TULIPs decorate the three-dimensional genome of PFA ependymoma.

Posterior fossa group A (PFA) ependymoma is a lethal brain cancer diagnosed in infants and young children. The lack of driver events in the PFA linear genome led us to search its 3D genome for characteristic features. Here, we reconstructed 3D genomes from diverse childhood tumor types and uncovered a global topology in PFA that is highly reminiscent of stem and progenitor cells in a variety of human tissues. A remarkable feature exclusively present in PFA are type B ultra long-range interactions in PFAs (TULIPs), regions separated by great distances along the linear genome that interact with each other in the 3D nuclear space with surprising strength. TULIPs occur in all PFA samples and recur at predictable genomic coordinates, and their formation is induced by expression of EZHIP. The universality of TULIPs across PFA samples suggests a conservation of molecular principles that could be exploited therapeutically.

Direct observation of the effects of chemical fixation in MNT-1 cells: A SE-ADM and Raman study.

Aldehydes fixation was accidentally discovered in the early 20th century and soon became a widely adopted practice in the histological field, due to an excellent staining enhancement in tissues imaging. However, the fixation process itself entails cell proteins denaturation and crosslinking. The possible presence of artifacts, that depends on the specific system under observation, must therefore be considered to avoid data misinterpretation. This contribution takes advantage of scanning electron assisted-dielectric microscopy (SE-ADM) and Raman 2D imaging to reveal the possible presence and the nature of artifacts in unstained, and paraformldehyde, PFA, fixed MNT-1 cells. The high resolution of the innovative SE-ADM technique allowed the identification of globular protein clusters in the cell cytoplasm, formed after protein denaturation and crosslinking. Concurrently, SE-ADM images showed a preferential melanosome adsorption on the cluster's outer surface. The micron-sized aggregates were discernible in Raman 2D images, as the melanosomes signal, extracted through 2D principal component analysis, unequivocally mapped their location and distribution within the cells, appearing randomly distributed in the cytoplasm. Protein clusters were not observed in living MNT-1 cells. In this case, mature melanosomes accumulate preferentially at the cell periphery and are more closely packed than in fixed cells. Our results show that, although PFA does not affect the melanin structure, it disrupts melanosome distribution within the cells. Proteins secondary structure, conversely, is partially lost, as shown by the Raman signals related to α-helix, ß-sheets, and specific amino acids that significantly decrease after the PFA treatment.

Long-term outcomes of the pentaspline pulsed-field ablation catheter for the treatment of paroxysmal atrial fibrillation: results of the prospective, multicentre FARA-Freedom Study.

AIMS: Pulmonary vein isolation (PVI) is a well-established strategy for the treatment of paroxysmal atrial fibrillation (PAF). Despite randomized controlled trials and real-world data showing the promise of pulsed-field ablation (PFA) for this treatment, long-term efficacy and safety data demonstrating single-procedure outcomes off antiarrhythmic drugs remain limited. The aim of the FARA-Freedom Study was to evaluate the long-term efficacy and safety of PFA using the pentaspline catheter for PAF. METHODS AND RESULTS: FARA-Freedom, a prospective, non-randomized, multicentre study, enrolled patients with PAF undergoing de novo PVI with PFA, who were followed for 12 months with weekly transtelephonic monitoring and a 72-h Holter ECG at 6 and 12 months. The primary safety endpoint was a composite of device- or procedure-related serious adverse events out to 7 days post-ablation and PV stenosis or atrioesophageal (AE) fistula out to 12 months. Treatment success is a composite of acute PVI and chronic success, which includes freedom from any documented atrial tachyarrhythmia longer than 30 s, use of antiarrhythmic drugs or cardioversion after a 3-month blanking period, or use of amiodarone or repeat ablation at any time. The study enrolled 179 PAF patients (62 ± 10 years, 39% female) at 13 centres. At the index procedure, all PVs were successfully isolated with the pentaspline PFA catheter. Procedure and left atrial dwell times, with a 20-min waiting period, were 71.9 ± 17.6 and 41.0 ± 13.3 min, respectively. Fluoroscopy time was 11.5 ± 7.4 min. Notably, monitoring compliance was high, with 88.4 and 90.3% with weekly events and 72-h Holter monitors, respectively. Freedom from the composite primary effectiveness endpoint was 66.6%, and 41 patients had atrial tachyarrhythmia recurrence, mostly recurrent atrial fibrillation (31 patients). The composite safety endpoint occurred in two patients (1.1%), one tamponade and one transient ischaemic attack. There was no coronary spasm, PV stenosis, or AE fistula. There were four cases of transient phrenic nerve palsy, but all resolved during the index procedure. CONCLUSION: In this prospective, non-randomized, multicentre study, PVI using a pentaspline PFA catheter was effective in treating PAF patients despite rigourous endpoint definitions and high monitoring compliance and demonstrated favourable safety. REGISTRATION: Clinical Trials.gov Identifier: NCT05072964 (sponsor: Boston Scientific Corporation).

Optimizing neurotransmitter pathway detection by IR-MALDESI-MSI in mouse brain.

Mass spectrometry imaging (MSI) platforms such as infrared matrix-assisted laser desorption electrospray ionization (IR-MALDESI) are advantageous for a variety of applications, including elucidating the localization of neurotransmitters (NTs) and related molecules with respect to ion abundance across a sample without the need for derivatization or organic matrix application. While IR-MALDESI-MSI conventionally uses a thin exogenous ice matrix to improve signal abundance, it has been previously determined that sucrose embedding without the ice matrix improves detection of lipid species in striatal, coronal mouse brain sections. This work considers components of this workflow to determine the optimal sample preparation and matrix to enhance the detection of NTs and their related metabolites in coronal sections from the striatal region of the mouse brain. The discoveries herein will enable more comprehensive follow-on studies for the investigation of NTs to enrich biological pathways and interpretation related to neurodegenerative diseases and ischemic stroke.

Visualization of fibroblast activation using 68Ga-FAPI PET/CT after pulmonary vein isolation with pulsed field compared with cryoballoon ablation.

BACKGROUND: Pulsed-field ablation (PFA) is a novel ablation modality for atrial fibrillation (AF) ablating myocardium by electroporation without tissue-heating. With its different mechanism of tissue ablation, it is assumed that lesion creation is divergent to thermal energy sources. 68Ga-fibroblast-activation protein inhibitor (FAPI) PET/CT targets FAP-alpha expressed by activated fibroblasts. We aimed to assess 68Ga-FAPI uptake in pulmonary veins as surrogate for ablation damage after PFA and cryoballoon ablation (CBA). METHODS: 26 patients (15 PFA, 11 CBA) underwent 68Ga-FAPI-PET/CT after ablation. Standardized uptake values (SUV) and fibroblast-activation volumes of localized tracer uptake were assessed. RESULTS: Patient characteristics were comparable between groups. In PFA, focal FAPI uptake was only observed in 3/15 (20%) patients, whereas in the CBA cohort, 10/11 (90.9%) patients showed atrial visual uptake. We observed lower values of SUVmax (2.85 ± 0.56 vs 4.71 ± 2.06, P = 0.025) and FAV (1.13 ± 0.84 cm3 vs 3.91 ± 2.74 cm3, P = 0.014) along with a trend towards lower SUVpeak and SUVmean in PFA vs CBA patients, respectively. CONCLUSION: Tissue response with respect to fibroblast activation seems to be less pronounced in PFA compared to established thermal ablation systems. This functional assessment might contribute to a better understanding of lesion formation in thermal and PFA ablation potentially contributing to better safety outcomes.

Towards 50 years of platelet function analyser (PFA) testing.

The platelet function analyser (PFA) is a prevalent platelet function screening instrument, and comes in two models-the original PFA-100 and the contemporary PFA-200. The instruments have 'identical' output, being a 'closure time' (CT). Moreover, normal reference ranges provided by the manufacturer, for the specific test cartridges, are the same for both models. There are three different types of test cartridge: collagen/epinephrine (C/Epi), collagen/adenosine diphosphate (C/ADP), and "Innovance PFA P2Y" (only available in certain geographical locations). The PFA-100 was released in the mid 1990s, and so is approaching 50 years of age. The PFA-200, released in some locations in the mid 2010s, is destined to eventually replace the PFA-100, but is not yet available in the USA. The test system is highly sensitive to von Willebrand disease (VWD; C/Epi and C/ADP) and to aspirin therapy (C/Epi only), but only has moderate sensitivity to defects in platelet function and/or deficiencies in platelet number. Accordingly, recommendations for use for screening platelet function vary according to user experience. Some workers have alternatively used the PFA to assess thrombosis risk or pre-operative bleeding risk. In this review, we provide an overview of the history of PFA, and summarise its current clinical utility.

The effect of recombinant versus plasma-derived von Willebrand factor on prolonged PFA closure times in ECMO patients with acquired von Willebrand syndrome - an observational study.

BACKGROUND: Extracorporeal membrane oxygenation (ECMO) is applied in patients with respiratory or cardiopulmonary failure, but bleeding is a frequent complication contributing to the high mortality rates in this patient collective. A major factor predisposing patients to bleeding events is an acquired von Willebrand syndrome (aVWS). So far, specific treatment options for this phenomenon are lacking. In hereditary von Willebrand disease (VWD), treatment with recombinant or plasma-derived von Willebrand factor (rVWF or pVWF) is common practice. Closure time measured by the Platelet Function Analyser-200 (PFA-200) is an established assay to detect defects in primary hemostasis and the method is useful to monitor the effect of hemostatic therapy. The aim of this study was to assess the effect of recombinant (rVWF) vs. plasma-derived von Willebrand factor (pVWF) on closure times measured by PFA in blood obtained from ECMO patients with aVWS. METHODS: Blood was sampled from thirteen patients receiving extracorporeal membrane oxygenation and three patients with hereditary VWD. Diagnosis of aVWS was made by conventional coagulation parameters and by multimeric structure analysis. PFA analysis of blood spiked with rVWF or pVWF was performed. RESULTS: Thirteen patients receiving ECMO were recruited. Ten patients survived and three patients suffered major bleeding complications. PFA closure times in ECMO patients with aVWS spiked with rVWF were significantly shorter at all concentrations than with pVWF (e.g., rVWF vs. pVWF: 1 U/ml: 150.4 ± 21.7 s vs. 263.8 ± 11.7 s; 4 U/ml: 97.8 ± 9.8 s vs. 195.8 ± 15.4 s, p<0.001). PFA closure times were also significantly shorter in three patients with hereditary VWD treated with rVWF compared to pVWF (e.g., 1 U/ml rVWF vs. pVWF: 73.7±1.33 s vs. 231.3±43.4 s, p<0.01) CONCLUSION: In summary, this study shows that rVWF compared to pVWF more effectively reduced PFA closures times in blood samples of ECMO patients with aVWS. Higher doses of VWF are needed to normalize PFA closure time in blood samples of patients with ECMO-induced aVWS compared to hereditary VWD. These data support the use of PFA-200 to monitor hemostatic effects in a future clinical trial involving ECMO patients with aVWS.

Comparative analysis of sucrose-embedding for whole-body zebrafish MSI by IR-MALDESI.

Infrared matrix-assisted laser desorption electrospray ionization mass spectrometry imaging (IR-MALDESI) conventionally utilizes fresh-frozen biological tissues with an ice matrix to improve the detection of analytes. Sucrose-embedding with paraformaldehyde fixation has demonstrated feasibility as an alternative matrix for analysis by IR-MALDESI by preserving tissue features and enhancing ionization of lipids. However, investigating multi-organ systems provides broader context for a biological study and can elucidate more information about a disease state as opposed to a single organ. Danio rerio, or zebrafish, are model organisms for various disease states and can be imaged as a multi-organ sample to analyze morphological and metabolomic preservation as a result of sample preparation. Herein, whole-body zebrafish were imaged to compare sucrose-embedding with paraformaldehyde fixation against conventional fresh-frozen sample preparation. Serial sections were analyzed with and without an ice matrix to evaluate if sucrose functions as an alternative energy-absorbing matrix for IR-MALDESI applications across whole-body tissues. The resulting four conditions were compared in terms of total putative lipid annotations and category diversity, coverage across the entire m/z range, and ion abundance. Ultimately, sucrose-embedded zebrafish had an increase in putative lipid annotations for the combination of putative annotations with and without the application of an ice matrix relative to fresh-frozen tissues which require the application of an ice matrix. Upon the use of an ice matrix, a greater number of high mass putative lipid annotations (e.g., glycerophospholipids, glycerolipids, and sphingolipids) were identified. Conversely, without an ice matrix, sucrose-embedded sections elucidated more putative annotations in lower molecular weight lipids, including fatty acyls and sterol lipids. Similar to the mouse brain model, sucrose-embedding increased putative lipid annotation and abundance for whole-body zebrafish.

Patellofemoral arthroplasty with onlay prosthesis leads to higher rates of osteoarthritis progression than inlay design implants: a systematic review.

PURPOSE: The aim of this study was to report the clinical and functional outcomes, complication rates, implant survivorship and the progression of tibiofemoral osteoarthritis (OA), after new inlay or onlay patellofemoral arthroplasty (PFA), for isolated patellofemoral OA. Comparison of different implant types and models, where it was possible, also represented one of the objectives. METHODS: A systematic literature search following PRISMA guidelines was conducted on PubMed, Scopus, Embase and Cochrane databases, to identify possible relevant studies, published from the inception of these databases until 11.11.2022. Randomized control trials (RCTs), case series, case control studies and cohort studies, written in English or German, and published in peer-reviewed journals after 2010, were included. Not original studies, case reports, simulation studies, systematic reviews, or studies that included patients who underwent TKA or unicompartmental arthroplasty (UKA) of the medial or lateral compartment of the knee, were excluded. Additionally, only articles that assessed functional and/or clinical outcomes, patient-reported outcomes (PROMs), radiographic progression of OA, complication rates, implant survival rates, pain, as well as conversion to TKA rates in patients treated with PFA, using inlay or onlay trochlea designs, were included. For quality assessment, the Methodological Index for Non-Randomized Studies (MINORS) for non-comparative and comparative clinical intervention studies was used. RESULTS: The literature search identified 404 articles. 29 of them met all the inclusion criteria following the selection process. Median MINORS for non-comparative studies value was 12.5 (range 11-14), and for comparative studies 20.1 (range 17-24). In terms of clinical and functional outcomes, no difference between onlay and inlay PFA has been described. Both designs yielded satisfactory results at short, medium and long-term follow-ups. Both designs improved pain postoperatively and no difference between them in terms of postoperative VAS has been noted, although the onlay groups presented a higher preoperative VAS. When comparing the inlay to onlay trochlea designs, the inlay group displayed a lower progression of OA rate. CONCLUSION: There is no difference in functional or clinical outcomes after PFA between the new inlay and the onlay designs, with both presenting an improvement in most of the scores that were used. A higher rate of OA progression was observed in the onlay design group. LEVEL OF EVIDENCE: III.

Outcomes are Compromised When Revising Patellofemoral Arthroplasties for Patellar Component Failures.

BACKGROUND: Outcomes of patellofemoral arthroplasty (PFA) to total knee arthroplasty (TKA) conversion are reported to be similar to primary cases. The purpose of this study was to determine whether the cause for conversion from PFA to TKA correlated to outcomes when compared to a matched cohort. METHODS: A retrospective chart review was performed to identify aseptic PFA to TKA conversions between 2000 and 2021. A cohort of primary TKAs was matched by patient sex, body mass index, and American Society of Anesthesiology score. Clinical outcomes, including range of motion, complication rates, and patient reported outcomes measurement information systems scores, were compared. Chi-squared, Fisher's Exact, and t-tests were performed. There were 20 PFA to TKA conversions that met inclusion criteria and were matched to 60 primary cases. RESULTS: There were 7 cases revised for arthritis progression, 5 for femoral component failure, 5 for patellar component failure, and 3 for patellar maltracking. PFA to TKA conversions for patellar failure (fracture, component loosening) had worse postoperative flexion (115 versus 127°, P = .023) and more complications of stiffness (40 versus 0%, P = .046) than primary TKAs. Conversions for failed patellar components had worse patient reported outcomes measurement information systems physical function (32 versus 45, P = .0046), physical health (42 versus 49, P = .0258), and pain scores (45 versus 24, P = .0465). No differences were found in rates of infection, manipulations under anesthesia, or reoperations. CONCLUSION: PFA to TKA conversion outcomes were similar to primary TKA, except in patients who had failed patellar components and demonstrated worse postoperative range of motion and patient-reported outcomes. Surgeons should avoid thin patellar resections and extensive lateral releases to minimize patellar failures.

Exploiting Light Polarization for Deep HDR Imaging from a Single Exposure.

In computational photography, high dynamic range (HDR) imaging refers to the family of techniques used to recover a wider range of intensity values compared to the limited range provided by standard sensors. Classical techniques consist of acquiring a scene-varying exposure to compensate for saturated and underexposed regions, followed by a non-linear compression of intensity values called tone mapping. Recently, there has been a growing interest in estimating HDR images from a single exposure. Some methods exploit data-driven models trained to estimate values outside the camera's visible intensity levels. Others make use of polarimetric cameras to reconstruct HDR information without exposure bracketing. In this paper, we present a novel HDR reconstruction method that employs a single PFA (polarimetric filter array) camera with an additional external polarizer to increase the scene's dynamic range across the acquired channels and to mimic different exposures. Our contribution consists of a pipeline that effectively combines standard HDR algorithms based on bracketing and data-driven solutions designed to work with polarimetric images. In this regard, we present a novel CNN (convolutional neural network) model that exploits the underlying mosaiced pattern of the PFA in combination with the external polarizer to estimate the original scene properties, and a second model designed to further improve the final tone mapping step. The combination of such techniques enables us to take advantage of the light attenuation given by the filters while producing an accurate reconstruction. We present an extensive experimental section in which we validate the proposed method on both synthetic and real-world datasets specifically acquired for the task. Quantitative and qualitative results show the effectiveness of the approach when compared to state-of-the-art methods. In particular, our technique exhibits a PSNR (peak signal-to-noise ratio) on the whole test set equal to 23 dB, which is 18% better with respect to the second-best alternative.

Single-Molecule Localization Microscopy of Presynaptic Active Zones in Drosophila melanogaster after Rapid Cryofixation.

Single-molecule localization microscopy (SMLM) greatly advances structural studies of diverse biological tissues. For example, presynaptic active zone (AZ) nanotopology is resolved in increasing detail. Immunofluorescence imaging of AZ proteins usually relies on epitope preservation using aldehyde-based immunocompetent fixation. Cryofixation techniques, such as high-pressure freezing (HPF) and freeze substitution (FS), are widely used for ultrastructural studies of presynaptic architecture in electron microscopy (EM). HPF/FS demonstrated nearer-to-native preservation of AZ ultrastructure, e.g., by facilitating single filamentous structures. Here, we present a protocol combining the advantages of HPF/FS and direct stochastic optical reconstruction microscopy (dSTORM) to quantify nanotopology of the AZ scaffold protein Bruchpilot (Brp) at neuromuscular junctions (NMJs) of Drosophila melanogaster. Using this standardized model, we tested for preservation of Brp clusters in different FS protocols compared to classical aldehyde fixation. In HPF/FS samples, presynaptic boutons were structurally well preserved with ~22% smaller Brp clusters that allowed quantification of subcluster topology. In summary, we established a standardized near-to-native preparation and immunohistochemistry protocol for SMLM analyses of AZ protein clusters in a defined model synapse. Our protocol could be adapted to study protein arrangements at single-molecule resolution in other intact tissue preparations.

Effect of Oxyfluorination of PFA-Coated Metal Mesh with Superhydrophobic Properties on the Filtration Performance of SiO2 Microparticles.

Recently, semiconductor wastewater treatment has received much attention due to the emergence of environmental issues. Acid-resistant coatings are essential for metal prefilters used in semiconductor wastewater treatment. Perfluoroalkoxy alkane is mainly used as an acid-resistant coating agent, since PFA has inherent superhydrophobicity, water permeability is lowered. To solve this problem, the surface of the PFA-coated metal mesh was treated via an oxyfluorination method in which an injected mixed gas of fluorine and oxygen reacted with the surface functional groups. Surface analysis, water contact angle measurement, and water permeability tests were performed on the surface-treated PFA-coated mesh. Consequently, the superhydrophobic surface was effectively converted to a hydrophobic surface as the PFA coating layer was surface-modified with C-O-OH functional groups via the oxyfluorination reaction. As a result of using simulation solutions that float silica particles of various sizes, the permeability and particle removal rate of the surface-modified PFA-coated stainless-steel mesh were improved compared to those before surface modification. Therefore, the oxyfluorination treatment used in this study was suitable for improving the filtration performance of SiO2 microparticles in the PFA-coated stainless-steel mesh.

Implementing Psychological First Aid for Healthcare Workers During the COVID-19 Pandemic: A Feasibility Study of the ICARE Model.

Maintaining the resilience of healthcare workers (HCWs) during the protracted COVID-19 pandemic is critical as chronic stress is associated with burnout, inability to provide high-quality care, and decreased attentiveness to infection prevention protocols. Between May and July 2020, we implemented the ICARE model of psychological first aid (PFA) in a novel online (i.e., telehealth) format to address the psychological support needs of HCWs during the COVID-19 pandemic. We found that HCWs needed psychological support related to obtaining clear information about pandemic policies and guidelines, navigating new rules and responsibilities, and processing overwhelming and conflicting emotions. The HCWs in our program repeatedly expressed appreciation for the support we provided. Future directions include establishing online discussion forums, increasing opportunities for individual support, and training HCWs to provide peer support using PFA. This program has far-reaching potential benefit to HCWs and to society at large in the context of a pandemic.

Glyoxal as an alternative fixative to formaldehyde in immunostaining and super-resolution microscopy.

Paraformaldehyde (PFA) is the most commonly used fixative for immunostaining of cells, but has been associated with various problems, ranging from loss of antigenicity to changes in morphology during fixation. We show here that the small dialdehyde glyoxal can successfully replace PFA Despite being less toxic than PFA, and, as most aldehydes, likely usable as a fixative, glyoxal has not yet been systematically tried in modern fluorescence microscopy. Here, we tested and optimized glyoxal fixation and surprisingly found it to be more efficient than PFA-based protocols. Glyoxal acted faster than PFA, cross-linked proteins more effectively, and improved the preservation of cellular morphology. We validated glyoxal fixation in multiple laboratories against different PFA-based protocols and confirmed that it enabled better immunostainings for a majority of the targets. Our data therefore support that glyoxal can be a valuable alternative to PFA for immunostaining.

EZHIP: a new piece of the puzzle towards understanding pediatric posterior fossa ependymoma.

Ependymomas (EPN) are tumors of the central nervous system (CNS) that can arise in the supratentorial brain (ST-EPN), hindbrain or posterior fossa (PF-EPN) or anywhere in the spinal cord (SP-EPN), both in children and adults. Molecular profiling studies have identified distinct groups and subtypes in each of these anatomical compartments. In this review, we give an overview on recent findings and new insights what is driving PFA ependymomas, which is the most common group. PFA ependymomas are characterized by a young median age at diagnosis, an overall balanced genome and a bad clinical outcome (56% 10-year overall survival). Sequencing studies revealed no fusion genes or other highly recurrently mutated genes, suggesting that the disease is epigenetically driven. Indeed, recent findings have shown that the characteristic global loss of the repressive histone 3 lysine 27 trimethylation (H3K27me3) mark in PFA ependymoma is caused by aberrant expression of the enhancer of zeste homolog inhibitory protein (EZHIP) or in rare cases by H3K27M mutations, which both inhibit EZH2 thereby preventing the polycomb repressive complex 2 (PRC2) from spreading H3K27me3. We present the current status of the ongoing work on EZHIP and its essential role in the epigenetic disturbance of PFA biology. Comparisons to the oncohistone H3K27M and its role in diffuse midline glioma (DMG) are drawn, highlighting similarities but also differences between the tumor entities and underlying mechanisms. A strong focus is to point out missing information and to present directions of further research that may result in new and improved therapies for PFA ependymoma patients.

Psychological first aid for workers in care and nursing homes: systematic review.

BACKGROUND: The Covid-19 pandemic has produced unprecedented challenges across all aspects of health and social care sectors globally. Nurses and healthcare workers in care homes have been particularly impacted due to rapid and dramatic changes to their job roles, workloads, and working environments, and residents' multimorbidity. Developed by the World Health Organisation, Psychological First Aid (PFA) is a brief training course delivering social, emotional, supportive, and pragmatic support that can reduce the initial distress after disaster and foster future adaptive functioning. OBJECTIVES: This review aimed to synthesise findings from studies exploring the usefulness of PFA for the well-being of nursing and residential care home staff. METHODS: A systematic search was conducted across 15 databases (Social Care Online, Kings Fund Library, Prospero, Dynamed, BMJ Best Practice, SIGN, NICE, Ovid, Proquest, Campbell Library, Clinical Trials, Web of Knowledge, Scopus, Ebsco CINAHL, and Cochrane Library), identifying peer-reviewed articles published in English language from database inception to 20th June 2021. RESULTS: Of the 1,159 articles screened, 1,146 were excluded at title and abstract; the remaining 13 articles were screened at full text, all of which were then excluded. CONCLUSION: This review highlights that empirical evidence of the impact of PFA on the well-being of nursing and residential care home staff is absent. PFA has likely been recommended to healthcare staff during the Covid-19 pandemic. The lack of evidence found here reinforces the urgent need to conduct studies which evaluates the outcomes of PFA particularly in the care home staff population.

X-ray crystal structure and specificity of the Toxoplasma gondii ME49 TgAPN2.

Toxoplasmosis is a parasitic disease caused by infection with Toxoplasma gondii that currently has few therapeutic options. The M1 aminopeptidase enzymes have been shown to be attractive targets for anti-parasitic agents and/or vaccine candidates, suggesting potential to re-purpose inhibitors between parasite M1 aminopeptidase targets. The M1 aminopeptidase TgAPN2 has been suggested to be a potential new drug target for toxoplasmosis. Here we investigate the structure and function of TgAPN2, a homologue of the antimalarial drug target PfA-M1, and evaluate the capacity to use inhibitors that target PfA-M1 against TgAPN2. The results show that despite a similar overall fold, the TgAPN2 has a unique substrate specificity and inhibition profile. Sequence and structure differences are investigated and show how comparative structure-activity relationships may provide a route to obtaining potent inhibitors of TgAPN2.

Lessons for psychiatrists from the COVID pandemic: the need for expanded roles and additional competencies.

The disaster of the COVID-19 pandemic has fundamentally changed the norms of psychiatric practice: from its methods of care delivery to its methods of practice. Traditional methods of care delivery using in-person visits became impractical or unsafe. Meanwhile, the pandemic has resulted in an increased demand for services. The resulting pivot to telepsychiatry required a skillset that was not a part of traditional psychiatry training. To meet the demand for services, many providers needed to join collaborative models of care to help scale their expertise. Although many innovative collaborative models of care exist, providers remain in their traditional consultative roles within many of those models. In a disaster, when there is an expanding mental health care need in the population, psychiatrists need to adapt their practice to meet expanded roles that naturally build on their usual ones. We explore the expanded roles that psychiatrists will need to fill based on what is known about the field of disaster mental health and principles from Psychological First Aid (PFA). In preparation for a new normal, in what George Everly describes as a 'disaster of uncertainty,' we propose evolutions in the way psychiatrists are trained. Specific training on telepsychiatry best practices will prepare psychiatrists to use this method most effectively and appropriately. Additional training should focus on the core competencies of disaster psychiatry: effective crisis leadership and strategic planning, disaster surveillance, knowledge of benign vs. concerning symptoms, psychological triage, implementation of crisis interventions, resource facilitation, crisis communication, and self and peer care. Developing and integrating these competencies into psychiatry training programs will best prepare psychiatrists for the expanding mental health care needs of the community in this ongoing disaster and future ones.

Psychological first aid (PFA) and disasters.

A disaster is commonly thought of as an occurrence that results in property damage and physical injuries that exceed the response capabilities of local resources. History teaches that disasters also result in a surge in demand for psychological support amongst survivors and disaster responders. This surge quickly exceeds local response capacities and has the potential to exceed even the mental health resources that may be imported from neighbouring jurisdictions and disaster relief agencies. Efficient and effective acute mental health intervention is, therefore, needed. However, the effectiveness of traditional multi-session counselling during and shortly after disasters has been questioned. Instead, the utilization of efficient and effective crisis-focussed psychological interventions has been suggested as acute phase alternatives. This paper asserts psychological first aid (PFA) may be considered a specific crisis-focussed disaster mental health intervention for use during and after disasters. PFA is designed for use in assessing and mitigating acute distress, while serving as a platform for psychological triage complementing more traditional psychological and psychiatric interventions. PFA may be employed by mental health clinicians as well as 'peer responders'.