Personal protective equipment training & lived experience for healthcare staff during COVID-19.

Objectives: To describe the lived experience of healthcare staff during the Coronavirus Disease 2019 (COVID-19) pandemic relating to the use of personal protective equipment (PPE) and investigate risks associated with PPE use, error mitigation and acceptability of mindfulness incorporation into PPE practice. Methods: A qualitative human factors' study at two Irish hospitals occurred in late 2020. Data was collected by semi-structured interview and included role description, pre-COVID-19 PPE experience, the impact of COVID-19 on lived experience, risks associated with PPE use, contributory factors to errors, error mitigation strategies and acceptability of incorporating mindfulness into PPE practice. Results: Of 45 participants, 23 of whom were nursing staff (51%), 34 (76%) had previously worn PPE and 25 (56%) used a buddy system. COVID-19 lived experience impacted most on social life/home-work interface (n=36, 80%). Nineteen staff (42%) described mental health impacts. The most cited risk concerned 'knowledge of procedures' (n=18, 40%). Contributory factors to PPE errors included time (n=15, 43%) and staffing pressures (n=10, 29%). Mitigation interventions included training/education (n=12, 40%). The majority (n=35, 78%) supported mindfulness integration into PPE practice. Conclusions: PPE training should address healthcare staff lived experiences and consider incorporation of mindfulness and key organisational factors contributing to safety.

Arthroscopic Saucerization of a Symptomatic Posterior Horn Tear in a Discoid Medial Meniscus.

Background: Discoid medial meniscus is an extremely rare congenital anatomic variant with an estimated incidence of 0.12%. Arthroscopic meniscal saucerization and repair are reserved for symptomatic tears only. We present a case of discoid medial meniscus tear, outline the surgical arthroscopic technique used for treatment, and compare several surgical approaches. Case Report: An 18-year-old male presented with left knee pain and mechanical symptoms present for 2 years. Physical examination showed stability to both varus and valgus stresses with absence of locking or catching on McMurray testing. Magnetic resonance imaging confirmed discoid medial meniscus with a horizontal oblique tear of the posterior horn. The patient underwent saucerization of the left discoid medial meniscus and medial meniscus repair. Conclusion: Discoid medial meniscus predisposes individuals to meniscal tears that often require operative management. Careful consideration of surgical approach can help to optimize patient outcomes while minimizing the risk of iatrogenic injury.

When you care enough to do your very best: genetic counselor experiences of compassion fatigue.

Compassion fatigue is a phenomenon that occurs when a caregiver feels overwhelmed by repeated empathic engagement with distressed clients (Figley, 2002). Research demonstrates its existence among nurses, physicians, and mental health professionals, but to date no published study has specifically investigated the nature and prevalence of compassion fatigue among genetic counselors. The present study was an initial attempt to identify and describe the phenomena in genetic counseling by conducting focus group interviews with 12 genetic counselors. Data analysis yielded several themes: a) compassion fatigue occurs and may compromise professional and personal functioning; b) prevalent triggers include delivering bad news and difficult patient issues (e.g., terminal illness, anger, psychopathology); c) effective coping strategies include consulting with colleagues, setting boundaries, and humor; and d) risk factors include personality characteristics and traumatic memories. Training, practice, and research recommendations are provided.

Inhibition of obliterative airway disease development in murine tracheal allografts by matrix metalloproteinase-9 deficiency.

This study was designed to define the roles of matrix metalloproteinase (MMP)-2 and MMP-9 in obliterative airway disease (OAD) in heterotopic murine tracheal allografts, considered a suitable animal model for chronic lung allograft rejection. BALB/c tracheal allografts were transplanted into MMP-2-deficient (-/-) and MMP-9-/- mice. Also, wild-type recipients were treated with doxycycline, a nonspecific MMP inhibitor. After 10, 20 and 30 days, allografts were analyzed for OAD development, intragraft levels of MMP-2 and MMP-9 and the frequency and cytokine/chemokine production profile of alloreactive T cells. Allografts transplanted into wild-type mice developed OAD lesions within 30 days. These allografts revealed significant upregulation of both MMP-2 and MMP-9. Allografts transplanted into MMP-9-/- and doxycycline-treated recipients did not develop OAD. In contrast, allografts transplanted into MMP-2-/- mice developed OAD lesions with normal kinetics. Interestingly, MMP-9-/- recipients showed an enhanced T cell alloreactivity associated with an abnormal profile of cytokine/chemokine production. The enhanced T cell alloreactivity in MMP-9-/- mice was mediated by enhanced dendritic cell stimulatory capacity as well as enhanced T cell responsive capacity. These results suggest that MMP-9 plays an important role in the pathogenesis of OAD and may represent a target for the therapeutic intervention of chronic lung allograft rejection.

Different roles for matrix metalloproteinase-2 and matrix metalloproteinase-9 in the pathogenesis of cardiac allograft rejection.

Recent studies have shown an increased expression of several matrix metalloproteinases (MMP) during cardiac, renal and pulmonary allograft rejection. To further define the roles of MMP-2 and MMP-9 in the pathogenesis of cardiac allograft rejection, BALB/c cardiac allografts were transplanted into MMP-2-deficient (-/-) and MMP-9-/- mice. Allografts rejected by wild-type mice revealed a significant increase in MMP-2 and MMP-9 expression. MMP-2-deficiency significantly prolonged allograft survival time. Functioning allografts harvested from MMP-2-/- mice showed lower cellular infiltration and fibrosis than rejected allografts harvested from MMP-2+/+ mice at the same time. In contrast, MMP-9-deficiency significantly decreased allograft survival time. Functioning allografts harvested from MMP-9+/+ mice showed lower cellular infiltration and fibrosis than rejected allografts harvested from MMP-9-/- mice at the same time. MMP-2-/- recipients showed decreased T-cell alloreactivity mediated by a defect in dendritic cell stimulatory and T-cell responsive capacities. In contrast, MMP-9-/- recipients showed increased T-cell alloreactivity mediated by a significant increased in dendritic cell stimulatory and T-cell responsive capacities. These results indicate that MMP2 and MMP-9 play significantly different roles in the process of cardiac allograft rejection.

Recognition of HLA-A2-restricted mammaglobin-A-derived epitopes by CD8+ cytotoxic T lymphocytes from breast cancer patients.

A breast cancer-associated antigen, mammaglobin-A, is specifically expressed in 80% of primary breast tumors. The definition of immune responses against this highly expressed breast cancer-specific antigen should be of great value in the development of new therapeutic strategies for breast cancer. Thus, the purpose of this study was to identify HLA-A2-restricted mammaglobin-A-derived epitopes recognized by CD8+ cytotoxic T lymphocytes (CTL). We identified seven mammaglobin-A-derived candidate epitopes that bind the HLA-A2 molecule (Mam-A2.1-7) by means of a HLA class I-peptide binding computer algorithm from the Bioinformatics & Molecular Analysis Section of the National Institutes of Health. Subsequently, we determined that CD8+ CTLs from breast cancer patients reacted to the Mam-A2.1 (83-92, LIYDSSLCDL), Mam-A2.2 (2-10, KLLMVLMLA), Mam-A2.3 (4-12, LMVLMLAAL), Mam-A2.4 (66-74, FLNQTDETL), and Mam-A2.7 (32-40, TINPQVSKT) epitopes using an IFN-gamma ELISPOT assay. Interestingly, healthy individuals also showed high reactivity to the Mam-A2.2 epitope. Two CD8+ CTL lines generated in vitro against TAP-deficient T2 cells loaded with the candidate epitopes showed significant cytotoxic activity against the Mam-A2.1-4 epitopes. These CD8+CTL lines recognized a HLA-A2+breast cancer cell line expressing the Mam-A2.1 epitope. In addition, DNA vaccination of HLA-A2+/human CD8+ double-transgenic mice with a DNA construct encoding the Mam-A2.1 epitope and the HLA-A2 molecule induced a significant expansion of epitope-specific CD8+ CTLs that recognize the same HLA- A2+/Mam-A2.1+ breast cancer cell line. In conclusion, these results demonstrate the immunotherapeutic potential of mammaglobin-A for the treatment and prevention of breast cancer.

Response of established human breast tumors to vaccination with mammaglobin-A cDNA.

BACKGROUND: A novel breast cancer-associated antigen, mammaglobin-A, is expressed in 80% of primary breast tumors. The characterization of immune responses against this highly expressed breast cancer-specific antigen would be of value in the development of new therapeutic strategies for breast cancer. METHODS: We developed an in vivo model using human leukocyte antigen-A*0201/human CD8+ (HLA-A2+/hCD8+) double-transgenic mice to define the epitopes and to study the level of protection acquired by mammaglobin-A cDNA vaccination toward mammaglobin-A+/HLA-A2+ breast cancer cell lines. Mammaglobin-A epitopes were identified using an HLA class I peptide binding prediction computer program, and their activity was verified using gamma interferon ELISPOT and cytotoxicity assays. RESULTS: We identified seven mammaglobin-A-derived candidate epitopes that bind the HLA-A*0201 molecule (Mam-A2.1-7). CD8+ cytotoxic T lymphocytes (CTLs) from HLA-A2+/hCD8+ mice reacted to the Mam-A2.1 (amino acids [aa] 83-92, LIYDSSLCDL), Mam-A2.2 (aa 2-10, KLLMVLMLA), Mam-A2.4 (aa 66-74, FLNQTDETL), and Mam-A2.6 (aa 32-40, MQLIYDSSL) epitopes. CD8+ CTLs from breast cancer patients also recognized a similar epitope pattern as did those in the HLA-A2+/hCD8 mice and reacted to the Mam-A2.1, Mam-A2.2, Mam-A2.3, Mam-A2.4, and Mam-A2.7 epitopes. Passive transfer of mammaglobin-A-reactive CTLs into SCID (severe combined immunodeficient) beige mice with actively growing mammaglobin-A+ tumors resulted in statistically significant regression (P<.001) in the growth of the tumors. CONCLUSIONS: The HLA-A2+/hCD8+ mouse represents a valuable animal model to characterize the HLA-A*0201-restricted CD8+ CTL immune response to mammaglobin-A in vivo, and the data reported here demonstrate the immunotherapeutic potential of mammaglobin-A for the treatment and/or prevention of breast cancer.

Generation of CD8+ cytotoxic T lymphocytes against breast cancer cells by stimulation with mammaglobin-A-pulsed dendritic cells.

Mammaglobin-A is exclusively expressed by breast cancer cells. Thus, mammaglobin-A-specific T cell immune responses may be useful for the design of new breast cancer-specific immunotherapies. We show herein that CD8+ T cells generated against recombinant mammaglobin-A-pulsed dendritic cells display a marked cytotoxic activity against mammaglobin-A-positive breast cancer cell lines. This study indicates the immunotherapeutic potential of this novel antigen for the treatment of breast cancer.

User involvement in the design and evaluation of a smart mobility aid.

This paper describes the design and evaluation of an innovative smart mobility aid for the frail visually impaired. The Personal Adaptive Mobility AID (PAM-AID) was developed to address the difficulties in personal mobility of the frail and elderly visually impaired. The paper provides an overview of the PAM-AID research at Trinity College and describes the evolutionary nature of the design process. Because there were no existing systems to guide its development, a series of prototypes was constructed and they were regularly evaluated in the field. This approach views potential users as vital contributing members of the design team and led to rapid and hopefully useful improvements in the design.

Prolonged GABA(B) receptor-mediated synaptic inhibition in the cat spinal cord: an in vivo study.

In pentobarbitone-anaesthetised spinal cats, a comparison was made of the effects of intravenous bicuculline hydrochloride, a GABA(A)-receptor antagonist, and several (-)-baclofen (GABA(B)-receptor) antagonists (CGP 35348, 4638 , 56999A) on the prolonged inhibition of extensor-muscle monosynaptic reflexes, recorded from lumbar ventral roots, by brief or continuous tetanic stimulation of low-threshold afferent fibres of hindlimb flexor muscles. Two components of brief tetanus inhibition were detected. Whilst possibly of similar central latency, the inhibition associated with GABA(B) receptors had a longer time course than that reduced by bicuculline. Furthermore, whereas bicuculline reduced primary afferent depolarization, generated by the inhibitory volleys, and detected as dorsal-root potentials, such potentials were generally enhanced by intravenous baclofen antagonists. The inhibition of reflexes during and after continuous (333 Hz) tetanic flexor-nerve stimulation appeared to be predominantly associated with the activation of GABA(B) receptors. In the period following continuous tetanic flexor-nerve stimulation, during which monosynaptic extensor reflexes were reduced in amplitude, the action potentials of the intraspinal terminations of extensor-muscle group-Ia afferent fibres were reduced in duration, as detected by the time course of the recovery of the threshold to extracellular microstimulation following the arrival of an orthodromic impulse. A reduction in termination action-potential duration also accompanied the reduction by microelectrophoretic (-)-baclofen of the release of excitatory transmitter from group-Ia terminations, both presynaptic effects being blocked by microelectrophoretic baclofen antagonists. However, the reduction of the duration of the action potential of individual group-Ia terminations, which followed continuous flexor-nerve stimulation, was not sensitive to the baclofen antagonist CGP 55845A, but was diminished by bicuculline methochloride. Intravenously administered bicuculline hydrochloride, however, had little or no effect on the inhibition of reflexes following continuous flexor-nerve stimulation. These observations are discussed in the context of possible intraspinal pathways and pre- and postsynaptic mechanisms for GABA(A) and GABA(B) receptor-mediated inhibition of the monosynaptic excitation of spinal motoneurones and of the functional significance of central GABA(B) receptor-associated inhibitory processes, given the relatively minimal effects on motor activity and behaviour produced by baclofen antagonists that penetrate the mammalian blood-brain barrier.

Baclofen: reduction of presynaptic calcium influx in the cat spinal cord in vivo.

In the ventral horn of the lumbar spinal cord of cats anaesthetised with pentobarbitone sodium, micro-electrophoretically administered (-)-baclofen, but not (+)-baclofen, reversibly reduced the duration of the orthodromic action potential of muscle group Ia afferent terminations, but not those of muscle group I afferent myelinated fibres. The presumably submicromolar concentrations are already known to reversibly reduce excitatory transmitter release from muscle group Ia afferent terminations. Action potential durations were estimated from threshold recovery curves after an orthodromic impulse using an extracellular microstimulation technique. Both of these presynaptic effects of (-)-baclofen were blocked by baclofen antagonists, and neither appeared to be reduced by the potassium channel blocking agents tetraethylammonium and 4-aminopyridine. Tetraethylammonium and 4-aminopyridine also did not significantly modify the reduction by (-)-baclofen of monosynaptic field potentials in the lumbar cord of rats anaesthetised with pentobarbitone sodium. In the cat the maximum reduction by (-)-baclofen of termination action potentials was considerably less than that produced by cadmium ions, which, unlike (-)-baclofen, also reduced the action potential duration of group I myelinated fibres. These findings are consistent with a reduction by (-)-baclofen of the influx of calcium through voltage-activated channels in the membrane of group Ia terminations, a proposal which also accounts for the reduction by (-)-baclofen of the release of GABA at axo-axonic depolarizing synapses on these terminations. The results are discussed in relation to the mode of action of (-)-baclofen and the different sensitivities of transmitter release at various central synapses.

The lack of effect of baclofen on action potentials of spinal motor axon collateral terminations in vivo.

In the lumbar ventral horn of pentobarbitone-anaesthetised cats, (-)-baclofen reduces both the synaptic release of excitatory transmitter from muscle group Ia afferent terminations and the duration of the presynaptic action potentials of these terminations, presumably by interfering with the influx of calcium ions through voltage-activated channels. Baclofen, however, has little or no effect on cholinergic excitation at motor axon collateral synapses on spinal Renshaw cells and, in the present study, was found not to reduce the duration of the action potential of axon collateral terminations located in the vicinity of Renshaw cells in pentobarbitone-anaesthetised cats. Furthermore, in contrast to group Ia terminations, a 4-aminopyridine-sensitive potassium conductance could not be detected as contributing to axon collateral termination action potentials. These results suggest that there may be differences in presynaptic ion fluxes associated with transmitter release at the intraspinal terminations of group Ia afferent fibres and motor axon collaterals in the cat spinal cord.

The effect on patients of non-referral for skull radiography following mild head injury.

This paper assesses the attitude of 705 patients who attended the Accident department of a large metropolitan district general hospital, with a mild head injury and who were not referred for skull radiography. A questionnaire was sent to patients 5-7 months after they had attended. Fifty-one per cent had expected an X-ray, and when this did not occur, the majority of this group (63 per cent) left the Accident department disappointed. Furthermore, the duration of symptoms in this group was prolonged. The introduction of guidelines may reduce clinically unnecessary X-ray examinations, but some of the consequences may not be fully appreciated. In this study, a significant number of patients were dissatisfied with the lack of X-ray referral. The main cause for the associated prolongation of symptoms is not clear, but a contributory factory may be that lack of referral for radiography led to anxiety concerning the thoroughness of their management.

Synaptic inhibition mediated by GABAB receptors in the neonatal rat spinal cord in vitro.

In the neonatal rat spinal cord in vitro prolonged inhibition of dorsal root to ventral root reflexes was achieved by electrical stimulation of an adjacent ipsilateral dorsal root. This prolonged inhibition lasted in excess of 1 s. An early phase of the prolonged inhibition was reduced by the GABAA receptor antagonist bicuculline methochloride with a concomitant reduction of dorsal root potentials which are an indication of primary afferent depolarisation. A longer latency and duration component of prolonged inhibition could be blocked by the selective GABAB receptor antagonist CGP56999A and therefore appeared to be mediated by baclofen-sensitive GABAB receptors. This GABAB receptor antagonist did not reduce dorsal root potentials suggesting that the component of prolonged inhibition mediated by GABAB receptors did not involve primary afferent depolarisation.

Posters for accident departments: simple method of sustaining reduction in x ray examinations.

OBJECTIVE: To assess whether a simple strategy would sustain a reduction in the number of unnecessary x ray examinations. DESIGN: Use of posters to display guidelines encouraging the more effective use of radiology in patients with head injuries, twisted ankles, neck injuries, and abdominal pain. SETTING: Accident department of a large metropolitan district general hospital. PATIENTS: 15,875 patients attending the accident department over two years. MAIN OUTCOME MEASURE: Proportion of patients having radiography. RESULTS: Referrals for skull radiography fell from 56% to 20% and those for abdominal radiography fell from 31% to 7%. Referral patterns for adults attending with twisted ankles and cervical spine injuries did not change. Reductions were sustained over two years. CONCLUSION: Carefully designed posters provide a simple method of reducing unnecessary x ray examinations.

An in vivo electrophysiological investigation of group Ia afferent fibres and ventral horn terminations in the cat spinal cord.

An extracellular microstimulation technique has been used to investigate and compare the properties of group I primary afferent myelinated fibres in the dorsal column and group Ia unmyelinated terminations in the lumbar spinal cord of cats anaesthetised with pentobarbitone sodium. Fibres were distinguished from terminations on the basis of location, anodic blocking factor and sensitivity to GABAA mimetics. The recovery curves of threshold following an orthodromic impulse provided an estimate of both action potential duration and rate of repolarization. The action potentials of group Ia terminations were of briefer duration (by a factor of approximately 2) with more rapid rates of repolarization (factor of approximately 3) than those of the myelinated fibres. The prolongation of termination but not fibre action potentials by microelectrophoretic tetraethylammonium and 4-aminopyridine indicated the presence of voltage-activated potassium channels in the termination membrane. Differences in the effects on Ia termination action potentials of depolarizations (reductions in threshold) associated with a preceding action potential, synaptically released GABA, microelectrophoretic piperidine-4-sulphonic acid or DL-homocysteic acid suggest that an increase in termination membrane conductance is the major factor in the reduction of transmitter release during the activation of presynaptic GABAA receptors.

Differing actions of nitropropane analogs of GABA and baclofen in central and peripheral preparations.

In the guinea-pig isolated ileum, both baclofen (5-100 microM) and gamma-aminobutyric acid (GABA; 5-100 microM) induced a bicuculline-insensitive depression of cholinergic twitch contractions which was reversibly and competitively antagonised by 3-amino-1-nitropropane (50-250 microM). 3-Amino-1-nitropropane (pA2 = 5.0 +/- 0.1) was twice as potent as 2-hydroxysaclofen (pA2 = 4.5 +/- 0.1), but was equipotent with 3-aminopropyl(P-diethoxymethyl)phosphinic acid (CGP 35348) (pA2 = 4.9 +/- 0.2), and did not show any partial agonist activity at these peripheral GABAA or GABAB receptor sites. In rat neocortical slices, 3-amino-1-nitropropane did not activate GABAB receptor sites or affect baclofen-induced suppression of spontaneous discharges. In the cat spinal cord, however, under in vivo conditions, the corresponding nitro analog of baclofen 3-amino-2-(4-chloro)-nitropropane was an agonist at GABAB receptor sites, although more than 60 times weaker than baclofen in depressing monosynaptic excitatory field potentials, whereas 3-amino-1-nitropropane was an extremely weak agonist at bicuculline-sensitive GABAA sites. The differing actions of 3-amino-1-nitropropane at peripheral and central GABAB receptor sites suggest heterogeneity among these receptors.

Phosphinic acid derivatives as baclofen agonists and antagonists in the mammalian spinal cord: an in vivo study.

The actions of a series of derivatives of 3-aminopropyl-phosphinic acid as baclofen agonists and antagonists have been examined on the synaptic excitation of neurones by impulses in primary afferent fibres in the lumbar spinal cords of pentobarbitone-anaesthetised cats and rats. Both the pre- and postsynaptic inhibitory actions of microelectrophoretic (-)-baclofen were reduced by similarly administered CGP 35,348, 36,742, 46,381, 52,432, 54,626 and 55,845, the latter being the most potent antagonist. None of these antagonists either decreased or increased the excitability of spinal neurones, and the inhibitory action of GABA was reduced only by local concentrations of antagonists which also reduced the action of piperidine-4-sulphonic acid, a GABAA agonist. Although the weak inhibitory effect of 3-aminopropylphosphinic acid in both the rat and the cat was not reduced by these baclofen antagonists, the pre- and postsynaptic inhibitory effects of 3-aminopropyl-methyl-phosphinic acid (CGP 35,024), which was more potent than (-)-baclofen, were reduced by the antagonists. Like (-)-baclofen, CGP 35,024 was relatively ineffective in reducing transmitter release in the cord from the terminals of excitatory spinal interneurones, the terminals of excitatory tracts in the dorsolateral funiculus and the cholinergic terminals of motor axon collaterals. In both rat and cat cords, receptors for (-)-baclofen could not be demonstrated to be activated by microelectrophoretic GABA, possibly because of the predominantly dendritic location of GABAB receptors. Spinal pre- and postsynaptic baclofen receptors appeared to be pharmacologically similar but differed from those in the higher central nervous system of the rat, where 3-aminopropylphosphinic acid has been reported to be an effective baclofen agonist. The compounds tested, particularly CGP 55,845 and 46,381, will be of use in further investigations of the physiological relevance of baclofen receptors at central synapses where GABA may be the transmitter.