insight in the etiology of cardiovascular disease among race/ethnic groups. These insights aid the race/ethnic-specific implementation of primary prevention.

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Background and Purpose— Carotid intima-media thickness (IMT) is an independent predictor of vascular events in age groups >45 years. However, there is little information about the predictive value of IMT in younger individuals. Methods— In the Carotid Atherosclerosis Progression Study (CAPS; n=5056; age range 19 to 90 years; mean age 50.1 years), common carotid artery (CCA) IMT, bifurcation IMT, internal carotid artery IMT and vascular risk factors were evaluated at baseline. The incidence of stroke, myocardial infarction (MI), and death was determined prospectively. Data for younger ( Results— During a mean follow-up period of 4.2 years, there were 228 cases of MI, 107 strokes, and 50 deaths. IMT at all carotid segments was highly predictive of all end points (eg, hazard rate ratios [HRRs] per 1 SD CCA-IMT increase were 1.43 [95% CI: 1.35 to 1.51] for MI, 1.47 [1.35 to 1.60] for stroke, and 1.45 [1.38 to 1.52] for MI, stroke or death; all P P =0.011 for age-IMT interaction). Conclusions— Carotid IMT independently predicts future vascular events. Its predictive value is at least as high in younger subjects as in older subjects.

Walking activity of 3-day-old adult female Gryllus bimaculatus (de Geer) (Ensifera, Gryllidae) was measured over 24 h. A high level of locomotor activity during the scotophase was found, which was two- to three-fold higher than that during the photophase. The titre of lipid in the haemolymph was relatively low 2 h after lights on, increased significantly 2 h after lights off, although, 2 h after lights on in the next photophase, the lipid titre had decreased to the basal level. Topical application of homologous Grybi-adipokinetic hormone (AKH) (100 pmol in 20% 2-propanol) led to a significant increase in haemolymph lipids, comparable with the maximal increase caused by injection of AKH (3 pmol in water). Topical application of AKH also stimulated locomotor activity in crickets (maximal stimulation 1.8-fold with 100 pmol Grybi-AKH). The results suggest that AKH penetrates the cuticle quickly. It is assumed that AKH stimulates locomotory activity at least in part via the increase of haemolymph lipid titres; however, the stimulation of locomotor activity via a direct neuromodulatory effect of AKH cannot be excluded.