AAV8 vector induced gliosis following neuronal transgene expression.

Introduction: Expression of light sensitive ion channels by selected neurons has been achieved by viral mediated transduction with gene constructs, but for this to have therapeutic uses, for instance in treating epilepsy, any adverse effects of viral infection on the cerebral cortex needs to be evaluated. Here, we assessed the impact of adeno-associated virus 8 (AAV8) carrying DNA code for a soma targeting light activated chloride channel/FusionRed (FR) construct under the CKIIa promoter.

Methods: Viral constructs were harvested from transfected HEK293 cells and purified.

Downregulation of Dickkopf-3, a Wnt antagonist elevated in Alzheimer's disease, restores synapse integrity and memory in a disease mouse model.

Increasing evidence supports a role for deficient Wnt signaling in Alzheimer's disease (AD). Studies reveal that the secreted Wnt antagonist Dickkopf-3 (DKK3) colocalizes to amyloid plaques in AD patients. Here, we investigate the contribution of DKK3 to synapse integrity in healthy and AD brains.

Indirect Effects of Halorhodopsin Activation: Potassium Redistribution, Nonspecific Inhibition, and Spreading Depolarization.

The movement of ions in and out of neurons can exert significant effects on neighboring cells. Here we report several experimentally important consequences of activation of the optogenetic chloride pump, halorhodopsin. We recorded extracellular K concentration ([K]) in neocortical brain slices prepared from young adult mice (both sexes) which express halorhodopsin in pyramidal cells.

Altered synaptic connectivity in an in vitro human model of STXBP1 encephalopathy.

Early infantile developmental and epileptic encephalopathies are devastating conditions, generally of genetic origin, but the pathological mechanisms often remain obscure. A major obstacle in this field of research is the difficulty of studying cortical brain development in humans, at the relevant time period in utero. To address this, we established an in vitro assay to study the impact of gene variants on the developing human brain by using living organotypic cultures of the human subplate and neighbouring cortical regions, prepared from ethically sourced, 14-17 post-conception week brain tissue (www.

Closed-loop optogenetic control of the dynamics of neural activity in non-human primates.

Electrical neurostimulation is effective in the treatment of neurological disorders, but associated recording artefacts generally limit its applications to open-loop stimuli. Real-time and continuous closed-loop control of brain activity can, however, be achieved by pairing concurrent electrical recordings and optogenetics. Here we show that closed-loop optogenetic stimulation with excitatory opsins enables the precise manipulation of neural dynamics in brain slices from transgenic mice and in anaesthetized non-human primates.

Evaluation of the American College of Surgeons National Surgical Quality Improvement Program Risk Calculator to predict outcomes after hysterectomies.

Objective: To evaluate the American College of Surgeons (ACS) surgical risk calculator's reliability in predicting outcomes in hysterectomies.

Methods: This is a prospective cohort study at a large community-based hospital. Twenty-one preoperative and postoperative criteria were abstracted from the electronic medical record and entered into the online ACS calculator to determine a risk score.

The effect of COVID-19 pandemic on the mental health of Canadian critical care nurses providing patient care during the early phase pandemic: A mixed method study.

Background: Healthcare workers have historically experienced symptoms of post-traumatic stress disorder, depression and anxiety with previous infectious outbreaks. It is unknown if critical care nurses have similar experiences.

Objectives: The study aimed to examine the mental health of Critical Care Registered Nurses providing direct patient care during the initial phase of the COVID-19 pandemic in Canada.

Wnt Signaling Through Nitric Oxide Synthase Promotes the Formation of Multi-Innervated Spines.

Structural plasticity of synapses correlates with changes in synaptic strength. Dynamic modifications in dendritic spine number and size are crucial for long-term potentiation (LTP), the cellular correlate of learning and memory. Recent studies have suggested the generation of multi-innervated spines (MIS), in the form of several excitatory presynaptic inputs onto one spine, are crucial for hippocampal memory storage.

Clathrin light chain diversity regulates membrane deformation in vitro and synaptic vesicle formation in vivo.

Clathrin light chain (CLC) subunits in vertebrates are encoded by paralogous genes and , and both gene products are alternatively spliced in neurons. To understand how this CLC diversity influences neuronal clathrin function, we characterized the biophysical properties of clathrin comprising individual CLC variants for correlation with neuronal phenotypes of mice lacking either CLC-encoding gene. CLC splice variants differentially influenced clathrin knee conformation within assemblies, and clathrin with neuronal CLC mixtures was more effective in membrane deformation than clathrin with single neuronal isoforms nCLCa or nCLCb.

Bring back the tubal: An intervention to provide postpartum tubal ligation in the underserved population.

We aimed to improve educational awareness of postpartum bilateral tubal ligation (PPBTL), which we defined as a 15% improvement between pre-/post-intervention questionnaire scores. We followed patients desiring and undergoing PPBTL and reason for unfulfilled procedures from 2017-2018. OB/GYN, Nursing, and Anesthesia participated in educational sessions with pre-/post-intervention questionnaires.

CVT in the Peripartum Period: A Diagnostic Dilemma.

Women in the peripartum period can develop headache with a variety of etiologies that require a multidisciplinary approach if unresponsive to treatment (Stella et al. 2007). Neuroimaging needs to be undertaken even occasionally in the absence of focal neurologic signs to rule out life-threatening causes of headache.

Wnt proteins as modulators of synaptic plasticity.

Dynamic changes in the structure and function of synapses in response to the environment, termed synaptic plasticity, are the cellular basis of learning and memory. At excitatory synapses, activation of NMDA receptors by glutamate leads to calcium influx triggering intracellular pathways that promote the trafficking of AMPA receptors to the post-synaptic membrane and actin remodeling. New evidence shows that Wnt secreted proteins, known for their role in synapse development, are essential for early stages of long-term potentiation, a form of plasticity that increases synaptic strength.

Wnt7b signalling through Frizzled-7 receptor promotes dendrite development by coactivating CaMKII and JNK.

The formation of complex dendritic arbors is crucial for the assembly of functional networks as abnormal dendrite formation underlies several neurodevelopmental and psychiatric disorders. Many extracellular factors have been postulated as regulators of dendritic growth. Wnt proteins play a critical role in neuronal development and circuit formation.

Wnt Signaling Mediates LTP-Dependent Spine Plasticity and AMPAR Localization through Frizzled-7 Receptors.

The structural and functional plasticity of synapses is critical for learning and memory. Long-term potentiation (LTP) induction promotes spine growth and AMPAR accumulation at excitatory synapses, leading to increased synaptic strength. Glutamate initiates these processes, but the contribution from extracellular modulators is not fully established.

Promoting interprofessional learning and enhancing the pre-registration student experience through reciprocal cross professional peer tutoring.

Background: To improve collaboration and the quality of care, healthcare programmes are increasingly promoting interprofessional education thereby enabling students to learn with, from and about each other. A reciprocal peer learning model has developed among pre-registration physiotherapy and adult nursing students at Plymouth University, England. Embedded within the curriculum, it provides voluntary opportunities for year two students to become cross professional peer tutors to year one students while enhancing interprofessional understanding and skills acquisition.

Evaluation of Synapse Density in Hippocampal Rodent Brain Slices.

In the brain, synapses are specialized junctions between neurons, determining the strength and spread of neuronal signaling. The number of synapses is tightly regulated during development and neuronal maturation. Importantly, deficits in synapse number can lead to cognitive dysfunction.

Reversal of Synapse Degeneration by Restoring Wnt Signaling in the Adult Hippocampus.

Synapse degeneration occurs early in neurodegenerative diseases and correlates strongly with cognitive decline in Alzheimer's disease (AD). The molecular mechanisms that trigger synapse vulnerability and those that promote synapse regeneration after substantial synaptic failure remain poorly understood. Increasing evidence suggests a link between a deficiency in Wnt signaling and AD.

Wnt signalling tunes neurotransmitter release by directly targeting Synaptotagmin-1.

The functional assembly of the synaptic release machinery is well understood; however, how signalling factors modulate this process remains unknown. Recent studies suggest that Wnts play a role in presynaptic function. To examine the mechanisms involved, we investigated the interaction of release machinery proteins with Dishevelled-1 (Dvl1), a scaffold protein that determines the cellular locale of Wnt action.

Seven years of teenage pregnancy in an inner London genitourinary medicine service - a retrospective cohort study.

Young people attending genitourinary medicine services are at high risk of unplanned pregnancy. We performed a retrospective cohort study to identify characteristics of pregnant teenagers accessing an inner London genitourinary medicine service. There were 481 pregnancies in 458 teenagers with 54 previous pregnancies and 46 previous terminations of pregnancy.

Improving collection efficiency through remote monitoring of charity assets.

Collection costs associated with servicing a major UK charity's donation banks and collecting unsold goods from their retail shops can account for up to 20% of the overall income gained. Bank and shop collections are commingled and are typically made on fixed days of the week irrespective of the amounts of materials waiting to be collected. Using collection records from a major UK charity, this paper considers what vehicle routing and scheduling benefits could accrue if bank and shop servicing requirements were monitored, the former using remote sensing technology to allow more proactive collection scheduling.

Penicillin facilitates the entry of antisense constructs into Streptococcus mutans.

Antisense oligonucleotides (AS-ODN) target genes in a sequence-specific manner inhibit gene function and have potential use as antimicrobial agents. Cell barriers, such as peptidoglycan, cell surface proteins and lipopolysaccharide membranes, prevent delivery of AS-ODN into the bacterial cell, limiting their use as an effective treatment option. The β-lactam antibiotic penicillin was examined for its ability to deliver phosphorothioate oligodeoxyribonucleotides (PS-ODNs) and γ(32) P-ODN into Streptococcus mutans OMZ175.

Reduced seizure threshold and altered network oscillatory properties in a mouse model of Rett syndrome.

Rett syndrome (RTT) is a disorder with a pronounced neurological phenotype and is caused mainly by mutations in the X-linked gene MECP2. A common feature of RTT is an abnormal electroencephalography and a propensity for seizures. In the current study we aimed to assess brain network excitability and seizure propensity in a mouse model of RTT.

Synaptic plasticity deficits in an experimental model of rett syndrome: long-term potentiation saturation and its pharmacological reversal.

Rett syndrome (RTT), a disorder caused almost exclusively by mutations in the X-linked gene, MECP2, has a phenotype thought to be primarily of neurological origin. Disruption of Mecp2 in mice results in a prominent RTT-like phenotype. One of the consequences of MeCP2 absence in the brain is altered functional and structural plasticity.

Zoocin A facilitates the entry of antisense constructs into Streptococcus mutans.

The use of antisense oligodeoxyribonucleotides (asODNs) to inhibit gene function has proven to be an extremely powerful tool for establishing gene-function relationships. Diffusion limitations imposed by the thick peptidoglycan layer of Gram-positive bacteria have proven difficult to overcome for permeability of asODNs. Typically, introduction of the asODN is achieved by cloning the antisense sequence into a vector downstream of an inducible promoter and transforming this construct into the cell of interest.