Parental sleep-related practices and sleep in children aged 1-3 years: a systematic review.

The current systematic review sought to identify the relationship between the range of different parental sleep-related practices that had been explored in relations to child sleep outcomes in children aged 1-3 years. A systematic literature review was carried out in CINAHL, The Cochrane Library, PsycArticles, PsycInfo, PubMed and Web of Science, as well as relevant grey literature in August 2022 using the terms; population (children, aged 1-3 years), exposure (parental sleep-related practice) and outcome (child sleep). Any quantitative study published between 2010 and 2022 that explored the relationship between parental sleep-related practices and the sleep of children aged 1-3 years were included. The Mixed Methods Appraisal Tool was employed to quality appraise included studies and results were narratively synthesised. In all, 16 longitudinal and cross-sectional quantitative studies met inclusion criteria. Parental presence or physical involvement, as well as broader parental practices including using screens or devices at bedtime and night-time breastfeeding were all related to poorer child sleep outcomes. Consistent and relaxing routines, sleeping in a cot, and spending all night in their own sleep location were associated with better child sleep outcomes. Acknowledging the plethora of diverse parental sleep-related practices, which may have varying relationships with child sleep outcomes, could be usefully considered in theoretical models and to inform clinical practice. Issues of definitional and measurement ambiguity are highlighted and discussed.

A cross-sectional survey of healthcare professionals supporting children and young people with epilepsy and their parents/carers: which topics are raised in clinical consultations and can healthcare professionals provide the support needed?

BACKGROUND AND PURPOSE: Children and young people (CYP) with epilepsy see healthcare professionals (HCPs) for management of their seizures but may require information, advice and support with a range of broader topics. The purpose of the survey was to identify from HCPs, which topics CYP with epilepsy and their parents/carers ask about other than seizure management, and how adequately HCPs feel able to support them with these topics. METHOD: A cross-sectional online survey was used to collect data. Adverts which included a link to the survey were shared via social media channels, professional networks and United Kingdom (UK)-based epilepsy networks. Eighty-eight HCPs in the UK (who worked with CYP with epilepsy and their parents/carers) completed the survey. Quantitative data are presented descriptively. Qualitative data (free-text responses) were reflexively thematically analysed. RESULTS: CYP with epilepsy and their parents/carers were reported to ask HCPs for information, advice and support about a range of topics, most commonly, cognition and mental health. CYP were reported as also frequently asking about aspects of their social life while parents/carers commonly asked about sleep. HCPs varied in how able they felt to adequately support families about these topics, as well as in their views about which resources could be most useful. Having insufficient time and a lack of suitable services and resources to refer to, or draw upon, were key barriers to HCPs being able to support CYP and their families. DISCUSSION: Findings highlight the broad array of topics CYP with epilepsy and their families are reported as seeking support for. HCPs identified gaps in services and their abilities to meet those needs. There appeared to be a mismatch between the support that families were seeking and the ability of HCPs to meet these needs. Findings have implications for how HCPs could best be supported to deal with topics raised by CYP and families in clinic, highlighting the potential usefulness of informational resources on key topics for HCPs, parents/carers and CYP.

Changing Agendas on Sleep, Treatment and Learning in Epilepsy (CASTLE) Sleep-E: a protocol for a randomised controlled trial comparing an online behavioural sleep intervention with standard care in children with Rolandic epilepsy.

INTRODUCTION: Sleep and epilepsy have an established bidirectional relationship yet only one randomised controlled clinical trial has assessed the effectiveness of behavioural sleep interventions for children with epilepsy. The intervention was successful, but was delivered via face-to-face educational sessions with parents, which are costly and non-scalable to population level. The Changing Agendas on Sleep, Treatment and Learning in Epilepsy (CASTLE) Sleep-E trial addresses this problem by comparing clinical and cost-effectiveness in children with Rolandic epilepsy between standard care (SC) and SC augmented with a novel, tailored parent-led CASTLE Online Sleep Intervention (COSI) that incorporates evidence-based behavioural components. METHODS AND ANALYSES: CASTLE Sleep-E is a UK-based, multicentre, open-label, active concurrent control, randomised, parallel-group, pragmatic superiority trial. A total of 110 children with Rolandic epilepsy will be recruited in outpatient clinics and allocated 1:1 to SC or SC augmented with COSI (SC+COSI). Primary clinical outcome is parent-reported sleep problem score (Children's Sleep Habits Questionnaire). Primary health economic outcome is the incremental cost-effectiveness ratio (National Health Service and Personal Social Services perspective, Child Health Utility 9D Instrument). Parents and children (≥7 years) can opt into qualitative interviews and activities to share their experiences and perceptions of trial participation and managing sleep with Rolandic epilepsy. ETHICS AND DISSEMINATION: The CASTLE Sleep-E protocol was approved by the Health Research Authority East Midlands (HRA)-Nottingham 1 Research Ethics Committee (reference: 21/EM/0205). Trial results will be disseminated to scientific audiences, families, professional groups, managers, commissioners and policymakers. Pseudo-anonymised individual patient data will be made available after dissemination on reasonable request. TRIAL REGISTRATION NUMBER: ISRCTN13202325.

The impact of parent treatment preference and other factors on recruitment: lessons learned from a paediatric epilepsy randomised controlled trial.

BACKGROUND: In paediatric epilepsy, the evidence of effectiveness of antiseizure treatment is inconclusive for some types of epilepsy. As with other paediatric clinical trials, researchers undertaking paediatric epilepsy clinical trials face a range of challenges that may compromise external validity MAIN BODY: In this paper, we critically reflect upon the factors which impacted recruitment to the pilot phase of a phase IV unblinded, randomised controlled 3×2 factorial trial examining the effectiveness of two antiseizure medications (ASMs) and a sleep behaviour intervention in children with Rolandic epilepsy. We consider the processes established to support recruitment, public and patient involvement and engagement (PPIE), site induction, our oversight of recruitment targets and figures, and the actions we took to help us understand why we failed to recruit sufficient children to continue to the substantive trial phase. The key lessons learned were about parent preference, children's involvement and collaboration in decision-making, potential and alternative trial designs, and elicitation of stated preferences pre-trial design. Despite pre-funding PPIE during the trial design phase, we failed to anticipate the scale of parental treatment preference for or against antiseizure medication (ASMs) and consequent unwillingness to be randomised. Future studies should ensure more detailed and in-depth consultation to ascertain parent and/or patient preferences. More intense engagement with parents and children exploring their ideas about treatment preferences could, perhaps, have helped predict some recruitment issues. Infrequent seizures or screening children close to natural remission were possible explanations for non-consent. It is possible some clinicians were unintentionally unable to convey clinical equipoise influencing parental decision against participation. We wanted children to be involved in decisions about trial participation. However, despite having tailored written and video information to explain the trial to children we do not know whether these materials were viewed in each consent conversation or how much input children had towards parents' decisions to participate. Novel methods such as parent/patient preference trials and/or discrete choice experiments may be the way forward. CONCLUSION: The importance of diligent consultation, the consideration of novel methods such as parent/patient preference trials and/or discrete choice experiments in studies examining the effectiveness of ASMs versus no-ASMs cannot be overemphasised even in the presence of widespread clinician equipoise.

'No one's ever said anything about sleep': A qualitative investigation into mothers' experiences of sleep in children with epilepsy.

INTRODUCTION: Sleep problems in children with epilepsy (CWE) are common. However, little is known about parental experiences and feelings about managing sleep in their CWE. To provide the most appropriate services' provision, it is essential that the lived experience of parents of this patient group and the issues and problems that they face in managing their child's sleep is understood. METHOD: In 2018, nine mothers of CWE (aged 5-15 years) were interviewed about their perceptions and experiences around their child's sleep, sleep problems and their management, the impact of sleep difficulties on the child and their family and available support. RESULTS: Four themes were identified that represented the nature of the child's sleep problems, including settling and night-waking issues, parasomnias and child anxiety around sleep. Seven themes represented mothers' experiences of managing their child's sleep and any associated problems, including the longstanding challenging nature of child sleep issues, management strategies adopted, challenges related to managing sleep over time, the link between sleep and seizures, the negative impact of poor sleep on daytime functioning, role of antiseizure medication and maternal concerns about child sleep. One theme represented the perceived lack of information, help and support available. CONCLUSIONS: Findings suggest there are unmet needs in supporting parents to deal with sleep, sleep problems and their management in CWE. PATIENT OR PUBLIC CONTRIBUTION: This individual study was conducted under the umbrella of the CASTLE research programme (see https://castlestudy.org.uk/). Parents who have lived experience of parenting a child with epilepsy were co-applicants for the programme and were involved in the original conception, aims, design and funding application for the research programme (including the project reported in this paper) and advised on project design. Mothers of CWE who have lived experience of managing sleep and sleep problems in their child were participants who shared their experiences through the interviews, which formed the data of the current study.

The relationship between parents' cognitions, bedtime behaviours and sleep-related practices with their child's sleep.

Certain parental cognitions about child sleep and bedtime behaviours used with their child have been linked to poorer child sleep. However, previous research has focused on mothers and explored only a limited range of sleep-related cognitions and practices. The present study investigated whether parental cognitions and sleep-related practices (both in connection with their own sleep and their child's sleep), alongside the bedtime behaviours used with their child were associated with and/or were predictive of their child's sleep. Mothers and fathers from 44 families (with a child aged 12-24 months) separately completed questionnaires reporting (i) their cognitions (about their own sleep and their child's sleep), (ii) sleep-related practices (used in connection with their own and their child's sleep) and (iii) bedtime behaviours used with their child. Child sleep was assessed through parental report and actigraphy. Both parents' cognitions about their own sleep predicted cognitions about their child's sleep. Mothers' own sleep-related practices predicted the types of practices they used with their child. Different patterns of maternal and paternal variables influenced parental perceptions of their child having a sleep problem. The present findings highlight the importance of including mothers and fathers in child sleep research. Parents' dysfunctional cognitions (their own sleep) and broader sleep-related practices (their own and child sleep) should be considered when exploring influences on child sleep. Results have possible implications for targets of interventions for child sleep problems and also potential implications for theoretical models of child sleep.

School nursing: New ways of working with children and young people during the Covid-19 pandemic: A scoping review.

AIM: To examine how school nurse practice evolved as a result of the Covid-19 pandemic. DESIGN: A scoping review of international literature, conducted and reported in line with Arksey and O'Malley's (2005) framework. DATA SOURCES: Searches were conducted in September 2021. Ten databases were searched: The British Nursing Database, CINAHL, Cochrane Library, Consumer Health Database, Health and Medicine, Nursing and Allied Health, Public Health, PsycINFO, PubMed and Web of Science. Relevant grey literature was identified through hand searching. REVIEW METHODS: A minimum of three reviewers independently screened articles and two reviewers independently undertook data extraction, with any decisions made collaboratively with the wider team. Much of the literature was not empirical work and so it was not possible to apply a traditional quality appraisal framework. RESULTS: Searches identified 554 papers (after deduplication) which were screened against title and abstract. Following the full-text review, 38 articles underwent data extraction and analysis. The review findings highlighted that school nurses adapted their practice to ensure they were able to continue providing their formal and informal school health offer to children, young people and their families and continued working closely with the multidisciplinary team. In addition, the expanded public health role generated by Covid-19 for school nurses' work was considerable, multi-layered and added to their routine workload. School nurses displayed resilience, adaptability and creativity in their response to delivering services during Covid-19. CONCLUSION: School nurses took on a leading public health role during the Covid-19 pandemic. Some developments and practices were highlighted as beneficial to continue beyond the pandemic. However, formal evaluation is needed to identify which practices may merit integration into routine practice. Continued investment in staff and infrastructure will be essential to ensuring school nurses continue to expand their practice and influence as public health experts.

Parents'/caregivers' fears and concerns about their child's epilepsy: A scoping review.

BACKGROUND: Childhood epilepsy is a serious and common neurological condition and can have life-long consequences and its impact can pervade all aspects of family life. Whilst the medical management of seizures is important, much of the day-to-day home management of epilepsy is invisible to people external to the family, including health care professionals, and parents'/caregivers' fears and concerns can go unacknowledged and unaddressed by health care professionals. OBJECTIVE: This objective of this review was to examine parents'/caregivers' fears and concerns regarding their child's epilepsy, the impact of these fears and concerns on family life, the social and emotional well-being of parents/caregivers and any factors which mitigate these fears and concerns. DESIGN: Scoping review using a modified version of Arksey and O'Malley's framework. DATA SOURCES: Relevant studies were identified using key search terms in Scopus, Medline, CINAHL and PsychInfo databases in March 2021 with hand checking of reference lists. Search terms were developed using population (parents/caregivers of children aged ≤ 18 years with epilepsy, families); concept (parents'/caregivers' fears, concerns, anxiety about their child's epilepsy); and context (any setting). A further search was run in April 2022. Other inclusion criteria: English language empirical studies, 2010-2021. STUDY APPRAISAL METHODS: A minimum of two reviewers independently screened articles and undertook data extraction and decisions were consensually made. Methodological quality appraisal was undertaken using the Mixed Methods Appraisal Tool v2018. A data extraction table was created to chart all studies. The conduct and reporting of this study followed the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidance for Systematic reviews and Meta-Analyses extension for Scoping Reviews (PRISMA-ScR) (S1 Table). There is no published copy of the review protocol. MAIN FINDINGS: The search identified a total of 4077 papers (after duplicates were removed) of which 110 were assessed for eligibility. Twenty-four papers published between 2010-2021 were included in the review and each paper was treated as a separate study. The review findings indicate that parents'/caregivers' fears and concerns stem from more than their child's seizures and relate to many wider aspects of family life. These fears and concerns had far-reaching influences on their parenting/caregiving, and on the lifestyle and activities of their child and their family. What was less evident was what parents/caregivers wanted in terms of support or how they thought health professionals could acknowledge and/or allay their fears and concerns. The discussion is framed within the compassion-focused therapy model as a basis for generating new thinking about the impact of these fears and concerns and the need for a new agenda for clinical consultations in childhood epilepsy. CONCLUSIONS: The review concludes with a proposal that a more compassionate agenda underpins the dialogue between parents/caregivers and clinicians to encompass and mitigate the wider emotional, psychosocial, and societal threats that impact on the parent/caregivers of children with epilepsy.

UK parents' help-seeking for child sleep: A qualitative investigation into parental preferences and reservations about resources.

Child sleep is a common parental concern and there is an array of resources available to parents. However, an exploration of UK parents' help-seeking behaviours around child sleep is lacking. This study sought to identify the resources parents use to seek information and help for child sleep, as well as to explore what factors parents prefer about certain sources and their reservations about using other resources. Parents of 6-36 month old children residing in the United Kingdom (UK) completed an online questionnaire between October 2015 and October 2016 about their use, opinions and experiences regarding resources for child sleep. Quantitative data were descriptively analysed and thematic analysis was conducted on parents' open-ended text responses. Participants were 266 UK parents (97% mothers). Parents' ages ranged from 21 to 45 years (M = 33.49 years, SD = 4.71) and all resided in the United Kingdom (UK). General Internet searches were the most commonly reported source used by 47% of parents with a range of other informal resources also frequently consulted. Health Visitors (HVs) were the most accessed healthcare professional reportedly consulted by 38% of parents. Seven themes represented parental preferences for their resource use. Most strongly endorsed included a desire for information from other parents, particularly those with practical experience and accessing information that aligned with their parenting values. Parents preferred sources that provided support and reassurance, as well as those that afforded parents the ability to select relevant elements from a range of information. Seven themes represented parents' reservations about resources. Most strongly endorsed were concerns about reliability, being judged and challenges associated with filtering vast amounts of information. Parents reported having reservations towards sources if they had a previous negative experience with the source. Possible implications of the findings and specific suggestions about how existing and future resources could be adapted to better meet parents' needs are highlighted.

Ribosome profiling of porcine reproductive and respiratory syndrome virus reveals novel features of viral gene expression.

The arterivirus porcine reproductive and respiratory syndrome virus (PRRSV) causes significant economic losses to the swine industry worldwide. Here we apply ribosome profiling (RiboSeq) and parallel RNA sequencing (RNASeq) to characterise the transcriptome and translatome of both species of PRRSV and to analyse the host response to infection. We calculated programmed ribosomal frameshift (PRF) efficiency at both sites on the viral genome. This revealed the nsp2 PRF site as the second known example where temporally regulated frameshifting occurs, with increasing -2 PRF efficiency likely facilitated by accumulation of the PRF-stimulatory viral protein, nsp1ß. Surprisingly, we find that PRF efficiency at the canonical ORF1ab frameshift site also increases over time, in contradiction of the common assumption that RNA structure-directed frameshift sites operate at a fixed efficiency. This has potential implications for the numerous other viruses with canonical PRF sites. Furthermore, we discovered several highly translated additional viral ORFs, the translation of which may be facilitated by multiple novel viral transcripts. For example, we found a highly expressed 125-codon ORF overlapping nsp12, which is likely translated from novel subgenomic RNA transcripts that overlap the 3' end of ORF1b. Similar transcripts were discovered for both PRRSV-1 and PRRSV-2, suggesting a potential conserved mechanism for temporally regulating expression of the 3'-proximal region of ORF1b. We also identified a highly translated, short upstream ORF in the 5' UTR, the presence of which is highly conserved amongst PRRSV-2 isolates. These findings reveal hidden complexity in the gene expression programmes of these important nidoviruses.

Viruses have tiny genomes. Rather than carry all the genetic information they need, they rely on the cells they infect. This makes the few genes they do have all the more important. Many viruses store their genes not in DNA, but in a related molecule called RNA. When the virus infects cells, it uses the cells' ribosomes ­ the machines in the cells that make proteins ­ to build its own proteins. One of the central ideas in biology is that one molecule of RNA carries the instructions for just one type of protein. But many viruses break this rule. The ribosomes in cells read RNA instructions in blocks of three: three RNA letters correspond to one protein building block. But certain sequences in the RNA of viruses act as hidden signals that affect how ribosomes read these molecules. These signals make the ribosomes skip backward by one or two letters on the viral RNA, restarting part way through a three-letter block. Scientists call this a 'frameshift', and it is a bit like changing the positions of the spaces in a sentence. The virus causes these frameshifts using proteins or by folding its RNA into a knot-like structure. The frameshifts result in the production of different viral proteins over time. The porcine reproductive and respiratory syndrome virus (PRRSV) uses frameshifts to cause devastating disease in pigs. Besides the sequences in its RNA that allow the ribosomes to skip backwards, the viral enzyme that copies the RNA can also skip forward. This results in shortened copies of its genes, which also changes the proteins they produce. To find out exactly how PRRSV uses these frameshifting techniques, Cook et al. examined infected cells in the laboratory. They monitored the RNA made by the virus and looked closely at the way the cells read it using a technique called ribosome profiling. This revealed that frameshifting increases over the course of an infection. This is partly because the viral protein that causes frameshifts builds up as infection progresses, but it also happened with frameshifts caused by RNA knots. The reason for this is less clear. Cook et al. also discovered several new RNAs made later in infection, which could also change the proteins the virus makes. RNA viruses cause disease in humans as well as pigs. Examples include coronaviruses and HIV. Many of these also have frameshift sites in their genomes. A better understanding of how frameshifts change during infection may aid drug development. Future work could help researchers to understand which proteins viruses make at which stage of infection. This could lead to new treatments for viruses like PRRSV.

School Nurse Perspectives of Working with Children and Young People in the United Kingdom during the COVID-19 Pandemic: An Online Survey Study.

School nurses are public health specialists with an integral role in the safeguarding of children and young people. This study gathered information about school nurses' approaches to overcome practice restrictions as a result of COVID-19. A cross-sectional survey was administered to school nurses across the United Kingdom. Quantitative data were analysed descriptively. Qualitative data (free-text responses to open-ended questions) were analysed using reflexive thematic analysis. Seventy-eight participant responses were included in the analysis. Quantitative data highlighted increased workloads; decreased contact with service users; and difficulties in identifying safeguarding needs and working with known vulnerable children. Through qualitative data analysis, five themes were identified: a move from preventive to reactive school nursing; professional challenges of safeguarding in the digital context; the changing nature of inter-professional working; an increasing workload; and reduced visibility and representation of the child. The findings call for advocacy by policymakers and professional organisations representing school nurses to enable this professional group to lead in the evolving public health landscape; for commissioning that recognises the school nurse as a specialist public health practitioner; and for sufficient numbers of school nurses to respond to the emergent and ongoing health needs of children and young people.

Investigating molecular mechanisms of 2A-stimulated ribosomal pausing and frameshifting in Theilovirus.

The 2A protein of Theiler's murine encephalomyelitis virus (TMEV) acts as a switch to stimulate programmed -1 ribosomal frameshifting (PRF) during infection. Here, we present the X-ray crystal structure of TMEV 2A and define how it recognises the stimulatory RNA element. We demonstrate a critical role for bases upstream of the originally predicted stem-loop, providing evidence for a pseudoknot-like conformation and suggesting that the recognition of this pseudoknot by beta-shell proteins is a conserved feature in cardioviruses. Through examination of PRF in TMEV-infected cells by ribosome profiling, we identify a series of ribosomal pauses around the site of PRF induced by the 2A-pseudoknot complex. Careful normalisation of ribosomal profiling data with a 2A knockout virus facilitated the identification, through disome analysis, of ribosome stacking at the TMEV frameshifting signal. These experiments provide unparalleled detail of the molecular mechanisms underpinning Theilovirus protein-stimulated frameshifting.

A Qualitative Investigation Into What Parents Want From an Online Behavioural Sleep Intervention for Children With Epilepsy.

Many of the same sleep problems seen in typically developing (TD) children are frequently experienced by children with epilepsy (CWE). Behavioural sleep interventions (BSIs) are commonly and successfully used to treat these sleep problems in TD children and in some neurodevelopmental disorder populations. Therefore, BSIs should be effective in CWE, however, there are special seizure-related considerations for CWE and their parents which may be salient to consider in any future BSI development for this group. The current study sought to identify, from parents, if there were special considerations for the content and delivery of an online BSI for parents of CWE. Semi-structured interviews were conducted with nine mothers of CWE and thematic analysis was conducted on the interview data. Ten themes were apparent which represented what parents wanted from any online BSI for CWE. Parents wanted (i) other parents' views and real-life experiences to be included, (ii) recognition of how changes over time may influence the appropriateness of using various sleep-management options, (iii) to be presented with a range of sleep management options from which they could select, (iv) personalised information and suggestions for behaviour-change options, (v) help to address child anxiety around sleep, (vi) for the advice and behaviour-change options to be practical, (vii) general educational information about sleep and the relationship between sleep and epilepsy, (viii) for parental worries and concerns to be acknowledged, (ix) to receive help, support, and reassurance around children's sleep; and (x) to include the child in the intervention. It was clear that any online BSI would require specific adaptations and additions (to content and delivery format) to best meet the needs of parents of CWE. It is hoped that having identified what parents want from on online BSI for CWE will allow these factors to be acknowledged in future intervention development, with the intention to optimise parental engagement and intervention effectiveness. Practical suggestions for how these aspects could be integrated into any online BSI are suggested.

Development and Evaluation of the CASTLE Trial Online Sleep Intervention for Parents of Children with Epilepsy.

Introduction: Many of the sleep problems experienced by children with epilepsy (CWE) have the same behavioural basis as common sleep problems seen in typically developing (TD) children. Behavioural sleep interventions (BSIs) are widely used to treat these sleep problems in TD children and are hypothesised to be effective for CWE. However, specific considerations need to be addressed and incorporated into a BSI for CWE to ensure the intervention is tailored to this population's needs. This paper details developing and tailoring an online BSI for parents of CWE, to be used in the CASTLE (Changing Agendas on Sleep, Treatment and Learning in Epilepsy) Sleep-E clinical trial. Method: In phase one, two existing theory-driven paediatric BSIs were adapted into a novel online behavioural sleep intervention (CASTLE Online Sleep Intervention or COSI) which specifically incorporated the needs and requirements reported by nine parents of CWE. Scoping their needs included conducting interviews with three CWE so that they could contribute to the overall intervention content. In phase two, six of these parents evaluated COSI, reviewing and feeding back on COSI until parental approval for content and functionality was achieved. Results: In phase one, a range of adaptations was made to the content and presentation of standardised intervention material to acknowledge and emphasise the key seizure-specific issues to ensure COSI best met parents of CWE's needs. Adaptations included embedding parent and child experiences in the intervention, including particular information requested by parents, such as the links between sleep and seizures and managing child and parental anxieties around sleep, as well as developing functionality to personalise the delivery of content. In phase two, parents confirmed that they found the final version of COSI to be functional and appropriate (after one round of review) for use by parents of CWE and that 100% would recommend it to other families who have CWE. Discussion: It is hoped that the use of evidence-based BSIs, adapted to consider salient epilepsy-specific factors, will increase parent-engagement, COSI's relevance for this particular patient group and overall efficacy in improving sleep in CWE. The effectiveness of COSI will be tested in the CASTLE Sleep-E clinical trial (https://castlestudy.org.uk/).

Manipulation of the unfolded protein response: A pharmacological strategy against coronavirus infection.

Coronavirus infection induces the unfolded protein response (UPR), a cellular signalling pathway composed of three branches, triggered by unfolded proteins in the endoplasmic reticulum (ER) due to high ER load. We have used RNA sequencing and ribosome profiling to investigate holistically the transcriptional and translational response to cellular infection by murine hepatitis virus (MHV), often used as a model for the Betacoronavirus genus to which the recently emerged SARS-CoV-2 also belongs. We found the UPR to be amongst the most significantly up-regulated pathways in response to MHV infection. To confirm and extend these observations, we show experimentally the induction of all three branches of the UPR in both MHV- and SARS-CoV-2-infected cells. Over-expression of the SARS-CoV-2 ORF8 or S proteins alone is itself sufficient to induce the UPR. Remarkably, pharmacological inhibition of the UPR greatly reduced the replication of both MHV and SARS-CoV-2, revealing the importance of this pathway for successful coronavirus replication. This was particularly striking when both IRE1α and ATF6 branches of the UPR were inhibited, reducing SARS-CoV-2 virion release (~1,000-fold). Together, these data highlight the UPR as a promising antiviral target to combat coronavirus infection.

The International Virus Bioinformatics Meeting 2020.

The International Virus Bioinformatics Meeting 2020 was originally planned to take place in Bern, Switzerland, in March 2020. However, the COVID-19 pandemic put a spoke in the wheel of almost all conferences to be held in 2020. After moving the conference to 8-9 October 2020, we got hit by the second wave and finally decided at short notice to go fully online. On the other hand, the pandemic has made us even more aware of the importance of accelerating research in viral bioinformatics. Advances in bioinformatics have led to improved approaches to investigate viral infections and outbreaks. The International Virus Bioinformatics Meeting 2020 has attracted approximately 120 experts in virology and bioinformatics from all over the world to join the two-day virtual meeting. Despite concerns being raised that virtual meetings lack possibilities for face-to-face discussion, the participants from this small community created a highly interactive scientific environment, engaging in lively and inspiring discussions and suggesting new research directions and questions. The meeting featured five invited and twelve contributed talks, on the four main topics: (1) proteome and RNAome of RNA viruses, (2) viral metagenomics and ecology, (3) virus evolution and classification and (4) viral infections and immunology. Further, the meeting featured 20 oral poster presentations, all of which focused on specific areas of virus bioinformatics. This report summarizes the main research findings and highlights presented at the meeting.

Parentally reported barriers to seeking help and advice for child sleep from healthcare professionals.

BACKGROUND: Healthcare professionals (HCPs), largely doctors, paediatricians, health visitors, midwives, and practice nurses, are in a good position to provide information, help, advice, or guidance to parents for child sleep. However, evidence suggests that there is a gap between the number of parents who desire assistance from HCPs and those that make use of these sources, yet very little is known about the reason for this apparent disparity. The aim of this study was to understand the barriers reported by parents to consulting HCPs about child sleep. METHODS: In this study, 266 U.K.-based parents of children aged 6-36 months old completed an online questionnaire (between October 2015 and October 2016) about their help-seeking behaviours in relation to child sleep. This included reporting perceived barriers to consulting HCPs for child sleep information and advice about problems. RESULTS: Thematic analysis highlighted five themes, which parents reported acted as barriers to them consulting HCPs. Specifically, parents perceived HCPs to have a lack of knowledge or training around the topic of child sleep and that advice would be limited in terms of breadth of information or management options that would be offered. Parents were also concerned about wasting their own or HCPs' time, perceived there was a lack of continuity in the information they received, and held concerns about possible negative consequences for their family if they shared details about any child sleep difficulties. CONCLUSIONS: Possible practical approaches to address the barriers reported by parents are highlighted. This includes improving training around the topic of child sleep for HCPs and adapting the content or manner in which the topic of child sleep and any associated issues are addressed with parents.

Effects of Preferred and Non-Preferred Warm-Up Music on Resistance Exercise Performance.

The purpose of this study was to examine the effects of listening to preferred and non-preferred warm-up music on upper-body resistance exercise performance. Resistance-trained males (ages 18-24) participated in two separate bench press trials each with a different warm-up music condition: preferred warm-up music (PREF) or non-preferred warm-up music (NON-PREF). In each trial, participants listened to PREF or NON-PREF music during a standardized bench press warm-up. Following the warm-up, motivation to exercise was measured using a visual analog scale followed by two sets × repetitions to failure (RTF) at 75% of 1-RM separated by 1 min of rest. A linear position transducer was used to measure mean barbell velocity. Rate of perceived exertion (RPE) was obtained after each set. RTF, velocity, RPE, and motivation were analyzed. RTF were significantly higher during the PREF versus NON-PREF trail (p = 0.001) while mean barbell velocity remained unchanged (p = 0.777). RPE was not significantly different between PREF and NON-PREF trials (p = 0.735). Motivation to exercise was significantly higher during the PREF versus NON-PREF trial (p < 0.001). Findings show that listening to PREF music during a warm-up improves subsequent RTF performance during bench press exercise. However, barbell velocity was largely unaffected. While perceived exertion was similar between trials, motivation to exercise was markedly increased during the PREF warm-up music trial. These findings suggest that competitors listening to warm-up music before giving maximal effort during resistance exercise could optimize performance by ensuring self-selection of their own preferred music.

The mechanism of glycosphingolipid degradation revealed by a GALC-SapA complex structure.

Sphingolipids are essential components of cellular membranes and defects in their synthesis or degradation cause severe human diseases. The efficient degradation of sphingolipids in the lysosome requires lipid-binding saposin proteins and hydrolytic enzymes. The glycosphingolipid galactocerebroside is the primary lipid component of the myelin sheath and is degraded by the hydrolase ß-galactocerebrosidase (GALC). This enzyme requires the saposin SapA for lipid processing and defects in either of these proteins causes a severe neurodegenerative disorder, Krabbe disease. Here we present the structure of a glycosphingolipid-processing complex, revealing how SapA and GALC form a heterotetramer with an open channel connecting the enzyme active site to the SapA hydrophobic cavity. This structure defines how a soluble hydrolase can cleave the polar glycosyl headgroups of these essential lipids from their hydrophobic ceramide tails. Furthermore, the molecular details of this interaction provide an illustration for how specificity of saposin binding to hydrolases is encoded.