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1.
Background:Many animal studies suggested that the uremic toxin indoxyl sulphate can add to renal damage following induced nephrotoxicity and this effect has not been proved in patients with such complication. Methods:This is a prospective, case-control, and an observational study conducted on 74 critically ill patients with acute nephrotoxicity. It was designed to measure serum levels of indoxyl sulphate on the day of enrollment and over the course of their illness using high performance liquid chromatography (HPLC-UV) and to test the correlation between these levels and patient’s demographics, clinical characteristics, physiological variables, and their outcomes.Results:Critically ill patients with acute nephrotoxicity had significantly higher total (tIS) and free (fIS) indoxyl sulphate than healthy controls and significantly lower than patients with end-stage renal disease (ESRD). Although, no correlation was found between tIS or fIS and mortality, among survivors, tIS, fIS, creatinine and eGFR were independently associated with no renal recovery.Conclusion:Serum indoxyl sulphate levels were elevated in critically ill patients with acute nephrotoxicity. There is an association between high levels of indoxyl sulphate and no renal-recovery outcome among survivors of acute nephrotoxicity. Early removal of indoxyl sulphate from patients’ blood may improve their outcomes.Key Words: HPLC, Indoxyl sulphate, Mortality, Prognosis, Toxic acute kidney injury  相似文献   

2.

Background

Cerebrovascular diseases are a frequent cause of neurological symptoms in patients with cancer. The clinical characteristics of ischemic stroke (IS) in patients with cancer have been reported in several studies; however, limited data are available regarding critically ill patients with cancer who develop IS during their stay in the intensive care unit (ICU).

Methods

All consecutive patients who underwent brain magnetic resonance imaging (MRI) for suspicion of IS with acute abnormal neurologic symptoms or who developed signs of IS while in the ICU were retrospectively evaluated. We compared the clinical characteristics and diffusion-weighted imaging (DWI) lesion patterns between patients finally diagnosed as having or not having IS.

Results

Over the study period, a total of 88 patients underwent brain MRI for suspicion of IS, with altered mental status in 55 (63%), hemiparesis in 28 (32%), and seizure in 20 (23%). A total of 43 (49%) patients were ultimately diagnosed with IS. Multiple DWI lesions (41%) were more common than single lesions (8%). The etiologies of IS were not determined in the majority of patients (n = 27, 63%). In the remaining 16 (37%) patients, the most common aetiology of IS was cardioembolism (n = 8), followed by large-vessel atherosclerosis (n = 3) and small-vessel occlusion (n = 2). However, brain metastases were newly diagnosed in only 7 (8%) patients. Univariate comparison of the baseline characteristics between patients with or without IS did not reveal any significant differences in sex, malignancy type, recent chemotherapy, vascular risk factors, or serum D-dimer levels at the time of suspicion of IS. Thrombotic events were more common in the IS group than in the non-IS group (P = 0.028). However, patients who were ultimately diagnosed with IS had more hemiparesis symptoms at the time of suspicion of IS (P = 0.001). This association was significant even after adjusting for potentially confounding factors (adjusted odds ratio 5.339; 95% confidence interval, 1.521–19.163).

Conclusions

IS developed during ICU stays in critically ill patients with cancer have particular features that may be associated with cancer-related mechanism.  相似文献   

3.
This article was to have been written by Kees Weijer, an outstanding pioneer in Dictyostelium research. It was (and is) to celebrate J.T. Bonner’s and Weijer’s contributions to the field and those of the other great pioneers. Unfortunately, Weijer was unable to write his article, due to ill health and since I have some knowledge of this field, I took it over. The article summarises some main results and ideas in Dictyostelium research and their relevance for development of more advanced organisms.  相似文献   

4.
Replicability, the ability to replicate scientific findings, is a prerequisite for scientific discovery and clinical utility. Troublingly, we are in the midst of a replicability crisis. A key to replicability is that multiple measurements of the same item (e.g., experimental sample or clinical participant) under fixed experimental constraints are relatively similar to one another. Thus, statistics that quantify the relative contributions of accidental deviations—such as measurement error—as compared to systematic deviations—such as individual differences—are critical. We demonstrate that existing replicability statistics, such as intra-class correlation coefficient and fingerprinting, fail to adequately differentiate between accidental and systematic deviations in very simple settings. We therefore propose a novel statistic, discriminability, which quantifies the degree to which an individual’s samples are relatively similar to one another, without restricting the data to be univariate, Gaussian, or even Euclidean. Using this statistic, we introduce the possibility of optimizing experimental design via increasing discriminability and prove that optimizing discriminability improves performance bounds in subsequent inference tasks. In extensive simulated and real datasets (focusing on brain imaging and demonstrating on genomics), only optimizing data discriminability improves performance on all subsequent inference tasks for each dataset. We therefore suggest that designing experiments and analyses to optimize discriminability may be a crucial step in solving the replicability crisis, and more generally, mitigating accidental measurement error.  相似文献   

5.

Background

Rapid identification of the etiological agent in bloodstream infections is of vital importance for the early administration of the most appropriate antibiotic therapy. Molecular methods may offer an advantage to current culture-based microbiological diagnosis. The goal of this study was to evaluate the performance of IRIDICA, a platform based on universal genetic amplification followed by mass spectrometry (PCR/ESI-MS) for the molecular diagnosis of sepsis-related pathogens directly from the patient’s blood.

Methods

A total of 410 whole blood specimens from patients admitted to Emergency Room (ER) and Intensive Care Unit (ICU) with clinical suspicion of sepsis were tested with the IRIDICA BAC BSI Assay (broad identification of bacteria and Candida spp.). Microorganisms grown in culture and detected by IRIDICA were compared considering blood culture as gold standard. When discrepancies were found, clinical records and results from other cultures were taken into consideration (clinical infection criterion).

Results

The overall positive and negative agreement of IRIDICA with blood culture in the analysis by specimen was 74.8% and 78.6%, respectively, rising to 76.9% and 87.2% respectively, when compared with the clinical infection criterion. Interestingly, IRIDICA detected 41 clinically significant microorganisms missed by culture, most of them from patients under antimicrobial treatment. Of special interest were the detections of one Mycoplasma hominis and two Mycobacterium simiae in immunocompromised patients. When ICU patients were analyzed separately, sensitivity, specificity, positive and negative predictive values compared with blood culture were 83.3%, 78.6%, 33.9% and 97.3% respectively, and 90.5%, 87.2%, 64.4% and 97.3% respectively, in comparison with the clinical infection criterion.

Conclusions

IRIDICA is a promising technology that offers an early and reliable identification of a wide variety of pathogens directly from the patient’s blood within 6h, which brings the opportunity to improve management of septic patients, especially for those critically ill admitted to the ICU.  相似文献   

6.
Pre-mRNA splicing occurs in a large complex spliceosome. The steps of both spliceosome assembly and splicing reaction have been extensively analyzed, and many of the factors involved have been identified. However, the post-splicing intron turnover process, especially in vertebrates, remains to be examined. In this paper, we developed a two-tag affinity purification method for purifying lariat intron RNA–protein complexes obtained from an in vitro splicing reaction. Glycerol gradient sedimentation analyses revealed that there are at least two forms of post-splicing intron complexes, which we named the ‘Intron Large (IL)’ and the ‘Intron Small (IS)’ complexes. The IL complex contains U2, U5 and U6 snRNAs and other protein splicing factors, whereas the IS complex contains no such U snRNAs or proteins. We also showed that TFIP11, a human homolog of yeast Ntr1, is present in the IL complex and the TFIP11 mutant protein, which lacks the interaction domain with hPrp43 protein, caused accumulation of the IL complex and reduction of IS complex formation in vitro. Taken together, our results strongly suggest that TFIP11 in cooperation with hPrp43 mediates the transition from the IL complex to the IS complex, leading to efficient debranching and turnover of excised introns.  相似文献   

7.
Sustained molecular oscillations are ubiquitous in biology. The obtained oscillatory patterns provide vital functions as timekeepers, pacemakers and spacemarkers. Models based on control theory have been introduced to explain how specific oscillatory behaviors stem from protein interaction feedbacks, whereas the energy dissipation through the oscillating processes and its role in the regulatory function remain unexplored. Here we developed a general framework to assess an oscillator’s regulation performance at different dissipation levels. Using the Escherichia coli MinCDE oscillator as a model system, we showed that a sufficient amount of energy dissipation is needed to switch on the oscillation, which is tightly coupled to the system’s regulatory performance. Once the dissipation level is beyond this threshold, unlike stationary regulators’ monotonic performance-to-cost relation, excess dissipation at certain steps in the oscillating process damages the oscillator’s regulatory performance. We further discovered that the chemical free energy from ATP hydrolysis has to be strategically assigned to the MinE-aided MinD release and the MinD immobilization steps for optimal performance, and a higher energy budget improves the robustness of the oscillator. These results unfold a novel mode by which living systems trade energy for regulatory function.  相似文献   

8.

Background

Insertion sequences (ISs) are approximately 1 kbp long “jumping” genes found in prokaryotes. ISs encode the protein Transposase, which facilitates the excision and reinsertion of ISs in genomes, making these sequences a type of class I (“cut-and-paste”) Mobile Genetic Elements. ISs are proposed to be involved in the reductive evolution of symbiotic prokaryotes. Our previous sequencing of the genome of the cyanobacterium ‘Nostoc azollae’ 0708, living in a tight perpetual symbiotic association with a plant (the water fern Azolla), revealed the presence of an eroding genome, with a high number of insertion sequences (ISs) together with an unprecedented large proportion of pseudogenes. To investigate the role of ISs in the reductive evolution of ‘Nostoc azollae’ 0708, and potentially in the formation of pseudogenes, a bioinformatic investigation of the IS identities and positions in 47 cyanobacterial genomes was conducted. To widen the scope, the IS contents were analysed qualitatively and quantitatively in 20 other genomes representing both free-living and symbiotic bacteria.

Results

Insertion Sequences were not randomly distributed in the bacterial genomes and were found to transpose short distances from their original location (“local hopping”) and pseudogenes were enriched in the vicinity of IS elements. In general, symbiotic organisms showed higher densities of IS elements and pseudogenes than non-symbiotic bacteria. A total of 1108 distinct repeated sequences over 500 bp were identified in the 67 genomes investigated. In the genome of ‘Nostoc azollae’ 0708, IS elements were apparent at 970 locations (14.3%), with 428 being full-length. Morphologically complex cyanobacteria with large genomes showed higher frequencies of IS elements, irrespective of life style.

Conclusions

The apparent co-location of IS elements and pseudogenes found in prokaryotic genomes implies earlier IS transpositions into genes. As transpositions tend to be local rather than genome wide this likely explains the proximity between IS elements and pseudogenes. These findings suggest that ISs facilitate the reductive evolution in for instance in the symbiotic cyanobacterium ‘Nostoc azollae’ 0708 and in other obligate prokaryotic symbionts.

Electronic supplementary material

The online version of this article (doi:10.1186/s12864-015-1386-7) contains supplementary material, which is available to authorized users.  相似文献   

9.
Teachers’ emotions are critically important for the quality of classroom instruction, and they are key components of teachers’ psychological well-being. Past research has focused on individual differences between teachers, whereas within-teacher variation across contexts has rarely been considered. As such, the present research addresses the long-standing yet unresolved person-situation debate pertaining to the emotional experiences of teachers. In two diary studies (N = 135, 70% female, and N = 85, 28% female), we examined the role of person, academic subject, and group of students for teacher emotions; focusing on three of the most salient emotions found in teachers: enjoyment, anger, and anxiety. Findings from multi-level analysis confirmed the person specificity of enjoyment, anger, and, in particular, anxiety. In addition, underscoring the existence of within-teacher variability, findings supported that teachers’ emotions considerably varied depending on the subject and group of students taught, particularly so for enjoyment and anger. Implications of the person and context specificity of teacher emotions are discussed in relation to assessments and intervention programs aiming to improve teachers’ emotional lives in the classroom.  相似文献   

10.
Accurate and timely glucose monitoring is essential in intensive care units. Real-time continuous glucose monitoring system (CGMS) has been advocated for many years to improve glycemic management in critically ill patients. In order to determine the effect of calibration time on the accuracy of CGMS, real-time subcutaneous CGMS was used in 18 critically ill patients. CGMS sensor was calibrated with blood glucose measurements by blood gas/glucose analyzer every 12 hours. Venous blood was sampled every 2 to 4 hours, and glucose concentration was measured by standard central laboratory device (CLD) and by blood gas/glucose analyzer. With CLD measurement as reference, relative absolute difference (mean±SD) in CGMS and blood gas/glucose analyzer were 14.4%±12.2% and 6.5%±6.2%, respectively. The percentage of matched points in Clarke error grid zone A was 74.8% in CGMS, and 98.4% in blood gas/glucose analyzer. The relative absolute difference of CGMS obtained within 6 hours after sensor calibration (8.8%±7.2%) was significantly less than that between 6 to 12 hours after calibration (20.1%±13.5%, p<0.0001). The percentage of matched points in Clarke error grid zone A was also significantly higher in data sets within 6 hours after calibration (92.4% versus 57.1%, p<0.0001). In conclusion, real-time subcutaneous CGMS is accurate in glucose monitoring in critically ill patients. CGMS sensor should be calibrated less than 6 hours, no matter what time interval recommended by manufacturer.  相似文献   

11.

Objective

The acute physiology, age and chronic health evaluation (APACHE) II score and other related scores have been used for evaluation of illness severity in the intensive care unit (ICU), but there is still a need for real-time and sensitive prognostic biomarkers. Recently, alarmins from damaged tissues have been reported as alarm-signaling molecules. Although ATP is a member of the alarmins and its depletion in tissues closely correlates with multiple-organ failure, blood ATP level has not been evaluated in critical illness. To identify real-time prognostic biomarker of critical illness, we measured blood ATP levels and the lactate/ATP ratio (ATP-lactate energy risk score, A-LES) in critically ill patients.

Methods and Results

Blood samples were collected from 42 consecutive critically ill ICU patients and 155 healthy subjects. The prognostic values of blood ATP levels and A-LES were compared with APACHE II score. The mean ATP level (SD) in healthy subjects was 0.62 (0.19) mM with no significant age or gender differences. The median ATP level in severely ill patients at ICU admission was significantly low at 0.31 mM (interquartile range 0.25 to 0.44) than the level in moderately ill patient at 0.56 mM (0.38 to 0.70) (P<0.01). Assessment with ATP was further corrected by lactate and expressed as A-LES. The median A-LES was 2.7 (2.1 to 3.3) in patients with satisfactory outcome at discharge but was significantly higher in non-survivors at 38.9 (21.0 to 67.9) (P<0.01). Receiver operating characteristic analysis indicated that measurement of blood ATP and A-LES at ICU admission are as useful as APACHE II score for prediction of mortality.

Conclusion

Blood ATP levels and A-LES are sensitive prognostic biomarkers of mortality at ICU admission. In addition, A-LES provided further real-time evaluation score of illness severity during ICU stay particularly for critically ill patients with APACHE II scores of ≥20.0.  相似文献   

12.
The importance within sport expertise of cognitive factors has been emphasised in many research studies. Adaptations that take place in athletes’ long-term memories are going to condition their decision-making and performance, and training programmes must be developed that improve these adaptations. In our study, we provide a tactical-cognitive training programme based on video-feedback and questioning in order to improve tactical knowledge in tennis players and verify its effect when transferred to athletes’ decision-making. 11 intermediate tennis players participated in this study (12.9±0.7 years old), distributed into two groups (experimental, n = 5; control, n = 6). Tactical knowledge was measured by problem representation and strategy planning with a verbal protocol. Decision-making was measured by a systematic observation instrument. Results confirm the effectiveness of a combination of video-feedback and questioning on cognitive expertise, developing adaptations in long-term memory that produce an improvement in the quality of tactical knowledge (content, sophistication and structure). This, in turn, is transferred to the athletes’ decision-making capacity, leading to a higher percentage of successful decisions made during game play. Finally, we emphasise the need to develop effective programmes to develop cognitive expertise and improve athletes'' performance, and include it in athletes’ formative stages.  相似文献   

13.
The discovery of endogenous neural stem cells (eNSCs) in the adult mammalian brain with their ability to self-renew and differentiate into functional neurons, astrocytes and oligodendrocytes has raised the hope for novel therapies of neurological diseases. Experimentally, those eNSCs can be mobilized in vivo, enhancing regeneration and accelerating functional recovery after, e.g., focal cerebral ischemia, thus constituting a most promising approach in stem cell research. In order to translate those current experimental approaches into a clinical setting in the future, non-invasive imaging methods are required to monitor eNSC activation in a longitudinal and intra-individual manner. As yet, imaging protocols to assess eNSC mobilization non-invasively in the live brain remain scarce, but considerable progress has been made in this field in recent years. This review summarizes and discusses the current imaging modalities suitable to monitor eNSCs in individual experimental animals over time, including optical imaging, magnetic resonance tomography and-spectroscopy, as well as positron emission tomography (PET). Special emphasis is put on the potential of each imaging method for a possible clinical translation, and on the specificity of the signal obtained. PET-imaging with the radiotracer 3’-deoxy-3’-[18F]fluoro-L-thymidine in particular constitutes a modality with excellent potential for clinical translation but low specificity; however, concomitant imaging of neuroinflammation is feasible and increases its specificity. The non-invasive imaging strategies presented here allow for the exploitation of novel treatment strategies based upon the regenerative potential of eNSCs, and will help to facilitate a translation into the clinical setting.  相似文献   

14.
When sending text messages on their mobile phone to friends, children often use a special type of register, which is called textese. This register allows the omission of words and the use of textisms: instances of non-standard written language such as 4ever (forever). Previous studies have shown that textese has a positive effect on children’s literacy abilities. In addition, it is possible that children’s grammar system is affected by textese as well, as grammar rules are often transgressed in this register. Therefore, the main aim of this study was to investigate whether the use of textese influences children’s grammar performance, and whether this effect is specific to grammar or language in general. Additionally, studies have not yet investigated the influence of textese on children’s cognitive abilities. Consequently, the secondary aim of this study was to find out whether textese affects children’s executive functions. To investigate this, 55 children between 10 and 13 years old were tested on a receptive vocabulary and grammar performance (sentence repetition) task and various tasks measuring executive functioning. In addition, text messages were elicited and the number of omissions and textisms in children’s messages were calculated. Regression analyses showed that omissions were a significant predictor of children’s grammar performance after various other variables were controlled for: the more words children omitted in their text messages, the better their performance on the grammar task. Although textisms correlated (marginally) significantly with vocabulary, grammar and selective attention scores and omissions marginally significantly with vocabulary scores, no other significant effects were obtained for measures of textese in the regression analyses: neither for the language outcomes, nor for the executive function tasks. Hence, our results show that textese is positively related to children’s grammar performance. On the other hand, use of textese does not affect—positively nor negatively—children’s executive functions.  相似文献   

15.
Muscle ankyrin repeat protein 1 (MARP1) is frequently up-regulated in stressed muscle, but its effect on skeletal muscle function is poorly understood. Here, we focused on its interaction with the titin–N2A element, found in titin’s molecular spring region. We show that MARP1 binds to F-actin, and that this interaction is stronger when MARP1 forms a complex with titin–N2A. Mechanics and super-resolution microscopy revealed that MARP1 “locks” titin–N2A to the sarcomeric thin filament, causing increased extension of titin’s elastic PEVK element and, importantly, increased passive force. In support of this mechanism, removal of thin filaments abolished the effect of MARP1 on passive force. The clinical relevance of this mechanism was established in diaphragm myofibers of mechanically ventilated rats and of critically ill patients. Thus, MARP1 regulates passive force by locking titin to the thin filament. We propose that in stressed muscle, this mechanism protects the sarcomere from mechanical damage.  相似文献   

16.

Introduction

Regional citrate anticoagulation (RCA) is gaining popularity in continous renal replacement therapy (CRRT) for critically ill patients. The risk of citrate toxicity is a primary concern during the prolonged process. The aim of this study was to assess the pharmacokinetics of citrate in critically ill patients with AKI, and used the kinetic parameters to predict the risk of citrate accumulation in this population group undergoing continuous veno-venous hemofiltration (CVVH) with RCA.

Methods

Critically ill patients with AKI (n = 12) and healthy volunteers (n = 12) were investigated during infusing comparative dosage of citrate. Serial blood samples were taken before, during 120 min and up to 120 min after infusion. Citrate pharmacokinetics were calculated and compared between groups. Then the estimated kinetic parameters were applied to the citrate kinetic equation for validation in other ten patients’ CVVH sessions with citrate anticoagulation.

Results

Total body clearance of citrate was similar in critically ill patients with AKI and healthy volunteers (648.04±347.00 L/min versus 686.64±353.60 L/min; P = 0.624). Basal and peak citrate concentrations were similar in both groups (p = 0.423 and 0.247, respectively). The predicted citrate curve showed excellent fit to the measurements.

Conclusions

Citrate clearance is not impaired in critically ill patients with AKI in the absence of severe liver dysfunction. Citrate pharmacokinetic data can provide a basis for the clinical use of predicting the risk of citrate accumulation.

Trial Registration

ClinicalTrials.gov Identifier NCT00948558  相似文献   

17.
Due to their widespread popularity, decreasing costs, built-in sensors, computing power and communication capabilities, Android-based personal devices are being seen as an appealing technology for the deployment of wearable fall detection systems. In contrast with previous solutions in the existing literature, which are based on the performance of a single element (a smartphone), this paper proposes and evaluates a fall detection system that benefits from the detection performed by two popular personal devices: a smartphone and a smartwatch (both provided with an embedded accelerometer and a gyroscope). In the proposed architecture, a specific application in each component permanently tracks and analyses the patient’s movements. Diverse fall detection algorithms (commonly employed in the literature) were implemented in the developed Android apps to discriminate falls from the conventional activities of daily living of the patient. As a novelty, a fall is only assumed to have occurred if it is simultaneously and independently detected by the two Android devices (which can interact via Bluetooth communication). The system was systematically evaluated in an experimental testbed with actual test subjects simulating a set of falls and conventional movements associated with activities of daily living. The tests were repeated by varying the detection algorithm as well as the pre-defined mobility patterns executed by the subjects (i.e., the typology of the falls and non-fall movements). The proposed system was compared with the cases where only one device (the smartphone or the smartwatch) is considered to recognize and discriminate the falls. The obtained results show that the joint use of the two detection devices clearly increases the system’s capability to avoid false alarms or ‘false positives’ (those conventional movements misidentified as falls) while maintaining the effectiveness of the detection decisions (that is to say, without increasing the ratio of ‘false negatives’ or actual falls that remain undetected).  相似文献   

18.
An efficient and quantitative method to analyze the transposition of various insertion sequence (IS) elements in Burkholderia multivorans ATCC 17616 was devised. pGEN500, a plasmid carrying a Bacillus subtilis-derived sacB gene, was introduced into ATCC 17616 cells, and 25% of their sucrose-resistant derivatives were found to carry various IS elements on pGEN500. A PCR-based experimental protocol, in which a mixture of several specific primer pairs was used, revealed that pGEN500 captured, in addition to five previously reported IS elements (IS401, IS402, IS406, IS407, and IS408), three novel IS elements, ISBmu1, ISBmu2, and ISBmu3. The global transposition frequency of these IS elements was enhanced more than sevenfold under a high-temperature condition (42°C) but not under oxidative stress or starvation conditions. To our knowledge, this is the first report demonstrating the elevated transposition activities of several IS elements at a high temperature. The efficient experimental protocol developed in this study will be useful in quantitatively and simultaneously investigating various IS elements, as well as in capturing novel functional mobile elements from a wide variety of bacteria.  相似文献   

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