Fatal thrombolysis-related intracerebral haemorrhage associated with amyloid-ß-related angiitis in a middle-aged patient - case report and literature review.

BACKGROUND: Amyloid-ß-related angiitis (ABRA) is a rare complication of cerebral amyloid angiopathy, characterized by amyloid-ß deposition in the leptomeningeal and cortical vessels with associated angiodestructive granulomatous inflammation. The clinical presentation is variable, including subacute cognitive decline, behavioural changes, headaches, seizures and focal neurological deficits, which may mimic other conditions. Here, we present a case with fatal thrombolysis-related haemorrhage associated with ABRA in a middle-aged patient. CASE PRESENTATION: A 55-year-old man was admitted to hospital with sudden onset left-sided cheek, arm and hand sensory loss, blurred vision, and worsening headache, with a National Institutes of Health Stroke Scale (NIHSS) score of 3. An acute CT head scan showed no contraindications, and therefore the decision was made to give intravenous thrombolysis. Post-thrombolysis, he showed rapid deterioration with visual disturbances, headache and confusion, and a repeat CT head scan confirmed several areas of intracerebral haemorrhage. No benefit from surgical intervention was expected, and the patient died four days after the first presentation. Neuropathological examination found acute ischemic infarcts of three to five days duration in the basal ganglia, insular cortex and occipital lobe, correlating with the initial clinical symptoms. There were also extensive recent intracerebral haemorrhages most likely secondary to thrombolysis. Furthermore, the histological examination revealed severe cerebral amyloid angiopathy associated with granulomatous inflammatory reaction, consistent with ABRA. CONCLUSIONS: Presentation of ABRA in a middle-aged patient highlighted the difficulties in recognition and management of this rare condition. There is emerging evidence that patients with CAA may have increased risk of fatal intracerebral haemorrhages following thrombolysis. This may be further increased by a coexisting CAA-related inflammatory vasculopathy which is potentially treatable with steroid therapy if early diagnosis is made.

Association of maternal gestational weight gain with intellectual developmental disorder in the offspring: a nationwide follow-up study in Sweden.

OBJECTIVES: To investigate the association between maternal gestational weight gain (GWG) and offspring's intellectual developmental disorders (IDD); how this association is modified by maternal early-pregnancy BMI. DESIGN: Population-based cohort study. SETTING AND POPULATION: All liveborn singletons with information on maternal GWG in the Swedish Medical Register during 1992-2006 (n = 467 485). METHODS: We used three GWG classifications, (1) Institute of Medicine (IOM) guidelines ('ideal' GWG: maternal underweight = 12.7-18.1 kg; normal = 11.3-15.9 kg; overweight = 6.8-11.3 kg; obesity = 5.0-9.1 kg), (2) LifeCycle project recommendation ('ideal' GWG: maternal underweight = 14.0-16.0 kg; normal = 10.0-18.0 kg; overweight = 2.0-16.0 kg; obesity class I = 2.0-6.0 kg; obesity class II ≤0.0-4.0 kg; obesity class III ≤0.0-6.0 kg) and (3) GWG centiles. Hazard ratio (HR) and 95% CI for offspring's IDD risk using Cox regression. MAIN OUTCOME MEASURES: IDD was extracted from Swedish National Patient Register (code ICD-9:317-319/ICD-10:F70-F79). RESULTS: Forty-one per cent of children were born to mothers with excessive GWG, 32.8% with ideal GWG and 26.2% with inadequate GWG according to IOM guidelines. Inadequate GWG was associated with 21% higher risk of offspring's IDD (95% CI 1.11-1.31) relative to ideal GWG. In contrast, when using the LifeCycle classification, children of mothers with inadequate GWG (HR 1.14, 95% CI 1.05-1.24) or excessive GWG (HR 1.09, 95% CI 1.01-1.17) had higher risks of IDD than those of mothers with ideal GWG. When using GWG centiles, extremely low GWG (<20th centile) and low GWG (20th-40th centile) were associated with elevated offspring's IDD risk. Further stratified analysis by maternal early-pregnancy body mass index (BMI) showed that overweight/obese mothers (BMI ≥25 kg/m2 ) with extremely excessive GWG (>25 kg) was associated with an increased offspring's IDD. CONCLUSION: Our findings suggest that inadequate maternal GWG may increase offspring's IDD risk, irrespective of maternal early-pregnancy BMI. Extremely excessive GWG (>25 kg) may increase offspring's IDD risk, but only among mothers with an early-pregnancy BMI ≥25 kg/m2 . TWEETABLE ABSTRACT: Inadequate maternal weight gain during pregnancy may increase the risk of offspring's intellectual disability, regardless of maternal BMI.

Cerebral venous sinus thrombosis and thrombocytopenia after COVID-19 vaccination - A report of two UK cases.

Recent reports have highlighted rare, and sometimes fatal, cases of cerebral venous sinus thrombosis (CVST) and thrombocytopenia following the Vaxzevria vaccine. An underlying immunological mechanism similar to that of spontaneous heparin-induced thrombocytopenia (HIT) is suspected, with the identification of antibodies to platelet factor-4 (PF4), but without previous heparin exposure. This unusual mechanism has significant implications for the management approach used, which differs from usual treatment of CVST. We describe the cases of two young males, who developed severe thrombocytopenia and fatal CVST following the first dose of Vaxzevria. Both presented with a headache, with subsequent rapid neurological deterioration. One patient underwent PF4 antibody testing, which was positive. A rapid vaccination programme is essential in helping to control the COVID-19 pandemic. Hence, it is vital that such COVID-19 vaccine-associated events, which at this stage appear to be very rare, are viewed through this lens. However, some cases have proved fatal. It is critical that clinicians are alerted to the emergence of such events to facilitate appropriate management. Patients presenting with CVST features and thrombocytopenia post-vaccination should undergo PF4 antibody testing and be managed in a similar fashion to HIT, in particular avoiding heparin and platelet transfusions.

The role of D2 dopamine receptors in oxytocin induced place preference and anxiolytic effect.

Neuropeptide oxytocin (OT) is involved in the regulation of social and non-social behaviour. The central nucleus of amygdala (CeA), part of the limbic system, plays an important role in learning, memory, anxiety and reinforcing mechanisms. CeA has been shown to be rich in OT receptors in rodents. Our previous findings indicated that OT in the rat CeA has a dose dependent rewarding and anxiolytic effect. The aim of our present study was to examine in the CeA the possible interaction of OT and D2 dopamine (DA) receptor antagonist Sulpiride on reinforcement in place preference test and on anxiety in elevated plus maze test. Wistar rats were microinjected bilaterally with 10 ng OT. In different group of animals 4 µg D2 DA receptor antagonist was applied. Other animals received D2 DA receptor antagonist 15 min before 10 ng OT treatment or vehicle solution into the CeA. Rats receiving 10 ng OT spent significantly longer time in the treatment quadrant during the test session in conditioned place preference test. Prior treatment with D2 DA receptor antagonist blocked the rewarding effects of OT. Antagonist in itself did not influence the time rats spent in the treatment quadrant. In elevated plus maze test, rats receiving 10 ng OT spent significantly longer time on the open arms. Prior treatment with D2 DA receptor antagonist blocked the effects of OT. Our results show that DA system plays a role in positive reinforcing and anxiolytic effects of OT because D2 DA receptor antagonist can block these actions.

Blood pressure characteristics in patients with acute basilar artery occlusion undergoing endovascular thrombectomy.

Acute basilar artery occlusion (BAO) is a rare but potentially life-threatening neurological condition. While endovascular therapy (EVT) has been shown to improve outcome, there is limited knowledge about prognostic factors beyond early recanalization. We studied whether blood pressure (BP) exceeds or falls below suggested thresholds during intervention and whether these changes are associated with complications and outcome. BP measurements mostly with one-minute intervals were available in 39 patients. An individual systolic blood pressure (SBP) reference value was defined as the median of the first five intra-procedural measurements. Half of the patients (51.3%) received drugs for BP augmentation and two a BP lowering drug (5.1%). Thrombolysis in cerebral infarction grade 2b and 3 (TICI) was achieved in 29 (74.4%) and 23 patients (58.9%) had good outcome at three months. We observed a continuous intra-procedural increase of median SBP (+11%) and mean arterial pressure (MAP, +10%, both p < 0.001), and a unique temporal pattern of intermittent peaks and troughs. Successful recanalization was more common in patients whose intra-procedural duration with SBP under 140 mmHg was shorter (p = 0.009). Patients with isolated tip of basilar artery (TBA) occlusion had significantly more BP excursion of 20% below the reference SBP and required more frequent use of sympathomimetic drugs compared to vertebrobasilar occlusion (p = 0.008 and p = 0.041, respectively). Brain hemorrhage was more prevalent in patients who experienced SBP excursions at least 20% above the individual reference value (p = 0.038) and a longer duration of time spent with SBP above 180 mmHg (p = 0.029). Patients with higher pre-procedural mean SBP had a greater chance of a good outcome (p = 0.03). This study using high resolution BP monitoring suggests a relationship between intra-procedural BP characteristics and recanalization, hemorrhagic complications and outcome in patients receiving EVT for acute posterior circulation cerebrovascular syndromes. Differences with regard to BP regulation during recanalization therapy for vertebrobasilar and TBA occlusion deserves further attention.

Moderate alcohol consumption and depression - a longitudinal population-based study in Sweden.

BACKGROUND AND AIMS: The interrelationship between alcohol consumption and depression is complex, and the direction of the association is unclear. We investigated whether alcohol consumption influences the risk of depression while accounting for this potential bidirectionality. METHODS: A total of 10 441 individuals participated in the PART study in 1998-2000, 8622 in 2001-2003, and 5228 in 2010. Participants answered questions on their alcohol consumption, symptoms of depression, childhood adversity, and sociodemographic, socioeconomic, psychosocial, and lifestyle factors. A total of 5087 participants provided repeated information on alcohol consumption. We used marginal structural models to analyze the association between alcohol consumption and depression while controlling for previous alcohol consumption and depressive symptoms and other time-varying confounders. RESULTS: Non-drinkers had a higher depression risk than light drinkers (≤7 drinks/week) (risk ratio: 1.7; 95% confidence interval 1.3-2.1). Consumers of seven-fourteen drinks/week had a depression risk similar to that of light drinkers. Hazardous drinking was associated with a higher risk of depression than non-hazardous alcohol consumption (risk ratio: 1.8, 95% confidence interval: 1.4-2.4). CONCLUSION: Light and moderate alcohol consumption and non-hazardous drinking were associated with the lowest risk of subsequent depression after accounting for potential bidirectional effects. Hazardous drinking increased the risk of depression.

Endovascular Therapy for Tandem Occlusion in Acute Ischemic Stroke: Intravenous Thrombolysis Improves Outcomes.

Ischemic stroke related to tandem internal carotid and middle cerebral artery (TIM) occlusion is a challenging condition where endovascular treatment (EVT) is an emerging revascularization option. The identification of factors influencing clinical outcomes can assist in creating appropriate therapeutic algorithms for such patients. This study aimed to evaluate prognostic factors in the context of EVT for TIM occlusion. We performed a retrospective study of consecutive patients with TIM occlusion admitted within 6 h from symptom onset to two tertiary stroke centers. We recorded the etiology of stroke, clinical deficits at stroke onset and discharge, details of EVT, final infarct volume (FIV), in-hospital mortality, and outcome at three months. Among 73 patients with TIM occlusion, 53 were treated with EVT. The median age was 75.9 years (interquartile range (IQR) 64.6⁻82.6), with the most common etiology of cardioembolism (51.9%). Intravenous thrombolysis with tissue-plasminogen activator (t-PA) was performed in the majority (69.8%) of cases. EVT achieved successful recanalization with a thrombolysis in cerebral infarction (TICI) grade of 2b or 3 in 67.9%. A good outcome (modified Rankin score of 0⁻2 at three months) was observed in 37.7%. After adjustment for age, the National Institutes of Health Stroke Scale (NIHSS) at admission, and success of recanalization, smaller final infarct volume (odds ratio (OR) 0.021 for FIV above 25th percentile (95% CI 0.001⁻0.332, p = 0.005)) and administration of intravenous t-PA (OR 12.04 (95% CI 1.004⁻144.392, p = 0.049)) were associated with a good outcome at three months. Our study demonstrates that bridging with t-PA is associated with improved outcomes in the setting of tandem ICA and MCA occlusions treated with EVT and should therefore not be withheld in eligible patients.

Cerebrovascular manifestations of herpes simplex virus infection of the central nervous system: a systematic review.

BACKGROUND: Intracerebral hemorrhage and ischemic stroke are increasingly recognized complications of central nervous system (CNS) infection by herpes simplex virus (HSV). AIM OF THE STUDY: To analyze clinical, imaging, and laboratory findings and outcomes of cerebrovascular manifestations of HSV infection. METHODS: Systematic literature review from January 2000 to July 2018. RESULTS: We identified 38 patients (median age 45 years, range 1-73) comprising 27 cases of intracerebral hemorrhage, 10 of ischemic stroke, and 1 with cerebral venous sinus thrombosis. Intracerebral hemorrhage was predominantly (89%) a complication of HSV encephalitis located in the temporal lobe. Hematoma was present on the first brain imaging in 32%, and hematoma evacuation was performed in 30% of these cases. Infarction was frequently multifocal, and at times preceded by hemorrhage (20%). Both a stroke-like presentation and presence of HSV encephalitis in a typical location were rare (25% and 10%, respectively). There was evidence of cerebral vasculitis in 63%, which was exclusively located in large-sized vessels. Overall mortality was 21% for hemorrhage and 0% for infarction. HSV-1 was a major cause of hemorrhagic complications, whereas HSV-2 was the most prevalent agent in the ischemic manifestations. CONCLUSION: We found a distinct pathogenesis, cause, and outcome for HSV-related cerebral hemorrhage and infarction. Vessel disruption within a temporal lobe lesion caused by HSV-1 is the presumed mechanism for hemorrhage, which may potentially have a fatal outcome. Brain ischemia is mostly related to multifocal cerebral large vessel vasculitis associated with HSV-2, where the outcome is more favorable.

Contribution of Serum Lipid Profiles to Outcome After Endovascular Thrombectomy for Anterior Circulation Ischemic Stroke.

The contribution of lipids, including low- and high-density lipoprotein cholesterol (LDL-C and HDL-C, respectively) and triglycerides (TG), to stroke outcomes is still debated. We sought to determine the impact of LDL-C concentrations on the outcome of patients with ischemic stroke in the anterior circulation who received treatment with endovascular thrombectomy (EVT). We performed a retrospective analysis of consecutive patients with acute ischemic stroke treated at a tertiary center between 2012 and 2016. Patients treated with EVT for large artery occlusion in the anterior circulation were selected. The primary endpoint was functional outcome at 3 months as measured with the modified Rankin Scale (mRS). Secondary outcome measures included hospital death and final infarct volume (FIV). Blood lipid levels were determined in a fasting state, 1 day after admission. We studied a total of 174 patients (44.8% men) with a median age of 74 years (interquartile range [IQR] 61-82) and median National Institutes of Health Stroke Scale at admission of 18 (14-22). Bridging therapy with intravenous tissue-plasminogen activator (t-PA) was administered in 122 (70.5%). The median LDL-C was 90 mg/dl (72-115). LDL-C demonstrated a U-type relationship with FIV (p = 0.036). Eighty-three (50.0%) patients had an mRS of 0-2 at 3 months. This favorable outcome was independently associated with younger age (OR 0.944, 95% CI 0.90-0.99, p = 0.012), thrombolysis in cerebral infarction 2b-3 reperfusion (OR 5.12, 95% CI 1.01-25.80, p = 0.015), smaller FIV (0.97 per cm3, 95% CI 0.97-0.99, p < 0.001), good leptomeningeal collaterals (OR 5.29, 95% CI 1.48-18.9, p = 0.011), and LDL-C more than 77 mg/dl (OR 0.179, 95% CI 0.04-0.74, p = 0.018). A higher LDL-C concentration early in the course of a stroke caused by large artery occlusion in the anterior circulation is independently associated with a favorable clinical outcome at 3 months. Further studies into the pathophysiological mechanisms underlying this observation are warranted.

Neutrophil to lymphocyte ratio predicts intracranial hemorrhage after endovascular thrombectomy in acute ischemic stroke.

BACKGROUND: The development of intracranial hemorrhage (ICH) in acute ischemic stroke is associated with a higher neutrophil to lymphocyte ratio (NLR) in peripheral blood. Here, we studied whether the predictive value of NLR at admission also translates into the occurrence of hemorrhagic complications and poor functional outcome after endovascular treatment (EVT). METHODS: We performed a retrospective analysis of consecutive patients with anterior circulation ischemic stroke who underwent EVT at a tertiary care center from 2012 to 2016. Follow-up scans were examined for non-procedural ICH and scored according to the Heidelberg Bleeding Classification. Demographic, clinical, and laboratory data were correlated with the occurrence of non-procedural ICH. RESULTS: We identified 187 patients with a median age of 74 years (interquartile range [IQR] 60-81) and a median baseline National Institutes of Health Stroke scale (NIHSS) score of 18 (IQR 13-22). A bridging therapy with recombinant tissue-plasminogen activator (rt-PA) was performed in 133 (71%). Of the 31 patients with non-procedural ICH (16.6%), 13 (41.9%) were symptomatic. Patients with ICH more commonly had a worse outcome at 3 months (p = 0.049), and were characterized by a lower body mass index, more frequent presence of tandem occlusions, higher NLR, larger intracranial thrombus, and prolonged rt-PA and groin puncture times. In a multivariate analysis, higher admission NLR was independently associated with ICH (OR 1.09 per unit increase, 95% CI (1.00-1.20, p = 0.040). The optimal cutoff value of NLR that best distinguished the development of ICH was 3.89. CONCLUSIONS: NLR is an independent predictor for the development of ICH after EVT. Further studies are needed to investigate the role of the immune system in hemorrhagic complications following EVT, and confirm the value of NLR as a potential biomarker.

Reproduction after the loss of a child: a population-based matched cohort study.

STUDY QUESTION: Is the death of a child associated with higher subsequent fertility? SUMMARY ANSWER: Women who had lost a child had higher fertility both shortly after the loss and throughout the entire follow-up, independent of the child's age at the time of death. WHAT IS KNOWN ALREADY: Women who lose a child in the perinatal period often have another child shortly after. However, to our knowledge no previous study has investigated if the death of an older child affects reproductive behavior. STUDY DESIGN, SIZE, DURATION: The source population for this matched cohort study consisted of all women who gave birth in Denmark from 1978 to 2004 and in Sweden from 1973 to 2002 (N = 1 979 958). Women were followed through to the end of 2008 in Denmark and the end of 2006 in Sweden. PARTICIPANTS/MATERIALS, SETTING, METHODS: Women who had lost a child before the age of 45 years during the study period (exposed group; n = 36 511) were matched with up to five women who were from the same country and of similar age and family characteristics and had not lost a child at the time of matching (unexposed group; n = 182 522). MAIN RESULTS AND THE ROLE OF CHANCE: During follow-up, 74% of exposed and 46% of unexposed women had another birth (live- or stillbirth) after a gestation of 28 weeks or more. Compared with unexposed women, exposed women had a shorter interpregnancy interval and, consequently, a higher rate of conception leading to a birth (HR = 5.5 [95% CI: 5.4-5.6]). Rates for exposed women were higher from the first month following the child's death, but the largest difference was between 2 and 3 months after the event. This pattern was independent of the age of the deceased child. Exposed women had more subsequent children than unexposed, leading to a comparable number of living children at the end of follow-up. LIMITATIONS, REASONS FOR CAUTION: The use of population-based registers allows for the inclusion of virtually all eligible women and nearly complete follow-up; the potential for selection bias is thus negligible. However, only pregnancies that led to a live birth or a stillbirth could be identified, thus fetal losses occurring before week 28 of gestation were missing. WIDER IMPLICATIONS OF THE FINDINGS: Our findings corroborate the previous evidence suggesting that women try to conceive again shortly after a perinatal death, and many succeed. In addition, this is the first study to investigate the reproductive trajectory after losing an older child. The current study indicates that most women who lose a child between the ages of 6 months and 5 years conceive shortly after the loss, and they have a comparable number of living children at the end of the follow-up compared to those who do not lose a child. STUDY FUNDING/COMPETING INTEREST(S): This work was supported by Grant ERC-2010-StG-260242 from the European Research Council, 176673 and 186200 from the Nordic Cancer Union, DFF-6110-00019 from the Danish Council for Independent Research, 904414 and 15199 from TrygFonden, Karen Elise Jensens Fond (2016), and the Program for Clinical Research Infrastructure (PROCRIN) established by the Lundbeck Foundation and the Novo Nordisk Foundation. The authors do not declare any conflicts of interests. TRIAL REGISTRATION NUMBER: N/A.

The role of intraamygdaloid neurotensin and dopamine interaction in conditioned place preference.

Tridecapeptide Neurotensin (NT) is widely distributed in the central nervous system where it acts as a neurotransmitter and neuromodulator. The central nucleus of amygdala (CeA), part of the limbic system, plays an important role in learning, memory, anxiety and reinforcing mechanisms. Our previous data showed that NT microinjected into the CeA has positive reinforcing properties. We supposed that these effects might be due to modulations of the mesolimbic dopamine system. The aim of our study was to examine in the CeA the possible effects of NT and dopamine interaction on reinforcement by conditioned place preference test. Male Wistar rats were microinjected bilaterally with 100 ng NT or 2 µg D1 dopamine receptor antagonist alone, or D1 dopamine antagonist 15 min before 100 ng NT treatment or vehicle solution into the CeA. Other animals received 4 µg D2 dopamine receptor antagonist Sulpiride alone, or administration of D2 dopamine receptor antagonist 15 min before 100 ng NT treatment or vehicle solution into the CeA. Rats that received 100 ng NT spent significantly more time in the treatment quadrant during the test session. Pre-treatment with the D1 dopamine antagonist, blocked the effects of NT. D2 dopamine receptor antagonist pretreatment could prevent the positive reinforcing effects of NT as well. Antagonists themselves did not influence the place preference. Our results show that the rewarding effect of NT can be due to the modulation of DA system, since its effects could be blocked by either D1 dopamine or D2 dopamine antagonist preteatment.

Substance P and neurotensin in the limbic system: Their roles in reinforcement and memory consolidation.

Substance P (SP) and neurotensin (NT) are neuropeptides isolated in the periphery and in the central nervous system. They are involved in various regulatory processes in the gastrointestinal tract, in the circulatory and respiratory systems, kidney and endocrine system. In addition to the peripheral effects, SP and NT act as neurotransmitters and neuromodulators in the central nervous system, regulating various behavioural actions, such as general and motor activity, pain, food and water intake, anxiety, reward/reinforcement and memory consolidation. In the limbic system SPergic and NTergic pathways, terminals and related receptors have been identified. According to several data of literature and to our recently published results, SP and NT have rewarding/reinforcing effects and facilitate memory consolidation in various limbic regions. In this report evidences are provided about the interaction of these neuropeptides with dopaminergic and acetylcholinergic systems. A hypothesis is presented that rewarding/reinforcing effects of SP and NT develop by modulating the mesencephalic dopaminergic system, while their mnemonic effects are mediated via the mesencephalic dopaminergic and the basal forebrain cholinergic systems.

Idarucizumab in Dabigatran-Treated Patients with Acute Ischemic Stroke Receiving Alteplase: A Systematic Review of the Available Evidence.

BACKGROUND AND PURPOSE: Current guidelines do not recommend the use of intravenous recombinant tissue plasminogen activator in patients with acute ischemic stroke who receive direct oral anticoagulants. While the humanized monoclonal antibody idarucizumab can quickly reverse the anticoagulant effects of the thrombin inhibitor dabigatran, safety data for subsequent tissue plasminogen activator treatment are sparse. Here, we review current knowledge about dabigatran reversal prior to systemic reperfusion treatment in acute ischemic stroke. METHODS: We performed a systematic review of all published cases of intravenous tissue plasminogen activator treatment following the administration of a dabigatran antidote up to June 2017 and added five unpublished cases of our own. We analyzed clinical and radiological outcomes, symptomatic post-thrombolysis intracranial hemorrhage, and other serious systemic bleeding. Additional endpoints were allergic reaction to idarucizumab, and venous thrombosis in the post-acute phase. RESULTS: We identified a total of 21 patients (71% male) with a median age of 76 years (interquartile range 70-84). The median National Institute of Health Stroke Scale score at baseline was 10 (n = 20, interquartile range 5-11) and 18/20 patients (90%) had mild or moderate stroke severity. The time from symptom onset to start of tissue plasminogen activator was 155 min (n = 18, interquartile range 122-214). The outcome was unfavorable in 3/19 patients (16%). There was one fatality as a result of a symptomatic post-thrombolysis intracranial hemorrhage, and two patients experienced an increase in the National Institute of Health Stroke Scale compared with baseline. One patient had a recurrent stroke. No systemic bleeding, venous thrombosis, or allergic reactions were reported. CONCLUSION: Experience with idarucizumab administration prior to tissue plasminogen activator treatment in acute ischemic stroke is limited. Initial clinical experience in less severe stroke syndromes and short time windows seems favorable. Larger cohorts are required to confirm safety, including bleeding complications and the risk of thrombosis.

Food and water intake, body temperature and metabolic consequences of interleukin-1ß microinjection into the cingulate cortex of the rat.

In order to elucidate whether cytokine mechanisms of the cingulate cortex (cctx) are important in the central regulation of homeostasis, in the present study, feeding-metabolic effects of direct bilateral microinjection of interleukin-1ß (IL-1ß) into the cctx of the rat have been investigated. Short- (2h), medium (12h) and long-term (24h) food and water intakes and body temperature were measured after the intracerebral administration of this primary cytokine or vehicle solution, with or without paracetamol pretreatment. The effect of IL-1ß on the blood glucose level of animals was examined in glucose tolerance test (GTT), and concentrations of relevant plasma metabolites (total cholesterol, HDL, LDH, triglycerides, uric acid) were additionally also determined following the above microinjections. In contrast to causing no major alteration in the food and water intakes, the cytokine treatment evoked significant increase in the body temperature of the rats. Prostaglandin-mediated mechanisms were shown to have important role in the mode of this action of IL-1ß, since paracetamol pretreatment partially prevented the development of the above mentioned hyperthermia. In the GTT, no considerable difference was observed between the blood glucose levels of the cytokine treated and control animals. Following IL-1ß microinjection, however, significant decrease of HDL and total cholesterol was found. Our present findings indicate that elucidating the IL-1ß mediated homeostatic control mechanisms in the cingulate cortex may lead to the better understanding not only the regulatory entities of the healthy organism but also those found in obesity, diabetes mellitus and other worldwide rapidly spreading feeding-metabolic disorders.

Static and dynamic behaviour of responsive graphene oxide-poly(N-isopropyl acrylamide) composite gels.

Thermoresponsive hydrogels have enormous potential e.g., as sensors, actuators, and pollution control remedies or in drug delivery systems. Nevertheless, their application is often restricted by physical limitations (poor mechanical strength and uncontrolled thermal response). Composite systems may offer a means of overcoming these limitations. This paper presents a systematic study of the structure and dynamics of graphene oxide-poly-(N-isopropylacrylamide) composite systems, and investigates the effect of the nanoparticle filler content on the mechanical and swelling properties of the systems. A combination of macroscopic (swelling and elastic modulus) and microscopic (differential scanning microcalorimetry, small angle neutron scattering and neutron spin-echo spectroscopy) investigations reveals that the architecture of the polymer network is modified by chain nucleation at the surface of the GO platelets, and these form a percolating network inside the gel. Our results show that the elastic modulus of the gels is reinforced by the filler, but the mobility of the polymer chains in the swollen state is practically unaffected. The macroscopic deswelling of the composites, however, is slowed by the kinetics of ordering in the GO network.

Positive reinforcing effect of oxytocin microinjection in the rat central nucleus of amygdala.

Neuropeptide oxytocin (OT) receives increasing attention since, it plays a role in various behaviors including anxiety, drug addiction, learning, social recognition, empathy, pair bonding and decreased aggression. The central nucleus of the amygdala (CeA), part of the limbic system, plays an important role in learning, memory, anxiety and reinforcing mechanisms. CeA was shown to be rich in OT-receptors (OTR). The aim of our study was to examine the possible effects of OT and OTR antagonist in the CeA on reinforcement using the conditioned place preference test and on anxiety using the elevated plus maze test. Male Wistar rats were microinjected bilaterally with 10 ng OT or 100 ng OT (Sigma: O6379, injected in volume of 0.4µl) or 10ng OTR antagonist (Sigma: L-2540) alone, or OTR antagonist 15 min prior 10 ng OT treatment or vehicle solution into the CeA. Rats receiving 10 ng OT spent significantly more time in the treatment quadrant during the test session, while 100 ng OT treatment produced no effect. Prior treatment with the non-peptide OTR antagonist blocked the effects of OT. The antagonist in itself did not influence the place preference. The elevated plus maze test revealed that 10 ng OT significantly increased the time spent in the open arms. OTR antagonist pre-treatment could inhibit this effect and the antagonist in itself did not affect the time spent in the open arms. Our results show that in the rat CeA OT has dose-dependent, positive reinforcing and anxiolytic effects, via OTR demonstrated by the blocking effects of selective OTR antagonist.

Maternal bereavement and the risk of preterm delivery: the importance of gestational age and of the precursor of preterm birth.

BACKGROUND: Maternal stress during pregnancy may increase the risk of preterm delivery (PD), but the associations between stress and subtypes of PD are not clear. We investigated maternal loss of a close relative and risks of very and moderately PD (<32 and 32-36 weeks, respectively) and spontaneous and medically indicated PD. METHOD: We studied 4 940 764 live singleton births in Denmark (1978-2008) and Sweden (1973-2006). We retrieved information on death of women's family members (children, partner, siblings, parents), birth outcomes and maternal characteristics from nationwide registries. RESULTS: Overall, the death of a close family member the year before pregnancy or in the first 36 weeks of pregnancy was associated with a 7% increased risk of PD [95% confidence interval (CI) 1.04-1.10]. The highest hazard ratios (HR) for PD were found for death of an older child [HR (95% CI) 1.20 (1.10-1.31)] and for death of a partner [HR (95% CI) 1.31 (1.03-1.66)]. These losses were associated with higher risks of very preterm [HR (95% CI) 1.61 (1.29-2.01) and 2.07 (1.15-3.74), respectively] than of moderately preterm [HR (95% CI) 1.14 (1.03-1.26) and 1.22 (0.94-1.58), respectively] delivery. There were no substantial differences in the association between death of a child or partner and the risk of spontaneous v. medically indicated PD. CONCLUSIONS: Death of a close family member the year before or during pregnancy was associated with an increased risk of PD, especially very PD. Possible mechanisms include both spontaneous and medically indicated preterm birth.

Alcohol consumption is associated with a lower incidence of acute myocardial infarction: results from a large prospective population-based study in Norway.

AIMS: Compelling evidence suggests that light-to-moderate alcohol consumption is associated with a reduced risk of acute myocardial infarction (AMI), but several issues from previous studies remain to be addressed. The aim of this study was to investigate some of these key issues related to the association between alcohol consumption and AMI risk, including the strength and shape of the association in a low-drinking setting, the roles of quantity, frequency and beverage type, the importance of confounding by medical and psychiatric conditions, and the lack of prospective data on previous drinking. METHODS: A population-based prospective cohort study of 58 827 community-dwelling individuals followed for 11.6 years was conducted. We assessed the quantity and frequency of consumption of beer, wine and spirits at baseline in 1995-1997 and the frequency of alcohol intake approximately 10 years earlier. RESULTS: A total of 2966 study participants had an AMI during the follow-up period. Light-to-moderate alcohol consumption was inversely and linearly associated with AMI risk. After adjusting for major cardiovascular disease risk factors, the hazard ratio for a one-drink increment in daily consumption was 0.72 (95% confidence interval 0.62-0.86). Accounting for former drinking or comorbidities had almost no effect on the association. Frequency of alcohol consumption was more strongly associated with lower AMI risk than overall quantity consumed. CONCLUSIONS: Light-to-moderate alcohol consumption was linearly associated with a decreased risk of AMI in a population in which abstaining from alcohol is not socially stigmatized. Our results suggest that frequent alcohol consumption is most cardioprotective and that this association is not driven by misclassification of former drinkers.

Gene expression profiling in PC12 cells infected with an oncolytic Newcastle disease virus strain.

Although the oncolytic potential of natural, non-engineered Newcastle disease virus (NDV) isolates are well-known, cellular mechanisms determining NDV sensitivity of tumor cells are poorly understood. The aim of the present study was to look for gene expression changes in PC12 pheochromocytoma cells infected with an attenuated NDV strain that may be related to NDV susceptibility. PC12 cells were infected with the NDV strain MTH-68/H for 12h at a titer corresponding to the IC50 value. Total cytoplasmic RNA samples isolated from control and MTH-68/H-infected cells were analyzed using a rat specific Affymetrix exon chip. Genes with at least 2-fold increase or decrease in their expression were identified. MTH-68/H-induced gene expression changes of 9 genes were validated using quantitative reverse transcriptase PCR. A total of 729 genes were up- and 612 genes were down-regulated in PC12 cells infected with MTH-68/H. Using the DAVID functional annotation clustering tool, the up- and down-regulated genes can be categorized into 176 and 146 overlapping functional gene clusters, respectively. Gene expression changes affecting the most important signaling mechanisms (Toll-like receptor signaling, RIG-I-like receptor signaling, interferon signaling, interferon effector pathways, apoptosis pathways, endoplasmic reticulum stress pathways, cell cycle regulation) are analyzed and discussed in detail in this paper. NDV-induced gene expression changes described in this paper affect several regulatory mechanisms and dozens of putative key proteins that may determine the NDV susceptibility of various tumors. Further characterization of these proteins may identify susceptibility markers to predict the chances of virotherapeutic treatment of human tumors.