Accessing healthcare during the COVID-19 pandemic: a qualitative exploration of the experiences of parents and carers of children with chronic illness to inform future policies in times of crisis.

BACKGROUND: The purpose of thispaper is to explore the experiences of parents and carers of children with chronic health conditions in accessing healthcare during the Covid-19 pandemic. Children with chronic conditions typically rely on both planned and unplanned care, and contact with healthcare professionals over extensive periods of time. Their distinct care needs render these children vulnerable to even to minor changes in healthcare provision. The wide-ranging care disruptions during the pandemic were therefore likely drastically to affect their health and wellbeing; an assessment of the effects of Covid-19 policies on healthcare access and quality of care delivered for this group is needed. METHODS: From 25/01/2022 to 25/05/2022, four focus groups were held with parents/carers of children with diabetes, neurodivergence, mental health conditions, and medical complexities to explore their experiences in navigating the healthcare system during the pandemic. Interviews were transcribed and then subjected to thematic analysis using NVivo qualitative research software. RESULTS: Our results indicate that children with chronic health conditions (and their parents/carers) experienced difficulties accessing healthcare during the pandemic. Problems with late diagnosis, prolonged waiting times, and deficiencies with telemedicine were identified, as were impacts of healthcare disruptions on children's wellbeing, and the wellbeing of wider families. We found that children with neurodivergence and those with mental health conditions were particularly affected with their health needs repeatedly de-prioritised. Furthermore, the loss of contact with multi-specialty clinical teams profoundly affected parents and carers, leaving them feeling isolated in managing their children's health. These diminished relationships became another vector for uncertainty in supporting children's health. CONCLUSION: The effects of healthcare disruptions on the welfare of children with chronic conditions (and their families), are well evidenced in this work, providing deeper understandings of the relationships between these children, their families and clinicians. The evidence in this paper aims to inform future policy and ethical guidelines so that the needs of children with long-term health conditions can be properly considered in times of crisis.

Changes in Healthcare Provision During Covid-19 and Their Impact on Children With Chronic Illness: A Scoping Review.

This paper provides an overview of the evidence around how the health systems and policy response to the Covid-19 pandemic affected children with long-term conditions in the UK. We conducted a scoping review guided by the PRISMA-ScR Checklist. The PubMed and PsycINFO databases (2019-August 2021) were searched and screened for papers (of any design) by 2 reviewers independently. The electronic database search was supplemented by manual searching. A total of 32 papers were identified, including studies on UK paediatric populations, studies on chronic illness in the UK, and international studies on chronic illness and children (including data from the UK). Most studies focussed on epilepsy, cancer, diabetes or asthma. Three categories of impact were identified: (a) impact of policy response on the delivery of and access to child healthcare (b) impact of innovative practice on children's physical and mental health (c) impact of service restrictions on children's physical health. Our results showed that policy response to the pandemic significantly affected healthcare provision for children with chronic illness in the UK. However, the specific assessment of the impact of service restrictions and innovative practice on children's health and wellbeing is limited. Future research is required to fill knowledge gaps on changes in access to effective diagnostic and treatment investigations and their impact on a range of paediatric patients during the pandemic.

Oral immune priming with Bacillus thuringiensis induces a shift in the gene expression of Tribolium castaneum larvae.

BACKGROUND: The phenomenon of immune priming, i.e. enhanced protection following a secondary exposure to a pathogen, has now been demonstrated in a wide range of invertebrate species. Despite accumulating phenotypic evidence, knowledge of its mechanistic underpinnings is currently very limited. Here we used the system of the red flour beetle, Tribolium castaneum and the insect pathogen Bacillus thuringiensis (Bt) to further our molecular understanding of the oral immune priming phenomenon. We addressed how ingestion of bacterial cues (derived from spore supernatants) of an orally pathogenic and non-pathogenic Bt strain affects gene expression upon later challenge exposure, using a whole-transcriptome sequencing approach. RESULTS: Whereas gene expression of individuals primed with the orally non-pathogenic strain showed minor changes to controls, we found that priming with the pathogenic strain induced regulation of a large set of distinct genes, many of which are known immune candidates. Intriguingly, the immune repertoire activated upon priming and subsequent challenge qualitatively differed from the one mounted upon infection with Bt without previous priming. Moreover, a large subset of priming-specific genes showed an inverse regulation compared to their regulation upon challenge only. CONCLUSIONS: Our data demonstrate that gene expression upon infection is strongly affected by previous immune priming. We hypothesise that this shift in gene expression indicates activation of a more targeted and efficient response towards a previously encountered pathogen, in anticipation of potential secondary encounter.

Current analysis of host-parasite interactions with a focus on next generation sequencing data.

Among the most common forms of interaction between species are those between hosts and their parasites and they have important implications for evolutionary theory. Understanding both the phenotypic and genotypic processes governing such interactions is a major endeavour in biology, but is a complex and challenging task. The development of next generation sequencing technologies has recently opened up this field from a molecular perspective, allowing us access to the genomic data underlying laboratory or wild phenotypes. The data obtained from such technologies has many advantages over previous methods, such as being more abundant, often more accurate, less labour intensive to generate and more cost effective to produce. We present a review of the impact of next generation sequencing data on the study of host-parasite evolution and current topics being explored with this data. We focus on two main data types, genomic and transcriptomic. We discuss popular computational approaches which can help us characterise the molecular forces driving host-parasite systems and highlight some studies which have utilised such approaches to gain information about particular immune processes. We furthermore highlight some promising perspectives from emerging and new technologies which will allow researchers to reach a deeper understanding of these interactions.

Domain similarity based orthology detection.

BACKGROUND: Orthologous protein detection software mostly uses pairwise comparisons of amino-acid sequences to assert whether two proteins are orthologous or not. Accordingly, when the number of sequences for comparison increases, the number of comparisons to compute grows in a quadratic order. A current challenge of bioinformatic research, especially when taking into account the increasing number of sequenced organisms available, is to make this ever-growing number of comparisons computationally feasible in a reasonable amount of time. We propose to speed up the detection of orthologous proteins by using strings of domains to characterize the proteins. RESULTS: We present two new protein similarity measures, a cosine and a maximal weight matching score based on domain content similarity, and new software, named porthoDom. The qualities of the cosine and the maximal weight matching similarity measures are compared against curated datasets. The measures show that domain content similarities are able to correctly group proteins into their families. Accordingly, the cosine similarity measure is used inside porthoDom, the wrapper developed for proteinortho. porthoDom makes use of domain content similarity measures to group proteins together before searching for orthologs. By using domains instead of amino acid sequences, the reduction of the search space decreases the computational complexity of an all-against-all sequence comparison. CONCLUSION: We demonstrate that representing and comparing proteins as strings of discrete domains, i.e. as a concatenation of their unique identifiers, allows a drastic simplification of search space. porthoDom has the advantage of speeding up orthology detection while maintaining a degree of accuracy similar to proteinortho. The implementation of porthoDom is released using python and C++ languages and is available under the GNU GPL licence 3 at http://www.bornberglab.org/pages/porthoda .

Evaluating scenarios for the evolutionary assembly of the brachiopod body plan.

The fossil faunas of the Cambrian provide the only direct insight into the assembly of animal body plans. However, for many animal groups, their early fossil record is linked to disarticulated remains, interpretation of which is problematic since they possess few characters from which their affinity to phyla can be established and, indeed, few characters at all. One such group is the tommotiids, which has been interpreted, on the basis of skeletal anatomy, as a paraphyletic assemblage uniting brachiopods and phoronids, through the acquisition and subsequent modification, or loss, of an imbricated set of dorsal phosphatic sclerites. Here we present a reexamination of the fossil evidence uniting the tommotiids and brachiopods, supplemented with new anatomical data from synchrotron radiation X-ray tomographic microscopy of key tommotiid taxa. The characters used to support the complex hypothesis of character evolution in the brachiopod stem lineage relies on scleritome reconstructions and inferred mode of life which themselves rely on brachiopods being chosen as the interpretative model. We advocate a more conservative interpretation of the affinity of these fossils, based a priori on their intrinsic properties, rather than the modern analogue in whose light they have been interpreted.

A daily-updated tree of (sequenced) life as a reference for genome research.

We report a daily-updated sequenced/species Tree Of Life (sTOL) as a reference for the increasing number of cellular organisms with their genomes sequenced. The sTOL builds on a likelihood-based weight calibration algorithm to consolidate NCBI taxonomy information in concert with unbiased sampling of molecular characters from whole genomes of all sequenced organisms. Via quantifying the extent of agreement between taxonomic and molecular data, we observe there are many potential improvements that can be made to the status quo classification, particularly in the Fungi kingdom; we also see that the current state of many animal genomes is rather poor. To augment the use of sTOL in providing evolutionary contexts, we integrate an ontology infrastructure and demonstrate its utility for evolutionary understanding on: nuclear receptors, stem cells and eukaryotic genomes. The sTOL (http://supfam.org/SUPERFAMILY/sTOL) provides a binary tree of (sequenced) life, and contributes to an analytical platform linking genome evolution, function and phenotype.

Deciphering the fossil record of early bilaterian embryonic development in light of experimental taphonomy.

Experimental analyses of decay in a tunicate deuterostome and three lophotrochozoans indicate that the controls on decay and preservation of embryos, identified previously based on echinoids, are more generally applicable. Four stages of decay are identified regardless of the environment of death and decay. Embryos decay rapidly in oxic and anoxic conditions, although the gross morphology of embryos is maintained for longer under anoxic conditions. Under anoxic reducing conditions, the gross morphology of the embryos is maintained for the longest period of time, compatible with the timescale required for bacterially mediated mineralization of soft tissues. All four stages of decay were encountered under all environmental conditions, matching the spectrum of preservational qualities encountered in all fossil embryo assemblages. The preservation potential of embryos of deuterostomes and lophotrochozoans is at odds with the lack of such embryos in the fossil record. Rather, the fossil record of embryos, as sparse as it is, is dominated by forms interpreted as ecdysozoans, cnidarians, and stem-metazoans. The dearth of deuterostome and lophotrochozoan embryos may be explained by the fact that ecdysozoans, at least, tend to deposit their eggs in the sediment rather than through broadcast spawning. However, fossil embryos remain very rare and the main controlling factor on their fossilization may be the unique conspiracy of environmental conditions at a couple of sites. The preponderance of fossilized embryos of direct developers should not be used in evidence against the existence of indirect development at this time in animal evolutionary history.