Comparison of histomorphology and DNA preservation produced by fixatives in the veterinary diagnostic laboratory setting

Histopathology is the most useful tool for diagnosis of a number of diseases, especially cancer. To be effective, histopathology requires that tissues be fixed prior to processing. Formalin is currently the most common histologic fixative, offering many advantages: it is cheap, readily available, and pathologists are routinely trained to examine tissues fixed in formalin. However, formalin fixation substantially degrades tissue DNA, hindering subsequent use in diagnostics and research. We therefore evaluated three alternative fixatives, TissueTek® Xpress® Molecular Fixative, modified methacarn, and PAXgene®, all of which have been proposed as formalin alternatives, to determine their suitability for routine use in a veterinary diagnostic laboratory. This was accomplished by examining the histomorphology of sections produced from fixed tissues as well as the ability to amplify fragments from extracted DNA. Tissues were sampled from two dogs and four cats, fixed for 24–48 h, and processed routinely. While all fixatives produced acceptable histomorphology, formalin had significantly better morphologic characteristics than the other three fixatives. Alternative fixatives generally had better DNA amplification than formalin, although results varied somewhat depending on the tissue examined. While no fixative is yet ready to replace formalin, the alternative fixatives examined may be useful as adjuncts to formalin in diagnostic practices

Editorial: Design and Implementation of Rehabilitation Interventions for People With Complex Psychosis

Introduction Between one fifth and one quarter of people who become unwell with a psychotic disorder will develop particularly complex problems (1). These include severe, treatment-resistant symptoms and cognitive impairments that affect motivation, organizational, and social skills. Co-existing mental, neurodevelopmental, and physical health conditions can often complicate recovery further, and up to three quarters have been found to be vulnerable to self-neglect and/or exploitation by others (2). Despite their high levels of need, this group has been missing from recent mental health policy internationally, resulting in inadequate treatment and, worryingly, increasing levels of institutionalization (3). The publication in 2020 of the first National Institute for Health and Care Excellence (NICE) Guideline on the mental health rehabilitation of adults with complex psychosis (4) is therefore a very welcome and important milestone, but there is an ongoing, urgent need for research to identify effective interventions for this group. In this Research Topic we aimed to collate relevant work that can help to address this evidence gap

Strongly lensed SNe Ia in the era of LSST: observing cadence for lens discoveries and time-delay measurements

The upcoming Large Synoptic Survey Telescope (LSST) will detect many strongly lensed Type Ia supernovae (LSNe Ia) for time-delay cosmography. This will provide an independent and direct way for measuring the Hubble constant $H_0$, which is necessary to address the current $4.4 \sigma$ tension in $H_0$ between the local distance ladder and the early Universe measurements. We present a detailed analysis of different observing strategies for the LSST, and quantify their impact on time-delay measurement between multiple images of LSNe Ia. For this, we produced microlensed mock-LSST light curves for which we estimated the time delay between different images. We find that using only LSST data for time-delay cosmography is not ideal. Instead, we advocate using LSST as a discovery machine for LSNe Ia, enabling time delay measurements from follow-up observations from other instruments in order to increase the number of systems by a factor of 2 to 16 depending on the observing strategy. Furthermore, we find that LSST observing strategies, which provide a good sampling frequency (the mean inter-night gap is around two days) and high cumulative season length (ten seasons with a season length of around 170 days per season), are favored. Rolling cadences subdivide the survey and focus on different parts in different years; these observing strategies trade the number of seasons for better sampling frequency. In our investigation, this leads to half the number of systems in comparison to the best observing strategy. Therefore rolling cadences are disfavored because the gain from the increased sampling frequency cannot compensate for the shortened cumulative season length. We anticipate that the sample of lensed SNe Ia from our preferred LSST cadence strategies with rapid follow-up observations would yield an independent percent-level constraint on $H_0$.Comment: 25 pages, 22 figures; accepted for publication in A&

Transitioning from Stage-III to Stage-IV: cosmology from galaxy×CMB lensing and shear×CMB lensing

We examine the cosmological constraining power from two cross-correlation probes between galaxy and CMB surveys: the cross-correlation of lens galaxy density with CMB lensing convergence $\langle\delta\kappa\rangle$, and source galaxy weak lensing shear with CMB lensing convergence $\langle\gamma\kappa\rangle$. These two cross-correlation probes provide an independent cross-check of other large-scale structure constraints and are insensitive to galaxy-only or CMB-only systematic effects. In addition, when combined with other large-scale structure probes, the cross-correlations can break degeneracies in cosmological and nuisance parameters, improving both the precision and robustness of the analysis. In this work, we study how the constraining power of $\langle\delta\kappa\rangle+\langle\gamma\kappa\rangle$ changes from Stage-III (ongoing) to Stage-IV (future) surveys. Given the flexibility in selecting the lens galaxy sample, we also explore systematically the impact on cosmological constraints when we vary the redshift range and magnitude limit of the lens galaxies using mock galaxy catalogs. We find that in our setup, the contribution to cosmological constraints from $\langle\delta\kappa\rangle$ and $\langle\gamma\kappa\rangle$ are comparable in the Stage-III datasets; but in Stage-IV surveys, the noise in $\langle\delta\kappa\rangle$ becomes subdominant to cosmic variance, preventing $\langle\delta\kappa\rangle$ to further improve the constraints. This implies that to maximize the cosmological constraints from future $\langle\delta\kappa\rangle+\langle\gamma\kappa\rangle$ analyses, we should focus more on the requirements on $\langle\gamma\kappa\rangle$ instead of $\langle\delta\kappa\rangle$. Furthermore, the selection of the lens sample should be optimized in terms of our ability to characterize its redshift or galaxy bias instead of its number density.Comment: 18 pages, 13 figure

High prevalence of functional vitamin deficiencies in a psychogeriatric ward

Choline (Ch) is involved in relevant neurochemical processes. It is the precursor and metabolite of acetylcholine (ACh). It plays a role in single-carbon metabolism and is an essential component of different membrane phospholipids (PLs). These PLs are structural components of cell membranes, and involved in intraneuronal signal transduction. An increased ACh release was found after Ch treatment in rat corpus striatum slices. An in vivo proton magnetic resonance study has analyzed Ch ingestion effect. This work which represents the first non invasive study for exploring in vivo human brain neurochemistry showed the transfer of an oral Ch load in the brain of normal volunteers. These results were not confirmed by other in vivo studies. Cellular membranes breakdown is suggested as a feature of neurodegeneration in acute (stroke) and chronic (Alzheimer’s and vascular dementias) brain disorders. The effects of exogenous CCPLs on different brain areas were largely studied. Our group has assessed the influence of treatment with the CCPL, choline alphoscerate (GPC) on brain cholinergic neurotransmission markers in an animal model of brain vascular injury. A neuroprotective effect of GPC alone or in association with acetylcholinesterase inhibitor, galantamine was found. These results suggest that GPC could stimulate the expression of vesicular ACh transporter and Ch transporter primarily in areas involved in cognitive processes. These cholinergic markers could represent an appropriate mean to investigate brain cholinergic pathways. In the lack of novel therapeutic strategies, safe compounds developed since a long time such as the CCPLs could have still a place in pharmacotherapy and would merit to be investigated by new clinical studies

Healthcare system impacts of the 2017 Manchester Arena bombing: Evidence from a national trauma registry patient case series and hospital performance data

Introduction In response to detonation of an improvised explosive device at the Manchester Arena on 22 May 2017, we aimed to use detailed information about injured patients flowing through hospital healthcare to objectively evaluate the preplanned responses of a regional trauma care system and to show how routinely collected hospital performance data can be used to assess impact on regional healthcare. Methods Data about injury severity, management and outcome for patients presenting to hospitals were collated using England’s major trauma registry for 30 days following hospital attendance. System-wide data about hospital performance were collated by National Health Service England’s North West Utilisation Management Unit and presented as Shewhart charts from 15 April 2017 to 25 June 2017. Results Detailed information was obtained on 153 patients (109 adults and 44 children) who attended hospital emergency departments after the incident. Within 6 hours, a network of 11 regional trauma care hospitals received a total of 138 patients (90%). For the whole patient cohort, median Injury Severity Score (ISS) was 1 (IQR 1–10) and median New ISS (NISS) was 2 (IQR 1–14). For the 75 patients (49%) attending a major trauma centre, median ISS was 7.5 (IQR 1–14) and NISS was 10 (IQR 3–22). Limb and torso body regions predominated when injuries were classified as major life threatening (Abbreviated Injury Scale>3). Ninety-three patients (61%) required hospital admission following emergency department management, with 21 (14%) requiring emergency damage control surgery and 24 (16%) requiring critical care. Three fatalities occurred during early resuscitative treatment and 150 (98%) survived to day 30. The increased system-wide hospital admissions and care activity was linked to increases in regional hospital care capacity through cancellations of elective surgery and increased community care. Consequently, there were sustained system-wide hospital service improvements over the following weeks. Conclusions The systematic collation of injured patient and healthcare system data has provided an objective evaluation of a regional major incident plan and provided insight into healthcare system resilience. Hospital patient care data indicated that a prerehearsed patient dispersal plan at incident scene was implemented effectively

Determining the Repertoire of Immunodominant Proteins via Whole-Genome Amplification of Intracellular Pathogens

Culturing many obligate intracellular bacteria is difficult or impossible. However, these organisms have numerous adaptations allowing for infection persistence and immune system evasion, making them some of the most interesting to study. Recent advancements in genome sequencing, pyrosequencing and Phi29 amplification, have allowed for examination of whole-genome sequences of intracellular bacteria without culture. We have applied both techniques to the model obligate intracellular pathogen Anaplasma marginale and the human pathogen Anaplasma phagocytophilum, in order to examine the ability of phi29 amplification to determine the sequence of genes allowing for immune system evasion and long-term persistence in the host. When compared to traditional pyrosequencing, phi29-mediated genome amplification had similar genome coverage, with no additional gaps in coverage. Additionally, all msp2 functional pseudogenes from two strains of A. marginale were detected and extracted from the phi29-amplified genomes, highlighting its utility in determining the full complement of genes involved in immune evasion