Early intracellular trafficking of Waddlia chondrophila in human macrophages.

Waddlia chondrophila is an obligate intracellular bacterium considered as a potential agent of abortion in both humans and bovines. This member of the order Chlamydiales multiplies rapidly within human macrophages and induces lysis of the infected cells. To understand how this Chlamydia-like micro-organism invades and proliferates within host cells, we investigated its trafficking within monocyte-derived human macrophages. Vacuoles containing W. chondrophila acquired the early endosomal marker EEA1 during the first 30 min following uptake. However, the live W. chondrophila-containing vacuoles never co-localized with late endosome and lysosome markers. Instead of interacting with the endosomal pathway, W. chondrophila immediately co-localized with mitochondria and, shortly after, with endoplasmic reticulum- (ER-) resident proteins such as calnexin and protein disulfide isomerase. The acquisition of mitochondria and ER markers corresponds to the beginning of bacterial replication. It is noteworthy that mitochondrion recruitment to W. chondrophila inclusions is prevented only by simultaneous treatment with the microtubule and actin cytoskeleton-disrupting agents nocodazole and cytochalasin D. In addition, brefeldin A inhibits the replication of W. chondrophila, supporting a role for COPI-dependent trafficking in the biogenesis of the bacterial replicating vacuole. W. chondrophila probably survives within human macrophages by evading the endocytic pathway and by associating with mitochondria and the ER. The intracellular trafficking of W. chondrophila in human macrophages represents a novel route that differs strongly from that used by other members of the order Chlamydiales.

The Economic Effects of Christian Moralities

This article examines the different influences that Catholicism and Protestantism exert on economically relevant values. It argues that Catholic theology and practice facilitate personal transactions while Protestantism favors values and types of moral and legal enforcement better adapted for impersonal trade. Protestantism may thus be more conducive to economic growth through anonymous exchange while Catholicism may provide better support for personal contracting. Several components of this hypothesis are confirmed using statistical models with data from the 1998 ISSP international survey on religion. These show that Protestants are more trusting of anonymous counter parties, develop more reliable institutions for legal enforcement and are more willing to spend resources on monitoring and punishing other members of the community. Catholicism is more protective of the family and small-group relationships, and provides more tolerant and less motivating beliefs. Relatively smaller and less consistent differences appear in terms of worldly personal success and incentives.

Appropriateness of early management of newly diagnosed Crohn's disease in a European population-based cohort.

OBJECTIVE: The European Panel on the Appropriateness of Crohn's disease Therapy (EPACT) has developed appropriateness criteria. We have applied these criteria retrospectively to the population-based inception cohort of Crohn's disease (CD) patients of the European Collaborative Study Group on Inflammatory Bowel Disease (EC-IBD). MATERIAL AND METHODS: A total of 426 diagnosed CD patients from 13 European centers were enrolled at the time of diagnosis (first flare, naive patients). We used the EPACT definitions to identify 247 patients with active luminal CD. We then assessed the appropriateness of the initial drug prescription according to the EPACT criteria. RESULTS: Among the cohort patients 163 suffered from mild-to-moderate CD and 84 from severe CD. Among the mild-to-moderate disease group, 96 patients (59%) received an appropriate treatment, whereas for 66 patients (40%) the treatment was uncertain and in one case (1%) inappropriate. Among the severe disease group, 86% were treated medically and 14% required surgery. 59 (70%) were appropriately treated, whereas for one patient (1%) the procedure was considered uncertain and for 24 patients (29%) inappropriate. CONCLUSION: Initial treatment was appropriate in the majority of cases for non-complicated luminal CD. Inappropriate or uncertain treatment was given in a significant minority of patients, with an increased potential risk of adverse events.

New evidence for the social embeddedness of infants' early triangular capacities.

Infants appear to be active participants in complex interactional sequences with their parents far earlier than previously theorized. In this report, we document the capacity of 3-month-old infants to share attention with two partners (mothers and fathers) simultaneously, and trace links between this capacity and early family group-level dynamics. During comprehensive evaluations of the family's emergent coparenting alliance completed in 113 homes, we charted infants' eye gaze patterns during two different mother-father-infant assessment paradigms. Triangular capacities (operationalized as the frequency of rapid multishift gaze transitions between parents during interactions) were stable across interaction context. Infants exhibiting more advanced triangular capacities belonged to families showing evidence of better coparental adjustment. Theoretical and practice implications of these findings are discussed.

The Three Horsemen of Growth: Plague, War and Urbanization in Early Modern Europe

How did Europe overtake China? We construct a simple Malthusian model with two sectors, and use it to explain how European per capita incomes and urbanization rates could surge ahead of Chinese ones. That living standards could exceed subsistence levels at all in a Malthusian setting should be surprising. Rising fertility and falling mortality ought to have reversed any gains. We show that productivity growth in Europe can only explain a small fraction of rising living standards. Population dynamics - changes of the birth and death schedules - were far more important drivers of the longrun Malthusian equilibrium. The Black Death raised wages substantially, creating important knock-on effects. Because of Engel's Law, demand for urban products increased, raising urban wages and attracting migrants from rural areas. European cities were unhealthy, especially compared to Far Eastern ones. Urbanization pushed up aggregate death rates. This effect was reinforced by more frequent wars (fed by city wealth) and disease spread by trade. Thus, higher wages themselves reduced population pressure. Without technological change, our model can account for the sharp rise in European urbanization as well as permanently higher per capita incomes. We complement our calibration exercise with a detailed analysis of intra-European growth in the early modern period. Using a panel of European states in the period 1300-1700, we show that war frequency can explain a good share of the divergent fortunes within Europe.

Late Early Triassic climate change: Insights from carbonate carbon isotopes, sedimentary evolution and ammonoid paleobiogeography

The late Early Triassic sedimentary-facies evolution and carbonate carbon-isotope marine record (delta(13)C(carb)) of ammonoid-rich, outer platform settings show striking similarities between the South ChinaBlock (SCB) and the widely distant Northern Indian Margin (NIM). The studied sections are located within the Triassic Tethys Himalayan belt (Losar section, Himachal Pradesh, India) and the Nanpanjiang Basin in the South China Block (Jinya section, Guangxi Province), respectively. Carbon isotopes from the studied sections confirm the previously observed carbon cycle perturbations at a time of major paleoceanographic changes in the wake of the end-Permian biotic crisis. This study documents the coincidence between a sharp increase in the carbon isotope composition and the worldwide ammonoid evolutionary turnover (extinction followed by a radiation) occurring around the Smithian-Spathian boundary. Based on recent modeling studies on ammonoid paleobiogeography and taxonomic diversity, we demonstrate that the late Early Triassic (Smithian and Spathian) was a time of a major climate change. More precisely, the end Smithian climate can be characterized by a warm and equable climate underlined by a flat, pole-to-equator, sea surface temperature (SST) gradient, while the steep Spathian SST gradient suggests latitudinally differentiated climatic conditions. Moreover, sedimentary evidence suggests a transition from a humid and hot climate during the Smithian to a dryer climate from the Spathian onwards. By analogy with comparable carbon isotope perturbations in the Late Devonian, Jurassic and Cretaceous we propose that high atmospheric CO(2) levels could have been responsible for the observed carbon cycle disturbance at the Smithian-Spathian boundary. We suggest that the end Smithian ammonoid extinction has been essentially caused by a warm and equable climate related to an increased CO(2) flux possibly originating from a short eruptive event of the Siberian igneous province. This increase in atmospheric CO(2) concentrations could have additionally reduced the marine calcium carbonate oversaturation and weakened the calcification potential of marine organisms, including ammonoids, in late Smithian oceans. (c) 2006 Elsevier B.V. All rights reserved.

Early detection of idiopathic Parkinson's disease based on magnetic resonance imaging

The diagnosis of idiopathic Parkinson's disease (IPD) is entirely clinical. The fact that neuronal damage begins 5-10 years before occurrence of sub-clinical signs, underlines the importance of preclinical diagnosis. A new approach for in-vivo pathophysiological assessment of IPD-related neurodegeneration was implemented based on recently developed neuroimaging methods. It is based on non- invasive magnetic resonance data sensitive to brain tissue property changes that precede macroscopic atrophy in the early stages of IPD. This research aims to determine the brain tissue property changes induced by neurodegeneration that can be linked to clinical phenotypes which will allow us to create a predictive model for early diagnosis in IPD. We hypothesized that the degree of disease progression in IPD patients will have a differential and specific impact on brain tissue properties used to create a predictive model of motor and non-motor impairment in IPD. We studied the potential of in-vivo quantitative imaging sensitive to neurodegeneration- related brain tissue characteristics to detect changes in patients with IPD. We carried out methodological work within the well established SPM8 framework to estimate the sensitivity of tissue probability maps for automated tissue classification for detection of early IPD. We performed whole-brain multi parameter mapping at high resolution followed by voxel-based morphometric (VBM) analysis and voxel-based quantification (VBQ) comparing healthy subjects to IPD patients. We found a trend demonstrating non-significant tissue property changes in the olfactory bulb area using the MT and R1 parameter with p<0.001. Comparing to the IPD patients, the healthy group presented a bilateral higher MT and R1 intensity in this specific functional region. These results did not correlate with age, severity or duration of disease. We failed to demonstrate any changes with the R2* parameter. We interpreted our findings as demyelination of the olfactory tract, which is clinically represented as anosmia. However, the lack of correlation with duration or severity complicates its implications in the creation of a predictive model of impairment in IPD.

Analysis of the process of translation of knowledge regarding early childhood at the undergraduate level

Objective To analyze innovative contents on Early Child Development Promotion. Method This action-research involves nine faculties from four Higher Education Institutions at inner-state of São Paulo, Brazil.Data were collected by syllabi analyses (2009-2011), interviews and focus group. We have adopted an ECDP underpinning from international consensus, thus evaluating KT Results We have found relevant incorporation between teaching and extension in Nursing (87,5%) and Psychology (75%) undergraduate courses, while Pedagogy was restricted to teaching. Conclusion This KT evaluation has evinced innovative potential of extension, regardless teaching and research, for a better Early Childhood.


Modelling the effect of minor orthopaedic day surgery on patient mood at the early post-operative period: a prospective population-based cohort study.

OBJECTIVE: The effect of minor orthopaedic day surgery (MiODS) on patient's mood. METHODS: A prospective population-based cohort study of 148 consecutive patients with age above 18 and less than 65, an American Society of Anaesthesiology (ASA) score of 1, and the requirement of general anaesthesia (GA) were included. The Medical Outcomes Study - Short Form 36 (SF-36), Beck Anxiety Inventory (BAI) and Beck Depression Inventory (BDI) were used pre- and post-operatively. RESULTS: The mean physical component score of SF-36 before surgery was 45.3 (SD=+/-10.1) and 8 weeks following surgery was 44.9 (SD=+/-11.04) [n=148, p=0.51, 95% CI=(-1.03 to 1.52)]. For the measurement of the changes in mood using BDI, BAI and SF-36, latent construct modelling was employed to increase validity. The covariance between mood pre- and post-operatively (cov=69.44) corresponded to a correlation coefficient, r=0.88 indicating that patients suffering a greater number of mood symptoms before surgery continue to have a greater number of symptoms following surgery. When the latent mood constructs were permitted to have different means the model fitted well with chi(2) (df=1)=0.86 for which p=0.77, thus the null hypothesis that MiODS has no effect on patient mood was rejected. CONCLUSIONS: MiODS affects patient mood which deteriorates at 8 weeks post-operatively regardless of the pre-operative patient mood state. More importantly patients suffering a greater number of mood symptoms before MiODS continue to have a greater number of symptoms following surgery.

Ultra-early intravenous stroke thrombolysis: do all patients benefit similarly?

BACKGROUND AND PURPOSE: We previously reported increased benefit and reduced mortality after ultra-early stroke thrombolysis in a single center. We now explored in a large multicenter cohort whether extra benefit of treatment within 90 minutes from symptom onset is uniform across predefined stroke severity subgroups, as compared with later thrombolysis. METHODS: Prospectively collected data of consecutive ischemic stroke patients who received IV thrombolysis in 10 European stroke centers were merged. Logistic regression tested association between treatment delays, as well as excellent 3-month outcome (modified Rankin scale, 0-1), and mortality. The association was tested separately in tertiles of baseline National Institutes of Health Stroke Scale. RESULTS: In the whole cohort (n=6856), shorter onset-to-treatment time as a continuous variable was significantly associated with excellent outcome (P<0.001). Every fifth patient had onset-to-treatment time≤90 minutes, and these patients had lower frequency of intracranial hemorrhage. After adjusting for age, sex, admission glucose level, and year of treatment, onset-to-treatment time≤90 minutes was associated with excellent outcome in patients with National Institutes of Health Stroke Scale 7 to 12 (odds ratio, 1.37; 95% confidence interval, 1.11-1.70; P=0.004), but not in patients with baseline National Institutes of Health Stroke Scale>12 (odds ratio, 1.00; 95% confidence interval, 0.76-1.32; P=0.99) and baseline National Institutes of Health Stroke Scale 0 to 6 (odds ratio, 1.04; 95% confidence interval, 0.78-1.39; P=0.80). In the latter, however, an independent association (odds ratio, 1.51; 95% confidence interval, 1.14-2.01; P<0.01) was found when considering modified Rankin scale 0 as outcome (to overcome the possible ceiling effect from spontaneous better prognosis of patients with mild symptoms). Ultra-early treatment was not associated with mortality. CONCLUSIONS: IV thrombolysis within 90 minutes is, compared with later thrombolysis, strongly and independently associated with excellent outcome in patients with moderate and mild stroke severity.

Neurorééducation précoce au Centre hospitalier universitaire vaudois: du rêve à la réalité [Early neurorehabilitation in an acute university hospital: from dream to reality].

The need for an early neurorehabilitation pathway was identified in an acute university hospital. A team was formed to draw up and implement it. A neuro-sensorial, interdisciplinary and coordinated therapy program was developed, focused on tracheostomised patients as soon as they were admitted to the intermediate care in neurology and neurosurgery. The impact of this care plan was evaluated by comparing the results obtained with that pertaining to patients treated previously in the same services. The comparison showed a reduction of 48% of the mean duration of tracheostomy, of 39% in the time to inscription in a neurorehabilitation centre and of 20% in the length of stay in the intermediate care. An early neurorehabilitation care program, with an interdisciplinary and coordinated team, reduces complications and lengths of stay.

Report on the Early Out Incentive (EOI) programs, including a Buy Out Program, for the period November 20, 2001 through February 28, 2006

Report on the Early Out Incentive (EOI) programs, including a Buy Out Program, for the period November 20, 2001 through February 28, 2006