Characterizing phenotypes and clinical and health utilization associations of young people with chronic pain: latent class analysis using the electronic Persistent Pain Outcomes Collaboration database.

Using the Australiasian electronic Persistent Pain Outcomes Collaboration, a binational pain registry collecting standardized clinical data from paediatric ePPOC (PaedsePPOC) and adult pain services (AdultePPOC), we explored and characterized nationally representative chronic pain phenotypes and associations with clinical and sociodemographic factors, health care utilization, and medicine use of young people. Young people ≥15.0 and <25.

COVID Couple Therapy: Telehealth and Somatic Action Techniques.

In March of 2020, during the global COVID-19 pandemic, therapists quickly transitioned to telehealth platforms to provide their services. Teletherapy, while subject to some constraints, presents unique opportunities to work creatively with couples, particularly during these uncertain times. This paper offers a case study of work with a couple using systemic, developmental attachment, dialogical, and somatic trauma theories.

Pharmacological interventions for chronic pain in children: an overview of systematic reviews.

We know little about the safety or efficacy of pharmacological medicines for children and adolescents with chronic pain, despite their common use. Our aim was to conduct an overview review of systematic reviews of pharmacological interventions that purport to reduce pain in children with chronic noncancer pain (CNCP) or chronic cancer-related pain (CCRP). We searched the Cochrane Database of Systematic Reviews, Medline, EMBASE, and DARE for systematic reviews from inception to March 2018.

Career Opportunities for Theatre Practitioners.

Never have there been such a vast number of career opportunities for all levels of staff within the perioperative environment including healthcare support workers, operating department practitioners and nurses.

Antiepileptic drugs for chronic non-cancer pain in children and adolescents.

Background: Pain is a common feature of childhood and adolescence around the world, and for many young people, that pain is chronic. The World Health Organization (WHO) guidelines for pharmacological treatments for children's persisting pain acknowledge that pain in children is a major public health concern of high significance in most parts of the world. While in the past, pain was largely dismissed and was frequently left untreated, views on children's pain have changed over time, and relief of pain is now seen as importantWe designed a suite of seven reviews on chronic non-cancer pain and cancer pain (looking at antidepressants, antiepileptic drugs, non-steroidal anti-inflammatory drugs, opioids, and paracetamol) in order to review the evidence for children's pain utilising pharmacological interventions in children and adolescents.

Antidepressants for chronic non-cancer pain in children and adolescents.

Background: Pain is a common feature of childhood and adolescence around the world, and for many young people, that pain is chronic. The World Health Organization guidelines for pharmacological treatments for children's persisting pain acknowledge that pain in children is a major public health concern of high significance in most parts of the world. While in the past pain was largely dismissed and was frequently left untreated, views on children's pain have changed over time and relief of pain is now seen as important.

Factor XIIIa-dependent retention of red blood cells in clots is mediated by fibrin α-chain crosslinking.

Factor XIII(a) [FXIII(a)] stabilizes clots and increases resistance to fibrinolysis and mechanical disruption. FXIIIa also mediates red blood cell (RBC) retention in contracting clots and determines venous thrombus size, suggesting FXIII(a) is a potential target for reducing thrombosis. However, the mechanism by which FXIIIa retains RBCs in clots is unknown.

Does topology drive fiber polymerization?

We have developed new procedures to examine the early steps in fibrin polymerization. First, we isolated fibrinogen monomers from plasma fibrinogen by gel filtration. Polymerization of fibrinogen monomers differed from that of plasma fibrinogen.

Motoric cognitive risk syndrome: multicountry prevalence and dementia risk.

Objectives: Our objective is to report prevalence of motoric cognitive risk syndrome (MCR), a newly described predementia syndrome characterized by slow gait and cognitive complaints, in multiple countries, and its association with dementia risk.

Methods: Pooled MCR prevalence analysis of individual data from 26,802 adults without dementia and disability aged 60 years and older from 22 cohorts from 17 countries. We also examined risk of incident cognitive impairment (Mini-Mental State Examination decline ≥4 points) and dementia associated with MCR in 4,812 individuals without dementia with baseline Mini-Mental State Examination scores ≥25 from 4 prospective cohort studies using Cox models adjusted for potential confounders.

Submillisecond elastic recoil reveals molecular origins of fibrin fiber mechanics.

Fibrin fibers form the structural scaffold of blood clots. Thus, their mechanical properties are of central importance to understanding hemostasis and thrombotic disease. Recent studies have revealed that fibrin fibers are elastomeric despite their high degree of molecular ordering.

Hydrodynamic characterization of recombinant human fibrinogen species.

Introduction: Fibrinogen is a key component of the blood coagulation system and plays important, diverse roles in several relevant pathologies such as thrombosis, hemorrhage, and cancer. It is a large glycoprotein whose three-dimensional molecular structure is not fully known. Furthermore, circulating fibrinogen is highly heterogeneous, mainly due to proteolytic degradation and alternative mRNA processing.

The isolation of fibrinogen monomer dramatically influences fibrin polymerization.

Fibrin polymerization begins with the thrombin-catalyzed cleavage of fibrinopeptides from fibrinogen and proceeds through several assembly steps to form an insoluble fibrin clot. Using dynamic light scattering (DLS), we found that purified fibrinogens are polydisperse, containing small amounts of fibrinogen complexes. In order to characterize the impact of these complexes, we used gel filtration chromatography to isolate monomers from three fibrinogens: plasma, recombinant, and recombinant variant Aα251.

An engineered fibrinogen variant AαQ328,366P does not polymerise normally, but retains the ability to form α cross-links.

A fibrin clot is stabilised through the formation of factor XIIIa-catalysed intermolecular ε-lysyl-γ-glutamyl covalent cross-links between α chains to form α polymers and between γ chains to form γ dimers. In a previous study we characterised fibrinogen Seoul II, a heterozygous dysfibrinogen in which a cross-linking acceptor site in Aα chain, Gln328, was replaced with Pro (AαQ328P). Following on the previous study, we investigated whether the alteration of Gln residues Aα328 and Aα366 affects fibrin polymerisation and α chain cross-linking.

The assembly of nonadhesive fibrinogen matrices depends on the αC regions of the fibrinogen molecule.

Adsorption of fibrinogen on fibrin clots and other surfaces strongly reduces integrin-mediated adhesion of platelets and leukocytes with implications for the surface-mediated control of thrombus growth and blood compatibility of biomaterials. The underlying mechanism of this process is surface-induced aggregation of fibrinogen, resulting in the assembly of a nanoscale multilayered matrix. The matrix is extensible, which makes it incapable of transducing strong mechanical forces via cellular integrins, resulting in insufficient intracellular signaling and weak cell adhesion.

Cholinergic dysfunction contributes to gait disturbance in early Parkinson's disease.

Gait disturbance is an early feature in Parkinson's disease. Its pathophysiology is poorly understood; however, cholinergic dysfunction may be a non-dopaminergic contributor to gait. Short-latency afferent inhibition is a surrogate measure of cholinergic activity, allowing the contribution of cholinergic dysfunction to gait to be evaluated.

Fibrinogen residue γAla341 is necessary for calcium binding and 'A-a' interactions.

The fibrinogen γ-module has several important sites relating to fibrinogen function, which include the high affinity calcium binding site, hole 'a' that binds with knob 'A', and the D:D interface. Residue γAla341, which is located in the vicinity of these sites, is altered in three variant fibrinogens: fibrinogen Seoul (γAla341Asp), Tolaga Bay (γAla341Val), and Lyon III (γAla341Thr). In order to investigate the impaired polymerisation of fibrinogens γAla341Asp and γAla341Val to understand the role of γAla341 in fibrin polymerisation and fibrinogen synthesis, we have expressed γAla341Asp and γAla341Val in Chinese hamster ovary (CHO) cells, purified these fibrinogens from the culture media and performed biochemical tests to elucidate their function.

Substitution of the human αC region with the analogous chicken domain generates a fibrinogen with severely impaired lateral aggregation: fibrin monomers assemble into protofibrils but protofibrils do not assemble into fibers.

Fibrin polymerization occurs in two steps: the assembly of fibrin monomers into protofibrils and the lateral aggregation of protofibrils into fibers. Here we describe a novel fibrinogen that apparently impairs only lateral aggregation. This variant is a hybrid, where the human αC region has been replaced with the homologous chicken region.

Molecular mechanisms affecting fibrin structure and stability.

Fibrin structure and stability have been linked to many thrombotic diseases, including venous thromboembolism. Analysis of the molecular mechanisms that affect fibrin structure and stability became possible when the crystal structure of fibrinogen was solved. Biochemical studies of natural and recombinant variant fibrinogens have examined the interactions that mediate the conversion of soluble fibrinogen to the insoluble fibrin network.

Evidence that αC region is origin of low modulus, high extensibility, and strain stiffening in fibrin fibers.

Fibrin fibers form the structural scaffold of blood clots and perform the mechanical task of stemming blood flow. Several decades of investigation of fibrin fiber networks using macroscopic techniques have revealed remarkable mechanical properties. More recently, the microscopic origins of fibrin's mechanics have been probed through direct measurements on single fibrin fibers and individual fibrinogen molecules.

The molecular origins of the mechanical properties of fibrin.

When normal blood circulation is compromised by damage to vessel walls, clots are formed at the site of injury. These clots prevent bleeding and support wound healing. To sustain such physiological functions, clots are remarkably extensible and elastic.

Dynamic regulation of fibrinogen: integrin αIIbβ3 binding.

This study demonstrates that two orthogonal events regulate integrin αIIbβ3's interactions with fibrinogen, its primary physiological ligand: (1) conformational changes at the αIIb-β3 interface and (2) flexibility in the carboxy terminus of fibrinogen's γ-module. The first postulate was tested by capturing αIIbβ3 on a biosensor and measuring binding by surface plasmon resonance. Binding of fibrinogen to eptifibatide-primed αIIbβ3 was characterized by a k(on) of ~2 × 10(4) L mol(-1) s(-1) and a k(off) of ~8 × 10(-5) s(-1) at 37 °C.