All-optical reporting of inhibitory receptor driving force in the nervous system.

Ionic driving forces provide the net electromotive force for ion movement across receptors, channels, and transporters, and are a fundamental property of all cells. In the nervous system, fast synaptic inhibition is mediated by chloride permeable GABA and glycine receptors, and single-cell intracellular recordings have been the only method for estimating driving forces across these receptors (DF). Here we present a tool for quantifying inhibitory receptor driving force named ORCHID: all-Optical Reporting of CHloride Ion Driving force.

Training effectiveness evaluation: Advancing a Kirkpatrick model based composite framework.

The present study aims at ideating a quantitative protocol to evaluate effectiveness of training programmes especially meant for farmers, farm women, and rural youth. The specific objective was to develop a robust framework for measuring the effectiveness of rural training programmes organized by the Farmers Training Centres (FTCs) of India. Kirkpatrick's training evaluation model provides us the foundation to design a four-dimensional composite framework based on range-based indicator normalization, principal component analysis based indicator weight estimation, and rank correlation based framework sensitivity testing.

Reliability of In Vivo Creatine-Weighted Chemical Exchange Saturation Transfer (CrCEST) MRI in Calf Skeletal Muscle of Healthy Volunteers at 3 T.

Background: Skeletal muscle mitochondrial oxidative phosphorylation (mtOXPHOS) is important for ATP generation and its dysfunction leads to exercise intolerance. Phosphorus magnetic resonance spectroscopy (P-MRS) is a useful, noninvasive technique for mtOXPHOS assessment but has limitations. Creatine-weighted chemical exchange saturation transfer (CrCEST) MRI is a potential alternative to assess muscle bioenergetics.

Feasibility and acceptability of multidisciplinary team training in health coaching: Case study in adolescent rheumatology.

The central importance of the biopsychosocial model of chronic disease is increasingly recognised in the management of long-term conditions (LTC), which are often associated with chronic pain, fatigue and disability. Despite the physical and mental health impact, 'struggle' to maintain self-efficacy, gap in effective transition to adult pathways and long term consequences of poor disease control and lifestyle choices in young people with LTCs, innovation in this age range is rarely reported in generic journals. This paper explores the feasibility and acceptability of health coaching with young service users to increase engagement and self-management, achieved through multidisciplinary team (MDT) training in Adolescent Rheumatology.

Optogenetic Determination of Dynamic and Cell-Type-Specific Inhibitory Reversal Potentials.

The reversal potential refers to the membrane potential at which the net current flow through a channel reverses direction. The reversal potential is determined by transmembrane ion gradients and, in turn, determines how the channel's activity will affect the membrane potential. Traditional investigation into the reversal potential of inhibitory ligand-gated ion channels (E) has relied upon the activation of endogenous receptors, such as the GABA-A receptor (GABAR).

CSF-to-blood toxins clearance is modulated by breathing through cranio-spinal CSF oscillation.

Clearance of brain toxins occurs during sleep, although the mechanism remains unknown. Previous studies implied that the intracranial aqueductal cerebrospinal fluid (CSF) oscillations are involved, but no mechanism was suggested. The rationale for focusing on the aqueductal CSF oscillations is unclear.

Active cortical networks promote shunting fast synaptic inhibition in vivo.

Fast synaptic inhibition determines neuronal response properties in the mammalian brain and is mediated by chloride-permeable ionotropic GABA-A receptors (GABARs). Despite their fundamental role, it is still not known how GABARs signal in the intact brain. Here, we use in vivo gramicidin recordings to investigate synaptic GABAR signaling in mouse cortical pyramidal neurons under conditions that preserve native transmembrane chloride gradients.

Metastatic meningioma: a case series and systematic review.

Background: Meningiomas are the most common primary intracranial tumor. While the majority of meningiomas are benign, rarely they can metastasize extracranially. There is a need for a more comprehensive review of these patients to improve our understanding of this rare phenomenon and its prevalence globally.

Intracellular chloride regulation mediates local sleep pressure in the cortex.

Extended wakefulness is associated with reduced performance and the build-up of sleep pressure. In the cortex, this manifests as changes in network activity. These changes show local variation depending on the waking experience, and their underlying mechanisms represent targets for overcoming the effects of tiredness.

Precision medicine for developmental and epileptic encephalopathies in Africa-strategies for a resource-limited setting.

Purpose: Sub-Saharan Africa bears the highest burden of epilepsy worldwide. A presumed proportion is genetic, but this etiology is buried under the burden of infections and perinatal insults in a setting of limited awareness and few options for testing. Children with developmental and epileptic encephalopathies (DEEs) are most severely affected by this diagnostic gap in Africa, because the rate of actionable findings is highest in DEE-associated genes.

"I wanna live and not think about the future" what place for advance care planning for people living with severe multiple sclerosis and their families? A qualitative study.

Background: Little is known about how people with multiple sclerosis (MS) and their families comprehend advance care planning (ACP) and its relevance in their lives.

Aim: To explore under what situations, with whom, how, and why do people with MS and their families engage in ACP.

Methods: We conducted a qualitative study comprising interviews with people living with MS and their families followed by an ethical discussion group with five health professionals representing specialties working with people affected by MS and their families.

Why won't it stop? The dynamics of benzodiazepine resistance in status epilepticus.

Status epilepticus is a life-threatening neurological emergency that affects both adults and children. Approximately 36% of episodes of status epilepticus do not respond to the current preferred first-line treatment, benzodiazepines. The proportion of episodes that are refractory to benzodiazepines is higher in low-income and middle-income countries (LMICs) than in high-income countries (HICs).

Demonstrating the feasibility of digital health to support pediatric patients in South Africa.

Objective: Resources for management of epilepsy in Africa are extremely limited reinforcing the need to develop innovative strategies for optimizing care. Studies have shown that the prevalence of epilepsy in low- and middle-income countries is substantially greater than in more resourced countries. The objective of this report was to demonstrate that mobile Health (mHealth) technologies have the potential to improve the management of epilepsy in Africa.

Molecular and electrophysiological features of spinocerebellar ataxia type seven in induced pluripotent stem cells.

Spinocerebellar ataxia type 7 (SCA7) is an inherited neurodegenerative disease caused by a polyglutamine repeat expansion in the ATXN7 gene. Patients with this disease suffer from a degeneration of their cerebellar Purkinje neurons and retinal photoreceptors that result in a progressive ataxia and loss of vision. As with many neurodegenerative diseases, studies of pathogenesis have been hindered by a lack of disease-relevant models.

Role of the spinal canal compliance in regulating posture-related cerebrospinal fluid hydrodynamics in humans.

Mechanical compliance of a compartment is defined by the change in its volume with respect to a change in the inside pressure. The compliance of the spinal canal regulates the intracranial pressure (ICP) under postural changes. Understanding how gravity affects ICP is beneficial for poorly understood cerebrospinal fluid (CSF)-related disorders.

A realist review of advance care planning for people with multiple sclerosis and their families.

Background: Advance care planning (ACP) is reported to improve the quality of outcomes of care among those with life-limiting conditions. However, uptake is low among people living with multiple sclerosis (MS) and little is known about why or how people with MS engage in this process of decision-making.

Aims: To develop and refine an initial theory on engagement in ACP for people with MS and to identify ways to improve its uptake for those who desire it.

Effect of Short-term Integrated Palliative Care on Patient-Reported Outcomes Among Patients Severely Affected With Long-term Neurological Conditions: A Randomized Clinical Trial.

Importance: Palliative care has shown benefits in reducing symptom intensity and quality of life in patients with advanced cancer. However, high-quality evidence to support palliative care policy and service developments for patients with long-term neurological conditions (LTNCs) is lacking.

Objective: To determine the effectiveness of a short-term integrated palliative care (SIPC) intervention for people with LTNCs.

The transition to status epilepticus: how the brain meets the demands of perpetual seizure activity.

The pathophysiology leading to the development of status epilepticus (SE) remains a topic of significant scientific interest and clinical relevance. The use of multiple experimental and computational models has shown that SE relies on a complex interaction between mechanisms that operate at both a cellular and network level. In this narrative review, we will summarise the current knowledge on the factors that play a key role in allowing SE to develop and persist.

Training South African clinician-scientists: Lessons from the University of Cape Town's intercalated programme.

In 2011, the Faculty of Health Sciences at the University of Cape Town, South Africa (SA), established the Clinician-Scientist Training Programme (UCTCSTP), consisting of intercalated BMedSci Hons/MB ChB and integrated MB ChB/MSc/PhD tracks. We report and reflect on the programme's performance and challenges. The UCTCSTP has so far enrolled 71 students: 51 have received BMedSci Hons degrees and 4 have received Master's degrees, while there are 14 BMedSci Hons, 4 MSc and 4 PhD candidates.