Electroencephalogram variability in patients with cirrhosis associates with the presence and severity of hepatic encephalopathy

BACKGROUND & AIMS: The outputs of physiological systems fluctuate in a complex manner even under resting conditions. Decreased variability or increased regularity of these outputs is documented in several disease states. Changes are observed in the spatial and temporal configuration of the electroencephalogram (EEG) in patients with hepatic encephalopathy (HE), but there is no information on the variability of the EEG signal in this condition. The aim of this study was to measure and characterize EEG variability in patients with cirrhosis and to determine its relationship to neuropsychiatric status. METHODS: Eyes-closed, awake EEGs were obtained from 226 patients with cirrhosis, classified, using clinical and psychometric criteria, as neuropsychiatrically unimpaired (n=127) or as having minimal (n=21) or overt (n=78) HE, and from a reference population of 137 healthy controls. Analysis of EEG signal variability was undertaken using continuous wavelet transform and sample entropy. RESULTS: EEG variability was reduced in the patients with cirrhosis compared with the reference population (coefficient of variation: 21.2% [19.3-23.4] vs. 22.4% [20.8-24.5]; p<0.001). A significant association was observed between EEG variability and neuropsychiatric status; thus, variability was increased in the patients with minimal HE compared with their neuropsychiatrically unimpaired counterparts (sample entropy: 0.98 [0.87-1.14] vs. 0.83 [0.75-0.95]; p=0.02), and compared with the patients with overt HE (sample entropy: 0.98 [0.87-1.14] vs. 0.82 [0.71-1.01]; p=0.01). CONCLUSIONS: Variability of the EEG is associated with both the presence and severity of HE. This novel finding may provide new insights into the pathophysiology of HE and provide a means for monitoring patients over time. LAY SUMMARY: Decreased variability or increased regularity of physiological systems is documented in several disease states. Variability of the electroencephalogram was found to be associated with both the presence and severity of brain dysfunction in patients with chronic liver disease

Chronic migraine classification: current knowledge and future perspectives

In the field of so-called chronic daily headache, it is not easy for migraine that worsens progressively until it becomes daily or almost daily to find a precise and universally recognized place within the current international headache classification systems. In line with the 2006 revision of the second edition of the International Classification of Headache Disorders (ICHD-2R), the current prevailing opinion is that this headache type should be named chronic migraine (CM) and be characterized by the presence of at least 15 days of headache per month for at least 3 consecutive months, with headache having the same clinical features of migraine without aura for at least 8 of those 15 days. Based on much evidence, though, a CM with the above characteristics appears to be a heterogeneous entity and the obvious risk is that its definition may be extended to include a variety of different clinical entities. A proposal is advanced to consider CM a subtype of migraine without aura that is characterized by a high frequency of attacks (10–20 days of headache per month for at least 3 months) and is distinct from transformed migraine (TM), which in turn should be included in the classification as a complication of migraine. Therefore, CM should be removed from its current coding position in the ICHD-2 and be replaced by TM, which has more restrictive diagnostic criteria (at least 20 days of headache per month for at least 1 year, with no more than 5 consecutive days free of symptoms; same clinical features of migraine without aura for at least 10 of those 20 days)

A Genome-Wide Analysis of Promoter-Mediated Phenotypic Noise in Escherichia coli

Gene expression is subject to random perturbations that lead to fluctuations in the rate of protein production. As a consequence, for any given protein, genetically identical organisms living in a constant environment will contain different amounts of that particular protein, resulting in different phenotypes. This phenomenon is known as “phenotypic noise.” In bacterial systems, previous studies have shown that, for specific genes, both transcriptional and translational processes affect phenotypic noise. Here, we focus on how the promoter regions of genes affect noise and ask whether levels of promoter-mediated noise are correlated with genes' functional attributes, using data for over 60% of all promoters in Escherichia coli. We find that essential genes and genes with a high degree of evolutionary conservation have promoters that confer low levels of noise. We also find that the level of noise cannot be attributed to the evolutionary time that different genes have spent in the genome of E. coli. In contrast to previous results in eukaryotes, we find no association between promoter-mediated noise and gene expression plasticity. These results are consistent with the hypothesis that, in bacteria, natural selection can act to reduce gene expression noise and that some of this noise is controlled through the sequence of the promoter region alon

Performance of the CMS Cathode Strip Chambers with Cosmic Rays

The Cathode Strip Chambers (CSCs) constitute the primary muon tracking device in the CMS endcaps. Their performance has been evaluated using data taken during a cosmic ray run in fall 2008. Measured noise levels are low, with the number of noisy channels well below 1%. Coordinate resolution was measured for all types of chambers, and fall in the range 47 microns to 243 microns. The efficiencies for local charged track triggers, for hit and for segments reconstruction were measured, and are above 99%. The timing resolution per layer is approximately 5 ns

Brain age predicts mortality

Age-associated disease and disability are placing a growing burden on society. However, ageing does not affect people uniformly. Hence, markers of the underlying biological ageing process are needed to help identify people at increased risk of age-associated physical and cognitive impairments and ultimately, death. Here, we present such a biomarker, ‘brain-predicted age’, derived using structural neuroimaging. Brain-predicted age was calculated using machine-learning analysis, trained on neuroimaging data from a large healthy reference sample (N = 2001), then tested in the Lothian Birth Cohort 1936 (N = 669), to determine relationships with age-associated functional measures and mortality. Having a brain-predicted age indicative of an older-appearing brain was associated with: weaker grip strength, poorer lung function, slower walking speed, lower fluid intelligence, higher allostatic load and increased mortality risk. Furthermore, while combining brain-predicted age with grey matter and cerebrospinal fluid volumes (themselves strong predictors) not did improve mortality risk prediction, the combination of brain-predicted age and DNA-methylation-predicted age did. This indicates that neuroimaging and epigenetics measures of ageing can provide complementary data regarding health outcomes. Our study introduces a clinically-relevant neuroimaging ageing biomarker and demonstrates that combining distinct measurements of biological ageing further helps to determine risk of age-related deterioration and death

Effect of Chronic Kidney Diseases on Mortality among Digoxin Users Treated for Non-Valvular Atrial Fibrillation: A Nationwide Register-Based Retrospective Cohort Study.

PURPOSE: This study investigated the impact of chronic kidney disease on all-causes and cardiovascular mortality in patients with atrial fibrillation treated with digoxin. METHODS: All patients with non-valvular atrial fibrillation and/or atrial flutter as hospitalization diagnosis from January 1, 1997 to December 31, 2012 were identified in Danish nationwide administrative registries. Cox proportional hazard model was used to compare the adjusted risk of all-causes and cardiovascular mortality among patients with and without chronic kidney disease and among patients with different chronic kidney disease stages within 180 days and 2 years from the first digoxin prescription. RESULTS: We identified 37,981 patients receiving digoxin; 1884 patients had the diagnosis of chronic kidney disease. Cox regression analysis showed no statistically significant differences in all-causes (Hazard Ratio, HR 0.89; 95% confident interval, CI 0.78-1.03) and cardiovascular mortality (HR 0.88; 95%CI 0.74-1.05) among patients with and without chronic kidney disease within 180 days of follow-up period. No statistically significant differences was found using a 2 years follow-up period neither for all causes mortality (HR 0.90; 95%CI 0.79-1.03), nor for cardiovascular mortality (HR 0.87; 95%CI 0.74-1.02). No statistically significant differences was found comparing patients with and without estimated Glomerular Filtration Rate <30ml/min/1.73m2 and patients with different stages of chronic kidney disease, for all-causes and cardiovascular mortality within 180 days and 2 years from the first digoxin prescription. CONCLUSIONS: This study suggest no direct effect of chronic kidney disease and chronic kidney disease stages on all-causes and cardiovascular mortality within both 180 days and 2 years from the first digoxin prescription in patients treatment-naïve with digoxin for non-valvular atrial fibrillation

The Accuracy of Survival Time Prediction for Patients with Glioma Is Improved by Measuring Mitotic Spindle Checkpoint Gene Expression

Identification of gene expression changes that improve prediction of survival time across all glioma grades would be clinically useful. Four Affymetrix GeneChip datasets from the literature, containing data from 771 glioma samples representing all WHO grades and eight normal brain samples, were used in an ANOVA model to screen for transcript changes that correlated with grade. Observations were confirmed and extended using qPCR assays on RNA derived from 38 additional glioma samples and eight normal samples for which survival data were available. RNA levels of eight major mitotic spindle assembly checkpoint (SAC) genes (BUB1, BUB1B, BUB3, CENPE, MAD1L1, MAD2L1, CDC20, TTK) significantly correlated with glioma grade and six also significantly correlated with survival time. In particular, the level of BUB1B expression was highly correlated with survival time (p<0.0001), and significantly outperformed all other measured parameters, including two standards; WHO grade and MIB-1 (Ki-67) labeling index. Measurement of the expression levels of a small set of SAC genes may complement histological grade and other clinical parameters for predicting survival time

Depth-specific fluctuations of gene expression and protein abundance modulate the photophysiology in the seagrass Posidonia oceanica

Here we present the results of a multiple organizational level analysis conceived to identify acclimative/adaptive strategies exhibited by the seagrass Posidonia oceanica to the daily fluctuations in the light environment, at contrasting depths. We assessed changes in photophysiological parameters, leaf respiration, pigments, and protein and mRNA expression levels. The results show that the diel oscillations of P. oceanica photophysiological and respiratory responses were related to transcripts and proteins expression of the genes involved in those processes and that there was a response asynchrony between shallow and deep plants probably caused by the strong differences in the light environment. The photochemical pathway of energy use was more effective in shallow plants due to higher light availability, but these plants needed more investment in photoprotection and photorepair, requiring higher translation and protein synthesis than deep plants. The genetic differentiation between deep and shallow stands suggests the existence of locally adapted genotypes to contrasting light environments. The depth-specific diel rhythms of photosynthetic and respiratory processes, from molecular to physiological levels, must be considered in the management and conservation of these key coastal ecosystems.Portuguese funds from FCT - Foundation for Science and Technology [UID/Multi/04326/2013]; SZN PhD fellowship via the Open University; ESF COST Action Seagrass Productivity: From Genes to Ecosystem Management [ES0906]info:eu-repo/semantics/publishedVersio

The cystic fibrosis microbiome in an ecological perspective and its impact in antibiotic therapy

The recent focus on the cystic fibrosis (CF) complex microbiome has led to the recognition that the microbes can interact between them and with the host immune system, affecting the disease progression and treatment routes. Although the main focus remains on the interactions between traditional pathogens, growing evidence supports the contribution and the role of emergent species. Understanding the mechanisms and the biological effects involved in polymicrobial interactions may be the key to improve effective therapies and also to define new strategies for disease control. This review focuses on the interactions between microbe-microbe and host-microbe, from an ecological point of view, discussing their impact on CF disease progression. There are increasing indications that these interactions impact the success of antimicrobial therapy. Consequently, a new approach where therapy is personalized to patients by taking into account their individual CF microbiome is suggested.Portuguese Foundation for Science and Technology (FCT), the strategic funding of UID/BIO/04469/2013-CEB and UID/EQU/00511/2013-LEPABE units. This study was also supported by FCT and the European Community fund FEDER, through Program COMPETE, under the scope of the Projects “DNA mimics” PIC/IC/82815/2007, RECI/BBB-EBI/0179/2012 (FCOMP-01-0124-FEDER-027462), “BioHealth—Biotechnology and Bioengineering approaches to improve health quality”, Ref. NORTE-07-0124-FEDER-000027 and NORTE-07-0124-FEDER-000025—RL2_ Environment and Health, co-funded by the Programa Operacional Regional do Norte (ON.2 – O Novo Norte), QREN, FEDER. The authors also acknowledge the grant of Susana P. Lopes (SFRH/BPD/95616/2013) and of the COST-Action TD1004: Theragnostics for imaging and therapy

Chronic migraine plus medication overuse headache: two entities or not?

Chronic migraine (CM) represents migraine natural evolution from its episodic form. It is realized through a chronicization phase that may require months or years and varies from patient to patient. The transition to more frequent attacks pattern is influenced by lifestyle, life events, comorbid conditions and personal genetic terrain, and it often leads to acute drugs overuse. Medication overuse headache (MOH) may complicate every type of headache and all the drugs employed for headache treatment can cause MOH. The first step in the management of CM complicated by medication overuse must be the withdrawal of the overused drugs and a detoxification treatment. The goal is not only to detoxify the patient and stop the chronic headache but also to improve responsiveness to acute or prophylactic drugs. Different methods have been suggested: gradual or abrupt withdrawal; home treatment, hospitalization, or a day-hospital setting; re-prophylaxes performed immediately or at the end of the wash-out period. Up to now, only topiramate and local injection of onabotulinumtoxinA have shown efficacy as therapeutic agents for re-prophylaxis after detoxification in patients with CM with and without medication overuse. Although the two treatments showed similar efficacy, onabotulinumtoxinA is associated with a better adverse events profile. Recently, the Phase III Research Evaluating Migraine Prophylaxis Therapy (PREEMPT) clinical program proved that patients with CM, even those with MOH, are the ones most likely to benefit from onabotulinumtoxinA treatment. Furthermore, it provided an injection paradigm that can be used as a guide for a correct administration of onabotulinumtoxinA