208 research outputs found
Aspects of migraine and patent foramen ovale in ischemic stroke
Stroke is one of the main causes of death and disability worldwide, and only in Sweden approximately 25 000 individuals suffer from stroke each year. This thesis focuses on two common conditions; migraine and patent foramen ovale (PFO) and their role in stroke.
Migraine is a common primary headache disorder, affecting approximately 11-13 % of the population with a 3:1 female preponderance. One third of the patients have an initial aura of neurological symptoms before the headache, and clinically migraine can be divided into migraine with and without aura. The pathophysiological mechanisms are highly complex, and involve cortical spreading depression (CSD) as the substrate for migraine aura, and activation of the trigeminovascular system causing the headache.
PFO is an inborn anomaly, a remnant from the fetal circulation, that is prevalent in approximately 25 % of the population. PFO enables shunting of venous blood to the arterial circulation, bypassing the pulmonary system and enables paradoxial embolization. PFO is associated with ischemic stroke, as well as migraine with aura. The reason for the latter is unknown, but may relate to micro-embolisms through a PFO triggering migraine attacks.
For decades, migraine has been suggested as a risk factor for stroke and cardiovascular disease. The risk seems to be mostly related to migraine with aura, female gender and young age. The reasons for this are still unknown and probably multifactorial. Different theories involve increased prevalence of cardiovascular risk factors among migraineurs, co-existence of other co-morbid conditions increasing the risk for stroke (i.e. PFO and cervical artery dissection), and association to endothelial dysfunction with subsequent hypercoagulability and decreased vascular reactivity. Migraine with aura may also be associated with a phenotype, leading to an increased susceptibility for CSD, and an increased sensitivity to cerebral ischemia. This thesis involves four different projects concerning PFO and migraine in relation to stroke. The projects are performed in stroke populations (Study I-III) and in a population-based twin sample (Study IV).
In Study I, patients with ischemic stroke investigated with transesophageal echocardiography were included (N=117), and dichotomized depending on the co-existence of a PFO. The prevalence of PFO was 11.9 %. Patients were analyzed regarding cardiovascular risk factors and allele frequency of 100 different genetic markers, previously associated with cerebrovascular disease. Four genetic markers, located in the Prothrombin-, Selectin E- and Apolipoprotein C III- genes, were significantly associated with PFO. The strongest association was for Prothrombin 20210 G/A (p= 0.0049), which is a marker associated with increased risk of venous thromboembolism. There were no differences regarding risk factors in the two groups.
In Study II, patients with a diagnosis of TIA, ischemic or hemorrhagic stroke, admitted to the stroke ward during a six-month period, were included (N=175). Prevalence of migraine was investigated using a structured questionnaire, and patients were analyzed regarding cardiovascular risk factors and clinical characteristics of their stroke, depending on co-existing migraine or not. The prevalence of migraine was 20 %, which
is comparable to prevalence estimates in the general population. However, migraine with aura was more prevalent than expected (61 % of those with migraine). Migraine was associated with PFO. Most stroke patients had a favorable outcome after stroke and there was no difference in stroke severity depending on migraine status.
In Study III, patients with cryptogenic stroke and PFO, planned for closure of their PFO (N=20) or on medical treatment only (N=7), were included. Patients were followed prospectively from baseline to six month after closure. Fifty percent of the patients had co-existing migraine, whereof the majority had migraine with aura (84.6 %). Endothelial dysfunction was assessed at baseline and after one day, one month and six months. A majority of patients had an impaired endothelial function at baseline, but there was no change after PFO closure. In a few patients, migraine frequency was impacted after closure with a distinct increase in migraine attacks after the procedure. At a second, long-time follow-up, the majority of patients were improved regarding frequency of migraine attacks.
In Study IV, the risk for stroke related to migraine was investigated in a population from the Swedish Twin Registry (N=53 404). A diagnose of migraine with or without aura was identified through a symptom based algorithm. The twins were followed longitudinally for more than 10 years for the outcome of stroke, using data from national patient registries. There was no general increased risk for stroke associated with migraine, but twins with migraine with aura had a border-significant 27 % increased risk for stroke. Further analysis suggested that this could be impacted by familial factors. However, in comparison with previous studies, our results showed a considerably weaker association to stroke related to migraine
Arbetsterapeutiska interventioner för ökad aktivitetsbalans hos personer med Ängestsyndrom - en kvalitativ studie
Bakgrund: Ă
ngestsyndrom kan bidra till svĂ„righeter i vardagliga livet och pĂ„verka individens livssituation, aktivitetsbalans och hĂ€lsa. Arbetsterapeutiska interventioner genomförs för att pĂ„verka individens görande, tĂ€nkande och/eller kĂ€nnande för att uppnĂ„ enförĂ€ndring. Forskning visar att det finns en del interventioner riktade mot denna typ av grupp, men ytterst lite som fokuserar pĂ„ att frĂ€mja aktivitetsbalans i vardagen. Syfte: Syftet Ă€r att undersöka vilka interventioner arbetsterapeuter beskriver att de anvĂ€nder sig av för att deras klienter med Ă„ngestsyndrom ska kunna uppnĂ„ en bĂ€ttre aktivitetsbalans. Syftet Ă€r vidare att beskriva hur arbetsterapeuter upplever att dessa interventioner bidrar till förbĂ€ttrad hĂ€lsa och aktivitetsbalans för dessa klienter. Metod: En kvalitativ ansats valdes. Ă
tta arbetsterapeuter som valdes med snöbollsurval intervjuades. Data analyserades med manifest innehĂ„llsanalys. Resultat: Resultatet resulterade ett tema: âKlientcentreringâ och tre huvudkategorier: âSkapande aktiviteterâ, âKognitiv beteende terapiâ och âVardagsstrukturâ. Slutsats: Arbetsterapeuterna anvĂ€nde sig av olika interventioner; skapande aktiviteter, kognitiv beteende terapi och vardagsstruktur för att uppnĂ„ en god aktivitetsbalans och hĂ€lsa hos individer med Ă„ngestsyndrom. Interventionerna visade sig ge goda resultat enligt arbetsterapeuterna och interventionerna kunde bidra till ökad aktivitetsbalans och hĂ€lsa hos klienterna
Climate-energy-water nexus in Brazilian oil refineries
International audienceOil refineries are major CO2 emitters and are usually located in water-stress sites. While some CO2 mitigation options can reduce water demand, others can increase it, and still others are neutral. By simulating two parametric models, one for all Brazilian refineries, and the other locally detailing the water balance of the countryÂŽs largest refinery, this study aimed to quantify the impacts of CO2 mitigation options on the water use of oil refineries. Findings show that, by pricing CO2 emissions up to 100 US$/tCO2, the list of mitigation options was able to abate 25% of the annual emissions in Brazilian refineries. A relevant share of this abatement derives from the implementation of carbon capture (CC) facilities in fluid catalytic cracking and hydrogen generation units. However, these CC facilities offset the co-benefits of other CO2 mitigation options that can reduce steam and cold-water requirements in refineries. In fact, for the largest Brazilian oil refinery, the implementation of all mitigation measures had almost no effect on its water balance. This means that CO2 abatement in refineries has no significant impact on water demand (no negative trade-off). However, this also means that the water stress in oil refineries should be dealt with measures not directly linked to CO2 abatement (no significant co-benefits)
Toll-like receptor expression in smokers with and without COPD
SummaryIntroductionChronic obstructive pulmonary disease (COPD) is characterized by non-reversible airflow limitation and systemic engagement. Bacterial colonization in the lungs is common in COPD-patients and may be associated with frequent acute exacerbations. Pattern-recognition receptors (PRRs), like Toll-like receptor 2 (TLR2), TLR4 and CD14 are expressed on most immunologic active cell types and are most likely of importance in COPD patho-physiology.Material and methodsTwenty smokers with and 20 without COPD and 20 healthy non-smokers participated in the study. At two visits, induced sputum was collected after spirometry, blood was sampled and bronchoscopy with bronchoalveolar lavage was performed. Expression of TLR2, TLR4 and CD14 on different cell types and soluble receptors were assessed in the different compartments.ResultsExpression of TLR2 was lower on sputum neutrophils and soluble TLR2 (sTLR2) was higher in the supernatant in the COPD group, indicating a down regulation of TLR2 at the transit from blood to sputum. Expression of CD14 on sputum neutrophils and gene expression of CD14 on alveolar macrophages was up-regulated in the two smoking groups compared with non-smokers. No differences between the groups were found regarding TLR4 expression.ConclusionsPattern-recognition receptors (PRRs), that are expected to make a first line of defense against invading micro-organisms, are differently regulated in smokers with COPD compared with smokers without airflow limitation and non-smokers. This is likely of importance in COPD patho-physiology, in particular for exacerbations, which often are caused by micro-organisms
Differential proteomic analysis highlights metabolic strategies associated with balhimycin production in Amycolatopsis balhimycina chemostat cultivations
Background
Proteomics was recently used to reveal enzymes whose expression is associated with the production of the glycopeptide antibiotic balhimycin in Amycolatopsis balhimycina batch cultivations. Combining chemostat fermentation technology, where cells proliferate with constant parameters in a highly reproducible steady-state, and differential proteomics, the relationships between physiological status and metabolic pathways during antibiotic producing and non-producing conditions could be highlighted.
Results
Two minimal defined media, one with low Pi (0.6 mM; LP) and proficient glucose (12 g/l) concentrations and the other one with high Pi (1.8 mM) and limiting (6 g/l; LG) glucose concentrations, were developed to promote and repress antibiotic production, respectively, in A. balhimycina chemostat cultivations. Applying the same dilution rate (0.03 h-1), both LG and LP chemostat cultivations showed a stable steady-state where biomass production yield coefficients, calculated on glucose consumption, were 0.38+/-0.02 and 0.33+/-0.02 g/g (biomass dry weight/glucose), respectively. Notably, balhimycin was detected only in LP, where quantitative RT-PCR revealed upregulation of selected bal genes, devoted to balhimycin biosynthesis, and of phoP, phoR, pstS and phoD, known to be associated to Pi limitation stress response. 2D-Differential Gel Electrophoresis (DIGE) and protein identification, performed by mass spectrometry and computer-assisted 2D reference-map (http://www.unipa.it/ampuglia/Abal-proteome-maps) matching, demonstrated a differential expression for proteins involved in many metabolic pathways or cellular processes, including central carbon and phosphate metabolism. Interestingly, proteins playing a key role in generation of primary metabolism intermediates and cofactors required for balhimycin biosynthesis were upregulated in LP. Finally, a bioinformatic approach showed PHO box-like regulatory elements in the upstream regions of nine differentially expressed genes, among which two were tested by electrophoresis mobility shift assays (EMSA).
Conclusion
In the two chemostat conditions, used to generate biomass for proteomic analysis, mycelia grew with the same rate and with similar glucose-biomass conversion efficiencies. Global gene expression analysis revealed a differential metabolic adaptation, highlighting strategies for energetic supply and biosynthesis of metabolic intermediates required for biomass production and, in LP, for balhimycin biosynthesis. These data, confirming a relationship between primary metabolism and antibiotic production, could be used to increase antibiotic yield both by rational genetic engineering and fermentation processes improvement
Land-Based Wind Energy Cost Trends in Germany, Denmark, Ireland, Norway, Sweden and the UnitedStates
This paper presents work by the International Energy Agencyâs Task 26 âCost of Wind Energyâ on technological and cost trends in land-based wind energy in six participating countries (Denmark, Germany, Ireland, Norway, Sweden, United States) and the European Union between 2008 and 2016. Results indicate that there is a general trend towards larger, taller machines with lower specific powers resulting in higher capacity factors, despite small falls in new site wind resources in most countries, while wind project capital costs and project finance costs also fell. This resulted in an average levelized cost of energy (LCOE) fall of 33% for new projects to 48âŹ/MWh at the end of the study period. Analysis of the components of levelized cost change indicated that changes in specific power, financing cost and capital cost accounted for 45%, 25% and 17% respectively of the estimated reduction. It is therefore important that trends in technological factors such as specific power are considered when assessing wind energy learning rates, rather than just capital costs, which has been the primary focus heretofore. While LCOEs have fallen, the value of wind energy has fallen proportionately more, meaning grid parity appears no closer than at the beginning of the study. Policymakers must therefore consider both the cost and value of wind energy, and understand the volatility of this gap when designing land-based wind energy policy measures
Fragmentation Processes Following Core Excitation in Acetylene and Ethylene by Partial Ion Yield Spectroscopy
Partial ion yield spectroscopy provides a very detailed picture of fragmentation processes following core excitation in isolated molecules. We exploit this potential in the analysis of decay processes following C1sâÏ and C1sâRydberg excitations in ethylene and acetylene. We show that the relative intensity of spectral features related to the excitation to empty molecular orbitals or to Rydberg states is a function of the time variation of the fragmentation process. Namely, we see an intensity increase in the Rydberg states compared to the molecular orbitals as the fragmentation process becomes more extensive, a result attributable to the diffuse nature of the Rydberg virtual orbitals, which makes spectator decay more likely than participator decay. Therefore, the number of dissociative final states that can be reached from Rydberg excitation is higher than for excitation to empty molecular orbitals. In acetylene, we obtain the first direct evidence of the presence of a ÆĄ* excitation embedded in the Rydberg series. The formation of the fragment H2+ in ethylene occurs following a recombination process, while in acetylene it is related to excess vibrational energy stored in the intermediate state. Furthermore, we can use the enhancement in channels corresponding to doubly charged species as an indication for the presence of shape resonances
Population Health Solutions for Assessing Cognitive Impairment in Geriatric Patients.
In December 2017, the National Academy of Neuropsychology convened an interorganizational Summit on Population Health Solutions for Assessing Cognitive Impairment in Geriatric Patients in Denver, Colorado. The Summit brought together representatives of a broad range of stakeholders invested in the care of older adults to focus on the topic of cognitive health and aging. Summit participants speciïŹcally examined questions of who should be screened for cognitive impairment and how they should be screened in medical settings. This is important in the context of an acute illness given that the presence of cognitive impairment can have signiïŹcant implications for care and for the management of concomitant diseases as well as pose a major risk factor for dementia. Participants arrived at general principles to guide future screening approaches in medical populations and identiïŹed knowledge gaps to direct future research. Key learning points of the summit included: recognizing the importance of educating patients and healthcare providers about the value of assessing current and baseline cognition;emphasizing that any screening tool must be appropriately normalized and validated in the population in which it is used to obtain accurate information, including considerations of language, cultural factors, and education; andrecognizing the great potential, with appropriate caveats, of electronic health records to augment cognitive screening and tracking of changes in cognitive health over time
α(1,3)-Fucosyltransferases FUT4 and FUT7 Control Murine Susceptibility to Thrombosis
The α(1,3)-fucosyltransferases, types IV and VII (FUT4 and FUT7, respectively), are required for the synthesis of functional selectin-type leukocyte adhesion molecule ligands. The selectins and their ligands modulate leukocyte trafficking, and P-selectin and its ligand, P-selectin glycoprotein ligand-1, can modulate hemostasis and thrombosis. Regulation of thrombosis by FUT4 and/or FUT7 activity was examined in mouse models of carotid artery thrombosis and collagen/epinephrine-induced thromboembolism. Mice lacking both FUT4 and FUT7 (Futâ/â mice) had a shorter time to occlusive thrombus formation in the injured carotid artery and a higher mortality due to collagen/epinephrine-induced pulmonary thromboemboli. Mice lacking P-selectin or P-selectin glycoprotein ligand-1 did not have a prothrombotic phenotype. Whole blood platelet aggregation was enhanced, and plasma fibrinogen content, clot weight, and clot strength were increased in Futâ/â mice, and in vitro clot lysis was reduced compared with wild type. Fut4â/â, but not Fut7â/â, mice had increased pulmonary thromboembolism-induced mortality and decreased thromboemboli dissolution in vivo. These data show that FUT4 and FUT7 activity regulates thrombosis in a P-selectinâ and P-selectin glycoprotein ligand-1âindependent manner and suggest that FUT4 activity is important for thrombolysis
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