Achieving optimal cord management: a multidisciplinary quality improvement initiative.

Optimal cord management (OCM), defined as waiting at least 60 seconds (s) before clamping the umbilical cord after birth, is an evidence-based intervention that improves outcomes for both term and preterm babies. All major resuscitation councils recommend OCM for well newborns.National Neonatal Audit Programme (NNAP) benchmarking data identified our tertiary neonatal unit as a negative outlier with regard to OCM practice with only 12.1% of infants receiving the recommended minimum of 60 s. This inspired a quality improvement project (QIP) to increase OCM rates of ≥ 60 s for infants <34 weeks. A multidisciplinary QIP team (Neonatal medical and nursing staff, Obstetricians, Midwives and Anaesthetic colleagues) was formed, and robust evidence-based quality improvement methodologies employed. Our aim was to increase OCM of ≥ 60 s for infants born at <34 weeks to at least 40%.The percentage of infants <34 weeks receiving OCM increased from 32.4% at baseline (June-September 2022) to 73.6% in the 9 months following QIP commencement (October 2022-June 2023). The intervention period spanned two cohorts of rotational doctors, demonstrating its sustainability. Rates of admission normothermia were maintained following the routine adoption of OCM (89.2% vs 88.5%), which is a complication described by other neonatal units.This project demonstrates the power of a multidisciplinary team approach to embedding an intervention that relies on collaboration between multiple departments. It also highlights the importance of national benchmarking data in allowing departments to focus QIP efforts to achieve long-lasting transformational service improvements.

Outcomes following the adoption of standard parenteral nutrition in preterm infants: a whole-population non-concurrent control study.

OBJECTIVE: To evaluate the impact of a quality improvement project of the adoption of standard parenteral nutrition (SPN) in preterm infants. DESIGN: Retrospective, multicentre, whole-population, non-concurrent control study using data from the UK National Neonatal Research Database between 1 January 2014 and 31 December 2020. SETTING: Neonatal units in London UK organised by geographical network. PATIENTS: Preterm infants <31 weeks' gestation. INTERVENTIONS: Introduction of two SPN formulations previously tested in randomised controlled trials (NEON and SCAMP). SCAMP delivers a higher target macronutrient intake. MAIN OUTCOME MEASURES: The primary outcome was survival to discharge from neonatal care without major morbidities. Secondary outcomes included the individual components of the primary outcome and a comparison of outcomes between the NEON and the SCAMP formulations. RESULTS: Of 6538 eligible infants, 4693 were admitted to neonatal care before and 1845 after the adoption of SPN. Morbidity-free survival decreased by an average of 8.6% (95% CI 5.8% to 11.4%, p<0.0001) following adoption. The effect varied by type of formulation; the cohort that adopted NEON showed no difference in morbidity-free survival, whereas the cohort that adopted SCAMP showed a statistically significant decrease in morbidity-free survival. Overall survival decreased by an average of 2.0% (95% CI 0.01% to 4.0%, p=0.048). CONCLUSIONS: Research is urgently needed to identify the optimal composition of parenteral nutrition for preterm babies. This study also adds to the growing body of evidence that suggests that early and high intakes of macronutrients in preterm babies may be harmful.

An aging-susceptible circadian rhythm controls cutaneous antiviral immunity.

Aged skin is prone to viral infections, but the mechanisms responsible for this immunosenescent immune risk are unclear. We observed that aged murine and human skin expressed reduced levels of antiviral proteins (AVPs) and circadian regulators, including Bmal1 and Clock. Bmal1 and Clock were found to control rhythmic AVP expression in skin, and such circadian control of AVPs was diminished by disruption of immune cell IL-27 signaling and deletion of Bmal1/Clock genes in mouse skin, as well as siRNA-mediated knockdown of CLOCK in human primary keratinocytes. We found that treatment with the circadian-enhancing agents nobiletin and SR8278 reduced infection of herpes simplex virus 1 in epidermal explants and human keratinocytes in a BMAL1/CLOCK-dependent manner. Circadian-enhancing treatment also reversed susceptibility of aging murine skin and human primary keratinocytes to viral infection. These findings reveal an evolutionarily conserved and age-sensitive circadian regulation of cutaneous antiviral immunity, underscoring circadian restoration as an antiviral strategy in aging populations.

An Aging-Susceptible Circadian Rhythm Controls Cutaneous Antiviral Immunity.

Aged skin is prone to viral infections, but the mechanisms responsible for this immunosenescent immune risk are unclear. We observed that aged murine and human skin expressed reduced antiviral proteins (AVPs) and circadian regulators including Bmal1 and Clock. Bmal1 and Clock were found to control rhythmic AVP expression in skin and such circadian-control of AVPs was diminished by disruption of immune cell interleukin 27 signaling and deletion of Bmal1/Clock genes in mouse skins, as well as siRNA-mediated knockdown of CLOCK in human primary keratinocytes. We found that treatment of circadian enhancing agents, nobiletin and SR8278, reduced infection of herpes simplex virus 1 (HSV1) in epidermal explants and human keratinocytes in a Bmal1/Clock-dependent manner. Circadian enhancing treatment also reversed susceptibility of aging murine skin and human primary keratinocytes to viral infection. These findings reveal an evolutionarily conserved and age-sensitive circadian regulation of cutaneous antiviral immunity, underscoring circadian restoration as an antiviral strategy in aging populations.

Variation in use of extended pulse oximetry testing to guide decisions around home oxygen provision for ex-preterm infants; A nationwide survey of UK neonatal units.

Differences in the diagnostic approach to bronchopulmonary dysplasia (BPD) may contribute to variation in reported BPD rates. We undertook a nationwide survey of UK neonatal units (NNUs) to describe criteria applied by neonatologists to conduct pulse oximetry studies in ex-preterm infants to assess their need for supplemental oxygen near discharge, as well as criteria applied to interpret saturation studies. Responses from 112 (64.7%) NNUs demonstrated wide variation in both criteria used to select infants for assessment and thresholds for interpretation. Neither demonstrated a clear relationship with reported BPD rates. Variation in clinical practice requires further scrutiny to inform and streamline management of ex-preterm infants at risk of BPD, and potentially improve outcomes.

Human Skin Explant Preparation and Culture.

The ex vivo experimentation with surgically discarded human skin represents a unique methodology amenable for mechanism and pharmacologic agent studies without the involvement of human subjects. Here, we describe a protocol that includes preparation, culture, and stimulation of human skin explants, and subsequent analyses by quantitative reverse transcription PCR and immunostaining. This protocol may also be applied for ex vivo studies of murine skin, reducing animal numbers and potentially harmful treatments. In our hands, this protocol has been used for wound healing, viral infection, and hair growth-related studies. Graphical abstract: Cartoon of explant skin culture. Skin explant sits on top of a gelatin surgical sponge saturated with culture medium at an air-liquid interface.

Thymic stromal lymphopoietin controls hair growth.

Skin tissue regeneration after injury involves the production and integration of signals by stem cells residing in hair follicles (HFSCs). Much remains unknown about how specific wound-derived factors modulate stem cell contribution to hair growth. We demonstrate that thymic stromal lymphopoietin (TSLP) is produced in response to skin injury and during the anagen phase of the hair cycle. Intradermal injection of TSLP promoted wound-induced hair growth (WIHG), whereas neutralizing TSLP receptor (TSLPR) inhibited WIHG. Using flow cytometry and fluorescent immunostaining, we found that TSLP promoted proliferation of transit-amplifying cells. Lgr5CreER-mediated deletion of Tslpr in HFSCs inhibited both wound-induced and exogenous TSLP-induced hair growth. Our data highlight a novel function for TSLP in regulation of hair follicle activity during homeostasis and wound healing.

Do Paediatric Physiotherapists Promote Community-Based Physical Activity for Children and Youth with Disabilities? A Mixed-Methods Study.

Purpose: Although the importance of increased physical activity for children with disabilities is widely acknowledged, formal links between rehabilitation practitioners and community physical activity programmes are often lacking. The role of physiotherapists in the promotion of community physical activity is also often unclear. This study set out to describe the beliefs, knowledge, and practices of Canadian physiotherapists related to promoting community-based physical activity for children with disabilities. Method: We used a mixed-methods design: a survey of Canadian physiotherapists and qualitative focus group interviews with physiotherapists. Results: A total of 116 therapists participated in the survey. Of these, 80 (69.0%) considered the promotion of community-based physical activity programmes to be a physiotherapy role, and 89 (76.7%) recommended programmes to families. Therapists with less than 6 years of paediatric experience were less likely to recommend programmes to families (χ2 4 = 40.46, p < 0.001). Qualitative analysis resulted in three themes: (1) lack of clarity regarding the physiotherapy role, (2) "it's not easy" - challenges related to community-based physical activity promotion, and (3) one size does not fit all. Conclusions: Various factors shaped physiotherapists' ability to promote community physical activity, specifically their knowledge, practice setting expectations, and beliefs about their role. Concerted efforts to promote community-based physical activity may increase community capacity to support all children in physical activities.

Objectif : l'importance d'accroître l'activité physique chez les enfants qui ont des incapacités est largement reconnue, mais il n'existe souvent pas de liens officiels entre les praticiens de la réadaptation et les programmes d'activité physique communautaires. Le rôle des physiothérapeutes dans la promotion de l'activité physique est souvent flou. La présente étude vise à décrire les convictions, les connaissances et les pratiques des physiothérapeutes canadiens à l'égard de la promotion de l'activité physique communautaire pour les enfants ayant des incapacités. Méthodologie : méthodologie mixte: sondage auprès des physiothérapeutes canadiens et groupes de travail qualitatifs composés de physiothérapeutes. Conclusion : au total, 116 thérapeutes ont participé au sondage. De ce nombre, 80 (69,0%) considéraient que la promotion des programmes d'activité physique communautaires faisait partie du rôle de la physiothérapie, et 89 (76,7%) recommandaient des programmes aux familles. Les thérapeutes qui avaient moins de six ans d'expérience en pédiatrie étaient moins susceptibles de recommander des programmes aux familles (χ2 4 = 40,46, p < 0,001). L'analyse qualitative a fait ressortir trois thèmes : 1) manque de clarté quant au rôle de la physiothérapie, 2) « ce n'est pas facile ¼ : difficultés à promouvoir l'activité physique communautaire et 3) une solution unique ne convient pas à tous. Conclusions : divers facteurs influaient sur la capacité des physiothérapeutes à promouvoir l'activité physique communautaire, notamment leurs connaissances, les attentes du milieu de pratique et leurs convictions vis-à-vis de leur rôle. Par des efforts concertés pour promouvoir la santé communautaire, il serait possible d'accroître la capacité de la communauté à soutenir tous les enfants dans le cadre d'activités physiques.

IL-27 signaling activates skin cells to induce innate antiviral proteins and protects against Zika virus infection.

In the skin, antiviral proteins and other immune molecules serve as the first line of innate antiviral defense. Here, we identify and characterize the induction of cutaneous innate antiviral proteins in response to IL-27 and its functional role during cutaneous defense against Zika virus infection. Transcriptional and phenotypic profiling of epidermal keratinocytes treated with IL-27 demonstrated activation of antiviral proteins OAS1, OAS2, OASL, and MX1 in the skin of both mice and humans. IL-27-mediated antiviral protein induction was found to occur in a STAT1- and IRF3-dependent but STAT2-independent manner. Moreover, using IL27ra mice, we demonstrate a significant role for IL-27 in inhibiting Zika virus morbidity and mortality following cutaneous, but not intravenous, inoculation. Together, our results demonstrate a critical and previously unrecognized role for IL-27 in cutaneous innate antiviral immunity against Zika virus.

Polyglutamine binding protein 1 (PQBP1) inhibits innate immune responses to cytosolic DNA.

Recent studies have highlighted the importance of immune sensing of cytosolic DNA of both pathogen and host origin. We aimed to examine the role of DNA sensors interferon-γ-inducible protein 16 (IFI16) and cyclic GMP-AMP synthase (cGAS) in responding to cytosolic DNA. We show IFI16 and cGAS can synergistically induce IFNb transcriptional activity in response to cytoplasmic DNA. We also examined the role of polyglutamine binding protein 1 (PQBP1), a protein predominantly expressed in lymphoid and myeloid cells that has been shown to lead to type I interferon production in response to retroviral infection. We show PQBP1 associates with cGAS and IFI16 in THP-1 cells. Unexpectedly, knockout of PQBP1 in THP-1 cells causes significantly increased type I IFN production in response to transfected cytosolic nucleic acids or DNA damage, unlike what is seen in response to retroviral infection. Overexpression of PQBP1 in HEK293 T cells impairs IFI16/cGAS-induced IFNb transcriptional activity. In human cancer patients, low expression of PQBP1 is correlated with improved survival, the opposite correlation of that seen with cGAS or IFI16 expression. Our findings suggest that PQBP1 inhibits IFI16/cGAS-induced signaling in response to cytosolic DNA, in contrast to the role of this protein in response to retroviral infection.

Gonadal asymmetry and sex determination in birds.

Although vertebrates display a superficial bilateral symmetry, most internal organs develop and locate with a consistent left:right asymmetry. There is still considerable debate as to when this process actually begins, but it seems that, at least for some species, the initial steps occur at a very early stage of development. In recent years, a number of model systems, including the chick embryo, have been utilised to increase our understanding of the molecular basis of this complex developmental process. While the basic elements of asymmetry are clearly conserved in chick development, the chick embryo also exhibits an additional unusual asymmetry in terms of the development of the gonads. In the female chick embryo, only 1 gonad and accessory structures fully develop, with the result that the adult hen has only 1 ovary and a single oviduct - both on the left side. With a small number of exceptions, this is a consistent feature of avian development. Here, we describe the morphological development and molecular basis of this unusual asymmetry, consider the implications for avian sex determination, and discuss the possible biological reasons why many birds have adopted a single-ovary system.