Thrombin-receptor antagonist vorapaxar in acute coronary syndromes

Background: Vorapaxar is a new oral protease-activatedreceptor 1 (PAR-1) antagonist that inhibits thrombin-induced platelet activation. Methods: In this multinational, double-blind, randomized trial, we compared vorapaxar with placebo in 12,944 patients who had acute coronary syndromes without ST-segment elevation. The primary end point was a composite of death from cardiovascular causes, myocardial infarction, stroke, recurrent ischemia with rehospitalization, or urgent coronary revascularization. RESULTS: Follow-up in the trial was terminated early after a safety review. After a median follow-up of 502 days (interquartile range, 349 to 667), the primary end point occurred in 1031 of 6473 patients receiving vorapaxar versus 1102 of 6471 patients receiving placebo (KaplanMeier 2-year rate, 18.5% vs. 19.9%; hazard ratio, 0.92; 95% confidence interval [CI], 0.85 to 1.01; P = 0.07). A composite of death from cardiovascular causes, myocardial infarction, or stroke occurred in 822 patients in the vorapaxar group versus 910 in the placebo group (14.7% and 16.4%, respectively; hazard ratio, 0.89; 95% CI, 0.81 to 0.98; P = 0.02). Rates of moderate and severe bleeding were 7.2% in the vorapaxar group and 5.2% in the placebo group (hazard ratio, 1.35; 95% CI, 1.16 to 1.58; P<0.001). Intracranial hemorrhage rates were 1.1% and 0.2%, respectively (hazard ratio, 3.39; 95% CI, 1.78 to 6.45; P<0.001). Rates of nonhemorrhagic adverse events were similar in the two groups. Conclusions: In patients with acute coronary syndromes, the addition of vorapaxar to standard therapy did not significantly reduce the primary composite end point but significantly increased the risk of major bleeding, including intracranial hemorrhage. (Funded by Merck; TRACER ClinicalTrials.gov number, NCT00527943.)

Sensorimotor Plasticity after Music-Supported Therapy in Chronic Stroke Patients Revealed by Transcranial Magnetic Stimulation

BACKGROUND: Several recently developed therapies targeting motor disabilities in stroke sufferers have shown to be more effective than standard neurorehabilitation approaches. In this context, several basic studies demonstrated that music training produces rapid neuroplastic changes in motor-related brain areas. Music-supported therapy has been recently developed as a new motor rehabilitation intervention. METHODS AND RESULTS: In order to explore the plasticity effects of music-supported therapy, this therapeutic intervention was applied to twenty chronic stroke patients. Before and after the music-supported therapy, transcranial magnetic stimulation was applied for the assessment of excitability changes in the motor cortex and a 3D movement analyzer was used for the assessment of motor performance parameters such as velocity, acceleration and smoothness in a set of diadochokinetic movement tasks. Our results suggest that the music-supported therapy produces changes in cortical plasticity leading the improvement of the subjects' motor performance. CONCLUSION: Our findings represent the first evidence of the neurophysiological changes induced by this therapy in chronic stroke patients, and their link with the amelioration of motor performance. Further studies are needed to confirm our observations.

The effect of pesticides and alien invesive species on soil biota and litter decomposition rates in a Mediterrean-climate ecosystem of Western Australia

Ecosystems are complex systems and changing one of their components can alter their whole functioning. Decomposition and biodiversity are two factors that play a role in this stability, and it is vital to study how these two factors are interrelated and how other factors, whether of human origin or not, can affect them. This study has tested different hypotheses regarding the effects of pesticides and invasive species on the biodiversity of the soil fauna and litter decomposition rate. Decomposition was measured using the litterbags technique. Our results indicate that pesticides had a negative effect on decomposition whereas invasive species increased decomposition rate. At the same time, the diversity of the soil biota was unaffected by either factor. These results allow us to better understand the response of important ecosystem functions to human‐induced alterations, in order to mitigate harmful effects or restore them wherever necessary.

BadiRate: Estimating Family Turnover Rates by Likelihood-Based Methods

Motivation: The comparative analysis of gene gain and loss rates is critical for understanding the role of natural selection and adaptation in shaping gene family sizes. Studying complete genome data from closely related species allows accurate estimation of gene family turnover rates. Current methods and software tools, however, are not well designed for dealing with certain kinds of functional elements, such as microRNAs or transcription factor binding sites. Results: Here, we describe BadiRate, a new software tool to estimate family turnover rates, as well as the number of elements in internal phylogenetic nodes, by likelihood-based methods and parsimony. It implements two stochastic population models, which provide the appropriate statistical framework for testing hypothesis, such as lineage-specific gene family expansions or contractions. We have assessed the accuracy of BadiRate by computer simulations, and have also illustrated its functionality by analyzing a representative empirical dataset.

BadiRate: estimating family turnover rates by likelihood-based methods

Motivation: The comparative analysis of gene gain and loss rates is critical for understanding the role of natural selection and adaptation in shaping gene family sizes. Studying complete genome data from closely related species allows accurate estimation of gene family turnover rates. Current methods and software tools, however, are not well designed for dealing with certain kinds of functional elements, such as microRNAs or transcription factor binding sites. Results: Here, we describe BadiRate, a new software tool to estimate family turnover rates, as well as the number of elements in internal phylogenetic nodes, by likelihood-based methods and parsimony. It implements two stochastic population models, which provide the appropriate statistical framework for testing hypothesis, such as lineage-specific gene family expansions or contractions. We have assessed the accuracy of BadiRate by computer simulations, and have also illustrated its functionality by analyzing a representative empirical dataset.

Sensorimotor Plasticity after Music-Supported Therapy in Chronic Stroke Patients Revealed by Transcranial Magnetic Stimulation

BACKGROUND: Several recently developed therapies targeting motor disabilities in stroke sufferers have shown to be more effective than standard neurorehabilitation approaches. In this context, several basic studies demonstrated that music training produces rapid neuroplastic changes in motor-related brain areas. Music-supported therapy has been recently developed as a new motor rehabilitation intervention. METHODS AND RESULTS: In order to explore the plasticity effects of music-supported therapy, this therapeutic intervention was applied to twenty chronic stroke patients. Before and after the music-supported therapy, transcranial magnetic stimulation was applied for the assessment of excitability changes in the motor cortex and a 3D movement analyzer was used for the assessment of motor performance parameters such as velocity, acceleration and smoothness in a set of diadochokinetic movement tasks. Our results suggest that the music-supported therapy produces changes in cortical plasticity leading the improvement of the subjects' motor performance. CONCLUSION: Our findings represent the first evidence of the neurophysiological changes induced by this therapy in chronic stroke patients, and their link with the amelioration of motor performance. Further studies are needed to confirm our observations.

Prognostic value of cortically induced motor evoked activity by TMS in chronic stroke: caveats from a very revealing single clinical case

Background: We report the case of a chronic stroke patient (62 months after injury) showing total absence of motor activity evoked by transcranial magnetic stimulation (TMS) of spared regions of the left motor cortex, but near-to-complete recovery of motor abilities in the affected hand. Case presentation: Multimodal investigations included detailed TMS based motor mapping, motor evoked potentials (MEP), and Cortical Silent period (CSP) as well as functional magnetic resonance imaging (fMRI) of motor activity, MRI based lesion analysis and Diffusion Tensor Imaging (DTI) Tractography of corticospinal tract (CST). Anatomical analysis revealed a left hemisphere subinsular lesion interrupting the descending left CST at the level of the internal capsule. The absence of MEPs after intense TMS pulses to the ipsilesional M1, and the reversible suppression of ongoing electromyographic (EMG) activity (indexed by CSP) demonstrate a weak modulation of subcortical systems by the ipsilesional left frontal cortex, but an inability to induce efficient descending volleys from those cortical locations to right hand and forearm muscles. Functional MRI recordings under grasping and finger tapping patterns involving the affected hand showed slight signs of subcortical recruitment, as compared to the unaffected hand and hemisphere, as well as the expected cortical activations. Conclusions: The potential sources of motor voluntary activity for the affected hand in absence of MEPs are discussed. We conclude that multimodal analysis may contribute to a more accurate prognosis of stroke patients.

Plasticity in the sensorimotor cortex induced by Music-supported therapy in stroke patients: a TMS study.

Playing a musical instrument demands the engagement of different neural systems. Recent studies about the musician"s brain and musical training highlight that this activity requires the close interaction between motor and somatosensory systems. Moreover, neuroplastic changes have been reported in motor-related areas after short and long-term musical training. Because of its capacity to promote neuroplastic changes, music has been used in the context of stroke neurorehabilitation. The majority of patients suffering from a stroke have motor impairments, preventing them to live independently. Thus, there is an increasing demand for effective restorative interventions for neurological deficits. Music-supported Therapy (MST) has been recently developed to restore motor deficits. We report data of a selected sample of stroke patients who have been enrolled in a MST program (1 month intense music learning). Prior to and after the therapy, patients were evaluated with different behavioral motor tests. Transcranial Magnetic Stimulation (TMS) was applied to evaluate changes in the sensorimotor representations underlying the motor gains observed. Several parameters of excitability of the motor cortex were assessed as well as the cortical somatotopic representation of a muscle in the affected hand. Our results revealed that participants obtained significant motor improvements in the paretic hand and those changes were accompanied by changes in the excitability of the motor cortex. Thus, MST leads to neuroplastic changes in the motor cortex of stroke patients which may explain its efficacy.

Plasticity in the sensorimotor cortex induced by Music-supported therapy in stroke patients: a TMS study.

Playing a musical instrument demands the engagement of different neural systems. Recent studies about the musician"s brain and musical training highlight that this activity requires the close interaction between motor and somatosensory systems. Moreover, neuroplastic changes have been reported in motor-related areas after short and long-term musical training. Because of its capacity to promote neuroplastic changes, music has been used in the context of stroke neurorehabilitation. The majority of patients suffering from a stroke have motor impairments, preventing them to live independently. Thus, there is an increasing demand for effective restorative interventions for neurological deficits. Music-supported Therapy (MST) has been recently developed to restore motor deficits. We report data of a selected sample of stroke patients who have been enrolled in a MST program (1 month intense music learning). Prior to and after the therapy, patients were evaluated with different behavioral motor tests. Transcranial Magnetic Stimulation (TMS) was applied to evaluate changes in the sensorimotor representations underlying the motor gains observed. Several parameters of excitability of the motor cortex were assessed as well as the cortical somatotopic representation of a muscle in the affected hand. Our results revealed that participants obtained significant motor improvements in the paretic hand and those changes were accompanied by changes in the excitability of the motor cortex. Thus, MST leads to neuroplastic changes in the motor cortex of stroke patients which may explain its efficacy.

Plasticity in the sensorimotor cortex induced by Music-supported therapy in stroke patients: a TMS study.

Playing a musical instrument demands the engagement of different neural systems. Recent studies about the musician"s brain and musical training highlight that this activity requires the close interaction between motor and somatosensory systems. Moreover, neuroplastic changes have been reported in motor-related areas after short and long-term musical training. Because of its capacity to promote neuroplastic changes, music has been used in the context of stroke neurorehabilitation. The majority of patients suffering from a stroke have motor impairments, preventing them to live independently. Thus, there is an increasing demand for effective restorative interventions for neurological deficits. Music-supported Therapy (MST) has been recently developed to restore motor deficits. We report data of a selected sample of stroke patients who have been enrolled in a MST program (1 month intense music learning). Prior to and after the therapy, patients were evaluated with different behavioral motor tests. Transcranial Magnetic Stimulation (TMS) was applied to evaluate changes in the sensorimotor representations underlying the motor gains observed. Several parameters of excitability of the motor cortex were assessed as well as the cortical somatotopic representation of a muscle in the affected hand. Our results revealed that participants obtained significant motor improvements in the paretic hand and those changes were accompanied by changes in the excitability of the motor cortex. Thus, MST leads to neuroplastic changes in the motor cortex of stroke patients which may explain its efficacy.

Orthopantomography contribution to prevent isquemic stroke

Objectives: The ortopantomography (OPG) can be a valuable way for an early detection of calcified atheroma plaques, thus contributing for a preliminary stroke risk evaluation. The study looks for the existence of calcified atheroma plates through the use of OPG, comparing the results with the stenosis percentage found through eco-doppler. It has been analyzed the correlation of the number of years as a smoker, arterial hypertension and body mass index, against the risk of having calcified atheroma plaques. Study Design: Observational, transversal and prospective study with 84 patients from the Dental Center of Hospital Particular de Lisboa. First the patients answered to an inquiry and them they were submitted to an OPG and an eco-doppler. Results and Conclusions: It is possible to detect calcified atheroma plaques in the carotid artery through an OPG and patients who have them have got a fifteen fold greater risk of suffering from carotid stenosis. In this study, it has been confirmed the increase in carotid stenosis for long term smokers (OR = 1,033, n=18, 42,9%). The study results show that hypertension patients have a probability 5,426 greater than normal of developing atheroma plaques (with sig=0,049). Amid analyzed patients, the correlation between obesity and the existence of carotid atheroma plaques was significant, although negative (sig=0,047). OPG can help find patients with higher risk of isquemic stroke

Can Orthopantomography be used as a tool for screening of carotid atheromatous pathology and thus be used to help reduce the prevalence of ischemic stroke within the population?

Objective: To assess the possibility of Dentists being able to screen patients with higher risk of vascular diseases. Materials: Kodak 8000C Orthopantomographer, eco-Doppler Logiq-500 General Electric at the Lisbon Hospital Particular. Methods: Assessment of orthopantomographies made to 142 patients aged 50 or more, as well as the existing risk factors. Conduction of carotid eco-Doppler to patients who appear to have calcified plaques of the atheroma. Results: Strong dependence between dichotomised age and having the pathology (p = 0.02).Smokers are twice more likely to present plaques (OR= 2). Being hypertensive increases in about 1.4 the likelihood of having a stroke (OR= 1.4). Of the 27 individuals who presented calcifications in the Orthopantomography, they were all submitted to an eco-Doppler and 21 had the pathology confirmed. 27 individuals, who did not show any plaques in the Orthopantomography, were randomly selected to be the control group. They were submitted to an eco-Doppler. And 23 confirmed the non-existence of plaques. Conclusions: Orthopantomography used for assessing the oral cavity reveals more information which should be the object of the Dentist"s attention

Structural changes induced by daily music listening in the recovering brain after middle cerebral artery stroke: a voxel-based morphometry study

Music is a highly complex and versatile stimulus for the brain that engages many temporal, frontal, parietal, cerebellar, and subcortical areas involved in auditory, cognitive, emotional, and motor processing. Regular musical activities have been shown to effectively enhance the structure and function of many brain areas, making music a potential tool also in neurological rehabilitation. In our previous randomized controlled study, we found that listening to music on a daily basis can improve cognitive recovery and improve mood after an acute middle cerebral artery stroke. Extending this study, a voxel-based morphometry (VBM) analysis utilizing cost function masking was performed on the acute and 6-month post-stroke stage structural magnetic resonance imaging data of the patients (n = 49) who either listened to their favorite music [music group (MG), n = 16] or verbal material [audio book group (ABG), n = 18] or did not receive any listening material [control group (CG), n = 15] during the 6-month recovery period. Although all groups showed significant gray matter volume (GMV) increases from the acute to the 6-month stage, there was a specific network of frontal areas [left and right superior frontal gyrus (SFG), right medial SFG] and limbic areas [left ventral/subgenual anterior cingulate cortex (SACC) and right ventral striatum (VS)] in patients with left hemisphere damage in which the GMV increases were larger in the MG than in the ABG and in the CG. Moreover, the GM reorganization in the frontal areas correlated with enhanced recovery of verbal memory, focused attention, and language skills, whereas the GM reorganization in the SACC correlated with reduced negative mood. This study adds on previous results, showing that music listening after stroke not only enhances behavioral recovery, but also induces fine-grained neuroanatomical changes in the recovering brain.

Sensorimotor Plasticity after Music-Supported Therapy in Chronic Stroke Patients Revealed by Transcranial Magnetic Stimulation

BACKGROUND: Several recently developed therapies targeting motor disabilities in stroke sufferers have shown to be more effective than standard neurorehabilitation approaches. In this context, several basic studies demonstrated that music training produces rapid neuroplastic changes in motor-related brain areas. Music-supported therapy has been recently developed as a new motor rehabilitation intervention. METHODS AND RESULTS: In order to explore the plasticity effects of music-supported therapy, this therapeutic intervention was applied to twenty chronic stroke patients. Before and after the music-supported therapy, transcranial magnetic stimulation was applied for the assessment of excitability changes in the motor cortex and a 3D movement analyzer was used for the assessment of motor performance parameters such as velocity, acceleration and smoothness in a set of diadochokinetic movement tasks. Our results suggest that the music-supported therapy produces changes in cortical plasticity leading the improvement of the subjects' motor performance. CONCLUSION: Our findings represent the first evidence of the neurophysiological changes induced by this therapy in chronic stroke patients, and their link with the amelioration of motor performance. Further studies are needed to confirm our observations.

Heat shock response in yeast involves changes in both transcription rates and mRNA stabilities

We have analyzed the heat stress response in the yeast Saccharomyces cerevisiae by determining mRNA levels and transcription rates for the whole transcriptome after a shift from 25uC to 37uC. Using an established mathematical algorithm, theoretical mRNA decay rates have also been calculated from the experimental data. We have verified the mathematical predictions for selected genes by determining their mRNA decay rates at different times during heat stress response using the regulatable tetO promoter. This study indicates that the yeast response to heat shock is not only due to changes in transcription rates, but also to changes in the mRNA stabilities. mRNA stability is affected in 62% of the yeast genes and it is particularly important in shaping the mRNA profile of the genes belonging to the environmental stress response. In most cases, changes in transcription rates and mRNA stabilities are homodirectional for both parameters, although some interesting cases of antagonist behavior are found. The statistical analysis of gene targets and sequence motifs within the clusters of genes with similar behaviors shows that both transcriptional and post-transcriptional regulons apparently contribute to the general heat stress response by means of transcriptional factors and RNA binding proteins.