Objective
Timely evaluation and initiation of treatment is the key for improving stroke outcomes, although minimizing the time from symptom onset to the first contact with healthcare professionals ...remains a challenge. We aimed to identify patient‐related factors associated with early hospital arrival.
Materials and methods
In this cross‐sectional survey, we included patients with stroke or transient ischemic attack admitted directly to one of two noncomprehensive stroke units or transferred to the units from comprehensive stroke centers in the Capital Region of Denmark. Patient‐reported factors associated with early hospital arrival were analyzed using multivariable logistic regression analysis adjusted for age, sex, education, living arrangement, brain location of the stroke, stroke severity, patient‐perceived symptom severity, history of prior stroke, stroke risk factors, and knowledge of stroke symptoms.
Results
In total, 479 patients with acute stroke were included (median age 74 (25th–75th percentile, 64–80), 40% women), of whom 46.4% arrived within 180 min of symptom onset. Factors associated with early hospital arrival were patients or bystanders choosing emergency medical service (EMS) for the first contact with a medical professional (adjusted odds ratio (OR), 3.41; 95% confidence interval, CI 1.57, 7.35) or the patient's perceived symptom severity above the median score of 25 on a 100‐point verbal scale (adjusted OR, 2.44; 95% CI 1.57, 3.82). Living alone reduced the likelihood of early arrival (adjusted OR, 0.53; 95% CI 0.33, 0.86).
Conclusions
Only when patients perceived symptoms as severe or when EMS was selected as the first contact, early arrival for stroke treatment was ensured.
Patient‐related factors associated with hospital arrival within 180 minutes
Bird migration is commonly defined as a seasonal movement between breeding and non-breeding grounds. It generally involves relatively straight and directed large-scale movements, with a latitudinal ...change, and specific daily activity patterns comprising less or no foraging and more traveling time. Our main objective was to describe how this general definition applies to seabirds. We investigated migration characteristics of 6 pelagic seabird species (little auk
Alle alle
, Atlantic puffin
Fratercula arctica
, common guillemot
Uria aalge,
Brünnich’s guillemot
U
.
lomvia,
black-legged kittiwake
Rissa tridactyla
and northern fulmars
Fulmarus glacialis
). We analysed an extensive geolocator positional and saltwater immersion dataset from 29 colonies in the North-East Atlantic and across several years (2008-2019). We used a novel method to identify active migration periods based on segmentation of time series of track characteristics (latitude, longitude, net-squared displacement). Additionally, we used the saltwater immersion data of geolocators to infer bird activity. We found that the 6 species had, on average, 3 to 4 migration periods and 2 to 3 distinct stationary areas during the non-breeding season. On average, seabirds spent the winter at lower latitudes than their breeding colonies and followed specific migration routes rather than non-directionally dispersing from their colonies. Differences in daily activity patterns were small between migratory and stationary periods, suggesting that all species continued to forage and rest while migrating, engaging in a ‘fly-and-forage’ migratory strategy. We thereby demonstrate the importance of habitats visited during seabird migrations as those that are not just flown over, but which may be important for re-fuelling.
Abstract
Background
Cerebellar electrical stimulation has shown promise in improving motor recovery post-stroke in both rodent and human studies. Past studies have used motor evoked potentials (MEPs) ...to evaluate how cerebellar stimulation modulates ongoing activity in the cortex, but the underlying mechanisms are incompletely understood. Here we used invasive electrophysiological recordings from the intact and stroke-injured rodent primary motor cortex (M1) to assess how epidural cerebellar stimulation modulates neural dynamics at the level of single neurons as well as at the level of mesoscale dynamics.
Methods
We recorded single unit spiking and local field potentials (LFPs) in both the intact and acutely stroke-injured M1 contralateral to the stimulated cerebellum in adult Long-Evans rats under anesthesia. We analyzed changes in the firing rates of single units, the extent of synchronous spiking and power spectral density (PSD) changes in LFPs during and post-stimulation.
Results
Our results show that post-stimulation, the firing rates of a majority of M1 neurons changed significantly with respect to their baseline rates. These firing rate changes were diverse in character, as the firing rate of some neurons increased while others decreased. Additionally, these changes started to set in during stimulation. Furthermore, cross-correlation analysis showed a significant increase in coincident firing amongst neuronal pairs. Interestingly, this increase in synchrony was unrelated to the direction of firing rate change. We also found that neuronal ensembles derived through principal component analysis were more active post-stimulation. Lastly, these changes occurred without a significant change in the overall spectral power of LFPs post-stimulation.
Conclusions
Our results show that cerebellar stimulation caused significant, long-lasting changes in the activity patterns of M1 neurons by altering firing rates, boosting neural synchrony and increasing neuronal assemblies’ activation strength. Our study provides evidence that cerebellar stimulation can directly modulate cortical dynamics. Since these results are present in the perilesional cortex, our data might also help explain the facilitatory effects of cerebellar stimulation post-stroke.
Nonviral gene delivery systems based on conventional high-molecular-weight chitosans are efficient after lung administration in vivo, but have poor physical properties such as aggregated shapes, low ...solubility at neutral pH, high viscosity at concentrations used for in vivo delivery and a slow dissociation and release of plasmid DNA, resulting in a slow onset of action. We therefore developed highly effective nonviral gene delivery systems with improved physical properties from a series of chitosan oligomers, ranging in molecular weight from 1.2 to 10 kDa. First, we established structure-property relationships with regard to polyplex formation and in vivo efficiency after lung administration to mice. In a second step, we isolated chitosan oligomers from a preferred oligomer fraction to obtain fractions, ranging from 10 to 50-mers, of more homogeneous size distributions with polydispersities ranging from 1.01 to 1.09. Polyplexes based on chitosan oligomers dissociated more easily than those of a high-molecular-weight ultrapure chitosan (UPC, approximately a 1000-mer), and released pDNA in the presence of anionic heparin. The more easily dissociated polyplexes mediated a faster onset of action and gave a higher gene expression both in 293 cells in vitro and after lung administration in vivo as compared to the more stable UPC polyplexes. Already 24 h after intratracheal administration, a 120- to 260-fold higher luciferase gene expression was observed compared to UPC in the mouse lung in vivo. The gene expression in the lung was comparable to that of PEI (respective AUCs of 2756+/-710 and 3320+/-871 pg luciferase x days/mg of total lung protein). In conclusion, a major improvement of chitosan-mediated nonviral gene delivery to the lung was obtained by using polyplexes of well-defined chitosan oligomers. Polyplexes of oligomer fractions also had superior physicochemical properties to commonly used high-molecular-weight UPC.
Aim
To understand the role of the collagen‐binding integrin α11 in vivo, we have used a classical approach of creating a mouse strain overexpressing integrin α11. A transgenic mouse strain ...overexpressing α11 in muscle tissues was analysed in the current study with special reference to the heart tissue.
Methods
We generated and phenotyped integrin α11 transgenic (TG) mice by echocardiography, magnetic resonance imaging and histology. Wild‐type (WT) mice were subjected to aortic banding (AB) and the expression of integrin α11 was measured in flow cytometry‐sorted cardiomyocytes and non‐myocytes.
Results
TG mice developed left ventricular concentric hypertrophy by 6 months, with increased collagen deposition and reactivation of mRNA encoding foetal genes associated with cardiovascular pathological remodelling compared to WT mice. Masson's trichrome staining revealed interstitial fibrosis, confirmed additionally by magnetic resonance imaging and was found to be most prominent in the cardiac septum of TG but not WT mice. TG hearts expressed increased levels of transforming growth factor‐β2 and transforming growth factor‐β3 and upregulated smooth muscle actin. Macrophage infiltration coincided with increased NF‐κB signalling in TG but not WT hearts. Integrin α11 expression was increased in both cardiomyocytes and non‐myocyte cells from WT AB hearts compared to sham‐operated animals.
Conclusion
We report for the first time that overexpression of integrin α11 induces cardiac fibrosis and left ventricular hypertrophy. This is a result of changes in intracellular hypertrophic signalling and secretion of soluble factors that increase collagen production in the heart.
During maximal exercise lactate taken up by the human brain contributes to reduce the cerebral metabolic ratio, O 2 /(glucose + 1/2 lactate), but it is not known whether the lactate is metabolized or ...if it accumulates in a distribution volume.
In one experiment the cerebral arterio-venous differences (AV) for O 2 , glucose (glc) and lactate (lac) were evaluated in nine healthy subjects at rest and during and after exercise to exhaustion.
The cerebrospinal fluid (CSF) was drained through a lumbar puncture immediately after exercise, while control values were
obtained from six other healthy young subjects. In a second experiment magnetic resonance spectroscopy ( 1 H-MRS) was performed after exhaustive exercise to assess lactate levels in the brain ( n â=â5). Exercise increased the AV O2 from 3.2 ± 0.1 at rest to 3.5 ± 0.2 m m (mean ± s.e.m. ; P < 0.05) and the AV glc from 0.6 ± 0.0 to 0.9 ± 0.1 m m ( P < 0.01). Notably, the AV lac increased from 0.0 ± 0.0 to 1.3 ± 0.2 m m at the point of exhaustion ( P < 0.01). Thus, maximal exercise reduced the cerebral metabolic ratio from 6.0 ± 0.3 to 2.8 ± 0.2 ( P < 0.05) and it remained low during the early recovery. Despite this, the CSF concentration of lactate postexercise (1.2 ± 0.1
m m ; n = 7) was not different from baseline (1.4 ± 0.1 m m ; n = 6). Also, the 1 H-MRS signal from lactate obtained after exercise was smaller than the estimated detection limit of â¼1.5 m m . The finding that an increase in lactate could not be detected in the CSF or within the brain rules out accumulation in a
distribution volume and indicates that the lactate taken up by the brain is metabolized.
The binding of pyrene to a number of humic substances isolated from various aquatic sources and a commercial humic acid was measured using the solubility enhancement method. The humic materials used ...in this study were characterized by various spectroscopic and liquid chroma tography methods. A strong correlation was observed between the pyrene binding coefficient, K doc, and the molecular weights, molar absorptivities at 280 nm, and aromaticity of the aquatic humic substances. Binding of pyrene to the commercial humic acid, however, was significantly stronger and did not obey the relationships observed between K doc and the chemical properties of the aquatic humic substrates. These results suggest that the molecular weight and the aromatic content of the humic substrates exert influences on the binding of nonpolar and planar aromatic molecules and that the physicochemical properties of both humic materials and organic solutes are important in controlling the speciation of nonpolar organic contaminants in natural waters
Identification of the molecule(s) that globally induce a robust regenerative state in sensory neurons following peripheral nerve injury remains elusive. A potential candidate is brain-derived ...neurotrophic factor (BDNF), the sole neurotrophin upregulated in sensory neurons after peripheral nerve injury. Here we tested the hypothesis that BDNF plays a critical role in the regenerative response of mature rat sensory neurons following peripheral nerve lesion. Neutralization of endogenous BDNF was performed by infusing BDNF antibodies intrathecally via a mini-osmotic pump for 3 days at the level of the fifth lumbar dorsal root ganglion, immediately following unilateral spinal nerve injury. This resulted in decreased expression of the injury/regeneration-associated genes growth-associated protein-43 and Tα1 tubulin in the injured sensory neurons as compared to injury plus control IgG infused or injury alone animals. Similar results were observed following inhibition of BDNF expression by intrathecal delivery of small interfering RNAs (siRNA) targeting BDNF starting 3 days prior to injury. The reduced injury/regeneration-associated gene expression correlated with a significantly reduced intrinsic capacity of these neurons to extend neurites when assayed in vitro. In contrast, delayed infusion of BDNF antibody for 3 days beginning 1 week post-lesion had no discernible influence on the elevated expression of these regeneration-associated markers. These results support an important role for endogenous BDNF in induction of the cell body response in injured sensory neurons and their intrinsic ability to extend neurites, but BDNF does not appear to be necessary for maintaining the response once it is induced.
Asian Tsunami: A Protective Role for Coastal Vegetation Danielsen, Finn; Sørensen, Mikael K; Olwig, Mette F ...
Science (American Association for the Advancement of Science),
10/2005, Letnik:
310, Številka:
5748
Journal Article
Recenzirano
The 26 December 2004 Indian Ocean tsunami had major effects on coastal communities and ecosystems. An assessment of coastlines after the tsunami indicates that coastal vegetation such as mangroves ...and beach forests helped to provide protection and reduce effects on adjacent communities. In recent years, mangroves and other coastal vegetation have been cleared or degraded along many coastlines, increasing their vulnerability to storm and tsunami damage. Establishing or strengthening greenbelts of mangroves and other coastal forests may play a key role in reducing the effect of future extreme events.
Highlights • The study investigates response to structural change in repetitive musical rhythm. • Areas associated with increased musical-syntactical complexity are activated. • Findings concur with ...a possible role for the cerebellum in prediction error processes.