Preventive Antibacterial Therapy in Acute Ischemic Stroke: A Randomized Controlled Trial

BACKGROUND: Pneumonia is a major risk factor of death after acute stroke. In a mouse model, preventive antibacterial therapy with moxifloxacin not only prevents the development of post-stroke infections, it also reduces mortality, and improves neurological outcome significantly. In this study we investigate whether this approach is effective in stroke patients. METHODS: Preventive ANtibacterial THERapy in acute Ischemic Stroke (PANTHERIS) is a randomized, double-blind, placebo-controlled trial in 80 patients with severe, non-lacunar, ischemic stroke (NIHSS>11) in the middle cerebral artery (MCA) territory. Patients received either intravenous moxifloxacin (400 mg daily) or placebo for 5 days starting within 36 hours after stroke onset. Primary endpoint was infection within 11 days. Secondary endpoints included neurological outcome, survival, development of stroke-induced immunodepression, and induction of bacterial resistance. FINDINGS: On intention-to treat analysis (79 patients), the infection rate at day 11 in the moxifloxacin treated group was 15.4% compared to 32.5% in the placebo treated group (p = 0.114). On per protocol analysis (n = 66), moxifloxacin significantly reduced infection rate from 41.9% to 17.1% (p = 0.032). Stroke associated infections were associated with a lower survival rate. In this study, neurological outcome and survival were not significantly influenced by treatment with moxifloxacin. Frequency of fluoroquinolone resistance in both treatment groups did not differ. On logistic regression analysis, treatment arm as well as the interaction between treatment arm and monocytic HLA-DR expression (a marker for immunodepression) at day 1 after stroke onset was independently and highly predictive for post-stroke infections. INTERPRETATION: PANTHERIS suggests that preventive administration of moxifloxacin is superior in reducing infections after severe non-lacunar ischemic stroke compared to placebo. In addition, the results emphasize the pivotal role of immunodepression in developing post-stroke infections. TRIAL REGISTRATION: Controlled-Trials.com ISRCTN74386719

Association of severe hypertension with pneumonia in elderly patients with acute ischemic stroke

Pneumonia is one of the most frequent complications in elderly patients with acute ischemic stroke. Although severe hypertension is often observed in the early phase of acute stroke, there are few studies of acute hypertension as a factor influencing the incidence of stroke-associated pneumonia (SAP) in elderly subjects with acute ischemic stroke. To assess the association of acute phase blood-pressure elevation with the incidence of SAP, we compared 10 elderly patients with acute ischemic stroke complicated with severe hypertension (⩾200/120 mm Hg) with 43 patients with moderate hypertension (160–199/100–119 mm Hg), as well as with 65 control normotensive or mildly hypertensive (<160/100 mm Hg) controls on admission. Data were collected on known risk factors, type of ischemic stroke and underlying chronic conditions. The significance of differences in risk factors was analyzed using univariate and multivariate comparisons of 38 SAP cases and others, 8 SAP death cases and others, and 28 patients with poor outcome associated with in-hospital death or artificial feeding at discharge and others. After adjustment for potential confounding factors, the relative risk estimates for SAP, SAP death and poor outcome were 2.83 (95% confidence interval 1.14–7.05), 5.20 (1.01–26.8) and 6.84 (1.32–35.4), respectively, for severe hypertension relative to normotensive or mildly hypertensive controls. We conclude that severe hypertension on admission is an independent predictive factor for SAP in elderly patients with acute ischemic stroke

Pneumonia and in-hospital mortality in the context of neurogenic oropharyngeal dysphagia (NOD) in stroke and a new NOD step-wise concept

The aim of our work was to develop a step-wise concept for investigating neurogenic oropharyngeal dysphagia (NOD) that could be used by both trained nursing staff as well as swallowing therapists and physicians to identify patients with NOD at an early stage and so enable an appropriate therapy to be started. To achieve this objective, we assessed uniform terminology and standard operating procedures (SOP) in a new NOD step-wise concept. In-house stroke mortality rates and rates of pneumonia were measured over time (2003–2009) in order to show improvements in quality of care. In addition, outcome measures in a stroke-unit monitoring system were studied after neurorehabilitation (day 90) assessing quality of life (QL) and patient feedback. An investigation that was carried out in the context of internal and external quality assurance stroke projects revealed a significant correlation between the NOD step-wise concept and low rates of pneumonia and in-house mortality. The quality of life measures show a delta value that can contribute to “post-stroke” depression. The NOD step-wise concept (NSC) should, on the one hand, be capable of being routinely used in clinical care and, on the other, being able to fulfil the requirements of being scientifically based for investigating different stages of swallowing disorders. The value of our NSC relates to the effective management of clinical resources and the provision of adequate diagnostic and therapeutic options for different grades of dysphagia. We anticipate that our concept will provide substantial support to physicians, as well as swallowing therapists, in clinical settings and rehabilitation facilities, thereby promoting better guidance and understanding of neurogenic dysphagia as a concept in acute and rehabilitation care, especially stroke-unit settings

Force-Velocity Measurements of a Few Growing Actin Filaments

The authors propose a new mechanism for actin-based force generation based on results using chains of actin-grafted magnetic colloids

The elementary events underlying force generation in neuronal lamellipodia

We have used optical tweezers to identify the elementary events underlying force generation in neuronal lamellipodia. When an optically trapped bead seals on the lamellipodium membrane, Brownian fluctuations decrease revealing the underlying elementary events. The distribution of bead velocities has long tails with frequent large positive and negative values associated to forward and backward jumps occurring in 0.1–0.2 ms with varying amplitudes up to 20 nm. Jump frequency and amplitude are reduced when actin turnover is slowed down by the addition of 25 nM Jasplakinolide. When myosin II is inhibited by the addition of 20 μM Blebbistatin, jump frequency is reduced but to a lesser extent than by Jasplainolide. These jumps constitute the elementary events underlying force generation

Regional genome transcriptional response of adult mouse brain to hypoxia

<p>Abstract</p> <p>Background</p> <p>Since normal brain function depends upon continuous oxygen delivery and short periods of hypoxia can precondition the brain against subsequent ischemia, this study examined the effects of brief hypoxia on the whole genome transcriptional response in adult mouse brain.</p> <p>Result</p> <p>Pronounced changes of gene expression occurred after 3 hours of hypoxia (8% O₂) and after 1 hour of re-oxygenation in all brain regions. The hypoxia-responsive genes were predominantly up-regulated in hindbrain and predominantly down-regulated in forebrain - possibly to support hindbrain survival functions at the expense of forebrain cognitive functions. The up-regulated genes had a significant role in cell survival and involved both shared and unshared signaling pathways among different brain regions. Up-regulation of transcriptional signaling including hypoxia inducible factor, insulin growth factor (IGF), the vitamin D3 receptor/retinoid X nuclear receptor, and glucocorticoid signaling was common to many brain regions. However, many of the hypoxia-regulated target genes were specific for one or a few brain regions. Cerebellum, for example, had 1241 transcripts regulated by hypoxia only in cerebellum but not in hippocampus; and, 642 (54%) had at least one hepatic nuclear receptor 4A (HNF4A) binding site and 381 had at least two HNF4A binding sites in their promoters. The data point to HNF4A as a major hypoxia-responsive transcription factor in cerebellum in addition to its known role in regulating erythropoietin transcription. The genes unique to hindbrain may play critical roles in survival during hypoxia.</p> <p>Conclusion</p> <p>Differences of forebrain and hindbrain hypoxia-responsive genes may relate to suppression of forebrain cognitive functions and activation of hindbrain survival functions, which may coordinately mediate the neuroprotection afforded by hypoxia preconditioning.</p

Brain antigens in functionally distinct antigen-presenting cell populations in cervical lymph nodes in MS and EAE

Drainage of central nervous system (CNS) antigens to the brain-draining cervical lymph nodes (CLN) is likely crucial in the initiation and control of autoimmune responses during multiple sclerosis (MS). We demonstrate neuronal antigens within CLN of MS patients. In monkeys and mice with experimental autoimmune encephalomyelitis (EAE) and in mouse models with non-inflammatory CNS damage, the type and extent of CNS damage was associated with the frequencies of CNS antigens within the cervical lymph nodes. In addition, CNS antigens drained to the spinal-cord-draining lumbar lymph nodes. In human MS CLN, neuronal antigens were present in pro-inflammatory antigen-presenting cells (APC), whereas the majority of myelin-containing cells were anti-inflammatory. This may reflect a different origin of the cells or different drainage mechanisms. Indeed, neuronal antigen-containing cells in human CLN did not express the lymph node homing receptor CCR7, whereas myelin antigen-containing cells in situ and in vitro did. Nevertheless, CLN from EAE-affected CCR7-deficient mice contained equal amounts of myelin and neuronal antigens as wild-type mice. We conclude that the type and frequencies of CNS antigens within the CLN are determined by the type and extent of CNS damage. Furthermore, the presence of myelin and neuronal antigens in functionally distinct APC populations within MS CLN suggests that differential immune responses can be evoked

Tropical and Boreal Forest Atmosphere Interactions: A Review

This review presents how the boreal and the tropical forests affect the atmosphere, its chemical composition, its function, and further how that affects the climate and, in return, the ecosystems through feedback processes. Observations from key tower sites standing out due to their long-term comprehensive observations: The Amazon Tall Tower Observatory in Central Amazonia, the Zotino Tall Tower Observatory in Siberia, and the Station to Measure Ecosystem-Atmosphere Relations at Hyytiala in Finland. The review is complemented by short-term observations from networks and large experiments.The review discusses atmospheric chemistry observations, aerosol formation and processing, physiochemical aerosol, and cloud condensation nuclei properties and finds surprising similarities and important differences in the two ecosystems. The aerosol concentrations and chemistry are similar, particularly concerning the main chemical components, both dominated by an organic fraction, while the boreal ecosystem has generally higher concentrations of inorganics, due to higher influence of long-range transported air pollution. The emissions of biogenic volatile organic compounds are dominated by isoprene and monoterpene in the tropical and boreal regions, respectively, being the main precursors of the organic aerosol fraction.Observations and modeling studies show that climate change and deforestation affect the ecosystems such that the carbon and hydrological cycles in Amazonia are changing to carbon neutrality and affect precipitation downwind. In Africa, the tropical forests are so far maintaining their carbon sink.It is urgent to better understand the interaction between these major ecosystems, the atmosphere, and climate, which calls for more observation sites, providing long-term data on water, carbon, and other biogeochemical cycles. This is essential in finding a sustainable balance between forest preservation and reforestation versus a potential increase in food production and biofuels, which are critical in maintaining ecosystem services and global climate stability. Reducing global warming and deforestation is vital for tropical forests

Tropical and Boreal Forest Atmosphere Interactions : A Review

This review presents how the boreal and the tropical forests affect the atmosphere, its chemical composition, its function, and further how that affects the climate and, in return, the ecosystems through feedback processes. Observations from key tower sites standing out due to their long-term comprehensive observations: The Amazon Tall Tower Observatory in Central Amazonia, the Zotino Tall Tower Observatory in Siberia, and the Station to Measure Ecosystem-Atmosphere Relations at Hyytiala in Finland. The review is complemented by short-term observations from networks and large experiments. The review discusses atmospheric chemistry observations, aerosol formation and processing, physiochemical aerosol, and cloud condensation nuclei properties and finds surprising similarities and important differences in the two ecosystems. The aerosol concentrations and chemistry are similar, particularly concerning the main chemical components, both dominated by an organic fraction, while the boreal ecosystem has generally higher concentrations of inorganics, due to higher influence of long-range transported air pollution. The emissions of biogenic volatile organic compounds are dominated by isoprene and monoterpene in the tropical and boreal regions, respectively, being the main precursors of the organic aerosol fraction. Observations and modeling studies show that climate change and deforestation affect the ecosystems such that the carbon and hydrological cycles in Amazonia are changing to carbon neutrality and affect precipitation downwind. In Africa, the tropical forests are so far maintaining their carbon sink. It is urgent to better understand the interaction between these major ecosystems, the atmosphere, and climate, which calls for more observation sites, providing long-term data on water, carbon, and other biogeochemical cycles. This is essential in finding a sustainable balance between forest preservation and reforestation versus a potential increase in food production and biofuels, which are critical in maintaining ecosystem services and global climate stability. Reducing global warming and deforestation is vital for tropical forests.Peer reviewe