Content analysis of current role/job descriptors for Band 5/junior physiotherapists and mapping of these to Physiotherapy Professional standards of practice.

Background: KNOWBEST was a mixed methods study exploring the KNOWledge, BEhaviours and Skills required of the modern physioTherapy graduate.

Objectives: To undertake a content analysis of current role descriptors (RDs) for Band5/junior physiotherapists and map these to the knowledge, skills, behaviours and attributes required for contemporary physiotherapy practice.

Design: Content analyses and mapping.

Modulation of Lymphocyte Potassium Channel K1.3 by Membrane-Penetrating, Joint-Targeting Immunomodulatory Plant Defensin.

We describe a cysteine-rich, membrane-penetrating, joint-targeting, and remarkably stable peptide, EgK5, that modulates voltage-gated K1.3 potassium channels in T lymphocytes by a distinctive mechanism. EgK5 enters plasma membranes and binds to K1.

Enhanced Cardiomyocyte NLRP3 Inflammasome Signaling Promotes Atrial Fibrillation.

Background: Atrial fibrillation (AF) is frequently associated with enhanced inflammatory response. The NLRP3 (NACHT, LRR, and PYD domain containing protein 3) inflammasome mediates caspase-1 activation and interleukin-1β release in immune cells but is not known to play a role in cardiomyocytes (CMs). Here, we assessed the role of CM NLRP3 inflammasome in AF.

Targeting KCa1.1 Channels with a Scorpion Venom Peptide for the Therapy of Rat Models of Rheumatoid Arthritis.

Fibroblast-like synoviocytes (FLSs) are a key cell type involved in rheumatoid arthritis (RA) progression. We previously identified the KCa1.1 potassium channel (Maxi-K, BK, Slo 1, ) as a regulator of FLSs and found that KCa1.

A chronological framework connecting the early Upper Palaeolithic across the Central Asian piedmont.

Central Asia has delivered significant paleoanthropological discoveries in the past few years. New genetic data indicate that at least two archaic human species met and interbred with anatomically modern humans as they arrived into northern Central Asia. However, data are limited: known archaeological sites with lithic assemblages generally lack human fossils, and consequently identifying the archaeological signatures of different human groups, and the timing of their occupation, remains elusive.

N-Terminally extended analogues of the K⁺ channel toxin from Stichodactyla helianthus as potent and selective blockers of the voltage-gated potassium channel Kv1.3.

The voltage-gated potassium channel Kv1.3 is an important target for the treatment of autoimmune diseases and asthma. Blockade of Kv1.

KCa1.1 inhibition attenuates fibroblast-like synoviocyte invasiveness and ameliorates disease in rat models of rheumatoid arthritis.

Objective: Fibroblast-like synoviocytes (FLS) participate in joint inflammation and damage in rheumatoid arthritis (RA) and its animal models. The purpose of this study was to define the importance of KCa1.1 (BK, Maxi-K, Slo1, KCNMA1) channel expression and function in FLS and to establish these channels as potential new targets for RA therapy.

Big Potassium (BK) ion channels in biology, disease and possible targets for cancer immunotherapy.

The Big Potassium (BK) ion channel is commonly known by a variety of names (Maxi-K, KCNMA1, slo, stretch-activated potassium channel, KCa1.1). Each name reflects a different physical property displayed by this single ion channel.

Ion channels and anti-cancer immunity.

The outcome of a malignant disease depends on the efficacy of the immune system to destroy cancer cells. Key steps in this process, for example the generation of a proper Ca(2+) signal induced by recognition of a specific antigen, are regulated by various ion channel including voltage-gated Kv1.3 and Ca(2+)-activated KCa3.

Recombinant expression of margatoxin and agitoxin-2 in Pichia pastoris: an efficient method for production of KV1.3 channel blockers.

The K(v)1.3 voltage-gated potassium channel regulates membrane potential and calcium signaling in human effector memory T cells that are key mediators of autoimmune diseases such as multiple sclerosis, type 1 diabetes, and rheumatoid arthritis. Thus, subtype-specific K(v)1.

A C-terminally amidated analogue of ShK is a potent and selective blocker of the voltage-gated potassium channel Kv1.3.

ShK, a 35-residue peptide from a sea anemone, is a potent blocker of potassium channels. Here we describe a new ShK analogue with an additional C-terminus Lys residue and amide. ShK-K-amide is a potent blocker of Kv1.

Expression and isotopic labelling of the potassium channel blocker ShK toxin as a thioredoxin fusion protein in bacteria.

The polypeptide toxin ShK is a potent blocker of Kv1.3 potassium channels, which play a crucial role in the activation of human effector memory T-cells (T(EM)). Selective blockers constitute valuable therapeutic leads for the treatment of autoimmune diseases mediated by T(EM) cells, such as multiple sclerosis, rheumatoid arthritis, and type-1 diabetes.

Vm24, a natural immunosuppressive peptide, potently and selectively blocks Kv1.3 potassium channels of human T cells.

Blockade of Kv1.3 K(+) channels in T cells is a promising therapeutic approach for the treatment of autoimmune diseases such as multiple sclerosis and type 1 diabetes mellitus. Vm24 (α-KTx 23.

KCa1.1 potassium channels regulate key proinflammatory and invasive properties of fibroblast-like synoviocytes in rheumatoid arthritis.

Fibroblast-like synoviocytes (FLS) play important roles in the pathogenesis of rheumatoid arthritis (RA). Potassium channels have regulatory roles in many cell functions. We have identified the calcium- and voltage-gated KCa1.

The D-diastereomer of ShK toxin selectively blocks voltage-gated K+ channels and inhibits T lymphocyte proliferation.

The polypeptide toxin ShK is a potent blocker of Kv1.3 potassium channels, which are crucial in the activation of human effector memory T cells (T(EM)); selective blockers constitute valuable therapeutic leads for the treatment of autoimmune diseases mediated by T(EM) cells, such as multiple sclerosis, rheumatoid arthritis, and type-1 diabetes. The critical motif on the toxin for potassium channel blockade consists of neighboring lysine and tyrosine residues.

Parents of children with haemophilia--a transforming experience.

Owing to the improvements in the management of haemophilia, children with severe haemophilia in the United Kingdom have very different experiences of their condition compared with many adults' early experiences of haemophilia. However, haemophilia can still have physical and social effects which can impact on the quality of life, not only for a child who has the condition, but also for their parents. The purpose of this study was to undertake a qualitative exploration of the impact of haemophilia on parents.

Kv1.3 channels are a therapeutic target for T cell-mediated autoimmune diseases.

Autoreactive memory T lymphocytes are implicated in the pathogenesis of autoimmune diseases. Here we demonstrate that disease-associated autoreactive T cells from patients with type-1 diabetes mellitus or rheumatoid arthritis (RA) are mainly CD4+ CCR7- CD45RA- effector memory T cells (T(EM) cells) with elevated Kv1.3 potassium channel expression.

Recent developments in clinimetric instruments.

Assessment of impairment and function is essential in order to monitor joint status and evaluate therapeutic interventions in patients with haemophilia. The improvements in the treatment of haemophilia have required the development of more sensitive tools to detect the more minor dysfunctions that may now be apparent. This paper outlines some of the recent developments in this field.

Potassium channels, memory T cells, and multiple sclerosis.

Multiple sclerosis is a chronic inflammatory autoimmune disease of the central nervous system characterized by demyelination and axonal damage that result in disabling neurological deficits. Here the authors explain the rationale for the use of inhibitors of the Kv1.3 K+ channel in immune cells as a therapy for multiple sclerosis and other autoimmune disorders.

An exploration of health-related quality of life in adults with haemophilia--a qualitative perspective.

Musculoskeletal dysfunction is a common feature of haemophilia and along with other manifestations of this condition, there is a general perception that health-related quality of life (QoL) will be affected. Previous research using standardized questionnaires has demonstrated that QoL is lower in haemophilia groups compared with normal populations. However, disability studies and interviews with disabled people suggest that many disabled people experience positive life changes as a result of their illness and an affirmative model of disability has been proposed.

Targeting effector memory T cells with a selective peptide inhibitor of Kv1.3 channels for therapy of autoimmune diseases.

The voltage-gated Kv1.3 K(+) channel is a novel target for immunomodulation of autoreactive effector memory T (T(EM)) cells that play a major role in the pathogenesis of autoimmune diseases. We describe the characterization of the novel peptide ShK(L5) that contains l-phosphotyrosine linked via a nine-atom hydrophilic linker to the N terminus of the ShK peptide from the sea anemone Stichodactyla helianthus.

Evidence for domain-specific recognition of SK and Kv channels by MTX and HsTx1 scorpion toxins.

Maurotoxin (MTX) and HsTx1 are two scorpion toxins belonging to the alpha-KTx6 structural family. These 34-residue toxins, cross-linked by four disulfide bridges, share 59% sequence identity and fold along the classical alpha/beta scaffold. Despite these structural similarities, they fully differ in their pharmacological profiles.

[Ion channels and demyelination: basis of a treatment of experimental autoimmune encephalomyelitis (EAE) by potassium channel blockers].

Voltage-gated potassium channels (Kv channels) are ion channels, openings of which provide an outward flow of potassium ions repolarising the cell. In neurons, Kv channels play a crucial role in action potential repolarisation and in shaping neuronal excitability. In non-excitable cells, such as T lymphocytes, Kv channels and calcium-activated K+ channels (KCa channels) determine the driving force for Ca2+ entry.

Kv1.3-blocking 5-phenylalkoxypsoralens: a new class of immunomodulators.

The lymphocyte potassium channel Kv1.3 is widely regarded as a promising new target for immunosuppression. To identify a potent small-molecule Kv1.