Identifying immune signatures of sepsis to increase diagnostic accuracy in very preterm babies.

Bacterial infections are a major cause of mortality in preterm babies, yet our understanding of early-life disease-associated immune dysregulation remains limited. Here, we combine multi-parameter flow cytometry, single-cell RNA sequencing and plasma analysis to longitudinally profile blood from very preterm babies (<32 weeks gestation) across episodes of invasive bacterial infection (sepsis). We identify a dynamically changing blood immune signature of sepsis, including lymphopenia, reduced dendritic cell frequencies and myeloid cell HLA-DR expression, which characterizes sepsis even when the common clinical marker of inflammation, C-reactive protein, is not elevated. Furthermore, single-cell RNA sequencing identifies upregulation of amphiregulin in leukocyte populations during sepsis, which we validate as a plasma analyte that correlates with clinical signs of disease, even when C-reactive protein is normal. This study provides insights into immune pathways associated with early-life sepsis and identifies immune analytes as potential diagnostic adjuncts to standard tests to guide targeted antibiotic prescribing.

Intravenous antibiotics in preterm infants have a negative effect upon microbiome development throughout preterm life.

BACKGROUND: Intestinal dysbiosis is implicated in the origins of necrotising enterocolitis and late-onset sepsis in preterm babies. However, the effect of modulators of bacterial growth (e.g. antibiotics) upon the developing microbiome is not well-characterised. In this prospectively-recruited, retrospectively-classified, case-control study, high-throughput 16S rRNA gene sequencing was combined with contemporaneous clinical data collection, to assess the within-subject relationship between antibiotic administration and microbiome development, in comparison to preterm infants with minimal antibiotic exposure. RESULTS: During courses of antibiotics, diversity progression fell in comparison to that seen outside periods of antibiotic use (-0.71units/week vs. + 0.63units/week, p < 0.01); Enterobacteriaceae relative abundance progression conversely rose (+ 10.6%/week vs. -8.9%/week, p < 0.01). After antibiotic cessation, diversity progression remained suppressed (+ 0.2units/week, p = 0.02). CONCLUSIONS: Antibiotic use has an acute and longer-lasting impact on the developing preterm intestinal microbiome. This has clinical implications with regard to the contribution of antibiotic use to evolving dysbiosis, and affects the interpretation of existing microbiome studies where this effect modulator is rarely accounted for.

Chicken's best friend? Livestock guardian dog bonding with free-ranging chickens.

Growth in the free-range and pastured egg industries has increased globally, necessitating improvements in predator control. Some egg producers are turning to the use of livestock guardian dogs (LGD; Canis familiaris) to protect hens from predation. We worked on a property where pastured layer hens were protected by two Maremma LGDs that were released from their chicken enclosure for 2-3 nights a week. GPS tracking showed that the dogs were more strongly bonded to people than the chickens, spending most of their time at night (96.1% of location data) close to the farmhouse and only 0.09% near their chicken paddock. Despite this lack of attendance, we found no change in the paddock space use by chickens with or without the dogs present (P = 0.999). Furthermore, camera trapping revealed 40 red fox (Vulpes vulpes) events over the 46-d monitoring period, with less fox activity on nights when the LGDs were allowed to roam the property and motion-activated spotlights were also deployed (P = 0.048). An online survey of 59 poultry producers found strong belief in the effectiveness of LGDs, although half the respondents (52%) indicated that they were still experiencing predation issues. There was no association with the reported degree of human bonding of their LGDs, but respondents were more likely to report current issues with predators if they owned 100 or more chickens (P = 0.031). The present case study as well as the farmer survey have identified that LGDs can be strongly bonded to people. Although there was no evidence of subsequently increased risk of predation, bonding with people could draw LGDs away from the animals they should be defending, with predation risk for poultry likely to depend on how far away LGDs move from their livestock.

Targeting for nonpoint source pollution reduction: A synthesis of lessons learned, remaining challenges, and emerging opportunities.

The ability to identify, target, and treat critical pollution source areas on a landscape is an ongoing challenge for water quality programs that seek to address nonpoint source (NPS) pollution. In this article, we develop a conceptual framework for targeting program design, and review recent experience with the implementation of targeting programs that corresponds with a wide range of program characteristics. Through this review, we emphasize that the complex and locally dependent nature of NPS generation and transport makes it impossible to define a narrow set of rules to guide targeting programs everywhere. Instead, we evaluate key features of NPS targeting in several different contexts, highlighting lessons learned from recent experience. This synthesis of targeting program design and implementation points toward several areas of opportunity for improved NPS policy, however more research is needed to systematically document changes in behavior and pollutant loads. The lack of monitoring data at refined scales presents a major obstacle to targeting program success. This paper synthesizes new opportunities and ongoing challenges for the implementation of targeting in NPS water quality programs.

Demand for regional level III neonatal services is not reduced during national COVID lockdowns.

Following the first peak of the COVID-19 pandemic, reports from around the world suggested a reduction in preterm deliveries during lockdown periods. We reviewed preterm admissions to a large tertiary neonatal unit in inner North East London during two United Kingdom (UK) national lockdowns in 2020 and 2021. We found no evidence of difference in admissions during two national lockdowns compared to previous years. Based on these findings, we recommend that neonatal services remain as vigilant and prepared as ever for the unpredictable nature of preterm birth, and their staff protected to provide this highly specialist care.

Dental Research Waste in Design, Analysis, and Reporting: A Scoping Review.

Research waste is highly prevalent across biomedical investigations. We aimed to assess the evidence on the extent of research waste in dental research. We performed a scoping review of empirical evaluations of dental studies assessing the prevalence and impact of limitations in design, conduct, analysis, and reporting of research. PubMed was searched using specific terms to retrieve studies dealing with design, conduct, analysis, and reporting of studies in dentistry, with no year or language restrictions. Of the 1,807 publications identified from the search and from manual searches, 71 were included in this review. The topic and article selection was based on the expert opinion of the authors. The existing evidence suggests that, although there are improvements over time, substantial deficiencies in all areas (design, conduct, analysis, reporting) were prevalent in dental research publications. Waste in research is a multifaceted problem without a simple solution. However, an appreciation of optimal research design and execution is a prerequisite and should be underpinned by policies that include appropriate training in research methods and properly aligned incentives.

Isolation of Cryptococcus neoformans var. grubii (serotype A) and C. magnus from the nasal lining of free-ranging quokkas (Setonix brachyurus).

Cryptococcus species are environmental yeasts, with a worldwide distribution and remarkable environmental adaptation. Although many species do not cause disease, C. neoformans and C. gattii are causative agents of cryptococcosis, a life threatening infection and a significant public health problem worldwide. Infection especially affects immunocompromised animals and humans. In wildlife, cryptococcosis appears to be more prevalent in captive populations. The objective of this study was to assess whether apparently healthy quokkas (Setonix brachyurus) harbor Cryptococcus spp. Using cultural and molecular methods, we studied yeasts isolated from nasal swabs collected from 130 free-ranging quokkas on Rottnest Island (RI, n = 97) and the mainland (n = 33) of Western Australia. Unspeciated Cryptococcus spp. (from four quokkas), C. neoformans var. grubii (serotype A) (two quokkas) and C. magnus (one quokka) were isolated from the nasal lining of apparently healthy quokkas from RI. Cryptococcus neoformans var. grubii was isolated from animals captured in a human-populated area on RI. There was no significant effect of the presence of Cryptococcus on the results of haematology, blood chemistry, peripheral blood cell morphology or clinical examination. To the best of our knowledge, this is the first documented isolation of C. neoformans var. grubii (serotype A) and C. magnus in a free-ranging macropod in Western Australia. The public health implications of this finding should be further explored.

Perinatal inflammation influences but does not arrest rapid immune development in preterm babies.

Infection and infection-related complications are important causes of death and morbidity following preterm birth. Despite this risk, there is limited understanding of the development of the immune system in those born prematurely, and of how this development is influenced by perinatal factors. Here we prospectively and longitudinally follow a cohort of babies born before 32 weeks of gestation. We demonstrate that preterm babies, including those born extremely prematurely (<28 weeks), are capable of rapidly acquiring some adult levels of immune functionality, in which immune maturation occurs independently of the developing heterogeneous microbiome. By contrast, we observe a reduced percentage of CXCL8-producing T cells, but comparable levels of TNF-producing T cells, from babies exposed to in utero or postnatal infection, which precedes an unstable post-natal clinical course. These data show that rapid immune development is possible in preterm babies, but distinct identifiable differences in functionality may predict subsequent infection mediated outcomes.

Enamel Remineralization with Novel Bioactive Glass Air Abrasion.

Enamel demineralization or white spot lesions (WSLs) are a frequent complication associated with fixed appliance-based orthodontic treatment. The remineralization potential of a novel fluoride-containing bioactive glass (QMAT3) propelled via an air abrasion system was compared with Sylc glass and artificial saliva on artificially induced WSLs. Thirty extracted human premolars were randomly assigned into 3 groups ( n = 10) per method of treatment and scanned with optical coherence tomography and noncontact profilometer in the 4 enamel states: sound, demineralized, after glass propulsion, and after immersion in artificial saliva. Knoop hardness testing was also performed. Twenty additional prepared teeth samples were also randomly selected for examination by scanning electron microscopy and energy-dispersive X-ray spectroscopy (2 teeth per technique) under each of the 4 enamel conditions. 19F MAS-NMR (magic angle spinning-nuclear magnetic resonance) was also used to detect the type of apatite formed on the enamel surface. Significant enamel remineralization with surface roughness and intensity of light backscattering similar to that of sound enamel was observed following treatment with QMAT3. In addition, mineral deposits were detected on the remineralized enamel surfaces, forming a protective layer and improving its hardness. This layer was rich in calcium, phosphate, and fluoride; 19F MAS-NMR confirmed the formation of fluorapatite. This finding is particularly beneficial since fluorapatite is more chemically stable than hydroxyapatite and has greater resistance to acid attack. Hence, a promising fluoride-containing bioactive glass for enamel remineralization has been developed, although further clinical evaluation and refinement is required.

Collaboration in orthodontic clinical trials: prevalence and association with sample size and funding.

BACKGROUND: To assess patterns of research collaboration in orthodontics and possible relationships with sample size and funding status. METHODS: Orthodontic randomised and non-randomised controlled clinical trials published between 2013 and 2017 were identified through electronic searching. The nature of collaboration, author institutions, study setting, sample size, and funding status were assessed. Linear and logistic regression analyses were applied. RESULTS: Of 1153 studies, 217 met the selection criteria. The majority of studies were authored by university academics (86%), were conducted in a single centre (71.9%) and in at least one university hospital (68.2%). The number of practice-based trials (10.1%), as well as the involvement of specialist practitioners (5.2%) in co-authorship, was limited. Multi-centred studies within a single country were associated with a significantly larger sample size compared to single-centred trials (P = 0.00; 95% confidence interval [CI] 33.59, 106.93). However, authorship collaboration either nationally (odds ratio [OR] 2.37; 95% CI 0.85, 6.57) or internationally across different continents (OR 5.54; 95% CI 0.62, 49.52) did not translate into increased funding. CONCLUSIONS: Most orthodontic studies were undertaken in university hospital settings within a single country. Collaboration is common in orthodontics but involvement of practice settings remains limited, suggesting a need for stimulation of practice-based research and research partnerships.

Smoking in pregnancy is a key factor for sudden infant death among Maori.

AIM: To examine the sudden unexpected death in infancy (SUDI) disparity between Maori and non-Maori in New Zealand. METHODS: A nationwide prospective case-control study ran from March 2012 to February 2015. Exposure to established SUDI risk factors was analysed to investigate the disparity experienced by Maori. Infant ethnicity was based on mother's ethnicity. Maori ethnicity was prioritised. Non-Maori includes Pacific, Asian, NZ European and Other. RESULTS: There were 137 cases and 649 controls. The Maori SUDI rate was 1.41/1000 live births compared to 0.53/1000 for non-Maori. Parents/caregivers of 132 cases (96%) and 258 controls (40%) were interviewed. Smoking in pregnancy was associated with an equally increased SUDI risk for Maori (adjusted OR = 8.11, 95% CI = 2.64, 24.93) and non-Maori (aOR = 5.09, 95% CI = 1.79, 14.47), as was bed-sharing (aOR = 3.66, 95% CI = 1.49, 9.00 vs aOR = 11.20, 95% CI = 3.46, 36.29). Bed-sharing prevalence was similar; however, more Maori controls smoked during pregnancy (46.7%) than non-Maori (22.8%). The main contributor relating to increased SUDI risk for Maori/non-Maori infants is the combination of smoking in pregnancy and bed sharing. CONCLUSION: The association between known SUDI risk factors, including bed sharing and/or smoking in pregnancy and SUDI risk, is the same regardless of ethnicity. Maori infants are exposed more frequently to both behaviours because of the higher Maori smoking rate.

A cross-sectional analysis of Wits and Riedel in adults with skeletal III malocclusion: How informative are they?

OBJECTIVES: To compare the relationship between Riedel and Wits appraisal in skeletal III malocclusions and to assess the effect of variation in the vertical skeletal measurements. SETTING AND SAMPLE POPULATION: One-hundred and twenty consecutive subjects with Class III malocclusions attending orthognathic clinics were analysed. MATERIALS AND METHODS: Lateral cephalograms were hand-traced under standardized conditions. Cephalometric measurements included Riedel analysis, Wits appraisal, A point/B point to Frankfurt plane (AF-BF) and vertical measurements. RESULTS: The mean ANB and Wits values were -3.22° and -11.39 mm, respectively. A positive correlation was found between ANB and Wits overall (r = -.49; P < .001). However, there was poor agreement between both Wits (r = .087) and Riedel (r = .089) with AF-BF (P > .05). A negative correlation existed between Wits and LAFH% (r = -.64, P-value < .001); however, no relationship was observed between ANB and LAFH% (P > .05) based on linear regression analysis. CONCLUSIONS: There is a positive relationship between ANB and Wits; however, neither correlated well with a purer antero-posterior assessment (AF-BF). Furthermore, variations in the vertical skeletal measurements affect the strength of agreement. Caution is advised in the interpretation of antero-posterior analysis especially in the presence of vertical discrepancy.

Effectiveness of systemic treatments for pyoderma gangrenosum: a systematic review of observational studies and clinical trials.

BACKGROUND: Pyoderma gangrenosum (PG) is a neutrophilic dermatosis with substantial morbidity. There is no consensus on gold-standard treatments. OBJECTIVES: To review the effectiveness of systemic therapy for PG. METHODS: We searched six databases for 24 systemic therapies for PG. Primary outcomes were complete healing and clinical improvement; secondary outcomes were time to healing and adverse effects. RESULTS: We found 3326 citations and 375 articles underwent full-text review; 41 studies met the inclusion criteria. There were 704 participants in 26 retrospective cohort studies, three prospective cohort studies, seven case series, one case-control study, two open-label trials and two randomized controlled trials (RCTs). Systemic corticosteroids were the most studied (32 studies), followed by ciclosporin (21 studies), biologics (16 studies) and oral dapsone (11 studies). One RCT (STOP-GAP, n = 121) showed that prednisolone and ciclosporin were similar: 15-20% of patients showed complete healing at 6 weeks and 47% at 6 months. Another RCT (n = 30) found that infliximab was superior to placebo at 2 weeks (46% vs. 6% response), with a 21% complete healing rate at 6 weeks. Two uncontrolled trials showed 60% and 37% healing within 4 months for canakinumab and infliximab, respectively; other data suggest that patients with concurrent inflammatory bowel disease may benefit from biologics. The remaining studies were poor quality and had small sample sizes but supported the use of corticosteroids, ciclosporin and biologics. CONCLUSIONS: Systemic corticosteroids, ciclosporin, infliximab and canakinumab had the most evidence in treating PG. However, current literature is limited to small and lower-quality studies with substantial heterogeneity.

A prospective cohort study assessing the appearance of retrieved aesthetic orthodontic archwires.

OBJECTIVES: To investigate the appearance of three esthetic nickel titanium (NiTi) wires after 6 weeks of intra-oral cycling and to determine the association between objective and subjective measures of esthetics. SETTING AND SAMPLE POPULATION: A prospective cohort study was undertaken involving participants undergoing upper fixed orthodontic appliance treatment with ceramic brackets. MATERIALS AND METHODS: Fifty participants were assigned to one of three groups of NiTi esthetic wires (American Orthodontics Ever White™, Forestadent Biocosmetic™ and GAC High Aesthetic™), with wires retrieved after 6 weeks in situ. Participants completed a bespoke questionnaire exploring perceptions of wire esthetics. Objective measurement of coating loss was undertaken using a custom arch wire jig. RESULTS: American Orthodontics Ever White™ had the greatest mean coating loss (50.7%) followed by Forestadent Biocosmetic™ (6%), with GAC High Aesthetic TM undergoing minimal loss (0.07%) (P < .001). The majority of coating loss with the American Orthodontics Ever White™ wires arose in the anterior region while Forestadent Biocosmetic™ wires and GAC High Aesthetic™ wires exhibited coating loss posteriorly (P < .001). These findings were reflected in the subjective assessment with a negative correlation found between coating loss and final Visual Analogue Scale scores (P < .001). CONCLUSIONS: Considerable esthetic variation between arch wires following 6 weeks of intraoral cycling was identified in this prospective cohort study. Intraoral cycling has a negative impact on participant perception of arch wire esthetics, and objective and subjective assessment of wire esthetics appears to be consistent.

A scoping review of outcomes related to orthodontic treatment measured in cleft lip and palate.

The aim of this study was to identify and summarize the outcomes measured in orthodontic studies of children with cleft lip and/or palate. The objectives were to categorize the outcomes into pre-determined domains and to explore whether any domains were under-represented. Electronic databases and grey literature were searched until December 2016 to identify all studies of orthodontic treatment interventions in children and adolescents with cleft lip and palate. Abstracts and subsequently eligible full-text articles were screened independently and in duplicate by two reviewers. All reported outcome measures were identified and categorized into six predetermined outcome domains. The search identified 833 abstracts. The majority of studies did not assess orthodontic interventions and were therefore not eligible for inclusion. Consequently, following screening 71 eligible articles were retrieved in full, of which 40 met the inclusion criteria. Morphological features of malocclusion were measured in 27 studies (68%) and adverse effects of orthodontic treatment in 10 (25%). Functional status (n=4; 10%), physical consequences of malocclusion (n=3; 7.5%), quality of life (n=3; 7.5%) and health resource utilization (n=2; 5%) were rarely considered. Relatively few studies concerning patients with cleft lip and palate focused on orthodontic interventions. Most of the identified outcomes were concerned with measuring morphological treatment-related changes and do not reflect patient perspectives.

Timing orthodontic treatment: early or late?

The timing of orthodontic interventions has been a contentious topic for many years with early treatment to address or indeed to prevent skeletal discrepancies in all three spatial planes and to alleviate crowding in common practice. In terms of effectiveness, however, broadly speaking early intervention has not been shown to be superior to later intervention. As such, in view of the additional burden and duration of early intervention, the weight of evidence points to reserving early treatment for localized problems and specific situations with definitive treatment typically initiated in the late mixed or early permanent dentition.