Clustering of Tadalafil API Samples According to their Manufacturer in the Context of API Falsification Detection.

This paper reports the results of the active pharmaceutical ingredient (API) fingerprint study, organised by the General European Official Medicines Control Laboratory Network (GEON), on tadalafil. A classical market surveillance study, evaluating compliance to the European Pharmacopoeia, was combined with a fingerprint study, the latter to obtain characteristic data for the different manufacturers, allowing the network laboratories to conduct authenticity tests for future samples, as well as to detect substandard and falsified samples. In total, 46 tadalafil API samples from 13 different manufacturers were collected. For all samples fingerprint data was collected through analysis of impurities and residual solvents, mass spectrometric screening, X-ray powder diffraction and proton nuclear magnetic resonance (1H-NMR). Chemometric analysis revealed that all manufacturers could be characterised based on the impurity, residual solvent and 1H-NMR data. Future suspicious samples in the network will therefore be analysed with these techniques in order to attribute the sample to one of the manufacturers. If the sample cannot be attributed, a more profound investigation will be necessary to reveal the origin of the sample. In cases where the suspect sample is claimed to be from one of the manufacturers included in this study, analysis can be limited to the test distinguishing that manufacturer.

Endovascular assisted vertebrobasilar junction aneurysm clipping in a hybrid operation room. Case report.

Introduction: We present a case of a 60-year-old female that underwent surgery for clipping a right vertebrobasilar junction aneurysm (VBJA) in a hybrid operation room. Research question: Does the retrograde suction technique with a proximal balloon is safe and effective as an adjuvant technique in surgery of VBJA? Material and methods: After an extended retrosigmoid approach was performed, a 6F Neuron catheter with an intermediate multipurpose catheter were navigated to the right vertebral artery (VA) through a 6-French sheath, which caused a severe catheter-induced vasospasm in the right VA. The aneurysm was then deflated and clipped. After the withdrawal of the catheter the vasospasm was resolved. Results: The patient had a good recovery, with VI cranial nerve palsy and mild dysphagia due to mild right vocal cord palsy, both improving at 1-month follow-up and fully recovered at 6-month follow-up. Discussion and conclusion: The combination of endovascular procedures and microsurgery at the same hybrid operation room in that case resulted in a safe and effective technique. It is an interesting tool that could help neurosurgeons deal with certain selected cases of VBJA. Intraoperative angiography offers the possibility to reposition a misplaced clip in the same surgery. Good collaboration between interventional neuroradiologists and vascular neurosurgeons helps in achieving good results in such difficult cases.

Acute symptomatic seizures and epilepsy after mechanical thrombectomy. A prospective long-term follow-up study.

INTRODUCTION: New treatments for acute ischaemic stroke, such as mechanical thrombectomy, can achieve reperfusion of large ischaemic tissue. Some studies have suggested that reperfusion therapies can increase the risk of suffering acute symptomatic seizure (ASS) and poststroke epilepsy (PSE). The aim of the study was to determine the incidence of ASS and PSE in patients undergoing thrombectomy, and related factors. PATIENTS AND METHODS: This was a retrospective single-centre study including patients with ischaemic stroke and NIHSS> 8 treated with thrombectomy with a follow-up ≥5 years. We evaluated several epidemiological, radiological, clinical and electroencephalographic variables. RESULTS: Of the 344 included patients, 21 (6.1%) presented ASS, 53 (15.40%) died in the acute phase, and 13 (4.46%) died during the first year. The degree of reperfusion (p 0.029), advanced age (p 0.035), and haemorrhagic transformation (p 0.038) increased the risk of suffering ASS, with degree of reperfusion being an independent factor, OR 2.02 (1.21-4.64). The incidence of PSE was 4.12% in the first year, 3.72% in the second, and 1.61% in the fifth. The accumulated incidence at 5 years was 8.93%. Related risk factor for suffering PSE was ASS (p < 0.001), yielding an OR value of 2.00 (1.28-3.145). CONCLUSIONS: Thrombectomy doesn´t increase the risk of ASS. A higher percentage of reperfusion, advanced age, and haemorrhagic transformation are associated with an increased risk of ASS. ASS is a risk factor for suffering PSE. In terms of mortality, having suffered ASS and/or PSE does not increase acute or long-term mortality.

Comparison of effectiveness and discontinuation of interferon-free therapy for hepatitis C in prison inmates and noninmates.

Chronic hepatitis C treatment with direct acting antiviral (DAA) therapy during incarceration is an attractive option, due to its short duration and to the possibility of directly observed treatment or supervision. The aim of this study is to compare the effectiveness and rates of discontinuation of DAA treatment in prisoners and nonprisoners. We studied all patients treated in the 10 prisons of Catalonia and at 3 public hospitals in the Barcelona area between 1 January 2015 and 30 April 2016. We analysed sustained viral response (SVR) and rates of discontinuation through intention-to-treat and modified-intention-to-treat analyses, the latter excluding discontinuations due to release from prison. One hundred and eighty-eight inmates and 862 noninmates were included. Prisoners were significantly younger than nonprisoners, with higher proportions of men, drug users, HIV infection, genotypes 1a and 3 and more treatment with psychiatric drugs. Overall, 98.4% of patients completed treatment. The discontinuation rate was low, but higher in inmates (3.7% vs 1.2% noninmates; P = .003) and in community patients >65 years old (2.8% vs 1.2% in under 65 seconds; P = .008). Among the inmates, 7 (42.8%) discontinuations were due to release. SVR was 93.1% in inmates vs 96.5% in noninmates (P = .08) by intention-to-treat and 95.1% vs 96.5% (P = .37) by modified intention-to-treat. Virologic failure rates were similar (3.8% vs 3% in noninmates; P = .60). SVR, virologic failure and discontinuation rates were similar in inmates and noninmates. Currently, prisons are considered a priority for the implementation of DAA. Improved coordination between penitentiary and community health systems would help to ensure therapeutic continuity in released prisoners.

Quantifying multiple sclerosis pathology in post mortem spinal cord using MRI.

Multiple sclerosis (MS) is a common inflammatory, demyelinating and degenerative disease of the central nervous system. The majority of people with MS present with symptoms due to spinal cord damage, and in more advanced MS a clinical syndrome resembling that of progressive myelopathy is not uncommon. Significant efforts have been undertaken to predict MS-related disability based on short-term observations, for example, the spinal cord cross-sectional area measured using MRI. The histo-pathological correlates of spinal cord MRI changes in MS are incompletely understood, however a surge of interest in tissue microstructure has recently led to new approaches to improve the precision with which MRI indices relate to underlying tissue features, such as myelin content, neurite density and orientation, among others. Quantitative MRI techniques including T1 and T2, magnetisation transfer (MT) and a number of diffusion-derived indices have all been successfully applied to post mortem MS spinal cord. Combining advanced quantification of histological features with quantitative - particularly diffusion-based - MRI techniques provide a new platform for high-quality MR/pathology data generation. To more accurately quantify grey matter pathology in the MS spinal cord, a key driver of physical disability in advanced MS, remains an important challenge of microstructural imaging.

Posttreatment Infarct Volumes when Compared with 24-Hour and 90-Day Clinical Outcomes: Insights from the REVASCAT Randomized Controlled Trial.

BACKGROUND AND PURPOSE: Endovascular therapy has become the standard of care for patients with disabling anterior circulation ischemic stroke due to proximal intracranial thrombi. Our aim was to determine whether the beneficial effect of endovascular treatment on functional outcome could be explained by a reduction in posttreatment infarct volume in the Endovascular Revascularization With Solitaire Device Versus Best Medical Therapy in Anterior Circulation Stroke Within 8 Hours (REVASCAT) trial. MATERIALS AND METHODS: The REVASCAT trial was a multicenter randomized open-label trial with blinded outcome evaluation. Among 206 enrolled subjects (endovascular treatment, n = 103; control, n = 103), posttreatment infarct volume was measured in 204 subjects. Posttreatment infarct volumes were compared with treatment assignment and recanalization status. Appropriate statistical models were used to assess the relationship among baseline clinical and imaging variables, posttreatment infarct volume, the 24-hour NIHSS score, and functional status with the 90-day modified Rankin Scale score. RESULTS: The median posttreatment infarct volume in all subjects was 23.7 mL (interquartile range = 68.9 mL) and 16.3 mL (interquartile range = 50.2 mL) in the endovascular treatment arm and 38.6 mL (interquartile range = 74.9 mL) in the control arm (P = .02 for endovascular treatment versus control subjects). Baseline NIHSS (P < .01), site of occlusion (P < .03), baseline NCCT ASPECTS (P < .01), and recanalization status (P = .02) were independently associated with posttreatment infarct volume. Baseline NIHSS (P < .01), time from symptom onset to randomization (P = .02), treatment type (P = .04), and recanalization status (P < .01) were independently associated with the 24-hour NIHSS scores. The 24-hour NIHSS score strongly mediated the relationship between treatment type and 90-day mRS (P < .01 for indirect effect when adjusted for age), while posttreatment infarct volume did not (P = .26). CONCLUSIONS: Endovascular treatment saves brain and improves 90-day clinical outcomes primarily through a beneficial effect on the 24-hour stroke severity.

FLAIR* to visualize veins in white matter lesions: A new tool for the diagnosis of multiple sclerosis?

OBJECTIVE: To explore the potential of a post-processing technique combining FLAIR and T2* (FLAIR*) to distinguish between lesions caused by multiple sclerosis (MS) from cerebral small vessel disease (SVD) in a clinical setting. METHODS: FLAIR and T2* head datasets acquired at 3T of 25 people with relapsing MS (pwRMS) and ten with pwSVD were used. After post-processing, FLAIR* maps were used to determine the proportion of white matter lesions (WML) showing the 'vein in lesion' sign (VIL), a characteristic histopathological feature of MS plaques. Sensitivity and specificity of MS diagnosis were examined on the basis of >45% VIL+ and >60% VIL+ WML, and compared with current dissemination in space (DIS) MRI criteria. RESULTS: All pwRMS had >45% VIL+ WML (range 58-100%) whilst in pwSVD the proportion of VIL+ WML was significantly lower (0-64%; mean 32±20%). Sensitivity based on >45% VIL+ was 100% and specificity 80% whilst with >60% VIL+ as the criterion, sensitivity was 96% and specificity 90%. DIS criteria had 96% sensitivity and 40% specificity. CONCLUSION: FLAIR* enables VIL+ WML detection in a clinical setting, facilitating differentiation of MS from SVD based on brain MRI. KEY POINTS: • FLAIR* in a clinical setting allows visualization of veins in white matter lesions. • Significant proportions of MS lesions demonstrate a vein in lesion on MRI. • Microangiopathic lesions demonstrate a lower proportion of intralesional veins than MS lesions. • Intralesional vein-based criteria may complement current MRI criteria for MS diagnosis.

Safety and efficacy of thrombectomy in acute ischaemic stroke (REVASCAT): 1-year follow-up of a randomised open-label trial.

BACKGROUND: The REVASCAT trial and other studies have shown that the neurovascular thrombectomy improves outcomes at 90 days post stroke. However, whether the observed benefit is sustained in the long term remains unknown. We report the results of the prespecified 12-month analysis of the REVASCAT trial. METHODS: Patients with acute ischaemic stroke who could be treated within 8 h of symptom onset were randomly assigned to medical therapy (including intravenous alteplase when eligible) and neurovascular thrombectomy with Solitaire FR or medical therapy alone. The main secondary outcome measure at 1 year follow-up was disability, measured using the modified Rankin Scale (mRS), ranging from 0 (no symptoms) to 6 (death) with categories 5 (severe disability) and 6 (death) collapsed into one category (severe disability or death), analysed as the distribution of the mRS. Additional prespecified secondary outcome measures included health-related quality of life measured with the EuroQol five dimensions questionnaire (EQ-5D) utility index (ranging from -0·3 to 1, higher values indicate better quality of life), the rate of functional independence (mRS 0-2), and cognitive function measured with the Trail Making Test (reported elsewhere). Treatment allocation was open label but endpoints at 12 months were assessed by masked investigators. The trial was registered at ClinicalTrials.gov, number NCT01692379. FINDINGS: From Nov 24, 2012, to Dec 12, 2014, 206 patients were randomly assigned to medical therapy plus endovascular treatment (n=103) or medical treatment alone (n=103), at four centres in Catalonia, Spain. At 12 months post randomisation, based on 205 of 206 outcomes available at 12 months, thrombectomy reduced disability over the range of the mRS (common adjusted odds ratio [aOR] 1·80, 95% CI 1·09-2·99), and improved functional independence (mRS=0-2; 45 [44%] of 103 patients vs 31 [30%] of 103 patients; aOR 1·86, 95% CI 1·01-3·44). Health-related quality of life was superior in the thrombectomy group (mean EQ-5D utility index score, 0·46 [SD 0·38] in the thrombectomy group vs 0·33 [0·33] in the control group, difference 0·12 [95% CI 0·03-0·22]; p=0·01). 1-year mortality was 23% (24 of 103 patients) in the thrombectomy group versus 24% (25 of 103 patients) in the control group. INTERPRETATION: At 12 months follow-up, neurovascular thrombectomy reduced post-stroke disability and improved health-related quality of life, indicating sustained benefit. These findings have important clinical and public health implications for evaluating the cost-effectiveness of the intervention in the long term. FUNDING: Fundació Ictus Malaltia Vascular through an unrestricted grant from Medtronic.

Monitoring MDMA metabolites in urban wastewater as novel biomarkers of consumption.

Consumption of 3,4-methylendioxymethamphetamine (MDMA) has been always estimated by measuring the parent substance through chemical analysis of wastewater. However, this may result in an overestimation of the use if the substance is directly disposed in sinks or toilets. Using specific urinary metabolites may overcome this limitation. This study investigated for the first time the suitability of a panel of MDMA metabolites as biomarkers of consumption, considering the specific criteria recently proposed, i.e. being detectable and stable in wastewater, being excreted in a known percentage in urine, and having human excretion as the sole source. A new analytical method was developed and validated for the extraction and analysis of MDMA and three of its main metabolites in wastewater. 24-h composite raw wastewater samples from three European cities were analysed and MDMA use was back-calculated. Results from single MDMA loads, 4-hydroxy-3-methoxymethamphetamine (HMMA) loads and from the sum of MDMA, HMMA and 4-hydroxy-3-methoxyamphetamine (HMA) loads were in line with the well-known recreational use of this drug: consumption was higher during the weekend in all cities. HMMA and HMA turned out to be suitable biomarkers of consumption; however, concentrations measured in wastewater did not resemble the expected pharmacokinetic profiles, quite likely due to the very limited information available on excretion profiles. Different options were tested to back-calculate MDMA use, including the sum of MDMA and its metabolites, to balance the biases associated with each single substance. Nevertheless, additional pharmacokinetic studies are urgently needed in order to get more accurate excretion rates and, therefore, improve the estimates of MDMA use.

Mitochondrial fusion/fission dynamics in neurodegeneration and neuronal plasticity.

Mitochondria are dynamic organelles that continually move, fuse and divide. The dynamic balance of fusion and fission of mitochondria determines their morphology and allows their immediate adaptation to energetic needs, keeps mitochondria in good health by restoring or removing damaged organelles or precipitates cells in apoptosis in cases of severe defects. Mitochondrial fusion and fission are essential in mammals and their disturbances are associated with several diseases. However, while mitochondrial fusion/fission dynamics, and the proteins that control these processes, are ubiquitous, associated diseases are primarily neurological disorders. Accordingly, inactivation of the main actors of mitochondrial fusion/fission dynamics is associated with defects in neuronal development, plasticity and functioning, both ex vivo and in vivo. Here, we present the central actors of mitochondrial fusion and fission and review the role of mitochondrial dynamics in neuronal physiology and pathophysiology. Particular emphasis is placed on the three main actors of these processes i.e. DRP1,MFN1-2, and OPA1 as well as on GDAP1, a protein of the mitochondrial outer membrane preferentially expressed in neurons. This article is part of a Special Issue entitled: Mitochondria & Brain.

Curative drug treatment of trypanosomosis leads to the restoration of B-cell lymphopoiesis and splenic B-cell compartments.

African trypanosomosis is a parasitic disease affecting both humans (sleeping sickness) and animals (nagana). In murine trypanosomosis, the B-cell compartment is rapidly destroyed after infection. In addition, B-cell lymphopoiesis in the bone marrow is abrogated, B-cell subsets in the spleen are irreversibly depleted, and B-cell memory is destroyed. Here, we investigated the effect of cure of infection on the B-cell compartment. Suramin and diminazene aceturate were used in this study as these drugs exhibit different modes of uptake and different mechanisms of trypanocidal action. Curative drug treatment of trypanosomosis infection led to the re-initiation of B-cell lymphopoiesis in the bone marrow, and to the repopulation of splenic B-cell subsets, independent of the drug used. Neither of these drugs by itself induced measurable effects on B-cell lymphopoiesis in the bone marrow or B-cell homoeostasis in the spleen in healthy, naïve animals.

Intermittent hypoxia is an independent marker of poorer glycaemic control in patients with uncontrolled type 2 diabetes.

AIM: This study investigated the association between intermittent hypoxia and glycaemic control in patients with uncontrolled type 2 diabetes (T2D) not treated for sleep apnoea. METHODS: This was a single-centre cross-sectional study of stable patients with T2D and HbA1c ≥7% (53 mmol/mol). Patients underwent overnight pulse oximetry and, if intermittent hypoxia-defined by a 4% oxyhaemoglobin desaturation index ≥15-was observed, respiratory polygraphy was performed. All participants completed the Pittsburgh Sleep Questionnaire and Hospital Anxiety and Depression Scale. The association between intermittent hypoxia and poorer glycaemic control (defined by an HbA1c level above the median of 8.5%) was estimated by multivariate logistic regression analysis. RESULTS: Out of 145 patients studied, 54 (37.2%) had intermittent hypoxia (with sleep apnoea confirmed in 53). Patients with intermittent hypoxia had 0.7% (7.7 mmol/mol) higher median HbA1c levels than patients without intermittent hypoxia (P=0.001). Intermittent hypoxia was associated with poorer glycaemic control after adjusting for obesity, age at onset and duration of diabetes, insulin requirement, sleep quality and depressive mood (OR: 2.31, 95% CI: 1.06-5.04, model adjusted for body mass index; OR: 2.46, 95% CI: 1.13-5.34, model adjusted for waist-to-height ratio). CONCLUSION: Intermittent hypoxia, a consequence of sleep apnoea, is frequent and has a strong independent association with poorer glycaemic control in patients with uncontrolled T2D.

Endovascular treatment for M2 occlusions in the era of stentrievers: a descriptive multicenter experience.

BACKGROUND: Patients with M2 middle cerebral artery (MCA) occlusions are not always considered for endovascular treatment. OBJECTIVE: To study outcomes in patients with M2 occlusion treated with endovascular procedures in the era of stentrievers. METHODS: We studied patients prospectively included in the SONIIA registry (years 2011-2012)-a mandatory, externally audited registry that monitors the quality of reperfusion therapies in Catalonia in routine practice. Good recanalization was defined as postprocedure Thrombolysis in Cerebral Infarction (TICI) score 2b-3; dramatic recovery as drop in National Institutes of Health Stroke Scale (NIHSS) score >10 points or NIHSS score <2 at 24-36 h; and good outcome as modified Rankin score (mRS) 0-2 at 3months. A 24 h CT scan determined symptomatic intracranial hemorrhage (SICH) and infarct volume. RESULTS: Of 571 patients who received endovascular treatment, 65 (11.4%) presented an M2 occlusion on initial angiogram, preprocedure NIHSS 16 (IQR 6). Mean time from symptom onset to groin puncture was 289 ± 195 min. According to interventionalist preferences 86.2% (n=56) were treated with stentrievers (n=7 in combination with intra-arterial tissue plasminogen activator (tPA), 4.6% (n=3) received intra-arterial tPA only, and 9.2% (n=6) diagnostic angiography only. Good recanalization (78.5%) was associated with dramatic improvement (48% vs 14.8%; p=0.02), smaller infarct volumes (8 vs 82 cc; p=0.01) and better outcome (mRS 0-2: 66.3% vs 30%; p=0.03). SICH (9%) was not associated with treatment modality or device used. After adjusting for age and preprocedure NIHSS, good recanalization emerged as an independent predictor of dramatic improvement (OR=5.9 (95% CI 1.2 to 29.2), p=0.03). Independent predictors of good outcome at 3 months were age ( OR=1.067 (95% CI 1.005 to 1132), p=0.03) and baseline NIHSS ( OR=1.162 (95% CI 1.041 to 1.297), p<0.01). CONCLUSIONS: Endovascular treatment of M2 MCA occlusion with stentrievers seems safe. Induced recanalization may double the chances of achieving a favorable outcome, especially for patients with moderate or severe deficit.

Use of an internal reference in semi-quantitative dynamic contrast-enhanced MRI (DCE MRI) of indeterminate adnexal masses.

OBJECTIVE: Semi-quantitative dynamic contrast-enhanced MRI (DCE MRI) has proven useful in discriminating benign from borderline/malignant adnexal lesions. Our aim was to assess if the use of a lesion-to-internal-reference ratio improved the performance in characterizing adnexal masses and which internal reference was suitable. METHODS: Semi-quantitative DCE MRI images of 71 indeterminate adnexal lesions were retrospectively reviewed. A region of interest was manually drawn onto the enhancing solid component, psoas muscle and normal outer myometrium. The DCE parameters were evaluated, and the lesion-to-internal-reference ratios were calculated. RESULTS: When the wash in rate of the lesion was higher than that of the myometrium, 97% specificity and 12% sensitivity for borderline/malignancy was reached. When the maximum relative enhancement and maximum absolute enhancement (SImax) of the lesion was less than those of the psoas, 100% specificity for benignity was achieved. The highest area under the curve (AUC) (0.807) was achieved using a SImax lesion-myometrium ratio. A slightly lower AUC (0.799) was achieved using a SImax lesion-psoas ratio, but the psoas muscle was more frequently measurable in the same slice as the lesion ROI. Although the AUC was higher, when using ratios instead of individual DCE values, this was not significantly different. CONCLUSION: DCE MRI has added diagnostic value in the assessment of adnexal lesions, and the use of internal references enables high specificity for malignancy and benignity. Lesion-internal-reference ratios have no added diagnostic value over DCE values alone. ADVANCES IN KNOWLEDGE: Both psoas muscle and myometrium are suitable internal references in the DCE assessment of adnexal lesions enabling high specificity for malignancy and benignity.

Inducción del temblor mandibular por lesión electrolítica del estriado ventrolateral y por el tratamiento subcrónico con haloperidol en rata macho: un contraste electromiográfico / Induction of mandibular tremor using electrolytic lesion of the ventrolateral striatum or using subchronic haloperidol therapy in male rats: An electromyographic comparison

Introducción: El temblor mandibular (TM) en la rata es inducido farmacológicamente por la manipulación dopaminérgica estriatal y por lesión del estriado ventrolateral (EVL). Este temblor tiene características neuroquímicas, anatómicas y electromiográficas similares al temblor que presentan los pacientes con parkinsonismo. Pero se desconocen las características electromiográficas de los temblores generados por la lesión electrolítica del EVL. Método: En ese estudio, se describió electromiográficamente el temblor mandibular generado por la lesión electrolítica bilateral del EVL y se comparó con el inducido por el tratamiento subcrónico (i.p.) con haloperidol, neuroléptico de selectividad alta como antagonista dopaminérgico del receptor D2. A ratas con lesión en la región ventrolateral del estriado, con un tratamiento subcrónico de haloperidol, y a un grupo control que solo recibió el vehículo, se les registró la actividad electromiografía del músculo temporal en condiciones basales y durante los TM. Resultados: La distribución de frecuencias del TM entre los grupos varió, puesto que las ratas con la lesión en el EVL mostraron TM de mayor amplitud y frecuencia EMG que las ratas tratadas con el haloperidol. La amplitud en condiciones basales difirió en los distintos grupos de ratas. Conclusiones: Se concluye que los TM asociados a la lesión electrolítica del EVL son de mayor amplitud y frecuencia que los generados por haloperidol, esto puede estar relacionado con el tipo de afectación estriatal

Introduction: Tremulous jaw movement (TJMs) in rats can be induced pharmacologically by striatal dopaminergic manipulation or electrolytic lesion of ventrolateral striatum (VLS). This tremor has neurochemical, anatomical and electromyographic (EMG) characteristics similar to those of tremor in Parkinson patients. However, the EMG characteristics of tremors generated by electrolytic lesion to the VLS have not yet been studied. Method: This study used electromyography to describe tremulous jaw movement generated by bilateral electrolytic lesion in the VLS and compare it to tremors induced using subchronic IP treatment with haloperidol, a dopaminergic D2 receptor antagonist. The experimental groups contained rats with a lesion in the ventrolateral striatum and rats on subchronic haloperidol treatment; the control group received only the vehicle. The EMG signal from the temporal muscle was recorded at baseline and during TJMs in all groups. Results: TMJ frequencies were heterogeneous among the groups. Rats with VLS lesion showed higher amplitude and frequency values than the haloperidol-treated rats. Amplitudes at baseline also differed among the groups. Conclusions: We conclude that TMJs associated with electrolytic lesion to the VLS show a higher frequency and amplitude than tremors induced by haloperidol. This may be related to the way striatum neurons are affected

Brain activation by an olfactory stimulus paired with juvenile play in female rats.

We have previously shown that reward experienced during social play at juvenile age can be paired with artificial odors, and later in adulthood facilitate olfactory conditioned partner preferences (PP) in female rats. Herein, we examined the expression of FOS immunoreactivity (FOS-IR) following exposure to the odor paired with juvenile play (CS+). Starting at day P31 females received daily 30-min periods of social play with lemon-scented (paired group) or unscented females (unpaired group). At day P42, they were tested for play-PP with two juvenile males, one bearing the CS+ (lemon) and one bearing a novel odor (almond). Females were ovariectomized, hormone-primed and at day P55 tested for sexual-PP between two adult stud males scented with lemon or almond. In both tests, females from the paired group displayed conditioned PP (play or sexual) toward males bearing the CS+. In the present experiments females were exposed at day P59 to the CS+ during 60 min and their brains processed for FOS-IR. One group of female rats (Play+Sex) underwent play-PP and sexual-PP, whereas a second group of females (Play-only) underwent exclusively play-PP but not sexual-PP. Results showed that in the Play-only experiment exposure to the CS+ induced more FOS-IR in the medial prefrontal cortex, orbitofrontal cortex, dorsal striatum, and ventral tegmental area as compared to females from the unpaired group. In the Play+Sex experiment, more FOS-IR was observed in the piriform cortex, dorsal striatum, lateral septum, nucleus accumbens shell, bed nucleus of the stria terminalis and medial amygdala as compared to females from the unpaired group. Taken together, these results indicate mesocorticolimbic brain areas direct the expectation and/or choice of conditioned partners in female rats. In addition, transferring the meaning of play to sex preference requires different brain areas.

Beyond the basal ganglia: cFOS expression in the cerebellum in response to acute and chronic dopaminergic alterations.

The suggestion of an anatomical and functional relationship between the basal ganglia and cerebellum is recent. Traditionally, these structures were considered as neuronal circuits working separately to organize and control goal-directed movements and cognitive functions. However, several studies in rodents and primates have described an anatomical interaction between cortico-basal and cortico-cerebellar networks. Most importantly, functional changes have been observed in one of these circuits when altering the other one. In this context, we aimed to accomplish an extensive description of cerebellar activation patterns using cFOS expression (cFOS-IR) after acute and chronic manipulation of dopaminergic activity. In the acute study, substantia nigra pars compacta (SNc) activity was stimulated or suppressed by intra cerebral administration of picrotoxin or lidocaine, respectively. In addition, we analyzed cerebellar activity after the induction of a parkinsonism model, the tremulous jaw movements. In this model, tremulous jaw movements were induced in male rats by IP chronic administration of the dopamine antagonist haloperidol (1.5mg/kg). Acute stimulation of SNc by picrotoxin increased cFOS-IR in the vermis and cerebellar hemispheres. However, lidocaine did not produce an effect. After 14days of haloperidol treatment, the vermis and cerebellar hemispheres showed an opposite regulation of cFOS expression. Chronic dopaminergic antagonism lessened cFOS expression in the vermis but up-regulated such expression in the cerebellar hemisphere. Overall, the present data indicate a very close functional relationship between the basal ganglia and the cerebellum and they may allow a better understanding of disorders in which there are dopamine alterations.

Trevo versus solitaire a head-to-head comparison between two heavy weights of clot retrieval.

BACKGROUND AND PURPOSE: Recent reports have indicated that mechanical thrombectomy may have potential to treat acute ischemic stroke. However, few comparative studies of neurothrombectomy devices are reported. This study aims to compare the safety and effectiveness of two retrievable stent systems in acute ischemic stroke patients. METHODS: A prospective study comparing the clinical, radiological, and functional outcome of 33 patients with an angiographically verified occlusion of the anterior cerebral circulation. Patients were treated either with Trevo Retriever(TM) or Solitaire Stent(TM) according to the neurointerventionalist preference. Successful recanalization was defined as TICI grade 2a to 3. Good outcome was defined as a modified Rankin Scale score ≤ 2 at 3 months. RESULTS: Revascularization was achieved in 10 patients (77%) in the Trevo group and in 12 (60%) of the Solitaire group (P = .456). Rate of symptomatic ICH was 0% for Trevo versus 15% for Solitaire (P = .261). Four patients (30%) died during the 3-month follow-up period in the Trevo versus 5 patients (25%) in the solitaire group (P = 1.000). Rate of good outcome was 38% and 40% for Trevo and Solitaire respectively (P = .435). CONCLUSIONS: Our study showed no significant differences between both stentrievers. Moderately high recanalization rates are possible with both, however larger series may depict safety-related variations.