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William Shakespeare and others : collaborative plays
The first edition in over 100 years of the fascinatingly varied body of plays that has become known as \"The Shakespeare Apocrypha\". Among the highlights are the whole text of Sir Thomas More, which includes the only scene from any play to survive in Shakespeare's own handwriting; the history play Edward III, including a superb seduction scene by Shakespeare; and the domestic murder tragedy Arden of Faversham, in which Shakespeare's hand has been detected by recent computer-assisted analysis. This is also the first ever Shakespeare edition to include the 1602 edition of Thomas Kyd's pioneering The Spanish Tragedy, with \"additions\" that the latest research attributes to Shakespeare. Included is a comprehensive account of the authorship and attribution of each play.
Book
Long-term Follow-up of In-stent Stenosis After Pipeline Flow Diversion Treatment of Intracranial Aneurysms
Abstract
BACKGROUND:
There is scant information on in-stent stenosis after flow diversion treatment of intracranial aneurysms with the Pipeline Embolization Device (PED).
OBJECTIVE:
To assess the incidence, severity, nature, and clinical consequences of in-stent stenosis on angiographic follow-up after treatment with the PED.
METHODS:
A retrospective study of patients who underwent aneurysm treatment with the PED was conducted. In-stent stenosis was assessed on subsequent follow-up angiography. Intimal hyperplasia was defined as a uniform growth process beyond the limits of the metallic mesh at <25%. In-stent stenosis represented an area of parent vessel narrowing, most often focal, graded as mild (25%-50%), moderate (50%-75%), or severe (>75%).
RESULTS:
Between June 2011 and April 2015, 80 patients were treated with the PED. Angiographic follow-up was available for 51 patients (representing 76% of available or 64% of all patients). Mean follow-up was 12.5 months. In-stent stenosis was detected in 5 patients (9.8%) at a median of 6 months. Stenosis was mild in 4 of 5 (80%) and moderate in 1 of 5 (20%) patients. There were no cases of severe stenosis. No stenosis caused flow limitation, clinical symptoms, or required re-treatment. Additional follow-up angiography was available in 2 of 5 stenosis patients showing marked improvement. Sixteen patients (31%) had intimal hyperplasia, and 28 patients (55%) had no stenosis. Asymptomatic stent occlusion occurred in 2 patients (4%) related to medication noncompliance.
CONCLUSION:
Treatment with the PED was associated with a 9.8% rate of in-stent stenosis, detected on first angiographic follow-up, at a median of 6 months. None were symptomatic or required re-treatment, and they showed significant improvement on follow-up.
Journal Article
Unraveling the mechanisms of deep-brain stimulation of the internal capsule in a mouse model
Deep-brain stimulation (DBS) is an effective treatment for patients suffering from otherwise therapy-resistant psychiatric disorders, including obsessive-compulsive disorder. Modulation of cortico-striatal circuits has been suggested as a mechanism of action. To gain mechanistic insight, we monitored neuronal activity in cortico-striatal regions in a mouse model for compulsive behavior, while systematically varying clinically-relevant parameters of internal-capsule DBS. DBS showed dose-dependent effects on both brain and behavior: An increasing, yet balanced, number of excited and inhibited neurons was recruited, scattered throughout cortico-striatal regions, while excessive grooming decreased. Such neuronal recruitment did not alter basic brain function such as resting-state activity, and only occurred in awake animals, indicating a dependency on network activity. In addition to these widespread effects, we observed specific involvement of the medial orbitofrontal cortex in therapeutic outcomes, which was corroborated by optogenetic stimulation. Together, our findings provide mechanistic insight into how DBS exerts its therapeutic effects on compulsive behaviors.
The mechanisms of deep-brain stimulation for psychiatric disorders remain insufficiently understood. Here, the authors identified recruitment of cortico-striatal regions, in particular the medial orbitofrontal cortex, as a mechanism to treat compulsivity.
Journal Article
Prognostic factors for disease activity in newly diagnosed teriflunomide-treated patients with multiple sclerosis: a nationwide Danish study
BackgroundClinicians frequently rely on relapse counts, T2 MRI lesion load (T2L) and Expanded Disability Status Scale (EDSS) scores to guide treatment decisions for individuals diagnosed with multiple sclerosis (MS). This study evaluates how these factors, along with age and sex, influence prognosis during treatment with teriflunomide (TFL).MethodsWe conducted a nationwide cohort study using data from the Danish Multiple Sclerosis Registry.Eligible participants had relapsing-remitting MS or clinically isolated syndrome and initiated TFL as their first treatment between 2013 and 2019. The effect of age, pretreatment relapses, T2L and EDSS scores on the risk of disease activity on TFL were stratified by sex.ResultsIn total, 784 individuals were included (57.4% females). A high number of pretreatment relapses (≥2) was associated with an increased risk of disease activity in females only (OR and (95% CI): 1.76 (1.11 to 2.81)). Age group 50+ was associated with a lower risk of disease activity in both sexes (OR females=0.28 (0.14 to 0.56); OR males=0.22 (0.09 to 0.55)), while age 35–49 showed a different impact in males and females (OR females=0.79 (0.50 to 1.23); OR males=0.42 (0.24 to 0.72)). EDSS scores and T2L did not show any consistent associations.ConclusionA high number of pretreatment relapses was only associated with an increased risk of disease activity in females, while age had a differential impact on the risk of disease activity according to sex. Clinicians may consider age, sex and relapses when deciding on TFL treatment.
Journal Article
Treatment Outcomes of A Randomized Trial of Unruptured Brain Arteriovenous Malformation-Eligible Unruptured Brain Arteriovenous Malformation Patients
Abstract
BACKGROUND
The guideline for treating unruptured brain arteriovenous malformations (ubAVMs) remains controversial. A Randomized Trial of Unruptured Brain Arteriovenous Malformations (ARUBA) reported lower risk of stroke or death with conservative management compared to interventional treatment. There were numerous limitations to the study, including short follow-up period and disproportionate number of patients treated with surgery and embolization.
OBJECTIVE
To evaluate whether treatment of ARUBA-eligible patients have acceptable outcomes at our institution.
METHODS
Retrospective analysis was performed on 673 patients with brain AVMs treated at our institution between 2001 and 2014. One hundred five patients were ARUBA eligible and included in the study. Patients were divided into the microsurgery or Gamma Knife Radiosurgery (GKS; Elekta, Stockholm, Sweden) arm depending on their final treatment. Mean follow-up period was 43 mo (range 4-136 mo). Primary outcome was stroke or death.
RESULTS
A total of 8 (7.6%) patients had a stroke or died. The overall risk of stroke or death was 11.4% (5 of 44 patients) for the microsurgery arm and 4.9% (3 of 61 patients) for the GKS arm. The annual rates of stroke or death were 2.1%, 4.0%, and 1.2% for the entire patient cohort, microsurgery arm, and GKS arm, respectively. AVM obliteration rates at the end of the follow-up period were 95.5% and 47.5% for the microsurgery and GKS arms, respectively.
CONCLUSION
We report a lower overall risk of stroke or death in our ARUBA-eligible patients following treatment than ARUBA. Our results suggest that microsurgery and GKS may be appropriate treatments for patients with ubAVM.
Journal Article
Plant Based Diet and Its Effect on Cardiovascular Disease
Cardiovascular disease remains the leading cause of death globally and here in the United States. Diet has a major impact on the pathogenesis of atherosclerosis and subsequent cardiovascular morbidity and mortality. An unhealthy diet is the most significant potential behavioral and modifiable risk factor for ischemic heart disease. Despite these established facts, dietary interventions are far less frequent than pharmaceutical and procedural interventions in the management of cardiovascular disease. The beneficial effects of a plant-based diet on cardiovascular morbidity and mortality have been demonstrated in a number of recent clinical studies. The significant findings of each study are discussed in this review article, highlighting the role of a healthy plant-based diet in improving cardiovascular outcomes. From a clinician’s standpoint, the knowledge and understanding of the facts and data points from these recent clinical studies would ensure more effective patient counseling on the substantial benefits of dietary interventions.
Journal Article
Occurrence of Pre- and Post-Harvest Mycotoxins and Other Secondary Metabolites in Danish Maize Silage
Maize silage is a widely used feed product for cattle worldwide, which may be contaminated with mycotoxins, pre- and post-harvest. This concerns both farmers and consumers. To assess the exposure of Danish cattle to mycotoxins from maize silage, 99 samples of whole-crop maize (ensiled and un-ensiled) were analyzed for their contents of 27 mycotoxins and other secondary fungal metabolites by liquid chromatography-tandem mass spectrometry. The method specifically targets the majority of common pre- and post-harvest fungi associated with maize silage in Denmark. Sixty-one samples contained one or more of the 27 analytes in detectable concentrations. The most common mycotoxins were zearalenone, enniatin B nivalenol and andrastin A, found in 34%, 28%, 16% and 15% of the samples, respectively. None of the samples contained mycotoxins above the EU recommended maximum concentrations for Fusarium toxins in cereal-based roughage. Thus, the present study does not indicate that Danish maize silage in general is a cause of acute single mycotoxin intoxications in cattle. However, 31 of the samples contained multiple analytes; two samples as much as seven different fungal metabolites. Feed rations with maize silage may therefore contain complex mixtures of fungal secondary metabolites with unknown biological activity. This emphasizes the need for a thorough examination of the effects of chronic exposure and possible synergistic effects.
Journal Article
The Effects of Transit Time Heterogeneity on Brain Oxygenation during Rest and Functional Activation
The interpretation of regional blood flow and blood oxygenation changes during functional activation has evolved from the concept of ‘neurovascular coupling’, and hence the regulation of arteriolar tone to meet metabolic demands. The efficacy of oxygen extraction was recently shown to depend on the heterogeneity of capillary flow patterns downstream. Existing compartment models of the relation between tissue metabolism, blood flow, and blood oxygenation, however, typically assume homogenous microvascular flow patterns. To take capillary flow heterogeneity into account, we modeled the effect of capillary transit time heterogeneity (CTH) on the ‘oxygen conductance’ used in compartment models. We show that the incorporation of realistic reductions in CTH during functional hyperemia improves model fits to dynamic blood flow and oxygenation changes acquired during functional activation in a literature animal study. Our results support earlier observations that oxygen diffusion properties seemingly change during various physiologic stimuli, and posit that this phenomenon is related to parallel changes in capillary flow patterns. Furthermore, our results suggest that CTH must be taken into account when inferring brain metabolism from changes in blood flow- or blood oxygenation-based signals .
Journal Article