The experiences of patients attending the emergency department who were managed by physiotherapists: a person-centred perspective.

PURPOSE: The expectation for all clinicians to deliver person-centred practices extends to the growing number of primary contact physiotherapists based in United Kingdom emergency departments (ED). Research on ED patients' experience of this physiotherapy role has yet to consider this through the lens of person-centredness. A qualitative exploration of person-centredness among ED physiotherapists through the experiences of attending patients targeted this knowledge gap to inform future clinical practice. METHODS: Semi-structured interviews with thematic analysis. RESULTS: 13 interviews were completed with four overarching themes generated: (1) patient experience of the ED; (2) the importance of connection, competence, and time; (3) recognising the benefits of being seen by a physiotherapist in ED; and (4) patient experience of the ED physical environment. CONCLUSION: Novel contributions from the patient perspective, here, reflected a cognisance of certain environment limitations to PCP, as well as institutional challenges to their personhood, with a suggestion that ED patients anticipated a validation of their visit and valued the educational aspects that the physiotherapists provided. Considering this new knowledge can help ED physiotherapists to be more person-centred.

Those emergency department (ED) physiotherapists who validated an ED patient's attendance also provided an antidote to any incivility that they might have initially experienced.The ED environment had a negative impact on the patient experience because it was not designed through the lens of the service users or with person-centred practice in mind.Even in the maelstrom of ED, taking the time to fully educate patients on their condition was seen as an invaluable aspect of an ED physiotherapist's practice.Despite relentless pressures for rapid processing of patients, ED physiotherapists must take care to avoid adopting an impersonal checklist approach that denies a patient's personhood.

An exploration of person-centredness among emergency department physiotherapists: a mixed methods study.

PURPOSE: There is a growing number of primary contact physiotherapists based in United Kingdom emergency departments (ED) who are expected to deliver person-centred practices. Perceptions of physiotherapists working in these high-pressure environments on person-centredness are currently unknown. A mixed methods exploration of person-centredness among ED physiotherapists targeted this knowledge gap to inform future clinical practice. METHODS: Online survey and semi-structured interviews followed a convergent mixed methods design with sequential explanatory features. Data sets were analysed separately using descriptive statistics and thematic analysis, respectively, before merged analysis using joint display. RESULTS: Twenty-six surveys and 11 in-depth interviews were completed. The three overarching themes of ED patients, ED physiotherapists, and ED environment were generated. Themes were integrated and analysed alongside quantitative survey findings. This produced three novel contributions that further our understanding of person-centred practices among ED physiotherapists. CONCLUSION: ED physiotherapists were mindful of an apparent, yet unspoken struggle between the competing philosophies of biomedicine and person-centredness. The results here support entering a patient's world as a person-centred approach to help navigate the line between what an ED attender wants and the clinical need of their visit.

Most primary contact physiotherapists believe in the possibility of achieving person-centred practices within emergency departments (ED) and endorse attempts to deliver on this.Any idealised visions of delivering person-centred practice in ED must be adapted to local operational limitations and the acuity of the presenting case in question.ED physiotherapist could consider the notion of 'entering a patient's world' as a route to the meaning of a patient's problems to them by using a more narrative approach to assessment.A framework to support an ED-specific version of person-centred practice is currently lacking.

What are the views of musculoskeletal physiotherapists and patients on person-centred practice? A systematic review of qualitative studies.

PURPOSE: There is a growing expectation of physiotherapists to adopt a person-centred approach to their practice. Person-centredness for musculoskeletal physiotherapy, however, remains an under-researched area. A synthesis of the findings from qualitative studies exploring perceptions of person-centredness in musculoskeletal physiotherapy was conducted to inform future clinical practice. METHODS: ENTREQ and PRISMA guidelines were used to develop a protocol for a qualitative systematic review registered with PROSPERO (registration number: CRD42020170762). Five electronic databases were searched to identify relevant primary studies. Studies were assessed for quality and data extracted. Data were analysed using thematic synthesis. RESULTS: A total of 3250 studies were identified and screened. Nine studies met the inclusion criteria. Four main themes emerged from the data: treating each patient as a unique person, the importance of communication for achieving a therapeutic alliance, necessary physiotherapist traits for person-centredness, and supporting patient empowerment. CONCLUSION: Empowerment of patients in musculoskeletal physiotherapy contexts might be improved through a more narrative approach to assessment, with clinical bravery recognised as a specific person-centred physiotherapy trait able to facilitate this. Physiotherapists should also consider the meaningfulness of any treatment activities they provide to maximise the person-centredness of their approach.IMPLICATIONS FOR REHABILITATIONEmpowerment of patients in musculoskeletal physiotherapy contexts might be improved through a more narrative approach to assessment.Clinical bravery is a person-centred physiotherapy trait that facilitates certain conversational freedom to elicit the true patient narrative.Person-centred physiotherapists should reflect on how meaningful their treatment activities are for individual MSK outpatients.

MINERVA: A facility to study Microstructure and INterface Evolution in Realtime under VAcuum.

A sample environment to enable real-time X-ray scattering measurements to be recorded during the growth of materials by thermal evaporation in vacuum is presented. The in situ capabilities include studying microstructure development with time or during exposure to different environmental conditions, such as temperature and gas pressure. The chamber provides internal slits and a beam stop, to reduce the background scattering from the X-rays passing through the entrance and exit windows, together with highly controllable flux rates of the evaporants. Initial experiments demonstrate some of the possibilities by monitoring the growth of bathophenanthroline (BPhen), a common molecule used in organic solar cells and organic light emitting diodes, including the development of the microstructure with time and depth within the film. The results show how BPhen nanocrystal structures coarsen at room temperature under vacuum, highlighting the importance of using real time measurements to understand the as-deposited pristine film structure and its development with time. More generally, this sample environment is versatile and can be used for investigation of structure-property relationships in a wide range of vacuum deposited materials and their applications in, for example, optoelectronic devices and energy storage.

Human IRGM regulates autophagy and cell-autonomous immunity functions through mitochondria.

IRGM, a human immunity-related GTPase, confers autophagic defence against intracellular pathogens by an unknown mechanism. Here, we report an unexpected mode of IRGM action. IRGM demonstrated differential affinity for the mitochondrial lipid cardiolipin, translocated to mitochondria, affected mitochondrial fission and induced autophagy. Mitochondrial fission was necessary for autophagic control of intracellular mycobacteria by IRGM. IRGM influenced mitochondrial membrane polarization and cell death. Overexpression of IRGMd, but not IRGMb splice isoforms, caused mitochondrial depolarization and autophagy-independent, but Bax/Bak-dependent, cell death. By acting on mitochondria, IRGM confers autophagic protection or cell death, explaining IRGM action both in defence against tuberculosis and in the damaging inflammation caused by Crohn's disease.

The molecular basis of species-specific ligand activation of trace amine-associated receptor 1 (TAAR(1)).

The trace amine-associated receptor 1 (TAAR(1)) is an aminergic G protein-coupled receptor (GPCR) potently activated by 3-iodothyronamine (1), an endogenous derivative of thyroid hormone. Structure-activity relationship studies on 1 and related agonists showed that the rat and mouse species of TAAR(1) accommodated structural modifications and functional groups on the ethylamine portion and the biaryl ether moiety of the molecule. However, the two receptors clearly exhibited distinct, species-specific ligand preferences despite being remarkably similar with 93% sequence similarity. In this study, we generated single and double mutants of rat and mouse TAAR(1) to probe the molecular recognition of agonists and the underlying basis for the ligand selectivity of rat and mouse TAAR(1). Key, nonconserved specificity determinant residues in transmembranes helices 4 and 7 within the ligand binding site appear to be the primary source of a number of the observed ligand preferences. Residue 7.39 in transmembrane 7 dictated the preference for a beta-phenyl ring, while residue 4.56 in transmembrane 4 was partially responsible for the lower potency of 1 and tyramine for the mouse receptor. Additionally, 1 and tyramine were found to have the same binding mode in rat TAAR(1) despite structure-activity relationship data suggesting the possibility of each molecule having different binding orientations. These findings provide valuable insights into the critical binding site residues involved in the ligand-receptor interaction that can influence compound selectivity and functional activity of aminergic GPCRs.

Phosphoinositides in phagolysosome and autophagosome biogenesis.

Interconversions of phosphoinositides play a pivotal role during phagocytosis and at the subsequent stages of phagosomal maturation into the phagolysosome. Several model systems have been used to study the role of phosphoinositides in phagosomal membrane remodelling. These include phagosomes formed by inanimate objects such as latex beads, or pathogenic bacteria, e.g. Mycobacterium tuberculosis. The latter category provides naturally occurring tools to dissect membrane trafficking processes governing phagolysosome biogenesis. M. tuberculosis persists in infected macrophages by blocking Rab conversion and affecting Rab effectors. One of the major Rab effectors involved in this process is the type III phosphatidylinositol 3-kinase hVPS34. The lipid kinase hVPS34 and its enzymatic product PtdIns3P are critical for the default pathway of phagosomal maturation into phagolysosomes. Mycobacteria block PtdIns3P production and thus arrest phagosomal maturation. PtdIns3P is also critical for the process of autophagy, recently recognized as an effector of innate immunity defenses. Induction of autophagy by pharmacological, physiological, or immunological means, overcomes mycobacterial phagosome maturation block in a PtdIns3P generation dependent manner and eliminates intracellular M. tuberculosis. PtdIns3P and PtdIns3P-dependent processes represent an important cellular nexus where fundamental trafficking processes, disease causing host-pathogen interactions, and innate and adaptive immunity defense mechanisms meet.

Molecular interaction of serotonin 5-HT2A receptor residues Phe339(6.51) and Phe340(6.52) with superpotent N-benzyl phenethylamine agonists.

Experiments were conducted to examine the molecular basis for the high affinity and potency of a new class of 5-HT(2A) receptor agonists, N-benzyl phenethylamines. Competition binding assays at several serotonin receptors confirmed that an N-arylmethyl substitution was necessary for affinity increases up to 300-fold over simple N-alkyl homologs, as well as enhanced selectivity for 5-HT(2A) versus 5-HT(2C) and 5-HT(1A) receptors. PI hydrolysis functional assays confirmed that these N-benzyl phenethylamines are potent and highly efficacious agonists at the rat 5-HT(2A) receptor. Virtual docking of these compounds into a human 5-HT(2A) receptor homology model indicated that the N-benzyl moiety might be interacting with Phe339((6.51)), whereas the phenethylamine portion was likely to be interacting with Phe340((6.52)). Experiments in h5-HT(2A) receptors with Phe339((6.51))L and Phe340((6.52))L mutations seem to support this hypothesis. Dramatic detrimental effects on affinity, potency, and intrinsic activity were observed with the Phe339((6.51))L mutation for all N-benzyl analogs, whereas most N-unsubstituted phenethylamines and traditional agonists were only weakly affected, if at all. Consistent with other published studies, the Phe340((6.52))L mutation detrimentally affected affinity, potency, and intrinsic activity of nearly all compounds tested, although a strong change in intrinsic activity was not seen with most N-aryl analogs. These data further validate the topology of our h5-HT(2A) receptor homology model. It is noteworthy that this study is the first to identify a hitherto unrecognized role for residue 6.51 in agonist activation of a serotonin G protein-coupled receptor (GPCR), whereas most previous reports have suggested a varied and sometimes contradictory role in homologous GPCRs.

Autophagy in immune defense against Mycobacterium tuberculosis.

Autophagy is a newly recognized innate and adaptive immunity defense against intracellular pathogens, in keeping with its role as a cytoplasmic maintenance pathway. Induction of autophagy by physiological, pharmacological or immunological means can eliminate intracellular Mycobacterium tuberculosis, providing one of the first examples of the immunological role of autophagy. Under normal circumstances, M. Tuberculosis survives in macrophages by inhibiting phagolysosome biogenesis. Induction of autophagy overcomes the mycobacterial phagosome maturation block, and delivers the tubercle bacilli to degradative compartments where they are eliminated.

Mycobacterium tuberculosis inhibition of phagolysosome biogenesis and autophagy as a host defence mechanism.

A marquee feature of the powerful human pathogen Mycobacterium tuberculosis is its macrophage parasitism. The intracellular survival of this microorganism rests upon its ability to arrest phagolysosome biogenesis, avoid direct cidal mechanisms in macrophages, and block efficient antigen processing and presentation. Mycobacteria prevent Rab conversion on their phagosomes and elaborate glycolipid and protein trafficking toxins that interfere with Rab effectors and regulation of specific organellar biogenesis in mammalian cells. One of the major Rab effectors affected in this process is the type III phosphatidylinositol 3-kinase hVPS34 and its enzymatic product phosphatidylinositol 3-phosphate (PI3P), a regulatory lipid earmarking organellar membranes for specific trafficking events. PI3P is also critical for the process of autophagy, recently recognized as an effector of innate and adaptive immunity. Induction of autophagy by physiological, pharmacological or immunological signals, including the major antituberculosis Th1 cytokine IFN-gamma and its downstream effector p47 GTPase LRG-47, can overcome mycobacterial phagosome maturation block and inhibit intracellular M. tuberculosis survival. This review summarizes the findings centred around the PI3P-nexus where the mycobacterial phagosome maturation block and execution stages of autophagy intersect.

Growth kinetics of extremely halophilic archaea (family halobacteriaceae) as revealed by arrhenius plots.

Members of the family Halobacteriaceae in the domain Archaea are obligate extreme halophiles. They occupy a variety of hypersaline environments, and their cellular biochemistry functions in a nearly saturated salty milieu. Despite extensive study, a detailed analysis of their growth kinetics is missing. To remedy this, Arrhenius plots for 14 type species of the family were generated. These organisms had maximum growth temperatures ranging from 49 to 58 degrees C. Nine of the organisms exhibited a single temperature optimum, while five grew optimally at more than one temperature. Generation times at these optimal temperatures ranged from 1.5 h (Haloterrigena turkmenica) to 3.0 h (Haloarcula vallismortis and Halorubrum saccharovorum). All shared an inflection point at 31 +/- 4 degrees C, and the temperature characteristics for 12 of the 14 type species were nearly parallel. The other two species (Natronomonas pharaonis and Natronorubrum bangense) had significantly different temperature characteristics, suggesting that the physiology of these strains is different. In addition, these data show that the type species for the family Halobacteriaceae share similar growth kinetics and are capable of much faster growth at higher temperatures than those previously reported.