Multifocal posterior uveitis in Crohn's disease

PURPOSE To report a case of rare posterior eye manifestation of Crohn's disease preceding recurrence of inflammatory bowel disease. METHODS Case report with ophthalmoscopic findings, fluorescein/indocyanin green angiograms, automated perimetry and multifocal-ERG. RESULTS The perimetry revealed absolute and relative scotomas corresponding to multifocal inflammatory lesions in the retina and choroid, reduced a/b amplitudes in multifocal-ERG and hypofluorescent dots in angiography. Under oral prednisolone visual defects, ophthalmoscopic and angiographic findings resolved, while a/b amplitudes remained mildly reduced. The ocular changes occurred without systemic hypertension and were followed by a new episode of intestinal symptoms. CONCLUSION Multifocal inflammatory lesions in the retina and choroid in patients with Crohn's disease may occur and may precede a recurrent intestinal episode. Crohn's patients should be carefully followed up in collaboration with internal medicine specialists.

Biologika – Genese und Charakteristika immunvermittelter Nebenwirkungen

Die Therapie immunvermittelter und maligner Erkrankungen befindet sich im Umbruch. Zunehmend kommen gezielt mit molekularen Zellstrukturen interagierende therapeutische Proteine, sogenannte Biologika oder Biopharmaka, zum Einsatz. Biologika sind in der Regel Antikörper oder Fusionsproteine und werden gentechnologisch nach dem Vorbild körpereigener Strukturen in zellulären Expressionssystemen, wie zum Beispiel Hamster-Ovarzellen, hergestellt und in hochreiner Form verabreicht. Biologika haben mit den klassischen kleinmolekularen Medikamenten, den sogenannten Synthetika, sowohl in der Wirkungsweise wie auch hinsichtlich der Nebenwirkungen nur noch wenig gemein. Der zunehmende Einsatz von Biologika im klinischen Alltag stellt eine Herausforderung für die anwendenden Ärzte dar, die nebst den neuen Wirkmechanismen auch den Umgang mit komplexen Nebenwirkungsmustern von direkt mit dem Immunsystem interagierenden Substanzen kennen und behandeln lernen müssen. Akute Infusionreaktionen (infusion-related reaction, IRR) stellen mit einer Inzidenz von 0,1 – 3% die häufigste Nebenwirkung dar. Interessanterweise handelt es sich in den meisten Fällen nicht um IgE-vermittelte Reaktionen und lassen sogar eine Reexposition zu. Während regulatorische Behörden und die Pharmaindustrie sich vor allem auf anti-drug-antibodies (ADA)-vermittelte Nebenwirkungen konzentrieren, wollen wir hier einen Überblick über das Nebenwirkungsspektrum und mögliche Abklärungsalgorithmen geben.

Lifshitz holographic renormalization from anti-de Sitter 1

Lifshitz space–times with critical exponent z = 2 can be obtained by dimensional reduction of Schrödinger space–times with critical exponent z = 0. The latter space–times are asymptotically anti-de Sitter (AdS) solutions of AdS gravity coupled to an axion–dilaton system (or even just a massless scalar field). This basic observation is used to perform holographic renormalization for four-dimensional asymptotically locally Lifshitz space–times by dimensional reduction of the corresponding problem of holographic renormalization for five-dimensional asymptotically AdS space–times coupled to an axion–dilaton system. In this setup the four-dimensional structure of the Lifshitz – Fefferman-Graham expansion and the structure of the counterterm action, including the scale anomaly, will be summarized.

EAU guidelines on surgical treatment of urinary incontinence

CONTEXT The European Association of Urology (EAU) guidelines on urinary incontinence published in March 2012 have been rewritten based on an independent systematic review carried out by the EAU guidelines panel using a sustainable methodology. OBJECTIVE We present a short version here of the full guidelines on the surgical treatment of patients with urinary incontinence, with the aim of dissemination to a wider audience. EVIDENCE ACQUISITION Evidence appraisal included a pragmatic review of existing systematic reviews and independent new literature searches based on Population, Intervention, Comparator, Outcome (PICO) questions. The appraisal of papers was carried out by an international panel of experts, who also collaborated in a series of consensus discussions, to develop concise structured evidence summaries and action-based recommendations using a modified Oxford system. EVIDENCE SUMMARY The full version of the guidance is available online (www.uroweb.org/guidelines/online-guidelines/). The guidance includes algorithms that refer the reader back to the supporting evidence and have greater accessibility in daily clinical practice. Two original meta-analyses were carried out specifically for these guidelines and are included in this report. CONCLUSIONS These new guidelines present an up-to-date summary of the available evidence, together with clear clinical algorithms and action-based recommendations based on the best available evidence. Where high-level evidence is lacking, they present a consensus of expert panel opinion.

Different adaptation of IGF-I and its IGFBPs in dairy cows during a negative energy balance in early lactation and a negative energy balance induced by feed restriction in mid-lactation

Control of metabolic pathways is a major task of the somatotropic axis and its constituents. Insulinlike growth-factor binding proteins (IGFBPs) bind IGF-I and -II and act as carriers and regulators of their activities in blood, body fluids and tissues. Over two periods of physiological adaptation, this study investigated the binding pattern of IGF-I to IGFBPs in the plasma of 50 multiparous Holstein dairy cows and identified relationships with the hepatic mRNA abundance of IGFBPs and plasma IGF-I during the lactational negative energy balance (NEB) and during a deliberately induced NEB by feed restriction. Period 1 lasted from week 3 antepartum (a.p.) to week 12 postpartum (p.p.) and period 2, the period of feed restriction, started at around 100 DIM and lasted for three weeks with a control (C) and a restricted group (R). Blood samples and liver biopsies were collected in week 3 a.p., and in weeks 1 and 4 p.p. of period 1 and in weeks 0 and 3 of period 2. For column chromatography of IGFBPs, plasma samples of all animals were pooled by group and time points of sampling. Plasma IGF-I dropped from week 3 a.p. to week 1 p.p. and thereafter increased until week 0 (period 2) and did not change up to week 3 of period 2. The binding of IGF-I to plasma IGFBP-1 and -2 increased in period 1 from week 3 a.p. to week 4 p.p., while at the same time it decreased for IGFBP-3. During period 2, the binding of IGF-I to plasma IGFBP-1 and -2 decreased for both groups, but less for R cows. In C cows, the IGF-I binding to IGFBP-3 in plasma increased from week 0 to week 3 of period 2, whereas R cows showed a slight decrease. In period 1, hepatic mRNA abundance of IGFBP-3 followed the plasma IGFBP-3 binding in contrast to the mRNA abundances of IGFBP-1 and -2. The latter increased from week 3 a.p. to week 1 p.p. and decreased afterwards whereas IGF-I binding to IGFBP-1 and -2 increased. In week 3 of period 2, the binding of IGF-I to IGFBP-1 and -2 and their hepatic mRNA abundance were higher in R cows compared to C cows. Hepatic mRNA abundance of IGF-I was consistently positively correlated with plasma IGF-I, especially pronounced during the NEBs in week 1 p.p. (period 1) and in week 3 (period 2) in R cows. While no distinct relation between mRNA abundance of IGFBP-1 and plasma IGF-I was evident, the mRNA abundance of IGFBP-2 was inversely related to plasma IGF-I over all experimental time points independent of treatment. The mRNA abundance of IGFBP-3 was particularly correlated with plasma IGF-I during the 2 experimental stages of a NEB. Obviously IGFBP-3, but not IGFBP-1 and -2, binding in plasma closely followed the respective pattern of hepatic mRNA abundance during the entire experimental period. The fact that changes in the different plasma IGFBPs during altering metabolic stages in different stages of lactation do not always strictly follow their mRNA abundance in liver suggests tissues other than the liver flexibly contributing to the IGFBP pool in plasma as well as a partially post-transcriptional regulation of IGFBP synthesis.

An innovative blended learning approach using virtual patients as preparation for skills laboratory training: perceptions of students and tutors

BACKGROUND Currently only a few reports exist on how to prepare medical students for skills laboratory training. We investigated how students and tutors perceive a blended learning approach using virtual patients (VPs) as preparation for skills training. METHODS Fifth-year medical students (N=617) were invited to voluntarily participate in a paediatric skills laboratory with four specially designed VPs as preparation. The cases focused on procedures in the laboratory using interactive questions, static and interactive images, and video clips. All students were asked to assess the VP design. After participating in the skills laboratory 310 of the 617 students were additionally asked to assess the blended learning approach through established questionnaires. Tutors' perceptions (N=9) were assessed by semi-structured interviews. RESULTS From the 617 students 1,459 VP design questionnaires were returned (59.1%). Of the 310 students 213 chose to participate in the skills laboratory; 179 blended learning questionnaires were returned (84.0%). Students provided high overall acceptance ratings of the VP design and blended learning approach. By using VPs as preparation, skills laboratory time was felt to be used more effectively. Tutors perceived students as being well prepared for the skills laboratory with efficient uses of time. CONCLUSION The overall acceptance of the blended learning approach was high among students and tutors. VPs proved to be a convenient cognitive preparation tool for skills training.

Introduction to “A Compendium of Strategies to Prevent Healthcare-Associated Infections in Acute Care Hospitals: 2014 Updates”

Abstract Since the publication of "A Compendium of Strategies to Prevent Healthcare-Associated Infections in Acute Care Hospitals" in 2008, prevention of healthcare-associated infections (HAIs) has become a national priority. Despite improvements, preventable HAIs continue to occur. The 2014 updates to the Compendium were created to provide acute care hospitals with up-to-date, practical, expert guidance to assist in prioritizing and implementing their HAI prevention efforts. It is the product of a highly collaborative effort led by the Society for Healthcare Epidemiology of America (SHEA), the Infectious Diseases Society of America (IDSA), the American Hospital Association (AHA), the Association for Professionals in Infection Control and Epidemiology (APIC), and The Joint Commission, with major contributions from representatives of a number of organizations and societies with content expertise, including the Centers for Disease Control and Prevention (CDC), the Institute for Healthcare Improvement (IHI), the Pediatric Infectious Diseases Society (PIDS), the Society for Critical Care Medicine (SCCM), the Society for Hospital Medicine (SHM), and the Surgical Infection Society (SIS).

Thermochronological Evidence for Late Proterozoic (Vendian) Cooling in Southwest Wedel Jarlsberg Land, Spitsbergen

Two Proterozoic terranes with different metamorphic histories are distinguished from geological mapping in southwestern Wedel Jarlsberg Land: a northern greenschist facies terrane and a southern amphibolite facies terrane which has been overprinted by greenschist facies metamorphism. To better characterize the tectonothermal history of these terranes we have obtained new Ar-40/Ar-39 mineral dates from this area. A muscovite separate from the northern terrane yielded a Caledonian plateau age of 432 +/- 7 Ma. The southern terrane yielded significantly older Ar-40/Ar-39 ages with three muscovite plateau dates of 584 +/- 14 Ma, 575 +/- 15 Ma, and 459 +/- 9 Ma, a 484 +/- 5 Ma biotite plateau date, and a 616 +/- 17 Ma hornblende plateau date. The oldest thermochronological dates are over 300 Ma younger than the age of amphibolite facies metamorphism and therefore probably do not represent uplift-related cooling. Instead, the Vendian dates correlate well with a regionally widespread magmatic and metamorphic/thermal resetting event recognized within Caledonian complexes of northwestern Spitsbergen and Nordaustlandet. The apparent Ordovician dates are interpreted to represent partial resetting, suggesting that late Caledonian greenschist facies overprinting of the southern terrane was of variable intensity.

Herbivores differentially limit the seedling growth and sapling recruitment of two dominant rain forest trees

Resource heterogeneity may influence how plants are attacked and respond to consumers in multiple ways. Perhaps a better understanding of how this interaction might limit sapling recruitment in tree populations may be achieved by examining species’ functional responses to herbivores on a continuum of resource availability. Here, we experimentally reduced herbivore pressure on newly established seedlings of two dominant masting trees in 40 canopy gaps, across c. 80 ha of tropical rain forest in central Africa (Korup, Cameroon). Mesh cages were built to protect individual seedlings, and their leaf production and changes in height were followed for 22 months. With more light, herbivores increasingly prevented the less shade-tolerant Microberlinia bisulcata from growing as tall as it could and producing more leaves, indicating an undercompensation. The more shade-tolerant Tetraberlinia bifoliolata was much less affected by herbivores, showing instead near to full compensation for leaf numbers, and a negligible to weak impact of herbivores on its height growth. A stage-matrix model that compared control and caged populations lent evidence for a stronger impact of herbivores on the long-term population dynamics of M. bisulcata than T. bifoliolata. Our results suggest that insect herbivores can contribute to the local coexistence of two abundant tree species at Korup by disproportionately suppressing sapling recruitment of the faster-growing dominant via undercompensation across the light gradient created by canopy disturbances. The functional patterns we have documented here are consistent with current theory, and, because gap formations are integral to forest regeneration, they may be more widely applicable in other tropical forest communities. If so, the interaction between life-history and herbivore impact across light gradients may play a substantial role in tree species coexistence.

C-reactive protein predicts mortality in patients referred for coronary angiography and symptoms of heart failure with preserved ejection fraction

AIMS Heart failure with preserved ejection fraction (HFpEF) has a different pathophysiological background compared to heart failure with reduced ejection fraction (HFrEF). Tailored risk prediction in this separate heart failure group with a high mortality rate is of major importance. Inflammation may play an important role in the pathogenesis of HFpEF because of its significant contribution to myocardial fibrosis. We therefore aimed to assess the predictive value of C-reactive protein (CRP) in patients with HFpEF. METHODS AND RESULTS Plasma levels of CRP were determined in 459 patients with HFpEF in the LUdwigshafen Risk and Cardiovascular Health (LURIC) study using a high-sensitivity assay. During a median follow-up of 9.7 years 40% of these patients died. CRP predicted all-cause mortality with an adjusted hazard ratio (HR) of 1.20 [95% confidence interval (CI) 1.02-1.40, P = 0.018] and cardiovascular mortality with a HR of 1.32 (95% CI 1.08-1.62, P = 0.005) per increase of one standard deviation. CRP was a significantly stronger mortality predictor in HFpEF patients than in a control group of 522 HFrEF patients (for interaction, P = 0.015). Furthermore, CRP added prognostic value to N-terminal pro B-type natriuretic peptide (Nt-proBNP): the lowest 5-year mortality rate of 6.8% was observed for patients in the lowest tertile of Nt-proBNP as well as CRP. The mortality risk peaked in the group combining the highest values of Nt-proBNP and CRP with a 5-year rate of 36.5%. CONCLUSION It was found that CRP was an independent and strong predictor of mortality in HFpEF. This observation may reflect immunological processes with an adverse impact on the course of HFpEF.

How do different aspects of self-regulation predict successful adaptation to school?

Self-regulation plays an important role in successful adaptation to preschool and school contexts as well as in later academic achievement. The current study relates different aspects of self-regulation such as temperamental effortful control and executive functions (updating, inhibition, and shifting) to different aspects of adaptation to school such as learning-related behavior, school grades, and performance in standardized achievement tests. The relationship between executive functions/effortful control and academic achievement has been established in previous studies; however, little is known about their unique contributions to different aspects of adaptation to school and the interplay of these factors in young school children. Results of a 1-year longitudinal study (N = 459) revealed that unique contributions of effortful control (parental report) to school grades were fully mediated by children’s learning-related behavior. On the other hand, the unique contributions of executive functions (performance on tasks) to school grades were only partially mediated by children’s learning-related behavior. Moreover, executive functions predicted performance in standardized achievement tests exclusively, with comparable predictive power for mathematical and reading/writing skills. Controlling for fluid intelligence did not change the pattern of prediction substantially, and fluid intelligence did not explain any variance above that of the two included aspects of self-regulation. Although effortful control and executive functions were not significantly related to each other, both aspects of self-regulation were shown to be important for fostering early learning and good classroom adjustment in children around transition to school.