Neurodegenerative pathways as targets for acquired epilepsy therapy development.

There is a growing body of clinical and experimental evidence that neurodegenerative diseases and epileptogenesis after an acquired brain insult may share common etiological mechanisms. Acquired epilepsy commonly develops as a comorbid condition in patients with neurodegenerative diseases such as Alzheimer's disease, although it is likely much under diagnosed in practice. Progressive neurodegeneration has also been described after traumatic brain injury, stroke, and other forms of brain insults.

Prevention of pathogen transmission during ultrasound use in the Intensive Care Unit: Recommendations from the College of Intensive Care Medicine Ultrasound Special Interest Group (USIG).

ICU ultrasonography constitutes important part of modern car patient care. Current standards and practice of infection control and prevention are inadequate. This purpose of this document is to adapt and expand the 2017 Australasian Society for Ultrasound in Medicine (ASUM) and the Australasian College for Infection Prevention Control (ACIPC) guidelines on minimum standards for reprocessing/cleaning of ultrasound transducers to the specifics of intensive care medicine and provide advice to the ICU practitioners and health care administrators.

Circulating gluten-specific, but not CMV-specific, CD39 regulatory T cells have an oligoclonal TCR repertoire.

Objectives: Understanding the T cell receptor (TCR) repertoire of regulatory CD4 T-cell (Treg) populations is important for strategies aiming to re-establish tolerance in autoimmune diseases. We studied circulating deamidated gluten-epitope-specific CD39 Tregs in patients with coeliac disease following an oral gluten challenge, and we used cytomegalovirus (CMV)-specific CD39 Tregs from healthy controls as a comparator population.

Methods: We used the OX40 assay to isolate antigen-specific Tregs by induced surface co-expression of CD25, OX40 and CD39.

A potential association between IL-3 and type I and III interferons in systemic lupus erythematosus.

Objectives: Plasmacytoid dendritic cells (pDCs), through the production of type 1 interferons (IFNs) and other cytokines, are major contributors to systemic lupus erythematosus (SLE) pathogenesis. IL-3 promotes pDC survival, but its role in SLE is not well characterised. This study investigated serum IL-3 and IFN levels, and a whole blood 'IL-3 gene signature', in human SLE.

The utility of an automated and ambulatory device for detecting and differentiating epileptic and psychogenic non-epileptic seizures.

Objective: Accurate differentiation between epileptic seizures (ES) and psychogenic non-epileptic seizures (PNES) can be challenging based on history alone. Inpatient video EEG monitoring (VEM) is often needed for a definitive diagnosis. However, VEM is highly resource intensive, is of limited availability, and cannot be undertaken over long periods.

Randomized trial of add-on triheptanoin vs medium chain triglycerides in adults with refractory epilepsy.

Objective: To investigate the feasibility, safety, and tolerability of add-on treatment of the triglycerides of heptanoate (triheptanoin) vs the triglycerides of octanoate and decanoate (medium chain triglycerides [MCTs]) in adults with treatment-refractory epilepsy.

Methods: After an 8-week prospective baseline period, people with drug-resistant epilepsy were randomized in a double-blind fashion to receive triheptanoin or MCTs. Treatment was titrated over 3 weeks to a maximum of 100 mL/d to be distributed over 3 meals and mixed into food, followed by 12-week maintenance before tapering.

Understanding the burden of focal epilepsy as a function of seizure frequency in the United States, Europe, and Brazil.

Objective: To understand the current burden of focal epilepsy (FE) as a function of seizure frequency.

Methods: Patients were identified from the United States (2011, 2012, and 2013), five European countries (EU; France, Germany, Italy, Spain, United Kingdom) (2011 and 2013), and Brazil (2011 and 2012) National Health and Wellness Survey (NHWS), a nationally representative, Internet-based survey of adults (18+ years). The NHWS collected data on respondents' quality of life (QoL), health utilities, productivity loss, and healthcare resource utilization.

Objective Measurement and Characterization of Sleep Benefit in Parkinson's Disease.

Background: Sleep benefit (SB) in Parkinson's disease refers to improved motor symptoms upon waking despite an entire night without medications. Although it was first proposed 30 years ago, this phenomenon proved difficult to investigate, and its true prevalence and underlying mechanisms remain unclear.

Objective: This study aimed to identify and quantify SB through measurement of motor function using a validated smartphone application and to identify disease characteristics that predicted SB.

Early treatment intensification with R-ICE and 90Y-ibritumomab tiuxetan (Zevalin)-BEAM stem cell transplantation in patients with high-risk diffuse large B-cell lymphoma patients and positive interim PET after 4 cycles of R-CHOP-14.

In the treatment of diffuse large B-cell lymphoma, a persistently positive [F]fluorodeoxyglucose positron emission tomography (PET) scan typically carries a poor prognosis. In this prospective multi-center phase II study, we sought to establish whether treatment intensification with R-ICE (rituximab, ifosfamide, carboplatin, and etoposide) chemotherapy followed by 90Y-ibritumomab tiuxetan-BEAM (BCNU, etoposide, cytarabine, and melphalan) for high-risk diffuse large B-cell lymphoma patients who are positive on interim PET scan after 4 cycles of R-CHOP-14 (rituximab, cyclophosphamide, doxorubicin, and prednisone) can improve 2-year progression-free survival from a historically unfavorable rate of 40% to a rate of 65%. Patients received 4 cycles of R-CHOP-14, followed by a centrally-reviewed PET performed at day 17-20 of cycle 4 and assessed according to International Harmonisation Project criteria.

Characterizing neurocognitive impairment in young people with major depression: state, trait, or scar?

Background: Major depressive disorder (MDD) affects a quarter of adolescents and young adults and is associated with the greatest global burden of disease in this population. There is a growing literature, mostly in adults, showing that significant neurocognitive impairments are common in MDD. It remains unclear whether these impairments are pre-existing trait markers of MDD, state-related impairments that fluctuate with depressive symptoms, or 'scar' impairments that worsen with illness progression.

Immunomodulation of inflammatory leukocyte markers during intravenous immunoglobulin treatment associated with clinical efficacy in chronic inflammatory demyelinating polyradiculoneuropathy.

Objective: The objective of the study was to profile leukocyte markers modulated during intravenous immunoglobulin (IVIg) treatment, and to identify markers and immune pathways associated with clinical efficacy of IVIg for chronic inflammatory demyelinating polyradiculoneuropathy (CIDP) with potential for monitoring treatment efficacy.

Methods: Response to IVIg treatment in newly diagnosed IVIg-naïve and established IVIg-experienced patients was assessed by changes in expression of inflammatory leukocyte markers by flow cytometry. The adjusted INCAT disability and Medical Research Council sum scores defined clinical response.

Predictors of disability worsening in clinically isolated syndrome.

Objective: To assess demographic, clinical, magnetic resonance imaging, and treatment exposure predictors of time to 3 or 12-month confirmed disability worsening in clinically isolated syndrome (CIS) and early multiple sclerosis (MS).

Methods: We utilized the MSBase Incident Study (MSBasis), a prospective cohort study of outcome after CIS. Predictors of time to first 3 and 12-month confirmed expanded disability status scale worsening were analyzed using Cox proportional hazards regression.

A review of β-amyloid neuroimaging in Alzheimer's disease.

Alzheimer's disease (AD) is the most common cause of dementia worldwide. As advancing age is the greatest risk factor for developing AD, the number of those afflicted is expected to increase markedly with the aging of the world's population. The inability to definitively diagnose AD until autopsy remains an impediment to establishing effective targeted treatments.

Altered cortical thickness following prenatal sodium valproate exposure.

Prenatal exposure to sodium valproate (VPA) is associated with neurodevelopmental impairments. Cortical thickness was measured in 16 children exposed prenatally to VPA and 16 controls. We found increased left inferior frontal gyrus (IFG; BA45) and left pericalcarine sulcus (BA18) thickness, an association between VPA dose and right IFG thickness, and a close relationship between verbal skills and left IFG thickness.

Hypoxia enhances the proliferative response of macrophages to CSF-1 and their pro-survival response to TNF.

In chronic inflammatory lesions there are increased numbers of macrophages with a possible contribution of enhanced survival/proliferation due, for example, to cytokine action; such lesions are often hypoxic. Prior studies have found that culture in low oxygen can promote monocyte/macrophage survival. We show here, using pharmacologic inhibitors, that the hypoxia-induced pro-survival response of macrophages exhibits a dependence on PI3-kinase and mTOR activities but surprisingly is suppressed by Akt and p38 MAPK activities.

Managing a stroke unit: an example from Australia with an emphasis on nursing roles.

Stroke care units (SCUs), which are co-ordinated by dedicated multidisciplinary teams and geographically located in one area, are currently the most generaliseable form of effective treatment for stroke. Although the evidence for SCUs is compelling, to date there has been limited evidence regarding the contribution of the different clinical team members who assist in producing the better patient outcomes observed in SCUs. In particular, there has been limited exploration of the different nursing roles.

Body fluid proteomics: Prospects for biomarker discovery.

Many diseases are caused by perturbations of cellular signaling pathways and related pathway networks as a result of genetic aberrations. These perturbations are manifested by altered cellular protein profiles in the fluids bathing tissue/organs (i.e.

Neurotrophin receptor expression and responsiveness by postnatal cerebral oligodendroglia.

The low affinity neurotrophin receptor (p75(NTR)) is implicated in promoting oligodendrocytic death after nerve growth factor (NGF) stimulation but NGF and neurotrophin-3 (NT-3) can also potentiate oligodendrocytic survival. We show regional variability in p75(NTR) expression within the central nervous system of the postnatal rat; expression is readily detectable by immunohistochemistry upon a subset of CNPase-positive oligodendroglia in optic nerve but not within the cerebrum. Nevertheless, oligodendroglia isolated from the cerebrum and cultured for 16 hours express p75(NTR) as well as the trkC but not the TrkA gene.

Molecular cloning and chromosomal localisation of the human homologue of a receptor related to tyrosine kinases (RYK).

A cDNA encoding the human homologue of mouse RYK (related to receptor tyrosine kinases) has been cloned from an interleukin 1 (IL-1)-stimulated human hepatoma cDNA library by cross-species hybridization using the mouse RYK cDNA as a probe. The sequence of the 3067-bp cDNA clone encoding human RYK predicts a transmembrane protein with a cytoplasmic domain that contains the consensus sequences (subdomains I-XI) of the protein tyrosine kinase (PTK) family. The highly conserved motif -D-F-G- (subdomain VII) of the catalytic domain of other receptor-type tyrosine kinases is altered to -D-N-A- in human RYK.