New zebrafish models of neurodegeneration

In modern biomedicine, the increasing need to develop experimental models to further our understanding of disease conditions and delineate innovative treatments has found in the zebrafish (Danio rerio) an experimental model, and indeed a valuable asset, to close the gap between in vitro and in vivo assays. Translation of ideas at a faster pace is vital in the field of neurodegeneration, with the attempt to slow or prevent the dramatic impact on the society's welfare being an essential priority. Our research group has pioneered the use of zebrafish to contribute to the quest for faster and improved understanding and treatment of neurodegeneration in concert with, and inspired by, many others who have primed the study of the zebrafish to understand and search for a cure for disorders of the nervous system. Aware of the many advantages this vertebrate model holds, here, we present an update on the recent zebrafish models available to study neurodegeneration with the goal of stimulating further interest and increasing the number of diseases and applications for which they can be exploited. We shall do so by citing and commenting on recent breakthroughs made possible via zebrafish, highlighting their benefits for the testing of therapeutics and dissecting of disease mechanisms

Gender differences in sex life issues – A population-based study of migraine sufferers

<p>Abstract</p> <p>Background</p> <p>Migraine is considered to have a negative influence on sex life. The present study was to analyse the perceptions of importance of and satisfaction with sex life as well as the expression of interest in sex among people having migraines in a prospective follow-up mail survey in 1998 and 2003.</p> <p>Methods</p> <p>The random sample was stratified according to gender and age in four age groups (20–24, 30–34, 40–44, and 50–54 years). Altogether 25 898 individuals responded to the baseline and 19 626 to the follow-up questionnaire (75.8% response rate). We examined as to how the perceptions of sex life of those suffering from migraine changed during a 5-year follow-up. Conditional logistic regression was used to analyse the data of the responses on self-reported migraine in the baseline and follow-up surveys (N = 2 977, 79.2% women). Each person with migraine was assigned a gender- and age-matched control in the analysis.</p> <p>Results</p> <p>All three outcome variables tended to decrease in value. Importance of sex life was higher among men with migraine than among their controls. Among women migraine lessened interest in sex life.</p> <p>Conclusion</p> <p>Our findings suggested that migraine has a different impact on sex life among women from that among men.</p

Are Menstrual and Nonmenstrual Migraine Attacks Different?

Migraine is the second most common headache condition next to tension-type headache. Up to one fourth of all women have migraine, and 20% of them experience migraine without aura attack in at least two thirds of their menstrual cycles. The current literature is analyzed in response to the question of whether menstrual and nonmenstrual migraine attacks are different. The different studies provide conflicting results, so it is not possible to answer the question firmly. Future studies should be based on the general population. Collection of both prospective and retrospective data is warranted, and headache diagnosis base on interviews by physicians with interest in headache are more precise than lay interviews or questionnaires

Thermodynamic analysis of the Quantum Critical behavior of Ce-lattice compounds

A systematic analysis of low temperature magnetic phase diagrams of Ce compounds is performed in order to recognize the thermodynamic conditions to be fulfilled by those systems to reach a quantum critical regime and, alternatively, to identify other kinds of low temperature behaviors. Based on specific heat ($C_m$) and entropy ($S_m$) results, three different types of phase diagrams are recognized: i) with the entropy involved into the ordered phase ($S_{MO}$) decreasing proportionally to the ordering temperature ($T_{MO}$), ii) those showing a transference of degrees of freedom from the ordered phase to a non-magnetic component, with their $C_m(T_{MO})$ jump ($\Delta C_m$) vanishing at finite temperature, and iii) those ending in a critical point at finite temperature because their $\Delta C_m$ do not decrease with $T_{MO}$ producing an entropy accumulation at low temperature. Only those systems belonging to the first case, i.e. with $S_{MO}\to 0$ as $T_{MO}\to 0$, can be regarded as candidates for quantum critical behavior. Their magnetic phase boundaries deviate from the classical negative curvature below $T\approx 2.5$\,K, denouncing frequent misleading extrapolations down to T=0. Different characteristic concentrations are recognized and analyzed for Ce-ligand alloyed systems. Particularly, a pre-critical region is identified, where the nature of the magnetic transition undergoes significant modifications, with its $\partial C_m/\partial T$ discontinuity strongly affected by magnetic field and showing an increasing remnant entropy at $T\to 0$. Physical constraints arising from the third law at $T\to 0$ are discussed and recognized from experimental results

Inter-rater reliability of data elements from a prototype of the Paul Coverdell National Acute Stroke Registry

<p>Abstract</p> <p>Background</p> <p>The Paul Coverdell National Acute Stroke Registry (PCNASR) is a U.S. based national registry designed to monitor and improve the quality of acute stroke care delivered by hospitals. The registry monitors care through specific performance measures, the accuracy of which depends in part on the reliability of the individual data elements used to construct them. This study describes the inter-rater reliability of data elements collected in Michigan's state-based prototype of the PCNASR.</p> <p>Methods</p> <p>Over a 6-month period, 15 hospitals participating in the Michigan PCNASR prototype submitted data on 2566 acute stroke admissions. Trained hospital staff prospectively identified acute stroke admissions, abstracted chart information, and submitted data to the registry. At each hospital 8 randomly selected cases were re-abstracted by an experienced research nurse. Inter-rater reliability was estimated by the kappa statistic for nominal variables, and intraclass correlation coefficient (ICC) for ordinal and continuous variables. Factors that can negatively impact the kappa statistic (i.e., trait prevalence and rater bias) were also evaluated.</p> <p>Results</p> <p>A total of 104 charts were available for re-abstraction. Excellent reliability (kappa or ICC > 0.75) was observed for many registry variables including age, gender, black race, hemorrhagic stroke, discharge medications, and modified Rankin Score. Agreement was at least moderate (i.e., 0.75 > kappa ≥; 0.40) for ischemic stroke, TIA, white race, non-ambulance arrival, hospital transfer and direct admit. However, several variables had poor reliability (kappa < 0.40) including stroke onset time, stroke team consultation, time of initial brain imaging, and discharge destination. There were marked systematic differences between hospital abstractors and the audit abstractor (i.e., rater bias) for many of the data elements recorded in the emergency department.</p> <p>Conclusion</p> <p>The excellent reliability of many of the data elements supports the use of the PCNASR to monitor and improve care. However, the poor reliability for several variables, particularly time-related events in the emergency department, indicates the need for concerted efforts to improve the quality of data collection. Specific recommendations include improvements to data definitions, abstractor training, and the development of ED-based real-time data collection systems.</p

Regular Exercise or Changing Diet Does Not Influence Aortic Valve Disease Progression in LDLR Deficient Mice

BACKGROUND: The development and progression of calcific aortic valve disease (CAVD) shares a number of similarities with atherosclerosis. Recently we could demonstrate that regular exercise training (ET) as primary prevention prevents aortic valve disease in LDL-receptor deficient (LDLR(-/-)) mice. We aimed to investigate the impact of exercise training on the progression of CAVD in LDLR(-/-) mice in the setting of secondary prevention METHODS AND RESULTS: Sixty-four LDLR(-/-) mice were fed with high cholesterol diet to induce aortic valve sclerosis. Thereafter the animals were divided into 3 groups: group 1 continuing on high cholesterol diet, group 2 continuing with cholesterol diet plus 1 h ET per day, group 3 continuing with normal mouse chow. After another 16 weeks the animal were sacrificed. Histological analysis of the aortic valve thickness demonstrated no significant difference between the three groups (control 98.3±4.5 µm, ET 88.2±6.6 µm, change in diet 87.5±4.0). Immunohistochemical staining for endothelial cells revealed a disrupted endothelial cell layer to the same extend in all groups. Furthermore no difference between the groups was evident with respect to the expression of inflammatory, fibroblastic and osteoblastic markers. CONCLUSION: Based on the present study we have to conclude that once the development of a CAVD is initiated, exercise training or a change in diet does not have the potential to attenuate the progress of the CAVD

Treatment of recurrent malignant gliomas with fotemustine monotherapy: impact of dose and correlation with MGMT promoter methylation

<p>Abstract</p> <p>Background</p> <p>In recurrent malignant gliomas (MGs), a high rate of haematological toxicity is observed with the use of fotemustine at the conventional schedule (100 mg/m²weekly for 3 consecutive weeks followed by triweekly administration after a 5-week rest period). Also, the impact of O6-methylguanine-DNA methyltransferase (MGMT) promoter methylation status on fotemustine activity has never been explored in the clinical setting.</p> <p>Methods</p> <p>40 patients with recurrent pretreated MG were identified as being treated with fotemustine at doses ranging from 65 mg/m²to 100 mg/m². Patients were classified into 3 groups according to the dose of fotemustine received, from the lowest dosage received in group A, to the highest in group C. Analysis of MGMT promoter methylation in tumor tissue was successfully performed in 19 patients.</p> <p>Results</p> <p>Overall, 20% of patients responded to treatment, for a disease control rate (DCR, responses plus stabilizations) of 47.5%. Groups A and B experienced a response rate of 40% and 26.5% respectively, while the corresponding value for group C was 10%. Out of 19 patients, MGMT promoter was found methylated in 12 cases among which a DCR of 66.5% was observed. All 7 patients with unmethylated MGMT promoter were progressive to fotemustine.</p> <p>Conclusion</p> <p>Low-dose fotemustine at 65–75 mg/m²(induction phase) followed by 75–85 mg/m²(maintenance phase) has an activity comparable to that of the conventional schedule. By determination of the MGMT promoter methylation status patients might be identified who are more likely to benefit from fotemustine chemotherapy.</p

Excess cardiovascular mortality associated with cold spells in the Czech Republic

<p>Abstract</p> <p>Background</p> <p>The association between cardiovascular mortality and winter cold spells was evaluated in the population of the Czech Republic over 21-yr period 1986–2006. No comprehensive study on cold-related mortality in central Europe has been carried out despite the fact that cold air invasions are more frequent and severe in this region than in western and southern Europe.</p> <p>Methods</p> <p>Cold spells were defined as periods of days on which air temperature does not exceed -3.5°C. Days on which mortality was affected by epidemics of influenza/acute respiratory infections were identified and omitted from the analysis. Excess cardiovascular mortality was determined after the long-term changes and the seasonal cycle in mortality had been removed. Excess mortality during and after cold spells was examined in individual age groups and genders.</p> <p>Results</p> <p>Cold spells were associated with positive mean excess cardiovascular mortality in all age groups (25–59, 60–69, 70–79 and 80+ years) and in both men and women. The relative mortality effects were most pronounced and most direct in middle-aged men (25–59 years), which contrasts with majority of studies on cold-related mortality in other regions. The estimated excess mortality during the severe cold spells in January 1987 (+274 cardiovascular deaths) is comparable to that attributed to the most severe heat wave in this region in 1994.</p> <p>Conclusion</p> <p>The results show that cold stress has a considerable impact on mortality in central Europe, representing a public health threat of an importance similar to heat waves. The elevated mortality risks in men aged 25–59 years may be related to occupational exposure of large numbers of men working outdoors in winter. Early warnings and preventive measures based on weather forecast and targeted on the susceptible parts of the population may help mitigate the effects of cold spells and save lives.</p

Spring-Block Model Reveals Region-Like Structures

A mechanical spring-block model is used for realizing an objective space partition of settlements from a geographic territory in region-like structures. The method is based on the relaxation-dynamics of the spring-block system and reveals in a hierarchical manner region-like entities at different spatial scales. It takes into account in an elegant manner both the spatiality of the elements and the connectivity relations among them. Spatiality is taken into account by using the geographic coordinates of the settlements, and by detecting the neighbors with the help of a Delaunay triangulation. Connectivity between neighboring settlements are quantified using a Pearson-like correlation for the relative variation of a relevant socio-economic parameter (population size, GDP, tax payed per inhabitant, etc.). The method is implemented in an interactive JAVA application and it is applied with success for an artificially generated society and for the case of USA, Hungary and Transylvania

Post-stenotic aortic dilatation

Aortic stenosis is the most common valvular heart disease affecting up to 4% of the elderly population. It can be associated with dilatation of the ascending aorta and subsequent dissection. Post-stenotic dilatation is seen in patients with AS and/or aortic regurgitation, patients with a haemodynamically normal bicuspid aortic valve and following aortic valve replacement. Controversy exists as to whether to replace the aortic root and ascending aorta at the time of aortic valve replacement, an operation that potentially carries a higher morbidity and mortality. The aetiology of post-stenotic aortic dilatation remains controversial. It may be due to haemodynamic factors caused by a stenotic valve, involving high velocity and turbulent flow downstream of the stenosis, or due to intrinsic pathology of the aortic wall. This may involve an abnormality in the process of extracellular matrix remodelling in the aortic wall including inadequate synthesis, degradation and transport of extracellular matrix proteins. This article reviews the aetiology, pathology and management of patients with post-stenotic aortic dilatation