The experiences of a therapeutic relationship between dietitians and patients in UK eating disorder treatment: A qualitative study.

OBJECTIVE: Dietitians have a central role in eating disorder (ED) treatment, however few studies exist investigating therapeutic aspects of dietetic care and factors influencing the dietitian-patient relationship. To address the gap, this study aimed to use a qualitative description approach to explore the experiences of delivering and receiving dietetic care in ED treatment in the UK. METHOD: Semi-structured interviews were conducted with 6 specialist ED dietitians and focus groups with 11 recovered ED patients. Interviews were transcribed and inductive thematic analysis was performed to identify key themes describing the data. RESULTS: Six key themes were generated: (1) Building trust, (2) Appropriate timing, (3) Adapting, (4) Dietitians as experts, (5) Boundaries, and (6) Difficult relationships. Participants highlighted the importance of building trust and considering nutritional risk and readiness in treatment approach. Patients expressed a desire for dietitians to have experience in EDs, facilitating understanding of their illness. However, dietitians identified the nature of EDs making their role challenging at times. DISCUSSION: This study described various factors affecting dietetic care in EDs and provided a valuable insight into patients' perceptions of treatment. The findings support advancements in ED dietitians' knowledge and understanding, helping to enhance quality of care.

Immunometabolic adaptation in monocytes underpins functional changes during pregnancy.

Metabolic heterogeneity is a determinant of immune cell function. The normal physiological metabolic reprogramming of pregnancy that ensures the fuel requirements of mother and baby are met, might also underpin changes in immunity that occur with pregnancy and manifest as altered responses to pathogens and changes to autoimmune disease symptoms. Using peripheral blood from pregnant women at term, we reveal that monocytes lose M2-like and gain M1-like properties accompanied by reductions in mitochondrial mass, maximal respiration, and cardiolipin content in pregnancy; glycolysis is unperturbed. We establish that muramyl dipeptide (MDP)-stimulated cytokine production relies on oxidative metabolism, then show in pregnancy reduced cytokine production in response to MDP but not LPS. Overall, mitochondrially centered metabolic capabilities of late gestation monocytes are down-regulated revealing natural plasticity in monocyte phenotype and function that could reveal targets for improving pregnancy outcomes but also yield alternative therapeutic approaches to diverse metabolic and/or immune-mediated diseases beyond pregnancy.

Physiotherapy students' attitudes toward the use of telehealth in clinical practice: A cross-sectional survey.

Background and Aims: Provision of physiotherapy services using telehealth has drastically increased since the COVID-19 pandemic and continues to be utilized in clinical practice suggesting telehealth in physiotherapy will become common practice. Prior research has explored the attitudes of physiotherapists with many years of in-person clinical experience toward telehealth. However, little is known about the emerging workforce's attitudes. This study aims to explore physiotherapy students' attitudes toward the use of telehealth in clinical practice. Methods: A cross-sectional online survey of physiotherapy students enrolled in the Doctor of Physiotherapy program at Macquarie University between November 2022 and February 2023. Participants rated their level of agreement across 11 statements regarding telehealth use in physiotherapy clinical practice using a 5-point Likert scale ranging from "strongly disagree" to "strongly agree." Participants answered two open-ended questions regarding when they might use telehealth in clinical practice as a physiotherapist and why they believe physiotherapists might be reluctant to use telehealth in clinical practice. Results: A total of 118 participants completed the survey (response rate 53%). Overall, most participants believed telehealth would continue being offered post-Covid-19 (86%, n = 101), participants would use some form of telehealth in clinical practice (82%, n 96), believe a blended approach would be beneficial for patients (84%, n = 99), and were interested in further training in telehealth (90%, n = 107). We identified six broad themes, including accessibility, subsequent consultations, inability to provide manual therapies, limited training/education, perceived ineffectiveness, and digital literacy of the patient. Conclusion: Overall physiotherapy students believe telehealth will continue being offered in clinical practice, form part of contemporary physiotherapy practice, and are interested in further training to upskill in the delivery of care via telehealth. Given the continued use and students' demand for future training, it may be time to reimagine the inclusion of telehealth education and training in the entry-level physiotherapy curriculum.

Lentiviral Vector Preparation for Efficient Gene and MicroRNA Modulation of Peritoneal Cavity Tissue-Resident Macrophages In Vivo in Mice.

Peritoneal tissue-resident macrophages have broad functions in the maintenance of homeostasis and are involved in pathologies within local and neighboring tissues. Their functions are dictated by microenvironmental cues; thus, it is essential to investigate their behavior in an in vivo physiological niche. Currently, specific peritoneal macrophage-targeting methodologies employ whole-mouse transgenic models. Here, a protocol for effective in vivo modulation of mRNA and small RNA species (e.g., microRNA) expression in peritoneal macrophages using lentivirus particles is described. Lentivirus preparations were made in HEK293T cells and purified on a single sucrose layer. In vivo validation of lentivirus effectivity following intraperitoneal injection revealed predominant infection of macrophages restricted to local tissue. Targeting of peritoneal macrophages was successful during homeostasis and thioglycolate-induced peritonitis. The limitations of the protocol, including low-level inflammation induced by intraperitoneal delivery of lentivirus and time restrictions for potential experiments, are discussed. Overall, this study presents a quick and accessible protocol for the rapid assessment of gene function in peritoneal macrophages in vivo.

Practitioners preference in using electrotherapy to treat paediatric lower limb conditions: an online survey.

PURPOSE: Electrotherapies are commonly used to treat adult musculoskeletal pathologies. However, there is insufficient evidence supporting the use of electrotherapies for lower limb conditions in children. Currently, it is unknown how electrotherapies are used in paediatric clinical practice. This study aimed to investigate if practitioners use electrotherapy to treat children's lower limb conditions, frequency and why. MATERIALS AND METHODS: A custom-built online survey was disseminated via social media targeting international medical and healthcare practitioners who treat children with lower limb conditions using electrotherapy. Practitioners were asked if they did or did not use electrotherapies, and their reasons. Responses were described in frequencies and with thematic analysis. RESULTS: There were 445 practitioners who responded. From these, 301(68%) indicated they used electrotherapy, with the most frequently used being Transcutaneous Electrical Nerve Stimulation (n = 110). The most common reason cited for using electrotherapy was practitioner preference due to the alleged effectiveness of the chosen modality. The remaining 144 (32%) practitioners reported not using electrotherapy, the most common reason being lack of evidence. CONCLUSIONS: We found that a majority of practitioners used electrotherapies on children. The reasons for using or not using electrotherapy were practitioner centred.

Electrotherapy modalities are commonly used to treat musculoskeletal injuries in adultsThe management of children differs from adults due to physiological and psychological differences.The use of electrotherapy to treat musculoskeletal lower limb pathologies children is currently not supported by evidence, and the frequency of use of these modalities in children is not known.This study found that despite that, a majority of medical and health practitioners surveyed in this study routinely use electrotherapy to treat paediatric musculoskeletal injuries.

Immune and metabolic markers for identifying and investigating severe Coronavirus disease and Sepsis in children and young people (pSeP/COVID ChYP study): protocol for a prospective cohort study.

INTRODUCTION: Early recognition and appropriate management of paediatric sepsis are known to improve outcomes. A previous system's biology investigation of the systemic immune response in neonates to sepsis identified immune and metabolic markers that showed high accuracy for detecting bacterial infection. Further gene expression markers have also been reported previously in the paediatric age group for discriminating sepsis from control cases. More recently, specific gene signatures were identified to discriminate between COVID-19 and its associated inflammatory sequelae. Through the current prospective cohort study, we aim to evaluate immune and metabolic blood markers which discriminate between sepses (including COVID-19) from other acute illnesses in critically unwell children and young persons, up to 18 years of age. METHODS AND ANALYSIS: We describe a prospective cohort study for comparing the immune and metabolic whole-blood markers in patients with sepsis, COVID-19 and other illnesses. Clinical phenotyping and blood culture test results will provide a reference standard to evaluate the performance of blood markers from the research sample analysis. Serial sampling of whole blood (50 µL each) will be collected from children admitted to intensive care and with an acute illness to follow time dependent changes in biomarkers. An integrated lipidomics and RNASeq transcriptomics analyses will be conducted to evaluate immune-metabolic networks that discriminate sepsis and COVID-19 from other acute illnesses. This study received approval for deferred consent. ETHICS AND DISSEMINATION: The study has received research ethics committee approval from the Yorkshire and Humber Leeds West Research Ethics Committee 2 (reference 20/YH/0214; IRAS reference 250612). Submission of study results for publication will involve making available all anonymised primary and processed data on public repository sites. TRIAL REGISTRATION NUMBER: NCT04904523.

Telehealth education and training in entry-to-practice physiotherapy programs in Australian universities: A qualitative study with university educators.

BACKGROUND: To explore attitudes to telehealth education and experiences incorporating telehealth education into entry-to-practice physiotherapy programs in Australia, from the perspective of university educators. METHODS: Qualitative design based on a constructivist paradigm and a phenomenological approach. Sixteen university educators (who had a responsibility for telehealth curriculum or oversight of the broader curriculum in an entry-to-practice physiotherapy programme at an Australian university) were recruited. Individual semi-structured interviews were conducted via Zoom. Interviews were recorded, transcribed verbatim, and analysed thematically using an inductive approach. RESULTS: Three themes (with associated subthemes) were identified: (i) telehealth education has a role in contemporary physiotherapy practice (COVID-19 pandemic was a driver for telehealth education, acknowledgement that telehealth is here to stay and identified areas of focus for telehealth education and training); (ii) telehealth education and training vary substantially (content delivered and assessment of telehealth competency is ad hoc and student exposure to telehealth on clinical placements is inconsistent); (iii) challenges in telehealth education (finding space and time in the curriculum, as well as insufficient knowledge and expertise of staff, are challenges for implementation of telehealth education, however, course and subject development and/or reviews provide opportunities for implementing telehealth education and training). CONCLUSION: Current content and volume of telehealth education and training in entry-to-practice physiotherapy programs across Australia varies substantially. Although educators believe telehealth is an important component of contemporary physiotherapy practice, many barriers exist for including telehealth training into the curriculum.

Immune-metabolic adaptations in pregnancy: A potential stepping-stone to sepsis.

Physiological shifts during pregnancy predispose women to a higher risk of developing sepsis resulting from a maladapted host-response to infection. Insightful studies have delineated subtle point-changes to the immune system during pregnancy. Here, we present an overlay of these point-changes, asking what changes and when, at a physiological, cellular, and molecular systems-level in the context of sepsis. We identify distinct immune phases in pregnancy delineated by placental hormone-driven changes in homeostasis setpoints of the immune and metabolic systems that subtly mirrors changes observed in sepsis. We propose that pregnancy immune-metabolic setpoint changes impact feedback thresholds that increase risk for a maladapted host-response to infection and thus act as a stepping-stone to sepsis. Defining maternal immune-metabolic setpoint changes is not only vital for tailoring the right diagnostic tools for early management of maternal sepsis but will facilitate an unravelling of the pathophysiological pathways that predispose an individual to sepsis.

mSep: investigating physiological and immune-metabolic biomarkers in septic and healthy pregnant women to predict feto-maternal immune health - a prospective observational cohort study protocol.

INTRODUCTION: Maternal sepsis remains a leading cause of death in pregnancy. Physiological adaptations to pregnancy obscure early signs of sepsis and can result in delays in recognition and treatment. Identifying biomarkers that can reliably diagnose sepsis will reduce morbidity and mortality and antibiotic overuse. We have previously identified an immune-metabolic biomarker network comprising three pathways with a >99% accuracy for detecting bacterial neonatal sepsis. In this prospective study, we will describe physiological parameters and novel biomarkers in two cohorts-healthy pregnant women and pregnant women with suspected sepsis-with the aim of mapping pathophysiological drivers and evaluating predictive biomarkers for diagnosing maternal sepsis. METHODS AND ANALYSIS: Women aged over 18 with an ultrasound-confirmed pregnancy will be recruited to a pilot and two main study cohorts. The pilot will involve blood sample collection from 30 pregnant women undergoing an elective caesarean section. Cohort A will follow 100 healthy pregnant women throughout their pregnancy journey, with collection of blood samples from participants at routine time points in their pregnancy: week 12 'booking', week 28 and during labour. Cohort B will follow 100 pregnant women who present with suspected sepsis in pregnancy or labour and will have at least two blood samples taken during their care pathway. Study blood samples will be collected during routine clinical blood sampling. Detailed medical history and physiological parameters at the time of blood sampling will be recorded, along with the results of routine biochemical tests, including C reactive protein, lactate and white blood cell count. In addition, study blood samples will be processed and analysed for transcriptomic, lipidomic and metabolomic analyses and both qualitative and functional immunophenotyping. ETHICS AND DISSEMINATION: Ethical approval has been obtained from the Wales Research Ethics Committee 2 (SPON1752-19, 30 October 2019). TRIAL REGISTRATION NUMBER: NCT05023954.

Disclosure and help-seeking behaviors related to sexual and physical violence in childhood and adolescence: Results from the Namibia Violence Against Children and Youth Survey.

BACKGROUND: Violence disclosure and help-seeking can mitigate adverse health effects associated with childhood violence, but little is known about facilitators and barriers of disclosure and help-seeking behaviors in sub-Saharan Africa. OBJECTIVE: To understand factors associated with disclosure and help-seeking to inform care. PARTICIPANTS AND SETTING: Participants aged 13-24 years old in the 2019 Namibia Violence Against Children and Youth Survey (VACS). METHODS: We assessed the prevalence of victimization, disclosure, and help-seeking and examined factors associated with violence disclosure and help-seeking, separately, by gender. RESULTS: 4211 girls and 980 boys participated in the Namibia VACS. The prevalence of childhood sexual violence differed significantly by gender (15.7% among girls, 9.8% among boys), but physical violence prevalence did not differ by gender. Among victims of sexual violence, 57.3% of girls disclosed and 10.4% sought help, compared with only 30.7% and 3.2% of boys. Among victims of physical violence, 61.1% of girls and 53.4% of boys disclosed, and 16.9% of girls and 17.7% of boys sought help. Older age, social support, and experiencing more types of violence were associated with sexual violence disclosure among boys, but none of these factors were associated with sexual violence disclosure among girls. Lower education, perpetrator type, and witnessing violence were associated with physical violence disclosure among girls, while peer support and perpetrator type were associated with physical violence disclosure among boys. CONCLUSIONS: Factors associated with childhood violence differed by gender and violence type in Namibia, highlighting a need for gender-specific violence services to facilitate violence disclosure and help-seeking.

An international core capability framework for physiotherapists delivering telephone-based care.

QUESTION: What are the core capabilities that physiotherapists need in order to deliver quality telephone-based care? DESIGN: Three-round modified e-Delphi survey. PARTICIPANTS: An international Delphi panel comprising experts in the field, including consumers, physiotherapy researchers, physiotherapy clinicians and representatives of physiotherapy organisations. METHODS: A modified e-Delphi survey was conducted. A draft framework was adapted from a previously developed core capability framework for physiotherapists delivering care via videoconferencing. The panel considered the draft framework of 39 individual capabilities across six domains. Over three rounds, panellists rated their agreement (via Likert or 0-to-10 numerical rating scales) on whether each capability was essential (core) for physiotherapists to deliver telephone-based care. Capabilities achieving consensus, defined as 75% of the panel rating the item at least 7 out of 10 in Round 3, were retained. RESULTS: Seventy-one panellists from 17 countries participated in Round 1, with retention of 89% in Round 2 and 82% in Round 3. The final framework comprised 44 capabilities across six domains: compliance (n = 7 capabilities); patient privacy and confidentiality (n = 4); patient safety (n = 7); telehealth delivery (n = 9); assessment and diagnosis (n = 7); and care planning and management (n = 10). CONCLUSION: This framework outlines the core capabilities that physiotherapists need to provide telephone-based care. It can help inform content of physiotherapy curricula and professional development initiatives in telehealth delivery and provide guidance for physiotherapists providing care over the telephone.

Cycles of Violence Among Young Women in Namibia: Exploring the Links Between Childhood Violence and Adult Intimate Partner Violence From the Violence Against Children and Youth Survey.

Background: Violence against children is a global public health crisis and is associated with poor mental and physical health outcomes. Childhood violence may also increase the risk of subsequent violence revictimization by an intimate partner. We aimed to understand cycles of violence among adolescent girls and young women in Namibia to inform violence prevention and treatment interventions. Methods: The 2019 Namibia Violence Against Children and Youth Survey (VACS) examined the prevalence of childhood violence and intimate partner violence among 18-24 year old adolescent girls and young women (N = 2434). Using the data, we assessed the prevalence of childhood violence, defined as any physical, sexual, or emotional violence victimization prior to age 18, and estimated the prevalence of intimate partner violence (IPV) after age 18. We used a weighted logistic regression to assess whether childhood violence exposure was associated with subsequent experience of IPV after age 18. Results: Adolescent girls and young women in Namibia had a statistically significant higher odds of experiencing IPV if they had experienced any childhood violence including physical, sexual, and/or emotional violence (adjusted odds ratio [aOR]: 2.93; 95% Confidence Interval [95% CI: 1.64-5.23). IPV was also significantly associated with childhood physical (aOR: 1.81; 95% CI: 1.07-3.05), sexual (aOR: 3.79; 95% CI: 2.54-5.67), or emotional (aOR: 2.39; 95% CI: 1.18-4.86) violence when each were considered separately. We also observed a dose-response relationship between the number of types of childhood violence and IPV experience as a young adult. Conclusions: Childhood violence is a significant predictor of subsequent violence revictimization by an intimate partner. This analysis provides unique insights on cycles of violence among adolescent girls and young women in Namibia and points to the need for interventions during childhood to prevent violence against children and break this cycle among young women in sub-Saharan Africa.

Oxylipin metabolism is controlled by mitochondrial ß-oxidation during bacterial inflammation.

Oxylipins are potent biological mediators requiring strict control, but how they are removed en masse during infection and inflammation is unknown. Here we show that lipopolysaccharide (LPS) dynamically enhances oxylipin removal via mitochondrial ß-oxidation. Specifically, genetic or pharmacological targeting of carnitine palmitoyl transferase 1 (CPT1), a mitochondrial importer of fatty acids, reveal that many oxylipins are removed by this protein during inflammation in vitro and in vivo. Using stable isotope-tracing lipidomics, we find secretion-reuptake recycling for 12-HETE and its intermediate metabolites. Meanwhile, oxylipin ß-oxidation is uncoupled from oxidative phosphorylation, thus not contributing to energy generation. Testing for genetic control checkpoints, transcriptional interrogation of human neonatal sepsis finds upregulation of many genes involved in mitochondrial removal of long-chain fatty acyls, such as ACSL1,3,4, ACADVL, CPT1B, CPT2 and HADHB. Also, ACSL1/Acsl1 upregulation is consistently observed following the treatment of human/murine macrophages with LPS and IFN-γ. Last, dampening oxylipin levels by ß-oxidation is suggested to impact on their regulation of leukocyte functions. In summary, we propose mitochondrial ß-oxidation as a regulatory metabolic checkpoint for oxylipins during inflammation.

In vitro evaluation of Sensi-IP®: A soluble and mineralizing sensitivity solution.

OBJECTIVES: Sensi-IP®OG (SIP-OG) and Sensi-IP®FF (SIP-FF) are soluble bioactive glasses developed to treat dentin hypersensitivity and promote remineralization. Evaluation of their therapeutic potential to reduce dentin hypersensitivity and recover enamel strength was evaluated using standardized in vitro assessments based on simulated use. METHODS: To assess dentin occlusion a visual occlusion methodology was employed. Dentin discs were subjected to twice-daily simulated brushing (for 5 days) using 0.67 g of toothpaste for 10 s. Simple prototype toothpastes containing SIP-OG and SIP-FF were compared to commercially available controls: Colgate® Sensitive Pro-Relief (CPR) and Sensodyne® Repair and Protect with NovaMin® (SRP). Samples were stored in artificial saliva between treatments. All samples were assessed at baseline and subsequent to each treatment and were scored on a 5-point categorical scale for occlusion. For enamel surface effects, test articles of SIP-OG, SIP-FF, and SIP-FF with NaF were compared to a positive (with NaF) and a negative (no NaF) control paste. Enamel samples were subjected to a pH cycling regime, providing exposure to the toothpaste slurry (i.e., 2 parts deionized water to 1 part toothpaste), mineralizing solution, and demineralizing solution over 5 days of simulated use. Samples were stored overnight in mineralizing solution. Samples were evaluated for fluoride uptake and changes to surface microhardness. RESULTS: Visual occlusion scores (1 fully occluded to 5 unoccluded) were 2.6, 3.8, 4.4 and 4.0 after 1 day of simulated use for SIP-OG, SIP-FF with NaF, Colgate® Sensitive Pro-Relief and Sensodyne® Repair and Protect, respectively, decreasing to 1.0, 1.8, 3.1 and 3.9 after 5 days of application. SIP-OG provided superior occlusion at the significance level of p ≤ 0.05 at 1, 2, 3, 4, and 5 days. SIP-FF with NaF provided superior occlusion at the significance level of p ≤ 0.05 at 2, 4, and 5 days. Fluoride uptake ranged from 9.0 µg/cm2 for SIP-OG to 12.4 µg/cm2 for SIP-FF with NaF. Surface microhardness after acid cycling allowed recovery of 59 % of surface microhardness after treatment with SIP-OG or SIP-FF with NaF. SIP-OG achieved significant surface microhardness recovery versus SIP-FF alone, a NaF control paste, and a fluoride free control paste at the significance level of p ≤ 0.05. SIP-FF with NaF achieved surface microhardness recovery versus SIP-FF alone, a NaF control paste, and a fluoride free control paste at the significance level of p ≤ 0.05. CONCLUSIONS: Superior occlusion of dentin tubules was observed with both novel additives compared to commercially available toothpastes. A build-up effect with increasing occlusion was noted with repeated application for both novel additives and ascribed to mineralization effects, as supported by surface microhardness recovery on initial enamel lesions.

An international core capability framework for physiotherapists to deliver quality care via videoconferencing: a Delphi study.

QUESTION: What are the core capabilities that physiotherapists need in order to deliver quality care via videoconferencing? DESIGN: A three-round modified e-Delphi survey. PARTICIPANTS: An international Delphi panel comprising a Steering Group and experts in the field, including physiotherapy researchers, physiotherapy clinicians, representatives of physiotherapy organisations, and consumers. METHODS: The draft framework was developed by the research team and Steering Group, based on relevant documents identified within the literature. The panel considered a draft framework of 73 specific capabilities mapped across eight domains. Over three rounds, panellists rated their agreement (Likert or numerical rating scales) on whether each capability was essential (core) for physiotherapists to deliver quality care via videoconferencing. Those capabilities achieving consensus, defined as 75% of the panel ratings being ≥ 7 out of 10 in Round 3, were retained. RESULTS: A total of 130 panellists from 32 countries participated in Round 1, with retention rates of 65% and 60% in Rounds 2 and 3, respectively. The final framework comprised 60 capabilities across seven domains: compliance (n = 7 capabilities); patient privacy and confidentiality (n = 4); patient safety (n = 7); technology skills (n = 7); telehealth delivery (n = 16); assessment and diagnosis (n = 7); and care planning and management (n = 12). CONCLUSION: This framework outlines the specific core capabilities required of physiotherapists to provide quality care via videoconferencing. The core capability framework provides guidance for physiotherapists to deliver care via videoconferencing and will help inform future development of physiotherapy curricula and professional development initiatives in the delivery of telehealth.

Prostaglandin E2 promotes intestinal inflammation via inhibiting microbiota-dependent regulatory T cells.

The gut microbiota fundamentally regulates intestinal homeostasis and disease partially through mechanisms that involve modulation of regulatory T cells (Tregs), yet how the microbiota-Treg cross-talk is physiologically controlled is incompletely defined. Here, we report that prostaglandin E2 (PGE2), a well-known mediator of inflammation, inhibits mucosal Tregs in a manner depending on the gut microbiota. PGE2 through its receptor EP4 diminishes Treg-favorable commensal microbiota. Transfer of the gut microbiota that was modified by PGE2-EP4 signaling modulates mucosal Treg responses and exacerbates intestinal inflammation. Mechanistically, PGE2-modified microbiota regulates intestinal mononuclear phagocytes and type I interferon signaling. Depletion of mononuclear phagocytes or deficiency of type I interferon receptor diminishes PGE2-dependent Treg inhibition. Together, our findings provide emergent evidence that PGE2-mediated disruption of microbiota-Treg communication fosters intestinal inflammation.

Randomised study of intra-oral kinetics of fluoride-containing toothpastes.

OBJECTIVES: This randomised, controlled, analyst blind, crossover study aimed to evaluate and compare salivary fluoride and calcium ion concentration over 60 min following brushing with an assigned treatment and following an orange juice (OJ) or deionised (DI) water rinse 60 min post-brushing. METHODS: Study treatments, both containing 1150 ppm fluoride as NaF and 5% w/w KNO3, were the Test (including 1.2 % w/w cocamidopropyl betaine) and Comparator (including tetrasodium pyrophosphate and sodium lauryl sulphate) toothpastes. Twenty nine participants were randomised to treatment. RESULTS: A sharp increase in salivary fluoride ion concentration immediately post-brushing with either toothpaste decreased over time. Fluoride concentration following Test toothpaste use was numerically higher than the Comparator at all timepoints, with a significant difference from 10 min post-brushing (p < .05). Following the 60 min rinse, there were no significant differences between the Test or Comparator + OJ groups in salivary fluoride concentration but the Test + DI water group was significantly lower than Test (p < .001) or Comparator (p < .001) + OJ groups. A reduction in salivary calcium ion concentration was seen immediately post-brushing and after the OJ rinse with both toothpastes. Significant differences were observed in favour of the Test toothpaste at all timepoints (p < .05) and for Test and Comparator + OJ group (p < .001) compared with Test + DI water rinse. Both treatments were generally well-tolerated. CONCLUSIONS: This study demonstrated that toothpaste formulations with identical declared fluoride concentrations and the same fluoride source give rise to differing intraoral fluoride concentrations over time, which are potentially related to different formulation excipient effects. CLINICAL SIGNIFICANCE: By understanding the interaction of toothpaste formulation excipients in the oral environment, formulations can be developed that maximise retention of fluoride in the oral environment.

nSeP: immune and metabolic biomarkers for early detection of neonatal sepsis-protocol for a prospective multicohort study.

INTRODUCTION: Diagnosing neonatal sepsis is heavily dependent on clinical phenotyping as culture-positive body fluid has poor sensitivity, and existing blood biomarkers have poor specificity.A combination of machine learning, statistical and deep pathway biology analyses led to the identification of a tripartite panel of biologically connected immune and metabolic markers that showed greater than 99% accuracy for detecting bacterial infection with 100% sensitivity. The cohort study described here is designed as a large-scale clinical validation of this previous work. METHODS AND ANALYSIS: This multicentre observational study will prospectively recruit a total of 1445 newborn infants (all gestations)-1084 with suspected early-or late-onset sepsis, and 361 controls-over 4 years. A small volume of whole blood will be collected from infants with suspected sepsis at the time of presentation. This sample will be used for integrated transcriptomic, lipidomic and targeted proteomics profiling. In addition, a subset of samples will be subjected to cellular phenotype and proteomic analyses. A second sample from the same patient will be collected at 24 hours, with an opportunistic sampling for stool culture. For control infants, only one set of blood and stool sample will be collected to coincide with clinical blood sampling. Along with detailed clinical information, blood and stool samples will be analysed and the information will be used to identify and validate the efficacy of immune-metabolic networks in the diagnosis of bacterial neonatal sepsis and to identify new host biomarkers for viral sepsis. ETHICS AND DISSEMINATION: The study has received research ethics committee approval from the Wales Research Ethics Committee 2 (reference 19/WA/0008) and operational approval from Health and Care Research Wales. Submission of study results for publication will involve making available all anonymised primary and processed data on public repository sites. TRIAL REGISTRATION NUMBER: NCT03777670.