Expression of hyperpolarization-activated current () in zonally defined vestibular calyx terminals of the crista.

Calyx terminals make afferent synapses with type I hair cells in vestibular epithelia and express diverse ionic conductances that influence action potential generation and discharge regularity in vestibular afferent neurons. Here we investigated the expression of hyperpolarization-activated current () in calyx terminals in central and peripheral zones of mature gerbil crista slices, using whole cell patch-clamp recordings. Slowly activating was present in >80% calyces tested in both zones.

TGFβ2 Induces the Soluble Isoform of CTLA-4 - Implications for CTLA-4 Based Checkpoint Inhibitor Antibodies in Malignant Melanoma.

Malignant melanoma is an aggressive form of cancer, which can be treated with anti-CTLA-4 and anti-PD-1 checkpoint inhibitor antibodies but while anti-CTLA-4 antibodies have clear benefits for some patients with melanoma, productive responses are difficult to predict and often associated with serious immune related adverse events. Antibodies specific to CTLA-4 bind two major isoforms of CTLA-4 in humans, the receptor isoform and a second naturally secretable, soluble isoform - sCTLA-4. The primary aim here was to examine the effect of selectively blocking the function of sCTLA-4 on immune responses from volunteer healthy or melanoma patient PBMC samples.

Dopaminergic Inhibition of Na Currents in Vestibular Inner Ear Afferents.

Inner ear hair cells form synapses with afferent terminals and afferent neurons carry signals as action potentials to the central nervous system. Efferent neurons have their origins in the brainstem and some make synaptic contact with afferent dendrites beneath hair cells. Several neurotransmitters have been identified that may be released from efferent terminals to modulate afferent activity.

Medically unexplained symptoms in children: an experimental investigation of the impact of internet searching on parental responses.

Background: Medically unexplained symptoms (MUS) are symptoms for which no medical cause can be identified. For children and adolescents, symptoms can be maintained through parental responses.

Aims: The present study investigated the impact that internet searching of symptoms has on parental responses to MUS.

Persistent and resurgent Na currents in vestibular calyx afferents.

Vestibular afferent neurons convey information from hair cells in the peripheral vestibular end organs to central nuclei. Primary vestibular afferent neurons can fire action potentials at high rates and afferent firing patterns vary with the position of nerve terminal endings in vestibular neuroepithelia. Terminals contact hair cells as small bouton or large calyx endings.

Achieving Self-Directed Integrated Cancer Aftercare (ASICA) in melanoma: protocol for a randomised patient-focused pilot trial of delivering the ASICA intervention as a means to earlier detection of recurrent and second primary melanoma.

Background: Melanoma is common; 15,906 people in the UK were diagnosed with melanoma in 2015 and incidence has increased fivefold in 30 years. Melanoma affects old and young people, with poor prognosis once metastatic. UK guidelines recommend people treated for cutaneous melanoma receive extended outpatient, hospital follow up to detect recurrence or new primaries.

Regional and Developmental Differences in Na Currents in Vestibular Primary Afferent Neurons.

The vestibular system relays information about head position afferent nerve fibers to the brain in the form of action potentials. Voltage-gated Na channels in vestibular afferents drive the initiation and propagation of action potentials, but their expression during postnatal development and their contributions to firing in diverse mature afferent populations are unknown. Electrophysiological techniques were used to determine Na channel subunit types in vestibular calyx-bearing afferents at different stages of postnatal development.

AMPA receptor-mediated rapid EPSCs in vestibular calyx afferents.

In the vestibular periphery neurotransmission between hair cells and primary afferent nerves occurs via specialized ribbon synapses. Type I vestibular hair cells (HCIs) make synaptic contacts with calyx terminals, which enclose most of the HCI basolateral surface. To probe synaptic transmission, whole cell patch-clamp recordings were made from calyx afferent terminals isolated together with their mature HCIs from gerbil crista.

Channeling your inner ear potassium: K(+) channels in vestibular hair cells.

During development of vestibular hair cells, K(+) conductances are acquired in a specific pattern. Functionally mature vestibular hair cells express different complements of K(+) channels which uniquely shape the hair cell receptor potential and filtering properties. In amniote species, type I hair cells (HCI) have a large input conductance due to a ubiquitous low-voltage-activated K(+) current that activates with slow sigmoidal kinetics at voltages negative to the membrane resting potential.

Kv1 channels and neural processing in vestibular calyx afferents.

Potassium-selective ion channels are important for accurate transmission of signals from auditory and vestibular sensory end organs to their targets in the central nervous system. During different gravity conditions, astronauts experience altered input signals from the peripheral vestibular system resulting in sensorimotor dysfunction. Adaptation to altered sensory input occurs, but it is not explicitly known whether this involves synaptic modifications within the vestibular epithelia.

Zonal variations in K+ currents in vestibular crista calyx terminals.

We developed a rodent crista slice to investigate regional variations in electrophysiological properties of vestibular afferent terminals. Thin transverse slices of the gerbil crista ampullaris were made and electrical properties of calyx terminals in central zones (CZ) and peripheral zones (PZ) compared with whole cell patch clamp. Spontaneous action potential firing was observed in 25% of current-clamp recordings and was either regular or irregular in both zones.

Vitiligo: an evidence-based update. Report of the 13th Evidence Based Update Meeting, 23 May 2013, Loughborough, U.K.

The Evidence Based Update (EBU) meetings are annual one-day meetings held by the Centre of Evidence Based Dermatology at the University of Nottingham. The aim of the meeting is to discuss high-quality evidence, mainly in the form of systematic reviews and randomized controlled trials, on a different topic each year. The meetings are designed to be interactive with a panel discussion between international experts and delegates forming a key part of the meeting.

Inhibition of K+ currents in type I vestibular hair cells by gentamicin and neomycin.

Significant ototoxicity limits the use of aminoglycoside (AG) antibiotics. Several mechanisms may contribute to the death of both auditory and vestibular hair cells. In this study the effects of gentamicin and neomycin on K(+) currents in mature and early postnatal type I vestibular hair cells (HCI) were tested directly.

The management of acne vulgaris in pregnancy.

Acne vulgaris is a common condition in adolescence and also for many women of childbearing age. The management of acne in pregnancy is complicated by the lack of clinical studies and pharmacokinetic data in this patient population and safety concerns regarding retinoid use in pregnancy. Of primary concern to both patients and clinicians is the safety profile of medications used during pregnancy.

Hyperpolarization-activated current (I(h)) in vestibular calyx terminals: characterization and role in shaping postsynaptic events.

Calyx afferent terminals engulf the basolateral region of type I vestibular hair cells, and synaptic transmission across the vestibular type I hair cell/calyx is not well understood. Calyces express several ionic conductances, which may shape postsynaptic potentials. These include previously described tetrodotoxin-sensitive inward Na(+) currents, voltage-dependent outward K(+) currents and a K(Ca) current.

Patient preferences for psoriasis treatment: process characteristics considered more important than outcome attributes.

In a recent paper by Schaarschmidt et al., patients with moderate-to-severe psoriasis completed a conjoint analysis survey (discrete choice experiment) to determine which factors had influenced their choice of treatment, and the relative importance of each factor. They also assessed how socioeconomic and demographic factors affected patient choice.

Postnatal expression of an apamin-sensitive k(ca) current in vestibular calyx terminals.

Afferent innervation patterns in the vestibular periphery are complex, and vestibular afferents show a large variation in their regularity of firing. Calyx fibers terminate on type I vestibular hair cells and have firing characteristics distinct from the bouton fibers that innervate type II hair cells. Whole-cell patch clamp was used to investigate ionic currents that could influence firing patterns in calyx terminals.

K+ currents in isolated vestibular afferent calyx terminals.

Vestibular hair cells transduce mechanical displacements of their hair bundles into an electrical receptor potential which modulates transmitter release and subsequent action potential firing in afferent neurons. To probe ionic mechanisms underlying sensory coding in vestibular calyces, we used the whole-cell patch-clamp technique to record action potentials and K(+) currents from afferent calyx terminals isolated from the semicircular canals of Mongolian gerbils. Calyx terminals showed minimal current at the mean zero-current potential (-60 mV), but two types of outward K(+) currents were identified at potentials above -50 mV.

Development of K(+) and Na(+) conductances in rodent postnatal semicircular canal type I hair cells.

The rodent vestibular system is immature at birth. During the first postnatal week, vestibular type I and type II hair cells start to acquire their characteristic morphology and afferent innervation. We have studied postnatal changes in the membrane properties of type I hair cells acutely isolated from the semicircular canals (SCC) of gerbils and rats using whole cell patch clamp and report for the first time developmental changes in ionic conductances in these cells.

Fumonisin concentration and ceramide synthase inhibitory activity of corn, masa, and tortilla chips.

Nixtamalization removes fumonisins from corn and reduces their amounts in masa and tortilla products. Fumonisin concentrations and potential toxicity could be underestimated, however, if unknown but biologically active fumonisins are present. Therefore, the relative amounts of fumonisins in extracts of fumonisin-contaminated corn and its masa and tortilla chip nixtamalization products were determined with an in vitro ceramide synthase inhibition bioassay using increased sphinganine (Sa) and sphinganine to sphingosine ratio (Sa/So) as endpoints.