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BACKGROUND: The prevalence of atrial fibrillation(AF) and diabetes mellitus is rising to epidemic proportions. We aimed to assess the impact of diabetes on the management and outcomes of patients with AF.METHODS: The EORP-AF General Long-Term Registry is a prospective, observational registry from 250 centres across 27 European countries. Outcomes of interest were as follows: i)rhythm control interventions; ii)quality of life; iii)healthcare resource utilisation; and iv)major adverse events.RESULTS: Of 11,028 patients with AF, the median age was 71 (63-77) years and 2537 (23.0%) had diabetes. Median follow-up was 24 months. Diabetes was related to increased use of anticoagulation but less rhythm control interventions. Using multivariable analysis, at 2-year follow-up, patients with diabetes were associated with greater levels of anxiety (p = 0.038) compared to those without diabetes. Overall, diabetes was associated with worse health during follow-up, as indicated by Health Utility Score and Visual Analogue Scale. Healthcare resource utilisation was greater with diabetes in terms of length of hospital stay (8.1 (±8.2) vs. 6.1 (±6.7) days); cardiology and internal medicine/general practitioner visits; and emergency room admissions. Diabetes was an independent risk factor of major adverse cardiovascular event (MACE; HR 1.26 [95% CI, 1.04-1.52]), all-cause mortality (HR 1.28 [95% CI, 1.08-1.52]), and cardiovascular mortality (HR 1.41 [95% CI, 1.09-1.83]).CONCLUSION: In this contemporary AF cohort, diabetes was present in 1 in 4 patients and it served as an independent risk factor for reduced quality of life, greater healthcare resource utilisation and excess MACE, all-cause mortality and cardiovascular mortality. There was increased use of anticoagulation therapy in diabetes but with less rhythm control interventions.

The paper depicts and describes the observation of a remarkable post-stroke production of paintings made by a 54-year-old, right-handed man who suffered an acute right hemispheric stroke. The patient’s post-stroke productivity and the spatial distribution of text and drawings were assessed by means of structural analysis of the paintings, as well as neuropsychological and creativity testing. Compared to the age-matched healthy control group, the patient did not only produce more valid answers in the verbal creativity task, but he also drew more images in the figural creativity task. Most strikingly, the painted images were located on the right side in 70% of the paintings, while the text was aligned to the left side in 42% of the paintings. This dissociation between writing and painting behavior was further mirrored in the patient’s neuropsychological performance in a reading test and in a design fluency task. This observation of an increased post-stroke production of paintings may coin a new term, i.e., “hyperzographia”, in analogy to hypergraphia. Additionally, the puzzling dissociation of the writing and painting behavior highlights an important new clinical aspect concerning a differential influence of hemispatial neglect on writing and painting.

The present study investigates how reading fluency in German, and monolingual versus bilingual language background influence the learning of English as a foreign language (EFL) in primary school. Data of 83 monolingual and bilingual children with varying degrees of German reading skills (including children with dyslexia) were analyzed after they had learned EFL for 1 year. The results showed that lower German reading fluency—but not bilingualism—was associated with poorer English skills. The results suggest that risk factors leading to poor reading skills (including dyslexia) also negatively impact foreign language learning.

This year, the Conference of Parties to the Convention on Biological Diversity will meet to finalize a post 2020-framework for biodiversity conservation, necessitating critical analysis of current barriers to conservation success. Here, we tackle one of the enduring puzzles about the U.S. Endangered Species Act, often considered a model for endangered species protection globally: Why have so few species been successfully recovered? For the period of 1992–2020, we analyzed trends in the population sizes of species of concern, trends in the time between when species are first petitioned for listing and when they actually receive protection, and trends in funding for the listing and recovery of imperiled species. We find that small population sizes at time of listing, coupled with delayed protection and insufficient funding, continue to undermine one of the world’s strongest laws for protecting biodiversity.

BACKGROUND: Cardiac troponins (cTn) have been reported to be predictors for adverse outcomes in atrial fibrillation (AF), patients, but their actual use is still unclear.AIM: To assess the factors associated with cTn testing in routine practice and evaluate the association with outcomes.METHODS: Patients enrolled in the ESC-EHRA EORP-AF General Long-Term Registry were stratified into 3 groups according to cTn levels as (i) cTn not tested, (ii) cTn in range (≤99th percentile), (iii) cTn elevated (>99th percentile). The composite outcome of any thromboembolism /any acute coronary syndrome/cardiovascular (CV) death, defined as Major Adverse Cardiovascular Events (MACE) and all-cause death were the main endpoints.RESULTS: Among 10 445 AF patients (median age 71 years, 40.3% females) cTn were tested in 2834 (27.1%). cTn was elevated in 904/2834 (31.9%) and in-range in 1930/2834 (68.1%) patients. Female sex, in-hospital enrollment, first-detected AF, CV risk factors, history of coronary artery disease, and atypical AF symptoms were independently associated with cTn testing. Elevated cTn were independently associated with a higher risk for MACE (Model 1, hazard ratio [HR] 1.74, 95% confidence interval [CI] 1.40-2.16, Model 2, HR 1.62, 95% CI 1.28-2.05; Model 3 HR 1.76, 95% CI 1.37-2.26) and all-cause death (Model 1, HR 1.45, 95% CI 1.21-1.74; Model 2, HR 1.36, 95% CI 1.12-1.66; Model 3, HR 1.38, 95% CI 1.12-1.71).CONCLUSIONS: Elevated cTn levels were associated with an increased risk of all-cause mortality and adverse CV events. Clinical factors that might enhance the need to rule out CAD were associated with cTn testing.

Transcranial Direct Current Stimulation (tDCS) has been employed to modulate visuo-spatial attentional asymmetries, however, further investigation is needed to characterize tDCS-associated variability in more ecological settings. In the present research, we tested the effects of offline, anodal conventional tDCS (Experiment 1) and HD-tDCS (Experiment 2) delivered over the posterior parietal cortex (PPC) and Frontal Eye Field (FEF) of the right hemisphere in healthy participants. Attentional asymmetries were measured by means of an eye tracking-based, ecological paradigm, that is, a Free Visual Exploration task of naturalistic pictures. Data were analyzed from a spatiotemporal perspective. In Experiment 1, a pre-post linear mixed model (LMM) indicated a leftward attentional shift after PPC tDCS; this effect was not confirmed when the individual baseline performance was considered. In Experiment 2, FEF HD-tDCS was shown to induce a significant leftward shift of gaze position, which emerged after 6 s of picture exploration and lasted for 200 ms. The present results do not allow us to conclude on a clear efficacy of offline conventional tDCS and HD-tDCS in modulating overt visuospatial attention in an ecological setting. Nonetheless, our findings highlight a complex relationship among stimulated area, focality of stimulation, spatiotemporal aspects of deployment of attention, and the role of individual baseline performance in shaping the effects of tDCS.

Fluent reading is characterized by fast and effortless decoding of visual and phonological information. Here we used event-related potentials (ERPs) and neuropsychological testing to probe the neurocognitive basis of reading in a sample of children with a wide range of reading skills. We report data of 51 children who were measured at two time points, i.e., at the end of first grade (mean age 7.6 years) and at the end of fourth grade (mean age 10.5 years). The aim of this study was to clarify whether next to behavioral measures also basic unimodal and bimodal neural measures help explaining the variance in the later reading outcome. Specifically, we addressed the question of whether next to the so far investigated unimodal measures of N1 print tuning and mismatch negativity (MMN), a bimodal measure of audiovisual integration (AV) contributes and possibly enhances prediction of the later reading outcome. We found that the largest variance in reading was explained by the behavioral measures of rapid automatized naming (RAN), block design and vocabulary (46%). Furthermore, we demonstrated that both unimodal measures of N1 print tuning (16%) and filtered MMN (7%) predicted reading, suggesting that N1 print tuning at the early stage of reading acquisition is a particularly good predictor of the later reading outcome. Beyond the behavioral measures, the two unimodal neural measures explained 7.2% additional variance in reading, indicating that basic neural measures can improve prediction of the later reading outcome over behavioral measures alone. In this study, the AV congruency effect did not significantly predict reading. It is therefore possible that audiovisual congruency effects reflect higher levels of multisensory integration that may be less important for reading acquisition in the first year of learning to read, and that they may potentially gain on relevance later on.

OBJECTIVE Slow waves are thought to mediate an overall reduction in synaptic strength during sleep. The specific contribution of the thalamus to this so-called synaptic renormalization is unknown. Thalamic stroke is associated with daytime sleepiness, along with changes to sleep electroencephalography and cognition making it a unique "experiment of nature" to assess the relationship between sleep rhythms, synaptic renormalization, and daytime functions. METHODS Sleep was studied by polysomnography and high-density electroencephalography over 17 nights in patients with thalamic (n = 12) and 15 nights in patients with extra-thalamic (n = 11) stroke. Sleep electroencephalography overnight slow wave slope changes, and their relationship with subjective daytime sleepiness, cognition, and other functional tests were assessed. RESULTS Thalamic and extra-thalamic patients did not differ in terms of age, sleep duration or apnea-hypopnea index. Conversely, overnight slope changes were reduced in a large cluster of electrodes in thalamic compared to extra-thalamic stroke patients. This reduction was related to increased daytime sleepiness. No significant differences were found in other functional tests between the two groups. INTERPRETATION In patients with thalamic stroke a reduction in overnight slow wave slope change and increased daytime sleepiness was found. Sleep- and wake-centered mechanisms for this relationship are discussed. Overall, this study suggests a central role of the thalamus in synaptic renormalization. This article is protected by copyright. All rights reserved.

When humans visually explore an image, they typically tend to start exploring its left side. This phenomenon, so-called pseudoneglect, is well known, but its time-course has only sparsely been studied. Furthermore, it is unclear whether age influences pseudoneglect, and the relationship between visuo-spatial attentional asymmetries in a free visual exploration task and a classical line bisection task has not been established. To address these questions, 60 healthy participants, aged between 22 and 86, were assessed by means of a free visual exploration task with a series of naturalistic, colour photographs of everyday scenes, while their gaze was recorded by means of a contact-free eye-tracking system. Furthermore, a classical line bisection task was administered, and information concerning handedness and subjective alertness during the experiment was obtained. The results revealed a time-sensitive window during visual exploration, between 260 and 960 ms, in which age was a significant predictor of the leftward bias in gaze position, i.e., of pseudoneglect. Moreover, pseudoneglect as assessed by the line bisection task correlated with the average gaze position throughout a time-window of 300–1490 ms during the visual exploration task. These results suggest that age influences visual exploration and pseudoneglect in a time-sensitive fashion, and that the degree of pseudoneglect in the line bisection task correlates with the average gaze position during visual exploration in a time-sensitive manner.

Previous studies showed that the small leftward bias found in healthy humans’ spatial judgments of lines (“pseudoneglect”) shifts to the right with increasing distance between stimuli and observer. In this study, we investigated whether such a modulation of attentional asymmetry can also be observed in free visual exploration. Participants freely explored photographs of naturalistic scenes for 7 s in near (60 cm) and far (140 cm) space. After an initial leftward bias, followed by a compensatory rightward bias, gaze positions were significantly more leftward in near compared to far space (around 4 s from scene onset). Our results show that the modulation of attentional asymmetries by viewing distance previously reported for spatial judgments generalizes to free visual exploration, and we revealed the temporal dynamics of these asymmetries by fine-grained eye movement analysis. In contrast, an effect of viewing distance was reduced or absent when eye movements are under strong top-down control, as in systematic serial visual search (Sensitive Negelct Test). Finally, there was no effect of viewing distance in the landmark task (as also reported in a minority of other studies), suggesting that this effect may depend on specific, yet unidentified task characteristics.

In the present work, we applied anodal transcranial direct current stimulation (tDCS) over the posterior parietal cortex (PPC) and frontal eye field (FEF) of the right hemisphere in healthy subjects to modulate attentional orienting and disengagement in a gap-overlap task. Both stimulations led to bilateral improvements in saccadic reaction times (SRTs), with larger effects for gap trials. However, analyses showed that the gap effect was not affected by tDCS. Importantly, we observed significant effects of baseline performance that may mediate side- and task-specific effects of brain stimulation.

It is frequently assumed that nitrogen (N2) fixation and denitrification do not co-occur in streams because each process should be favored under different concentrations of dissolved inorganic nitrogen (DIN), and therefore these processes are rarely quantified together. We asked if these processes could co-exist by conducting a spatial survey of N2 fixation using acetylene reduction and denitrification using acetylene block [with and without amendments of carbon (C) as glucose and nitrogen (N) as nitrate]. Rates were measured on rocks and sediment in 8 southeastern Idaho streams encompassing a DIN gradient of 26–615 µg L−1. Sampling at each site was repeated in summer 2015 and 2016. We found that both denitrification and N2 fixation occurred across the gradient of DIN concentrations, with N2 fixation occurring primarily on rocks and denitrification occurring in sediment. N2 fixation rates on rocks significantly decreased 100× across the DIN gradient in 1 year of the study, and amended (with N and C) denitrification rates increased 10× across the DIN gradient in both years. Multiple linear regression and partial least squares models with environmental characteristics measured at the scale of entire stream reaches showed that C and phosphorus were positive predictors of amended and unamended denitrification rates, but no significant model could explain N2 fixation rates across all streams and years. This, coupled with the observation that detectable rates of N2 fixation occurred primarily on rocks and denitrification occurred primarily on sediment, suggests that microhabitat scale factors may better predict the co-occurrence of these processes within stream reaches. Overlooking the potential co-occurrence of N2 fixation and denitrification in stream ecosystems will impede understanding by oversimplifying the contribution of each process to the N cycle.

Our own experiences with disturbances to sleep demonstrate its crucial role in the recovery of cognitive functions. This importance is likely enhanced in the recovery from stroke; both in terms of its physiology and cognitive abilities. Decades of experimental research have highlighted which aspects and mechanisms of sleep are likely to underlie these forms of recovery. Conversely, damage to certain areas of the brain, as well as the indirect effects of stroke, may disrupt sleep. However, only limited research has been conducted which seeks to directly explore this bidirectional link between both the macro and micro-architecture of sleep and stroke. Here we describe a series of semi-independent approaches that aim to establish this link through observational, perturbational, and interventional experiments. Our primary aim is to describe the methodology for future clinical and translational research needed to delineate competing accounts of the current data. At the observational level we suggest the use of high-density EEG recording, combined analysis of macro and micro-architecture of sleep, detailed analysis of the stroke lesion, and sensitive measures of functional recovery. The perturbational approach attempts to find the causal links between sleep and stroke. We promote the use of transcranial magnetic stimulation combined with EEG to examine the cortical dynamics of the peri-infarct stroke area. Translational research should take this a step further using optogenetic techniques targeting more specific cell populations. The interventional approach focuses on how the same clinical and translational perturbational techniques can be adapted to influence long-term recovery of function.

Learning a foreign language in a natural immersion context with high exposure to the new language has been shown to change the way speech sounds of that language are processed at the neural level. It remains unclear, however, to what extent this is also the case for classroom-based foreign language learning, particularly in children. To this end, we presented a mismatch negativity (MMN) experiment during EEG recordings as part of a longitudinal developmental study: 38 monolingual (Swiss-) German speaking children (7.5 years) were tested shortly before they started to learn English at school and followed up one year later. Moreover, 22 (Swiss-) German adults were recorded. Instead of the originally found positive mismatch response in children, an MMN emerged when applying a high-pass filter of 3 Hz. The overlap of a slow-wave positivity with the MMN indicates that two concurrent mismatch processes were elicited in children. The children's MMN in response to the non-native speech contrast was smaller compared to the native speech contrast irrespective of foreign language learning, suggesting that no additional neural resources were committed to processing the foreign language speech sound after one year of classroom-based learning.

During reading acquisition children learn to recognize orthographic stimuli and link them to phonology and semantics. The present study investigated neurocognitive processes of learning to read after one year of schooling. We aimed to elucidate the cognitive processes underlying neural tuning for print that has been shown to play an important role for reading and dyslexia. A 128-channel EEG was recorded while 68 (Swiss-)German monolingual first grade children (mean age: 7.6) performed a one-back task with different types of letter and false-font strings. Print tuning was indexed by the N1 difference in the ERPs between German words and false-font strings, while the N1 lexicality effect was indexed by the difference between German words and pseudowords. In addition, we measured reading fluency, rapid automatized naming, phonological awareness, auditory memory span, and vocabulary. After one year of formal reading instruction N1 print tuning was clearly present at the group level, and could be detected at the individual level in almost 90% of the children. The N1 lexicality effect, however, could not be reliably found. On the cognitive level, next to word-reading fluency, vocabulary was also associated with N1 print tuning, but not measures reflecting phonological processing. These results demonstrate the presence of print tuning in the first year of reading acquisition and its development at the individual level. Moreover, individual differences in print tuning are not only related to word-reading fluency, but also to semantic knowledge, indicating that at early stages of learning to read the top-down modulation of print tuning is semantic rather than phonological in nature.

In the course of reading development children become familiar with letter strings and learn to distinguish between lexical and non-lexical items. In previous studies, the N1 component of the ERP was shown to reflect print tuning but also to be sensitive to lexical effects. It remains unclear, however, whether these two aspects of orthographic processing occur at the same time or in different time windows during the lengthy N1 component. Moreover, it is unclear whether these processes develop late or occur already at early stages of literacy acquisition and whether this is similar for native languages and languages acquired later in life. To address these questions, 27 children were tested longitudinally, i.e. before (mean: 7.6 years) and after one year of classroom-based English instruction. Additionally, 22 adult speakers of English as a foreign language (mean: 25.1 years) were investigated. A 128-channel EEG was recorded while participants performed a one-back task with native German words, English words, pseudowords and false-font strings. The event-related EEG analysis of early and late N1 phases revealed early effects related to print tuning and late effects related to lexical processing in the native, but not in the second language of adult readers. In the absence of lexicality effects in children, print tuning effects were found across both early and late N1 segments. The temporally distinct N1 sensitivities to print and lexicality reflect temporal dynamics of visual word processing, which seem to depend on reading expertise or maturation.

Objective: To investigate the mortality rate and possible early predictive factors of mortality after 19-23 years in a cohort of patients with rheumatoid arthritis (RA) followed prospectively from disease onset. Patients and methods: A community-based cohort of 183 patients (63% female) with RA and disease duration < 2 years was recruited 1985-1989. The patients were followed yearly from diagnosis until death or 31 December 2008. Mean age and mean duration of symptoms (range) at diagnosis were 52 (18-78) years and 11 (0-24) months, respectively. Death certificates were obtained from the Swedish Cause of Death Register and causes of death were coded by the International Classification of Diseases (ICD-10). Death rates of RA patients were compared to those of age- and sex-matched controls. Possible predictors of mortality were analysed using a Cox regression model. Results: By 31 December 2008, 69 patients (37 women and 32 men) had died. The standardized mortality ratio (SMR) was 1.23 [95% confidence interval (CI) 0.97-1.55] and p < 0.09. Older age, male sex, smoking, and the presence of cardiovascular disease (CVD) at RA diagnosis were identified as early predictors of mortality. CVD was the most common cause of death (46%), followed by malignancies (29%) and infections (13%). RA was not stated as the direct cause of death in any patient and was mentioned among underlying causes in only 16/69 (23%) patients. Conclusion: Mortality rate after 19-23 years of disease duration in this cohort of patients with disease onset in the 1980s was not significantly increased compared to age- and sex-matched controls. No RA disease-related factor predicted mortality.

Introduction: A restorative sleep is essential for physical and psychological health. Even though literature is highly heterogeneous, stroke patients mostly tend to have a lower sleep efficiency, reduced N2, N3 and REM sleep, and generally a more fragmented sleep, especially in the acute phase. Crucially, there might be an association between an impaired sleep architecture and impaired cognitive outcome. As such, a poor sleep efficiency, a low amount of N2 and N3 and enhanced wakefulness after sleep onset have been linked to an acute impaired outcome. However, the specific role of macrosleep variations for the long-term recovery is still unknown. Therefore, we aim at observing the evolution of sleep macrostructure at several time points after stroke and relating them to the long-term clinical outcome. We will further apply transitional sleep scoring which might allow a more profound insight into sleep stability. Materials and methods: We have measured so far 8 adult stroke patients (6 m, 2f; age±SEM 50.7±4.0 years; range: 27–60; 5 hemispheric, 2 bithalamic, 1 cerebellar) in the acute (day range: 3–17) and 4 of those patients in the subacute phase (day range: 72–120). We applied high-density EEG during a full night of sleep, and investigated the cognitive outcome by neuropsychological examination. We relate our data also to 2 healthy not-yet age-matched controls (31±2.1 years), having spent one night at the hospital. The transitional sleep scoring method classifies the sleep recording epoch- and time-independently, thereby allowing for a detailed and continuous scoring of sleep stages and transitions throughout the night. Results: Our very preliminary analysis shows that in the acute phase, stroke patients, as compared to controls, descriptively tend to sleep less (values expressed as means±SEM; 64.3%3.9 vs. 75.3%±6.5), to be more awake (35.7%±3.9 vs. 24.7%±6.5), to have less N3 (10.6%±1.8 vs. 23.4%±0.5) and presumably less REM sleep (12.1%±2.2 vs. 16.6%±3.8). Patients might exhibit more sleep transitions than controls (211.6±20.7 vs. 157±38.2). In the subacute phase, patients sleep shows non-significant improvements (70.2%±35.1 sleep efficiency, 19.1%±9.5 of N3, 13.9%±6.9 of REM sleep). The classical sleep scoring captured less transitions (211.6±20.7) as compared to the transitional scoring (338.4±42.4) in the acute phase, while the percentage of sleep stayed almost similar (64.3%3.9 vs. 69.8%±3.6). Conclusions: In line with current literature, our preliminary results seem to support the evidence that stroke patients may display variations in macrosleep, especially in the acute phase, having a lower sleep efficiency, less N3 and less REM sleep. Our data also show that all-night high-density EEG recordings are feasible in this hospital setting. Furthermore, transitional scoring may provide a more profound insight into sleep stability. Acknowledgements: This study was funded by the SNF Sinergia Grant (Project number: 160803).

Integrating visual and auditory language information is critical for reading. Suppression and congruency effects in audiovisual paradigms with letters and speech sounds have provided information about low-level mechanisms of grapheme-phoneme integration during reading. However, the central question about how such processes relate to reading entire words remains unexplored. Using ERPs, we investigated whether audiovisual integration occurs for words already in beginning readers, and if so, whether this integration is reflected by differences in map strength or topography (aim 1); and moreover, whether such integration is associated with reading fluency (aim 2). A 128-channel EEG was recorded while 69 monolingual (Swiss)-German speaking first-graders performed a detection task with rare targets. Stimuli were presented in blocks either auditorily (A), visually (V) or audiovisually (matching: AVM; nonmatching: AVN). Corresponding ERPs were computed, and unimodal ERPs summated (A + V = sumAV). We applied TANOVAs to identify time windows with significant integration effects: suppression (sumAV–AVM) and congruency (AVN–AVM). They were further characterized using GFP and 3D-centroid analyses, and significant effects were correlated with reading fluency. The results suggest that audiovisual suppression effects occur for familiar German and unfamiliar English words, whereas audiovisual congruency effects can be found only for familiar German words, probably due to lexical-semantic processes involved. Moreover, congruency effects were characterized by topographic differences, indicating that different sources are active during processing of congruent compared to incongruent audiovisual words. Furthermore, no clear associations between audiovisual integration and reading fluency were found. The degree to which such associations develop in beginning readers remains open to further investigation., Brain Topography, 27 (6), ISSN:0896-0267, ISSN:1573-6792

Segmental muscle enlargement occurs in a variety of neurogenic conditions. We present a patient with calf hypertrophy, likely produced by continuous neuromuscular irritability and compensatory type 1 and type 2 muscle fiber hypertrophy. The underlying lesion of the SI nerve root was caused by scarring, which could be demonstrated by Cadolinum enhanced, fat saturated magnetic resonance imaging. Thus, the application of this technique is recommended in otherwise etiologically unclear cases of neurogenic muscular lesions in order to detect chronic nerve root pathology. [Neurol Res 2000; 22: 469-472]

To test the sepsis marker procalcitonin (PCT) for its applicability to discriminate between septic and nonseptic causes of acute respiratory distress syndrome (ARDS).Prospective study, assessing the course of PCT serum levels in early (within 72 hrs after onset) ARDS. The three other inflammation markers neopterin, interleukin-6 (IL-6), and C-reactive protein (CRP) were tested in parallel.Twenty-four-bed medical intensive care unit of a 1,990-bed primary hospital, providing health care for an estimated 39,000 patients.Twenty-seven patients, 18 male and nine female, aged 16-85 yrs, with early ARDS of known cause (17 with septic and ten with nonseptic ARDS) were enrolled in a prospective study between May 1994 and May 1995.Serum samples were drawn every 4-6 hrs for measurement of PCT, neopterin, IL-6, and CRP concentrations. Blood cultures, tracheal aspirates, and urine samples were obtained every 12-24 hrs. In 24 of 27 patients, bronchoscopic cultures were also obtained. Clinical sepsis criteria as defined by the American College of Chest Physicians/Society of Critical Care Medicine Consensus Conference were checked daily.Assessment of inflammation marker serum levels in septic vs. nonseptic ARDS. PCT serum levels were significantly higher (p.0005) in the patients with septic ARDS than in patients with nonseptic ARDS within 72 hrs after onset of ARDS. There was no overlap between the two groups. Also, neopterin allowed a differentiation (p.005), although a substantial overlap between serum levels of septic and nonseptic patients was observed. No discrimination could be achieved by determination of CRP and IL-6 levels.PCT determination in early ARDS could help to discriminate between septic and nonseptic underlying disease.

Background/Aims: A diet rich in polyunsaturated Ω3 fatty acids has been shown to modulate the course of several experimental models of renal disease. The short– and long–term effects of an 8% fish oil (FO) chow on proteinuria, renal blood flow and glomerular morphology were evaluated in Milan normotensive rats that spontaneously develop progressive glomerulosclerosis. Methods: Eight rats each were pairfed FO– versus cholesterol–enriched or control diets for either 2 or 32 weeks. 4/48 animals died (2–week trial: 1 rat on the FO and 1 rat on the control diet; 32–week trial: 1 rat on the cholesterol and 1 rat on the control diet) and were excluded from all statistic analyses. Results: After 2 weeks the renal blood flows were higher in the FO animals versus controls (8.75±2.19 vs. 6.87±1.91 ml/min/g, p2/thromboxane B2 ratio shifted towards the vasodilatative prostaglandin E2 (1.76±0.18 vs. 0.91±0.19, pConclusion: The short–time effects of FO on renal hemodynamics did not alleviate the progress of renal damage in Milan normotensive rats, but the morphologic and functional signs of injury were rather pronounced with FO feeding.

Background. Kaposi's sarcoma (KS) is an human herpesvirus 8-associated tumor, occurring in immunocompromised patients. We report here an increased incidence of KS among kidney graft recipients (KGRs) during the last 2 years, concomitant to the introduction of the immunosuppressant mycophenolate mofetil (MMF). Methods. A total of 1835 KGRs, receiving organs between 1987 and 1997, were surveyed for the development of KS. A total of 371 patients received therapy including MMF (group A), whereas 1464 patients were treated with an MMF-free protocol (group B). Results. 3/371 patients (0.8%) of group A versus 2/1464 patients (0.1%) of group B developed KS. In group A, KS became evident 7±2 months after initiation of MMF therapy. Conclusions. At our center, during the last 2 years, the incidence of KS has increased in KGRs, and it is not clear whether the introduction of MMF contributes to the phenomenon.

Objective. To investigate whether the determination of serum procalcitonin (PCT) in systemic autoimmune disease will help to discriminate invasive infection from highly active underlying disease. Methods. Three hundred ninety-seven serum samples, from 18 patients with systemic lupus erythematosus (SLE) and 35 patients with systemic antineutrophil cytoplasmic antibody-associated vasculitis (AAV), were analyzed. Clinical disease activity was assessed by the Systemic Lupus Activity Measure in SLE patients and by the Birmingham Vasculitis Activity Score in AAV patients. Procalcitonin concentrations were determined in parallel with concentrations of neopterin, interleukin-6 (IL-6), and C-reactive protein (CRP). Additionally, serum creatinine values were obtained. Results. In 321 of the 324 samples from the 42 patients with autoimmune disease but without systemic infection, serum PCT levels were within the normal range (i.e.

The acylation of aromatic compounds with aroyl triflates can be performed in organic solvents (1,2-dichloroethane) without Friedel−Crafts catalysts. These reaction conditions allow kinetic investig...

In this paper we address the problem of predicting gene activities by finding gene regulatory dependencies in experimental DNA microarray data. Only few approaches to infer the dependencies of complete gene interconnectivity networks can be found in the literature. Due to the limited number of available data, the inferring problem is under-determined and ambiguous. Therefore, we introduce a new algorithm to infer relationships only between selected genes and the unknown gene network. This method is able to predict gene activation by mathematical modeling of the network and its simulation. The parameters of the mathematical model are determined by optimization with evolutionary algorithms. In this paper we will show that our approach is able to correctly predict gene responses in immune related regulatory processes and correctly identify some of the true genomic relationships of these genes.

To the Editor: In acute pancreatitis, early detection of obstruction in the biliary tree is essential for urgent desobliteration (1). The endoscopic retrograde cholangiopancreaticography (ERCP) can identify ductal and gallbladder stones and allows immediate relief by endoscopic sphincterotomy (EPT). However, ERCP and EPT are not indicated in the majority of patients with nonbiliary pancreatitis and bear the risk of inducing pancreatitis itself. Several clinical and biochemical parameters have been proposed to differentiate between biliary and nonbiliary pancreatitis but lack specificity, whereas ultrasound (US) imaging is often not diagnostic because of technical limitations (bowel gas or ileus) (2). Increased serum concentrations of acute-phase proteins and cytokines have been emphasized to be of prognostic value, but to our knowledge they have not been used as differentiation markers between the types of pancreatitis. We tested whether the 116 amino-acid pep-tide procalcitonin (PCT), which is reported to be a sensitive and specific marker for bacterial inflammation (3, 4) allows early discrimination between biliary and nonbiliary pancreatitis.

Our aim was to assess the long-term risks for kidney donors of developing arterial hypertension and hypertension-associated diseases or hyperfiltration injury of the remaining solitary kidney. We conducted a cross-sectional study in which 29 donors who were nephrectomized at our center between October 1973 and March 1990 were enrolled. At the time of evaluation median age was 54 (37-70) yr. Since kidney donation an average time interval of 11.1 +/- 3.8 yr had elapsed. Body weight, casual blood pressure, S-creatinine and proteinuria were recorded. In 28/29 donors 24-h blood pressure monitoring was performed; all 29 were tested for microalbuminuria (MAU). The patient history was checked for treatment with antihypertensives, coronary heart disease and diabetes mellitus. From all 29 kidney donors surveyed up to 19.8 yr none developed marked renal insufficiency: median S-creatinine was 1.0 mg/dl (range 0.7-1.6), only 3 donors had a S-creatinine1.3 mg/dl. Glomerular filtration rate (GFR) decreased in an age-dependent manner. While all donors had been normotensive without an antihypertensive treatment at time of nephrectomy, actually 29% proved to be hypertensive with average values130/80 mmHg in the 24-h assessment. 5/29 donors received antihypertensives, 3 of whom nevertheless were hypertensive. Day-night profile was lost in 2 patients. After donation one patient developed coronary heart disease. 7/29 donors (24%) displayed positive testing for MAU, furthermore one had proteinuria (approx. 300 mg/l). MAU was associated in one case with slightly elevated S-creatinine (1.3 mg/dl) and in 3 cases with arterial hypertension. In the long-term course living related kidney donors do not seem to be at risk for developing hypertensive disorders more often than the general population. The prevalence of MAU in the 29 cases studied was higher than so far described for healthy subjects. This may reflect subclinical hyperfiltration damage of the glomerulus. Progressive renal insufficiency with clinical relevant function loss of the remaining solitary organ, however, was not observed up to 19.8 yr after kidney donation.

The impact of immunological factors in the development of chronic graft dysfunction in renal transplant recipients treated with cyclosporin A (CsA) and prednisolone is controversially discussed. Higher immunosuppression by a conversion to triple-drug therapy including azathioprine, while simultaneously reducing CsA, showed promising results, but bears the risk of infections. However, prospective trials on either patient numbers with use of standardized conversion criteria are lacking.

Nineteen patients with biopsy-confirmed ongoing acute rejection of renal allografts were converted from standard immunosuppression to FK506. Eight grafts showed vascular rejection and 11 had cellular rejection on biopsy. All patients had already received intravenous high-dose steroid treatment. Ten patients also had additional OKT3 rescue therapy. Initial FK506 doses were 0.13 +/- 0.06 mg/kg/day; the FK506 whole blood trough level after 3 days of treatment was 9.3 +/- 4.5 ng/ml. After conversion to FK506 all but four patients also received azathioprine, 1.5-2 mg/kg/day, and all patients received oral prednisolone. Concomitant with initiation of FK506, an anti-infective prophylaxis was prescribed, consisting of ganciclovir and trimethoprim/sulfamethoxazole. Sixteen out of 19 of the grafts (84%) were rescued successfully, including two grafts of patients already on hemodialysis at the time of conversion. Graft function of the responders improved from an average serum creatinine level of 364 +/- 109 mumol/L to 154 +/- 49 mumol/L. Of the patients receiving high-dose steroids alone prior to FK506 initiation, 8/9 responded to FK506 treatment, compared with 8/10 of those who had also received OKT3. During the mean follow-up of 35 weeks after conversion, no clinically apparent cytomegalovirus infection and no pneumonia were seen. Treatment with FK506 may successfully suppress ongoing acute rejection, even if antilymphocyte preparations have failed. FK506 can be used at a lower dose than so far recommended without impairing the antirejection potential. An additional anti-infective prophylaxis seems effective in preventing severe complications in the first months after rejection therapy.