Subtidal macrozoobenthos communities from northern Chile during and post El Niño 1997–1998

Despite a large amount of climatic and oceanographic information dealing with the recurring climate phenomenon El Niño (EN) and its well known impact on diversity of marine benthic communities, most published data are rather descriptive and consequently our understanding of the underlying mechanisms and processes that drive community structure during EN are still very scarce. In this study, we address two questions on the effects of EN on macrozoobenthic communities: (1) how does EN affect species diversity of the communities in northern Chile? and (2) is EN a phenomenon that restarts community assembling processes by affecting species interactions in northern Chile? To answer these questions, we compared species diversity and co-occurrence patterns of soft-bottoms macrozoobenthos communities from the continental shelf off northern Chile during (March 1998) and after (September 1998) the strong EN event 1997–1998. The methods used varied from species diversity and species co-occurrence analyses to multivariate ordination methods. Our results indicate that EN positively affects diversity of macrozoobenthos communities in the study area, increasing the species richness and diversity and decreasing the species dominance. EN represents a strong disturbance that affects species interactions that rule the species assembling processes in shallow-water, sea-bottom environments

Enhanced external counter pulsation in treatment of refractory angina pectoris: two year outcome and baseline factors associated with treatment failure

<p>Abstract</p> <p>Background</p> <p>Enhanced external counter pulsation (EECP) is a non-invasive treatment option for patients with refractory angina pectoris ineligible to further traditional treatment. The aim of this study was to evaluate the effect of EECP on patients at a Scandinavian medical centre and to investigate if outcome can be predicted by analysing baseline factors.</p> <p>Methods</p> <p>86 consecutive patients (70 male, 16 female) were treated with EECP and followed for two years post treatment. Canadian cardiovascular society (CCS) class was analysed, and medication and adverse clinical events were researched prior to EECP, at the end of the treatment, and at six, 12 and 24 months thereafter. Patients responding to therapy by improving at least one CCS class were compared with those who failed to respond. Any differences in background factors were recorded and analysed.</p> <p>Results</p> <p>79% of the patients responded to therapy by improving at least one CCS class. In general, the CCS class improved by one class after EECP treatment (3.05 before versus 2.14 after treatment). A total of 61.5% of the initial responders showed sustained improvement at the 12 month follow-up while 29% presented sustained improvement after 24 months. Treatment was most effective among patients suffering from CCS class III-IV angina pectoris, while patients suffering from CCS class II angina pectoris improved transiently but failed to show sustained improvement after the 12 month follow-up. Diabetes mellitus and calcium channel antagonists were more common among the non-responders (<it>p </it>< 0.05).</p> <p>Conclusion</p> <p>This study confirms the safety and efficiency of EECP as a treatment option for patients suffering from refractory angina pectoris. The therapy is most beneficial in patients suffering from severe angina (CCS III-IV) while sustained response to therapy could not be verified among patients suffering from CCS class II angina pectoris.</p

A targeted proteomic multiplex CSF assay identifies increased malate dehydrogenase and other neurodegenerative biomarkers in individuals with Alzheimer's disease pathology

Alzheimer's disease (AD) is the most common cause of dementia. Biomarkers are required to identify individuals in the preclinical phase, explain phenotypic diversity, measure progression and estimate prognosis. The development of assays to validate candidate biomarkers is costly and time-consuming. Targeted proteomics is an attractive means of quantifying novel proteins in cerebrospinal and other fluids, and has potential to help overcome this bottleneck in biomarker development. We used a previously validated multiplexed 10-min, targeted proteomic assay to assess 54 candidate cerebrospinal fluid (CSF) biomarkers in two independent cohorts comprising individuals with neurodegenerative dementias and healthy controls. Individuals were classified as 'AD' or 'non-AD' on the basis of their CSF T-tau and amyloid Aβ1-42 profile measured using enzyme-linked immunosorbent assay; biomarkers of interest were compared using univariate and multivariate analyses. In all, 35/31 individuals in Cohort 1 and 46/36 in Cohort 2 fulfilled criteria for AD/non-AD profile CSF, respectively. After adjustment for multiple comparisons, five proteins were elevated significantly in AD CSF compared with non-AD CSF in both cohorts: malate dehydrogenase; total APOE; chitinase-3-like protein 1 (YKL-40); osteopontin and cystatin C. In an independent multivariate orthogonal projection to latent structures discriminant analysis (OPLS-DA), these proteins were also identified as major contributors to the separation between AD and non-AD in both cohorts. Independent of CSF Aβ1-42 and tau, a combination of these biomarkers differentiated AD and non-AD with an area under curve (AUC)=0.88. This targeted proteomic multiple reaction monitoring (MRM)-based assay can simultaneously and rapidly measure multiple candidate CSF biomarkers. Applying this technique to AD we demonstrate differences in proteins involved in glucose metabolism and neuroinflammation that collectively have potential clinical diagnostic utility

Identification of novel CSF biomarkers for neurodegeneration and their validation by a high-throughput multiplexed targeted proteomic assay

BACKGROUND: Currently there are no effective treatments for many neurodegenerative diseases. Reliable biomarkers for identifying and stratifying these diseases will be important in the development of future novel therapies. Lewy Body Dementia (LBD) is considered an under diagnosed form of dementia for which markers are needed to discriminate LBD from other forms of dementia such as Alzheimer's Disease (AD). This work describes a Label-Free proteomic profiling analysis of cerebral spinal fluid (CSF) from non-neurodegenerative controls and patients with LBD. Using this technology we identified several potential novel markers for LBD. These were then combined with other biomarkers from previously published studies, to create a 10 min multiplexed targeted and translational MRM-LC-MS/MS assay. This test was used to validate our new assay in a larger cohort of samples including controls and the other neurodegenerative conditions of Alzheimer's and Parkinson's disease (PD). RESULTS: Thirty eight proteins showed significantly (p < 0.05) altered expression in LBD CSF by proteomic profiling. The targeted MRM-LC-MS/MS assay revealed 4 proteins that were specific for the identification of AD from LBD: ectonucleotide pyrophosphatase/phosphodiesterase 2 (p < 0.0001), lysosome-associated membrane protein 1 (p < 0.0001), pro-orexin (p < 0.0017) and transthyretin (p < 0.0001). Nineteen proteins were elevated significantly in both AD and LBD versus the control group of which 4 proteins are novel (malate dehydrogenase 1, serum amyloid A4, GM2-activator protein, and prosaposin). Protein-DJ1 was only elevated significantly in the PD group and not in either LBD or AD samples. Correlations with Alzheimer-associated amyloid β-42 levels, determined by ELISA, were observed for transthyretin, GM2 activator protein and IGF2 in the AD disease group (r(2) ≥ 0.39, p ≤ 0.012). Cystatin C, ubiquitin and osteopontin showed a strong significant linear relationship (r(2) ≥ 0.4, p ≤ 0.03) with phosphorylated-tau levels in all groups, whilst malate dehydrogenase and apolipoprotein E demonstrated a linear relationship with phosphorylated-tau and total-tau levels in only AD and LBD disease groups. CONCLUSIONS: Using proteomics we have identified several potential and novel markers of neurodegeneration and subsequently validated them using a rapid, multiplexed mass spectral test. This targeted proteomic platform can measure common markers of neurodegeneration that correlate with existing diagnostic makers as well as some that have potential to show changes between AD from LBD

Human arachnoid granulations Part I: a technique for quantifying area and distribution on the superior surface of the cerebral cortex

<p>Abstract</p> <p>Background</p> <p>The arachnoid granulations (AGs) are herniations of the arachnoid membrane into the dural venous sinuses on the surface of the brain. Previous morphological studies of AGs have been limited in scope and only one has mentioned surface area measurements. The purpose of this study was to investigate the topographic distribution of AGs on the superior surface of the cerebral cortex.</p> <p>Methods</p> <p><it>En face </it>images were taken of the superior surface of 35 formalin-fixed human brains. AGs were manually identified using Adobe Photoshop, with a pixel location containing an AG defined as 'positive'. A set of 25 standard fiducial points was marked on each hemisphere for a total of 50 points on each image. The points were connected on each hemisphere to create a segmented image. A standard template was created for each hemisphere by calculating the average position of the 25 fiducial points from all brains. Each segmented image was mapped to the standard template using a linear transformation. A topographic distribution map was produced by calculating the proportion of AG positive images at each pixel in the standard template. The AG surface area was calculated for each hemisphere and for the total brain superior surface. To adjust for different brain sizes, the proportional involvement of AGs was calculated by dividing the AG area by the total area.</p> <p>Results</p> <p>The total brain average surface area of AGs was 78.53 ± 13.13 mm²(n = 35) and average AG proportional involvement was 57.71 × 10^-4± 7.65 × 10^-4. Regression analysis confirmed the reproducibility of AG identification between independent researchers with r²= 0.97. The surface AGs were localized in the parasagittal planes that coincide with the region of the lateral lacunae.</p> <p>Conclusion</p> <p>The data obtained on the spatial distribution and <it>en face </it>surface area of AGs will be used in an <it>in vitro </it>model of CSF outflow. With an increase in the number of samples, this analysis technique can be used to study the relationship between AG surface area and variables such as age, race and gender.</p

Chronic constipation in adults: Contemporary perspectives and clinical challenges. 2: Conservative, behavioural, medical and surgical treatment

BACKGROUND: Chronic constipation is a prevalent disorder that affects quality of life of patients and consumes resources in healthcare systems worldwide. In clinical practice, it is still considered a challenge as clinicians frequently are unsure as to which treatments to use and when. Over a decade ago, a Neurogastroenterology and Motility journal supplement devoted to the investigation and management of constipation was published (Neurogastroenterol Motil 2009;21(Suppl 2):1). In October 2018, the 3rd London Masterclass, entitled "Contemporary management of constipation" was held. The faculty members of this symposium were invited to write two reviews to present a collective synthesis of talks presented and discussions held during this meeting. The first review addresses epidemiology, diagnosis, clinical associations, pathophysiology, and investigation. PURPOSE: The present is the second of these reviews, providing contemporary perspectives and clinical challenges regarding behavioral, conservative, medical, and surgical treatments for patients presenting with constipation. It includes a management algorithm to guide clinical practice

Effect of shoot parameters on cracking in vegetated soil

The relationship of shoot parameters, which play a major role in transpiration, with the cracking of soil has rarely been investigated. Such relation helps to analyse water use efficiency accurately. This study investigated the effect of vegetation (cowpea) age on crack formation and explored any correlation between age and cracking. The age of vegetation was expressed in the form of shoot parameters (shoot length (SL) and leaf area index (LAI)). Crack formation was expressed in the form of crack intensity factor (CIF). Ten experimental test pots were used to observe crack formation on vegetated and bare soil in a greenhouse. Image analysis in the experimental pots revealed that under drying–wetting cycles, the CIF of vegetated soil increased compared with that of bare soil. There was an evident increase in CIF with SL growth, up to a threshold length (400 mm), where lateral branch growth starts forming. There was no observable increase in CIF, with further SL growth (with negligible lateral branch formation). CIF increased with LAI up to a certain threshold value (0·56), after which the CIF was relatively the same. Two correlations have been identified for shoot parameters (SL, LAI) with the CIF for the selected species

Evaluating the Quality of Research into a Single Prognostic Biomarker: A Systematic Review and Meta-analysis of 83 Studies of C-Reactive Protein in Stable Coronary Artery Disease

Background Systematic evaluations of the quality of research on a single prognostic biomarker are rare. We sought to evaluate the quality of prognostic research evidence for the association of C-reactive protein (CRP) with fatal and nonfatal events among patients with stable coronary disease. Methods and Findings We searched MEDLINE (1966 to 2009) and EMBASE (1980 to 2009) and selected prospective studies of patients with stable coronary disease, reporting a relative risk for the association of CRP with death and nonfatal cardiovascular events. We included 83 studies, reporting 61,684 patients and 6,485 outcome events. No study reported a prespecified statistical analysis protocol; only two studies reported the time elapsed (in months or years) between initial presentation of symptomatic coronary disease and inclusion in the study. Studies reported a median of seven items (of 17) from the REMARK reporting guidelines, with no evidence of change over time. The pooled relative risk for the top versus bottom third of CRP distribution was 1.97 (95% confidence interval [CI] 1.78–2.17), with substantial heterogeneity (I2 = 79.5). Only 13 studies adjusted for conventional risk factors (age, sex, smoking, obesity, diabetes, and low-density lipoprotein [LDL] cholesterol) and these had a relative risk of 1.65 (95% CI 1.39–1.96), I2 = 33.7. Studies reported ten different ways of comparing CRP values, with weaker relative risks for those based on continuous measures. Adjusting for publication bias (for which there was strong evidence, Egger's p<0.001) using a validated method reduced the relative risk to 1.19 (95% CI 1.13–1.25). Only two studies reported a measure of discrimination (c-statistic). In 20 studies the detection rate for subsequent events could be calculated and was 31% for a 10% false positive rate, and the calculated pooled c-statistic was 0.61 (0.57–0.66). Conclusion Multiple types of reporting bias, and publication bias, make the magnitude of any independent association between CRP and prognosis among patients with stable coronary disease sufficiently uncertain that no clinical practice recommendations can be made. Publication of prespecified statistical analytic protocols and prospective registration of studies, among other measures, might help improve the quality of prognostic biomarker research

Embodiment and body awareness in meditators

[EN] Mindfulness practice consists of focusing attention in an intentional way on the experience of the present moment, including bodily sensations, thoughts or feelings, and the environment, with an attitude of acceptance and without judging. The body and, especially, body awareness are key elements in mindfulness. Embodiment or the feeling of being located within one's physical body is a related concept, and it is composed of the sense of ownership, location, and agency of the body. The rubber hand illusion (RHI) is an experimental paradigm that has been used to understand the mechanisms of embodiment, and evidence shows that body awareness modulates this illusion. To our knowledge, no studies have analyzed embodiment processes in meditators. The aim of this study is to use the RHI to analyze the mechanisms of embodiment and its relationship with body awareness and mindfulness in meditators and non-meditators. The sample was composed of long-term meditators (n = 15) and non-meditators (n = 15). Objective and self-report measures for embodiment with the RHI and self-report questionnaires of body awareness and mindfulness were administered. One-way ANOVA revealed significant differences between groups in sense of agency in the rubber hand. Meditators experienced less sense of agency in the rubber hand than non-meditators. Pearson's correlations showed that this lower sense of agency in the rubber hand was associated with higher body awareness and mindfulness. Results highlight the role of body awareness and mindfulness in embodiment mechanisms. 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Diminution of Voltage Threshold Plays a Key Role in Determining Recruitment of Oculomotor Nucleus Motoneurons during Postnatal Development

The size principle dictates the orderly recruitment of motoneurons (Mns). This principle assumes that Mns of different sizes have a similar voltage threshold, cell size being the crucial property in determining neuronal recruitment. Thus, smaller neurons have higher membrane resistance and require a lower depolarizing current to reach spike threshold. However, the cell size contribution to recruitment in Mns during postnatal development remains unknown. To investigate this subject, rat oculomotor nucleus Mns were intracellularly labeled and their electrophysiological properties recorded in a brain slice preparation. Mns were divided into 2 age groups: neonatal (1–7 postnatal days, n = 14) and adult (20–30 postnatal days, n = 10). The increase in size of Mns led to a decrease in input resistance with a strong linear relationship in both age groups. A well-fitted inverse correlation was also found between input resistance and rheobase in both age groups. However, input resistance versus rheobase did not correlate when data from neonatal and adult Mns were combined in a single group. This lack of correlation is due to the fact that decrease in input resistance of developing Mns did not lead to an increase in rheobase. Indeed, a diminution in rheobase was found, and it was accompanied by an unexpected decrease in voltage threshold. Additionally, the decrease in rheobase co-varied with decrease in voltage threshold in developing Mns. These data support that the size principle governs the recruitment order in neonatal Mns and is maintained in adult Mns of the oculomotor nucleus; but during postnatal development the crucial property in determining recruitment order in these Mns was not the modifications of cell size-input resistance but of voltage threshold