Screening for wound-induced oxylipins in Arabidopsis thaliana by differential HPLC-APCI/MS profiling of crude leaf extracts and subsequent characterisation by capillary-scale NMR

A simple non-targeted differential HPLC-APCI/MS approach has been developed in order to survey metabolome modifications that occur in the leaves of Arabidopsis thaliana following wound-induced stress. The wound-induced accumulation of metabolites, particularly oxylipins, was evaluated by HPLC-MS analysis of crude leaf extracts. A generic, rapid and reproducible pressure liquid extraction procedure was developed for the analysis of restricted leaf samples without the need for specific sample preparation. The presence of various oxylipins was determined by head-to-head comparison of the HPLC-MS data, filtered with a component detection algorithm, and automatically compared with the aid of software searching for small differences in similar HPLC-MS profiles. Repeatability was verified in several specimens belonging to different series. Wound-inducible jasmonates were efficiently highlighted by this non-targeted approach without the need for complex sample preparation as is the case for the 'oxylipin signature' procedure based on GC-MS. Furthermore this HPLC-MS screening technique allowed the isolation of induced compounds for further characterisation by capillary-scale NMR (CapNMR) after HPLC scale-up. In this paper, the screening method is described and applied to illustrate its potential for monitoring polar and non-polar stress-induced constituents as well as its use in combination with CapNMR for the structural assignment of wound-induced compounds of interest

Screening for latent tuberculosis infection among undocumented immigrants in Swiss healthcare centres; a descriptive exploratory study.

BACKGROUND: Migration is one of the major causes of tuberculosis in developed countries. Undocumented patients are usually not screened at the border and are not covered by a health insurance increasing their risk of developing the disease unnoticed. Urban health centres could help identify this population at risk. The objective of this study is to assess the prevalence of latent tuberculosis infection (LTBI) and adherence to preventive treatment in a population of undocumented immigrant patients. METHODS: All consecutive undocumented patients that visited two urban healthcare centres for vulnerable populations in Lausanne, Switzerland for the first time were offered tuberculosis screening with an interferon-gamma assay. Preventive treatment was offered if indicated. Adherence to treatment was evaluated monthly over a nine month period. RESULTS: Of the 161 participants, 131 (81.4%) agreed to screening and 125 had complete examinations. Twenty-four of the 125 patients (19.2%; CI95% 12.7;27.2) had positive interferon-gamma assay results, two of which had active tuberculosis. Only five patients with LTBI completed full preventive treatments. Five others initiated the treatment but did not follow through. CONCLUSION: Screening for tuberculosis infection in this hard-to-reach population is feasible in dedicated urban clinics, and the prevalence of LTBI is high in this vulnerable population. However, the low adherence to treatment is an important public health concern, and new strategies are needed to address this problem.

The role of auditory cortices in the retrieval of single-trial auditory-visual object memories.

Single-trial encounters with multisensory stimuli affect both memory performance and early-latency brain responses to visual stimuli. Whether and how auditory cortices support memory processes based on single-trial multisensory learning is unknown and may differ qualitatively and quantitatively from comparable processes within visual cortices due to purported differences in memory capacities across the senses. We recorded event-related potentials (ERPs) as healthy adults (n = 18) performed a continuous recognition task in the auditory modality, discriminating initial (new) from repeated (old) sounds of environmental objects. Initial presentations were either unisensory or multisensory; the latter entailed synchronous presentation of a semantically congruent or a meaningless image. Repeated presentations were exclusively auditory, thus differing only according to the context in which the sound was initially encountered. Discrimination abilities (indexed by d') were increased for repeated sounds that were initially encountered with a semantically congruent image versus sounds initially encountered with either a meaningless or no image. Analyses of ERPs within an electrical neuroimaging framework revealed that early stages of auditory processing of repeated sounds were affected by prior single-trial multisensory contexts. These effects followed from significantly reduced activity within a distributed network, including the right superior temporal cortex, suggesting an inverse relationship between brain activity and behavioural outcome on this task. The present findings demonstrate how auditory cortices contribute to long-term effects of multisensory experiences on auditory object discrimination. We propose a new framework for the efficacy of multisensory processes to impact both current multisensory stimulus processing and unisensory discrimination abilities later in time.

Prevalence of substance use in a Swiss psychiatric hospital: interview reports and urine screening.

BACKGROUND: Co-morbid substance misuse is common in psychiatric disorders, has potentially severe adverse consequences and may be frequently undetected. AIMS: To measure the prevalence of substance use among patients admitted to a Swiss psychiatric hospital and to examine the potential utility of routine urine drug screening in this setting. METHOD: 266 inpatients were included. 238 patients completed the interview and 240 underwent a urine drug screening. RESULTS: Lifetime prevalence of substance use among psychiatric patients was very high for alcohol (98%; 95% CI: 96-100), benzodiazepines (86%; 95% CI: 82-91) and cannabis (53%; 95% CI: 47-60), but also for "hard drugs" like cocaine (25% ; 95% CI: 19-30) or opiates (20%; 95% CI: 15-25). Regular current use of alcohol (32%; 95% CI: 26-38) or cannabis (17%; 95% CI: 12-22) was the most frequent. Substance use was associated with male sex, younger age, unmarried status and nicotine smoking. Urine screening confirms reports from patients on recent use, and remained positive for cannabis during hospitalisation, but not for cocaine nor for opiates. CONCLUSION: Substance use is frequent among psychiatric patients. Systematic interviewing of patients about their substance use remains essential, and is usually confirmed by urine screening. Urine screening can be useful to provide specific answers about recent use.

Variation in performance in low-volume mammography screening programmes: experience from Switzerland.

BACKGROUND: Reading volume and mammography screening performance appear positively correlated. Quality and effectiveness were compared across low-volume screening programmes targeting relatively small populations and operating under the same decentralised healthcare system. Except for accreditation of 2nd readers (restrictive vs non-restrictive strategy), these organised programmes had similar screening regimen/procedures and duration, which maximises comparability. Variation in performance and its determinants were explored in order to improve mammography practice and optimise screening performance. METHODS: Circa 200,000 screens performed between 1999 and 2006 (4 rounds) in 3 longest standing Swiss cantonal programmes (of Vaud, Geneva and Valais) were assessed. Indicators of quality and effectiveness were assessed according to European standards. Interval cancers were identified through linkage with cancer registries records. RESULTS: Swiss programmes met most European standards of performance with a substantial, favourable cancer stage shift. Up to a two-fold variation occurred for several performance indicators. In subsequent rounds, compared with programmes (Vaud and Geneva) that applied a restrictive selection strategy for 2nd readers, proportions of in situ lesions and of small cancers (≤1cm) were one third lower and halved, respectively, and the proportion of advanced lesions (stage II+) nearly 50% higher in the programme without a restrictive selection strategy. Discrepancy in second-year proportional incidence of interval cancers appears to be multicausal. CONCLUSION: Differences in performance could partly be explained by a selective strategy for second readers and a prior experience in service screening, but not by the levels of opportunistic screening and programme attendance. This study provides clues for enhancing mammography screening performance in low-volume programmes.

Working memory load improves early stages of independent visual processing.

Increasing evidence suggests that working memory and perceptual processes are dynamically interrelated due to modulating activity in overlapping brain networks. However, the direct influence of working memory on the spatio-temporal brain dynamics of behaviorally relevant intervening information remains unclear. To investigate this issue, subjects performed a visual proximity grid perception task under three different visual-spatial working memory (VSWM) load conditions. VSWM load was manipulated by asking subjects to memorize the spatial locations of 6 or 3 disks. The grid was always presented between the encoding and recognition of the disk pattern. As a baseline condition, grid stimuli were presented without a VSWM context. VSWM load altered both perceptual performance and neural networks active during intervening grid encoding. Participants performed faster and more accurately on a challenging perceptual task under high VSWM load as compared to the low load and the baseline condition. Visual evoked potential (VEP) analyses identified changes in the configuration of the underlying sources in one particular period occurring 160-190 ms post-stimulus onset. Source analyses further showed an occipito-parietal down-regulation concurrent to the increased involvement of temporal and frontal resources in the high VSWM context. Together, these data suggest that cognitive control mechanisms supporting working memory may selectively enhance concurrent visual processing related to an independent goal. More broadly, our findings are in line with theoretical models implicating the engagement of frontal regions in synchronizing and optimizing mnemonic and perceptual resources towards multiple goals.

Efficiency of coronary artery disease screening guidelines in asymptomatic and atypical chest pain type 2 diabetic patients

RESUME Objectifs. Évaluer la prévalence de maladie coronarienne chez les patients diabétiques de type 2 asymptomatiques ou avec angor atypique selon les recommandations américaines de l'American Diabetes Association et de l'American College of Cardiology. Méthodes. Cent cinquante-quatre patients diabétiques de type 2 asymptomatiques ou avec angor atypique et présentant au minimum 2 facteurs de risque cardio-vasculaires additionnels ont été dépistés par échocardiographie de stress (71%, n=109), scintigraphie myocardique de perfusion (26%, n=40) ou l'association des 2 examens (3%, n=5). Résultats. L'échocardiographie de stress s'est révélée positive chez 16 patients (14%) et 14 ont eu une coronarographie révélant des sténoses significatives chez 12 (86%). La scintigraphie myocardique de perfusion était positive chez 16 patients (36%). Huit patients ont eu une coronarographie et 4 (50%) présentaient des sténoses significatives. Au total, 31 patients (20%) ont montré des signes d'ischémie lors de l'examen non-invasif et 15 (10%) ont présenté des sténoses significatives à la coronarographie. Les facteurs prédictifs indépendants de la maladie coronarienne étaient le tabagisme (OR 6.5, p=0.05), la microalbuminurie (OR 3.9, p=0.03), ainsi que les souffles fémoraux (OR 17.1, p=0.008). Conclusions. En suivant les recommandations américaines, un patient sur cinq présentait une ischémie lors des examens non-invasifs, tandis que 1 sur 10 avait des sténoses significatives à la coronarographie. L'analyse multivariée suggère que des marqueurs des complications micro- et macro-vasculaires en combinaison avec des facteurs de risque cardio-vasculaire classiques pourraient améliorer le pouvoir diagnostic de ces recommandations. SUMMARY Aims. We evaluated the prevalence of coronary artery disease in asymptomatic and atypical chest pain type 2 diabetic patients according to the American Diabetes Association and American College of Cardiology guidelines. Methods. Asymptomatic or atypical chest pain type 2 diabetic patients (n=154), with at least two additional cardiovascular risk factors, were screened for coronary artery disease using stress echocardiography (71%, n=109), myocardial perfusion imaging (26%, n=40) or both (3%, n=5). Results. Stress echocardiography was positive in 16 patients (14%) and 14 had a coronary angiography, revealing significant stenoses in 12 (86%). Myocardial perfusion imaging was positive in 16 patients (36%). Eight patients underwent angiography and 4 (50%) presented significant stenoses. Overall, 31 patients (20%) demonstrated signs of ischemia on non-invasive tests and 15 (10%) presented significant stenoses on coronary angiography. Independent predictors of coronary artery disease were smoking (OR 6.5, p=0.05), microalbuminuria (OR 3.9, p=0.03) and femoral murmur (OR 17.1, p=0.008). Conclusions. Following the guidelines, one in five diabetic patient presented ischemia on noninvasive tests, while one in ten presented significant coronary stenoses. Multivariate analysis suggests that adding markers of micro- and macro-vascular complications to classical cardiovascular risk factors may enhance the diagnostic efficiency of the guidelines.

Precision of the Retinal Tomograph as a Screening Device.

Purpose: To assess the diagnostic accuracy of the Heidelberg Retinal Tomograph 3 (HRT3) as a screening device in comparison with the reference standard of Octopus standard automated perimetry results (SAP) combined with clinical findings. Methods: All patients underwent screening examinations and investigations within a single day. Abnormal screening results were classified as follows: The HRT3: Either "borderline" or "outside normal limits" using the global Moorfields classification (MFC); SAP and clinical exam: A mean defect > 2.4 dB or "outside normal limits" clear text analysis of SAP; and one of the following i) IOP > 21 mmHg, ii) Van Herrick < ¼, iii) cup disc ratio > 0.55, iv) optic nerve head abnormality, v) narrow iridocorneal angle or vi) evidence of peripheral anterior synechiae on gonioscopy. Results: The mean age of the participants was 59.9 years (± 14.8 [21, 91]). Twenty-three subjects (16 %) were classified as abnormal on SAP and clinical exam. The HRT3 classification had a sensitivity of 30 % (95 % CI [16 %, 51 %]) with associated specificity of 58 % (95 % CI [49 %, 66 %]). Of the sixty subjects classified as borderline or outside normal limits with the HRT MFC global result, seven subjects were also abnormal according to SAP and clinical exam. Conclusion: The results suggest that the HRT3 may not be suitable as a sole screening device; however, further investigation is necessary.

Once and for all - How people change strategy to ignore irrelevant information in visual tasks

Ignoring irrelevant visual information aids efficient interaction with task environments. We studied how people, after practice, start to ignore the irrelevant aspects of stimuli. For this we focused on how information reduction transfers to rarely practised and novel stimuli. In Experiment 1, we compared competing mathematical models on how people cease to fixate on irrelevant parts of stimuli. Information reduction occurred at the same rate for frequent, infrequent, and novel stimuli. Once acquired with some stimuli, it was applied to all. In Experiment 2, simplification of task processing also occurred in a once-for-all manner when spatial regularities were ruled out so that people could not rely on learning which screen position is irrelevant. Apparently, changes in eye movements were an effect of a once-for-all strategy change rather than a cause of it. Overall, the results suggest that participants incidentally acquired knowledge about regularities in the task material and then decided to voluntarily apply it for efficient task processing. Such decisions should be incorporated into accounts of information reduction and other theories of strategy change in skill acquisition.

Single-trial multisensory memories affect later auditory and visual object discrimination.

Multisensory memory traces established via single-trial exposures can impact subsequent visual object recognition. This impact appears to depend on the meaningfulness of the initial multisensory pairing, implying that multisensory exposures establish distinct object representations that are accessible during later unisensory processing. Multisensory contexts may be particularly effective in influencing auditory discrimination, given the purportedly inferior recognition memory in this sensory modality. The possibility of this generalization and the equivalence of effects when memory discrimination was being performed in the visual vs. auditory modality were at the focus of this study. First, we demonstrate that visual object discrimination is affected by the context of prior multisensory encounters, replicating and extending previous findings by controlling for the probability of multisensory contexts during initial as well as repeated object presentations. Second, we provide the first evidence that single-trial multisensory memories impact subsequent auditory object discrimination. Auditory object discrimination was enhanced when initial presentations entailed semantically congruent multisensory pairs and was impaired after semantically incongruent multisensory encounters, compared to sounds that had been encountered only in a unisensory manner. Third, the impact of single-trial multisensory memories upon unisensory object discrimination was greater when the task was performed in the auditory vs. visual modality. Fourth, there was no evidence for correlation between effects of past multisensory experiences on visual and auditory processing, suggestive of largely independent object processing mechanisms between modalities. We discuss these findings in terms of the conceptual short term memory (CSTM) model and predictive coding. Our results suggest differential recruitment and modulation of conceptual memory networks according to the sensory task at hand.

Preoperative nutritional screening by the specialist instead of the nutritional risk score might prevent excess nutrition: a multivariate analysis of nutritional risk factors.

BACKGROUND: The aim of the current study was to assess whether widely used nutritional parameters are correlated with the nutritional risk score (NRS-2002) to identify postoperative morbidity and to evaluate the role of nutritionists in nutritional assessment. METHODS: A randomized trial on preoperative nutritional interventions (NCT00512213) provided the study cohort of 152 patients at nutritional risk (NRS-2002 ≥3) with a comprehensive phenotyping including diverse nutritional parameters (n=17), elaborated by nutritional specialists, and potential demographic and surgical (n=5) confounders. Risk factors for overall, severe (Dindo-Clavien 3-5) and infectious complications were identified by univariate analysis; parameters with P<0.20 were then entered in a multiple logistic regression model. RESULTS: Final analysis included 140 patients with complete datasets. Of these, 61 patients (43.6%) were overweight, and 72 patients (51.4%) experienced at least one complication of any degree of severity. Univariate analysis identified a correlation between few (≤3) active co-morbidities (OR=4.94; 95% CI: 1.47-16.56, p=0.01) and overall complications. Patients screened as being malnourished by nutritional specialists presented less overall complications compared to the not malnourished (OR=0.47; 95% CI: 0.22-0.97, p=0.043). Severe postoperative complications occurred more often in patients with low lean body mass (OR=1.06; 95% CI: 1-1.12, p=0.028). Few (≤3) active co-morbidities (OR=8.8; 95% CI: 1.12-68.99, p=0.008) were related with postoperative infections. Patients screened as being malnourished by nutritional specialists presented less infectious complications (OR=0.28; 95% CI: 0.1-0.78), p=0.014) as compared to the not malnourished. Multivariate analysis identified few co-morbidities (OR=6.33; 95% CI: 1.75-22.84, p=0.005), low weight loss (OR=1.08; 95% CI: 1.02-1.14, p=0.006) and low hemoglobin concentration (OR=2.84; 95% CI: 1.22-6.59, p=0.021) as independent risk factors for overall postoperative complications. Compliance with nutritional supplements (OR=0.37; 95% CI: 0.14-0.97, p=0.041) and supplementation of malnourished patients as assessed by nutritional specialists (OR=0.24; 95% CI: 0.08-0.69, p=0.009) were independently associated with decreased infectious complications. CONCLUSIONS: Nutritional support based upon NRS-2002 screening might result in overnutrition, with potentially deleterious clinical consequences. We emphasize the importance of detailed assessment of the nutritional status by a dedicated specialist before deciding on early nutritional intervention for patients with an initial NRS-2002 score of ≥3.

Performance of parental history for the targeted screening of hypertension in children.

OBJECTIVES: Several guidelines recommend universal screening for hypertension in childhood and adolescence. Targeted screening to children with parental history of hypertension could be a more efficient strategy than universal screening. Therefore, we assessed the association between parental history of hypertension and hypertension in children, and estimated the sensitivity, specificity, negative, and positive predictive values of parental history of hypertension for hypertension in children. METHODS: The present study was a school-based cross-sectional study including 5207 children aged 10-14 years from all public 6th grade classes in the Canton of Vaud, Switzerland. Children had hypertension if they had sustained elevated blood pressure over three separate visits. RESULTS: In children, the prevalence of hypertension was 2.2%. Some 8.5% of mothers and 12.9% of fathers reported to be hypertensive. Maternal history of hypertension (odds ratio 2.0, 95% confidence interval 1.2-3.3) and paternal history of hypertension (odds ratio 2.2, 95% confidence interval 1.4-3.6) were independent risk factors for hypertension in children. Nevertheless, the sensitivity of parental history of hypertension for the identification of hypertension in children was low (from 4% for both parents' positive history up to 41% for at least one parent's positive history). Positive predictive values were also low (between 4 and 5%). CONCLUSION: Children with hypertensive parents were at higher risk of hypertension. Nevertheless, parental history of hypertension helped only marginally to identify hypertension in offspring. Targeting screening only toward children with a parental history of hypertension may not be a substantially better strategy to identify hypertension in children compared with universal screening.

Expanding the Mutation Spectrum Affecting αIIbβ3 Integrin in Glanzmann Thrombasthenia: Screening of the ITGA2B and ITGB3 Genes in a Large International Cohort.

We report the largest international study on Glanzmann thrombasthenia (GT), an inherited bleeding disorder where defects of the ITGA2B and ITGB3 genes cause quantitative or qualitative defects of the αIIbβ3 integrin, a key mediator of platelet aggregation. Sequencing of the coding regions and splice sites of both genes in members of 76 affected families identified 78 genetic variants (55 novel) suspected to cause GT. Four large deletions or duplications were found by quantitative real-time PCR. Families with mutations in either gene were indistinguishable in terms of bleeding severity that varied even among siblings. Families were grouped into type I and the rarer type II or variant forms with residual αIIbβ3 expression. Variant forms helped identify genes encoding proteins mediating integrin activation. Splicing defects and stop codons were common for both ITGA2B and ITGB3 and essentially led to a reduced or absent αIIbβ3 expression; included was a heterozygous c.1440-13_c.1440-1del in intron 14 of ITGA2B causing exon skipping in seven unrelated families. Molecular modeling revealed how many missense mutations induced subtle changes in αIIb and β3 domain structure across both subunits, thereby interfering with integrin maturation and/or function. Our study extends knowledge of GT and the pathophysiology of an integrin.