Revealing a brain network endophenotype in families with idiopathic generalised epilepsy

Idiopathic generalised epilepsy (IGE) has a genetic basis. The mechanism of seizure expression is not fully known, but is assumed to involve large-scale brain networks. We hypothesised that abnormal brain network properties would be detected using EEG in patients with IGE, and would be manifest as a familial endophenotype in their unaffected first-degree relatives. We studied 117 participants: 35 patients with IGE, 42 unaffected first-degree relatives, and 40 normal controls, using scalp EEG. Graph theory was used to describe brain network topology in five frequency bands for each subject. Frequency bands were chosen based on a published Spectral Factor Analysis study which demonstrated these bands to be optimally robust and independent. Groups were compared, using Bonferroni correction to account for nonindependent measures and multiple groups. Degree distribution variance was greater in patients and relatives than controls in the 6-9 Hz band (p = 0.0005, p = 0.0009 respectively). Mean degree was greater in patients than healthy controls in the 6-9 Hz band (p = 0.0064). Clustering coefficient was higher in patients and relatives than controls in the 6-9 Hz band (p = 0.0025, p = 0.0013). Characteristic path length did not differ between groups. No differences were found between patients and unaffected relatives. These findings suggest brain network topology differs between patients with IGE and normal controls, and that some of these network measures show similar deviations in patients and in unaffected relatives who do not have epilepsy. This suggests brain network topology may be an inherited endophenotype of IGE, present in unaffected relatives who do not have epilepsy, as well as in affected patients. We propose that abnormal brain network topology may be an endophenotype of IGE, though not in itself sufficient to cause epilepsy

Selected acute phase CSF factors in ischemic stroke: findings and prognostic value

<p>Abstract</p> <p>Background</p> <p>Study aimed at investigation of pathogenic role and prognostic value of several selected cerebrospinal fluid acute phase factors that can reflect the severity of ischemic brain damage.</p> <p>Methods</p> <p>Ninety five acute ischemic stroke patients were investigated. Ischemic region visualized at the twenty fourth hour by conventional Magnetic Resonance Imaging. Stroke severity evaluated by National Institute Health Stroke Scale. One month outcome of disease was assessed by Barthel Index. Cerebrospinal fluid was taken at the sixth hour of stroke onset. CSF pro- and anti-inflammatory cytokines were studied by Enzyme Linked Immunosorbent Assay. Nitric Oxide and Lipoperoxide radical were measured by Electron Paramagnetic Resonance. CSF Nitrate levels were detected using the Griess reagent. Statistics performed by SPSS-11.0.</p> <p><b>Results</b></p> <p>At the sixth hour of stroke onset, cerebrospinal fluid cytokine levels were elevated in patients against controls. Severe stroke patients had increased interleukin-6 content compared to less severe strokes (P < 0.05). Cerebrospinal fluid Electron Paramagnetic Resonance signal of nitric oxide was increased in patients against controls. Severe stroke group had an elevated Electron Paramagnetic Resonance signal of lipoperoxiradical compared to less severe stroke. Cerebrospinal fluid nitrate levels in less severe stroke patients were higher than those for severe stroke and control. Positive correlation was established between the initial interleukin-6 content and ischemic lesion size as well as with National Institute Health Stroke Scale score on the seventh day. Initial interleukin-6 and nitrate levels in cerebrospinal fluid found to be significant for functional outcome of stroke at one month.</p> <p><b>Conclusion</b></p> <p>According to present study the cerebrospinal fluid contents of interleukin-6 and nitrates seem to be the most reliable prognostic factors in acute phase of ischemic stroke.</p

Using Biotic Interaction Networks for Prediction in Biodiversity and Emerging Diseases

Networks offer a powerful tool for understanding and visualizing inter-species ecological and evolutionary interactions. Previously considered examples, such as trophic networks, are just representations of experimentally observed direct interactions. However, species interactions are so rich and complex it is not feasible to directly observe more than a small fraction. In this paper, using data mining techniques, we show how potential interactions can be inferred from geographic data, rather than by direct observation. An important application area for this methodology is that of emerging diseases, where, often, little is known about inter-species interactions, such as between vectors and reservoirs. Here, we show how using geographic data, biotic interaction networks that model statistical dependencies between species distributions can be used to infer and understand inter-species interactions. Furthermore, we show how such networks can be used to build prediction models. For example, for predicting the most important reservoirs of a disease, or the degree of disease risk associated with a geographical area. We illustrate the general methodology by considering an important emerging disease - Leishmaniasis. This data mining methodology allows for the use of geographic data to construct inferential biotic interaction networks which can then be used to build prediction models with a wide range of applications in ecology, biodiversity and emerging diseases

Spatio-Temporal Differentiation and Sociality in Spiders

Species that differ in their social system, and thus in traits such as group size and dispersal timing, may differ in their use of resources along spatial, temporal, or dietary dimensions. The role of sociality in creating differences in habitat use is best explored by studying closely related species or socially polymorphic species that differ in their social system, but share a common environment. Here we investigate whether five sympatric Anelosimus spider species that range from nearly solitary to highly social differ in their use of space and in their phenology as a function of their social system. By studying these species in Serra do Japi, Brazil, we find that the more social species, which form larger, longer–lived colonies, tend to live inside the forest, where sturdier, longer lasting vegetation is likely to offer better support for their nests. The less social species, which form single-family groups, in contrast, tend to occur on the forest edge where the vegetation is less robust. Within these two microhabitats, species with longer-lived colonies tend to occupy the potentially more stable positions closer to the core of the plants, while those with smaller and shorter-lived colonies build their nests towards the branch tips. The species further separate in their use of common habitat due to differences in the timing of their reproductive season. These patterns of habitat use suggest that the degree of sociality can enable otherwise similar species to differ from one another in ways that may facilitate their co-occurrence in a shared environment, a possibility that deserves further consideration

Performance measures of the specialty referral process: a systematic review of the literature

<p>Abstract</p> <p>Background</p> <p>Performance of specialty referrals is coming under scrutiny, but a lack of identifiable measures impedes measurement efforts. The objective of this study was to systematically review the literature to identify published measures that assess specialty referrals.</p> <p>Methods</p> <p>We performed a systematic review of the literature for measures of specialty referral. Searches were made of MEDLINE and HealthSTAR databases, references of eligible papers, and citations provided by content experts. Measures were eligible if they were published from January 1973 to June 2009, reported on validity and/or reliability of the measure, and were applicable to Organization for Economic Cooperation and Development healthcare systems. We classified measures according to a conceptual framework, which underwent content validation with an expert panel.</p> <p>Results</p> <p>We identified 2,964 potentially eligible papers. After abstract and full-text review, we selected 214 papers containing 244 measures. Most measures were applied in adults (57%), assessed structural elements of the referral process (60%), and collected data via survey (62%). Measures were classified into non-mutually exclusive domains: need for specialty care (N = 14), referral initiation (N = 73), entry into specialty care (N = 53), coordination (N = 60), referral type (N = 3), clinical tasks (N = 19), resource use (N = 13), quality (N = 57), and outcomes (N = 9).</p> <p>Conclusions</p> <p>Published measures are available to assess the specialty referral process, although some domains are limited. Because many of these measures have been not been extensively validated in general populations, assess limited aspects of the referral process, and require new data collection, their applicability and preference in assessment of the specialty referral process is needed.</p

An investigation of the phase locking index for measuring of interdependency of cortical source signals recorded in the EEG

The phase locking index (PLI) was introduced to quantify in a statistical sense the phase synchronization of two signals. It has been commonly used to process biosignals. In this article, we investigate the PLI for measuring the interdependency of cortical source signals (CSSs) recorded in the Electroencephalogram (EEG). To this end, we consider simple analytical models for the mapping of simulated CSSs into the EEG. For these models, the PLI is investigated analytically and through numerical simulations. An evaluation is made of the sensitivity of the PLI to the amount of crosstalk between the sources through biological tissues of the head. It is found that the PLI is a useful interdependency measure for CSSs, especially when the amount of crosstalk is small. Another common interdependency measure is the coherence. A direct comparison of both measures has not been made in the literature so far. We assess the performance of the PLI and coherence for estimation and detection purposes based on, respectively, a normalized variance and a novel statistical measure termed contrast. Based on these performance measures, it is found that the PLI is similar or better than the CM in most cases. This result is also confirmed through analysis of EEGs recorded from epileptic patients

A capillary blood ammonia bedside test following glutamine load to improve the diagnosis of hepatic encephalopathy in cirrhosis

<p>Abstract</p> <p>Background</p> <p>Hepatic encephalopathy (HE) is a frequent and severe complication of cirrhosis. A single determination of ammonia in venous blood correlates poorly with neurological symptoms. Thus, a better biological marker is needed.</p> <p>Aim</p> <p>To make a diagnosis of HE, we explored the value of ammonia in capillary blood, an equivalent to arterial blood, measured at bedside following an oral glutamine challenge.</p> <p>Methods</p> <p>We included 57 patients (age 56 yrs; M/F: 37/20) with cirrhosis (alcoholic = 42; MELD score 13.8 [7-29], esophageal varices = 38) and previous episodes of HE (n = 19), but without neurological deficits at time of examination, and 13 healthy controls (age 54 yrs). After psychometric tests and capillary (ear lobe) blood ammonia measurements, 20 gr of glutamine was administered orally. Tests were repeated at 60 minutes (+ blood ammonia at 30'). Minimal HE was diagnosed if values were > 1.5 SD in at least 2 psychometric tests. Follow-up lasted 12 months.</p> <p>Results</p> <p>The test was well tolerated (nausea = 1; dizziness = 1). Patients showed higher values of capillary blood ammonia over time as compared to controls (0'-30'-60 minutes: 75, 117, 169 versus 52, 59, 78 umol/L, p < 0.05). At baseline, 25 patients (44%) had minimal HE, while 38 patients (67%) met the criteria for HE at 60 minutes (chi²: p < 0.01). For the diagnosis of minimal HE, using the ROC curve analysis, baseline capillary blood ammonia showed an AUC of 0.541 (CI: 0.38-0.7, p = 0.6), while at 60 minutes the AUC was 0.727 (CI: 0.58-0.87, p < 0.006). During follow-up, 18 patients (31%) developed clinical episodes of HE. At multivariate analysis, the MELD score (1.12 [1.018-1.236]), previous episodes of HE (3.2[1.069-9.58]), but not capillary blood ammonia, were independent predictors of event.</p> <p>Conclusions</p> <p>In patients with cirrhosis and normal neurological examination, bedside determination of ammonia in capillary blood following oral glutamine load is well tolerated and achieves a better diagnostic performance for minimal HE than basal capillary ammonia levels. However, capillary blood ammonia is a poor predictor of development of clinically overt HE.</p

In Vitro and In Vivo High-Throughput Assays for the Testing of Anti-Trypanosoma cruzi Compounds

The treatment of Trypanosoma cruzi infection (the cause of human Chagas disease) remains a significant challenge. Only two drugs, both with substantial toxicity, are available and the efficacy of these dugs is often questioned – in many cases due to the limitations of the methods for assessing efficacy rather than to true lack of efficacy. For these reasons relatively few individuals infected with T. cruzi actually have their infections treated. In this study, we report on innovative methods that will facilitate the discovery of new compounds for the treatment of T. cruzi infection and Chagas disease. Utilizing fluorescent and bioluminescent parasite lines, we have developed in vitro tests that are reproducible and facile and can be scaled for high-throughput screening of large compound libraries. We also validate an in vivo screening test that monitors parasite replication at the site of infection and determines the effectiveness of drug treatment in less than two weeks. More importantly, results in this rapid in vivo test show strong correlations with those obtained in long-term (e.g. 40 day or more) treatment assays. The results of this study remove one of the obstacles for identification of effective and safe compounds to treat Chagas disease

Barriers and facilitators of effective self-management in asthma: systematic review and thematic synthesis of patient and healthcare professional views

Self-management is an established, effective approach to controlling asthma, recommended in guidelines. However, promotion, uptake and use among patients and health-care professionals remain low. Many barriers and facilitators to effective self-management have 25 been reported, and views and beliefs of patients and health care professionals have been explored in qualitative studies. We conducted a systematic review and thematic synthesis of qualitative research into self-management in patients, carers and health care professionals regarding self-management of asthma, to identify perceived barriers and facilitators associated with reduced effectiveness of asthma self-management interventions. Electronic databases and guidelines were searched systematically for qualitative literature that explored factors relevant to facilitators and barriers to uptake, adherence, or outcomes of self-management in patients with asthma. Thematic synthesis of the 56 included studies identified 11 themes: 1) partnership between patient and health care professional; 2) issues around medication; 3) education about asthma and its management; 4) health beliefs; 5) self-management interventions; 6) co-morbidities 7) mood disorders and anxiety; 8) social support; 9) non-pharmacological methods; 10) access to healthcare; 11) professional factors. From this, perceived barriers and facilitators were identified at the level of individuals with asthma (and carers), and health-care professionals. Future work addressing the concerns and beliefs of adults, adolescents and children (and carers) with asthma, effective communication and partnership, tailored support and education (including for ethnic minorities and at risk groups), and telehealthcare may improve how self-management is recommended by professionals and used by patients. Ultimately, this may achieve better outcomes for people with asthma