Cortico-thalamic tremor circuits and their associations with deep brain stimulation effects in essential tremor.

Essential tremor (ET) is one of the most common movement disorders in adults. Deep brain stimulation (DBS) of the ventralis intermediate nucleus (VIM) of the thalamus and/or the posterior subthalamic area (PSA) has been shown to provide significant tremor suppression in patients with ET, but with significant inter-patient variability and habituation to the stimulation. Several non-invasive neuromodulation techniques targeting other parts of the central nervous system, including cerebellar, motor cortex, or peripheral nerves, have also been developed for treating ET, but the clinical outcomes remain inconsistent.

Deep Brain Stimulation for Consciousness Disorders; Technical and Ethical Considerations.

Disorders of Consciousness (DoC) result in profound functional impairment, adversely affecting the lives of a predominantly younger patient population. Currently, effective treatment options for those who have reached chronicity (prolonged symptom duration over 4 weeks) are extremely limited, with the majority of such cases facing life-long dependence on carers and a poor quality of life. Here we briefly review the current evidence on caseload, diagnostic and management options in the United Kingdom (UK), United States of America (USA) and the European Union (EU).

Checkpoint inhibition enhances cell contacts between CD4 T cells and Hodgkin-Reed-Sternberg cells of classic Hodgkin lymphoma.

Although checkpoint molecules like CTLA-4 and PD1 have been described several years ago, checkpoint inhibitors such as nivolumab (an anti-PD-1 antibody) have only recently been used to treat classic Hodgkin lymphoma (cHL). Several studies have shown convincing therapeutic effects of nivolumab in cHL. However, the mechanism of action of nivolumab in cHL is not fully understood.

Bioelectronic Zeitgebers: targeted neuromodulation to re-establish circadian rhythms.

Existing neurostimulation systems implanted for the treatment of neurodegenerative disorders generally deliver invariable therapy parameters, regardless of phase of the sleep/wake cycle. However, there is considerable evidence that brain activity in these conditions varies according to this cycle, with discrete patterns of dysfunction linked to loss of circadian rhythmicity, worse clinical outcomes and impaired patient quality of life. We present a targeted concept of circadian neuromodulation using a novel device platform.

The Design of Brainstem Interfaces: Characterisation of Physiological Artefacts and Implications for Closed-loop Algorithms.

Surgical neuromodulation through implantable devices allows for stimulation delivery to subcortical regions, crucial for symptom control in many debilitating neurological conditions. Novel closed-loop algorithms deliver therapy tailor-made to endogenous physiological activity, however rely on precise sensing of signals such as subcortical oscillations. The frequency of such intrinsic activity can vary depending on subcortical target nucleus, while factors such as regional anatomy may also contribute to variability in sensing signals.

Regulation of arousal and performance of a healthy non-human primate using closed-loop central thalamic deep brain stimulation.

Application of closed-loop approaches in systems neuroscience and brain-computer interfaces holds great promise for revolutionizing our understanding of the brain and for developing novel neuromodulation strategies to restore lost function. The anterior forebrain mesocircuit (AFM) of the mammalian brain is hypothesized to underlie arousal regulation of the cortex and striatum, and support cognitive functions during wakefulness. Dysfunction of arousal regulation is hypothesized to contribute to cognitive dysfunctions in various neurological disorders, and most prominently in patients following traumatic brain injury (TBI).

Prescribing Patterns of Codeine and Alternative Medicines in Children in Europe.

Introduction: Concerns over serious respiratory depression in children led to two European Union (EU) referral procedures (in 2013 and 2015) to review the benefit-risk balance of codeine in this population when used for pain relief, cough or cold. Consequently, codeine should no longer be used in children aged < 12 years and restrictions were introduced for treatment in children ≥ 12 years.

Objective: This multinational collaborative study aimed to assess the effectiveness of these risk minimisation measures by evaluating changes in prescribing of codeine and alternative treatments.

Spatial and Temporal Distribution of Information Processing in the Human Dorsal Anterior Cingulate Cortex.

The dorsal anterior cingulate cortex (dACC) is a key node in the human salience network. It has been ascribed motor, pain-processing and affective functions. However, the dynamics of information flow in this complex region and how it responds to inputs remain unclear and are difficult to study using non-invasive electrophysiology.

Toxicity of Hypofractionated Whole Breast Radiotherapy Without Boost and Timescale of Late Skin Responses in a Large Cohort of Early-Stage Breast Cancer Patients.

Aim: To report toxicity of hypofractionated whole-breast radiotherapy in a large cohort of early-stage breast cancer (BCaients.

Materials And Methods: From 02/2009-05/2017, 1325 consecutive BCa patients were treated with 40.05 Gy/15 fractions, without boost.

Analyses of Protein Turnover at the Cell Plate by Fluorescence Recovery After Photobleaching During Cytokinesis.

Membrane trafficking is central to cell plate construction during plant cytokinesis. Studies on cell plate formation can provide answers to basic biology questions including molecular mechanisms of membrane trafficking, tissue patterning, and cytoskeletal dynamics. Consequently, a detailed understanding of cytokinesis depends on the characterization of molecules that function in the formation, transport, targeting, and fusion of membrane vesicles and delivery of proteins to the developing and maturing plate.

Gait-Phase Modulates Alpha and Beta Oscillations in the Pedunculopontine Nucleus.

The pedunculopontine nucleus (PPN) is a reticular collection of neurons at the junction of the midbrain and pons, playing an important role in modulating posture and locomotion. Deep brain stimulation of the PPN has been proposed as an emerging treatment for patients with Parkinson's disease (PD) or multiple system atrophy (MSA) who have gait-related atypical parkinsonian syndromes. In this study, we investigated PPN activities during gait to better understand its functional role in locomotion.

ERα36-GPER1 Collaboration Inhibits TLR4/NFκB-Induced Pro-Inflammatory Activity in Breast Cancer Cells.

Inflammation is important for the initiation and progression of breast cancer. We have previously reported that in monocytes, estrogen regulates TLR4/NFκB-mediated inflammation via the interaction of the Erα isoform ERα36 with GPER1. We therefore investigated whether a similar mechanism is present in breast cancer epithelial cells, and the effect of ERα36 expression on the classic 66 kD ERα isoform (ERα66) functions.

DyNeuMo Mk-2: An Investigational Circadian-Locked Neuromodulator with Responsive Stimulation for Applied Chronobiology.

Deep brain stimulation (DBS) for Parkinson's disease, essential tremor and epilepsy is an established palliative treatment. DBS uses electrical neuromodulation to suppress symptoms. Most current systems provide a continuous pattern of fixed stimulation, with clinical follow-ups to refine settings constrained to normal office hours.

Distinguishing psychogenic nonepileptic, mixed, and epileptic seizures using systemic measures and reported experiences.

Objectives: Our primary objective was to better discern features that can differentiate people with 'mixed' symptomatology from those who experience epileptic seizures (ES) or functional/psychogenic nonepileptic seizures (PNES) alone, in a population of patients referred for video-telemetry. We wished to see if we could establish the prevalence of PNES in this population of interest as well as compare both objective (e.g.

Impact of molecular subtype on 1325 early-stage breast cancer patients homogeneously treated with hypofractionated radiotherapy without boost: Should the indications for radiotherapy be more personalized?

Aim: We report molecular subtype impact on 1325 early breast cancer (BCa) patients treated with whole breast hypofractionated (WBH) adjuvant forward-planned intensity modulated radiotherapy (F-IMRT) without boost.

Methods And Materials: From 02/2009-05/2017 1325 patients with pTis-pT3, pNx-N1aM0 BCa who underwent breast conservation surgery were treated with WBHF-IMRT in our institute, to a total dose of 40 Gy/15 fractions, without boost. Median age: 62 (interquartile range-IQR-:51.

Histone H3.3G34-Mutant Interneuron Progenitors Co-opt PDGFRA for Gliomagenesis.

Histone H3.3 glycine 34 to arginine/valine (G34R/V) mutations drive deadly gliomas and show exquisite regional and temporal specificity, suggesting a developmental context permissive to their effects. Here we show that 50% of G34R/V tumors (n = 95) bear activating PDGFRA mutations that display strong selection pressure at recurrence.

Conditioning attenuates kidney and heart injury in rats following transient suprarenal occlusion of the abdominal aorta.

Suprarenal aortic clamping during abdominal aortic aneurysm (AAA) repair results in ischemia-reperfusion injury (IRI) in local (i.e. kidney) and distant (i.

An evaluation of the psychosocial impact of epilepsy on marriage in the United Kingdom.

Objectives: The primary objective of this study was to measure the psychosocial burden for persons with epilepsy (PWEs) and for their spouses and to compare and correlate this with the clinical burden of seizures. A secondary objective was to examine the presence of gender-specific differences in the perception of psychosocial burdens by both PWE and their spouses, as well as in the factors that may influence this perception. We also sought to delineate differences in perceived stigmatization if the onset of epilepsy was within matrimony or if seizure onset was prior to marriage.

A PML/Slit Axis Controls Physiological Cell Migration and Cancer Invasion in the CNS.

Cell migration through the brain parenchyma underpins neurogenesis and glioblastoma (GBM) development. Since GBM cells and neuroblasts use the same migratory routes, mechanisms underlying migration during neurogenesis and brain cancer pathogenesis may be similar. Here, we identify a common pathway controlling cell migration in normal and neoplastic cells in the CNS.

Policies for reirradiation of recurrent high-grade gliomas: a survey among Italian radiation oncologists.

Purpose: To assess the contribution of Italian radiation oncologists in the current management of recurrent high-grade gliomas (HGG), focusing on a reirradiation (reRT) approach.

Methods: In 2015, the Reirradiation and the Central Nervous System Study Groups on behalf of the Italian Association of Radiation Oncology (AIRO) proposed a survey. All Italian radiation oncologists were individually invited to complete an online questionnaire regarding their clinical management of recurrent HGG, focusing on a reRT approach.

Estrogen anti-inflammatory activity on human monocytes is mediated through cross-talk between estrogen receptor ERα36 and GPR30/GPER1.

Estrogens are known modulators of monocyte/macrophage functions; however, the underlying mechanism has not been clearly defined. Recently, a number of estrogen receptor molecules and splice variants were identified that exert different and sometimes opposing actions. We assessed the expression of estrogen receptors and explored their role in mediating estrogenic anti-inflammatory effects on human primary monocytes.

Inhibition of oxidative metabolism leads to p53 genetic inactivation and transformation in neural stem cells.

Alterations of mitochondrial metabolism and genomic instability have been implicated in tumorigenesis in multiple tissues. High-grade glioma (HGG), one of the most lethal human neoplasms, displays genetic modifications of Krebs cycle components as well as electron transport chain (ETC) alterations. Furthermore, the p53 tumor suppressor, which has emerged as a key regulator of mitochondrial respiration at the expense of glycolysis, is genetically inactivated in a large proportion of HGG cases.

Measuring impact: a cross-sectional multi-stage cluster survey to assess the attainment of durable solutions in post-tsunami Aceh, Indonesia.

Background: There exists little agreement on the choice of indicators to be used to assess the impact of humanitarian assistance. The 2004 Indian Ocean tsunami led to significant mortality and displacement in Aceh Province, Indonesia, as well as a nearly unprecedented humanitarian response. Six years after the disaster we conducted an impact assessment of humanitarian services rendered in Aceh using a comprehensive set of rights-based indicators and sought to determine modifiable predictors of improved outcomes in disaster-affected households.

Two-year outcome of an observe-and-plan regimen for neovascular age-related macular degeneration: how to alleviate the clinical burden with maintained functional results.

Purpose: The purpose of this study was to report the 2-year outcome of an individually tailored 'observe-and-plan' treatment regimen for neovascular age-related macular degeneration (nAMD), and to investigate its clinical value in terms of functional outcome. This regimen aimed to reduce the clinical burden (visits) by employing individually fixed injection intervals, based on the predictability of an individual's need for retreatment.

Methods: This prospective case series included 104 patients (115 eyes) with nAMD.