Relationship between early infant motor repertoire and neurodevelopment on the hammersmith infant neurological examination in a developmentally vulnerable First Nations cohort.

AIM: To implement a culturally-adapted screening program aimed to determine the ability of infant motor repertoire to predict early neurodevelopment on the Hammersmith Infant Neurological Examination (HINE) and improve Australian First Nations families' engagement with neonatal screening. METHODS: A prospective cohort of 156 infants (55 % male, mean (standard deviation [SD]) gestational age 33.8 (4.6) weeks) with early life risk factors for adverse neurodevelopmental outcomes (ad-NDO) participated in a culturally-adapted screening program. Infant motor repertoire was assessed using Motor Optimality Score-revised (MOS-R), captured over two videos, 11-13+6 weeks (V1; <14 weeks) and 14-18 weeks (V2; ≥14 weeks) corrected age (CA). At 4-9 months CA neurodevelopment was assessed on the HINE and classified according to age-specific cut-off and optimality scores as; developmentally 'on track' or high chance of either adverse neurodevelopmental outcome (ad-NDO) or cerebral palsy (CP). RESULTS: Families were highly engaged, 139/148 (94 %) eligible infants completing MOS-R, 136/150 (91 %), HINE and 123 (83 %) both. Lower MOS-R at V2 was associated with reduced HINE scores (ß = 1.73, 95 % confidence interval [CI] = 1.03-2.42) and high chance of CP (OR = 2.63, 95%CI = 1.21-5.69) or ad-NDO (OR = 1.38, 95%CI = 1.10-1.74). The MOS-R sub-category 'observed movement patterns' best predicted HINE, infants who score '4' had mean HINE 19.4 points higher than score '1' (95%CI = 12.0-26.9). Receiver-operator curve analyses determined a MOS-R cut-off of <23 was best for identifying mild to severely reduced HINE scores, with diagnostic accuracy 0.69 (sensitivity 0.86, 95%CI 0.76-0.94 and specificity 0.40, 95 % CI 0.25-0.57). A trajectory of improvement on MOS-R (≥2 point increase in MOS-R from 1st to 2nd video) significantly increased odds of scoring optimally on HINE (OR = 5.91, 95%CI 1.16-29.89) and may be a key biomarker of 'on track' development. INTERPRETATION: Implementation of a culturally-adapted program using evidence-based assessments demonstrates high retention. Infant motor repertoire is associated with HINE scores and the early neurodevelopmental status of developmentally vulnerable First Nations infants.

School readiness of children at high risk of cerebral palsy randomised to early neuroprotection and neurorehabilitation: protocol for a follow-up study of participants from four randomised clinical trials.

INTRODUCTION: School readiness includes cognitive, socio-emotional, language and physical growth and development domains which share strong associations with life-course opportunities. Children with cerebral palsy (CP) are at increased risk of poor school readiness compared with their typically developing peers. Recently, earlier diagnosis of CP has allowed interventions to commence sooner, harnessing neuroplasticity. First, we hypothesise that early referral to intervention for children at-risk of CP will lead to improved school readiness at 4-6 years relative to placebo or care as usual. Second, we hypothesise that receipt of early diagnosis and early intervention will lead to cost-savings in the form of reduced healthcare utilisation. METHODS AND ANALYSIS: Infants identified as at-risk of CP ≤6 months corrected age (n=425) recruited to four randomised trials of neuroprotectants (n=1), early neurorehabilitation (n=2) or early parenting support (n=1) will be re-recruited to one overarching follow-up study at age 4-6 years 3 months. A comprehensive battery of standardised assessments and questionnaires will be administered to assess all domains of school readiness and associated risk factors. Participants will be compared with a historical control group of children (n=245) who were diagnosed with CP in their second year of life. Mixed-effects regression models will be used to compare school readiness outcomes between those referred for early intervention versus placebo/care-as-usual. We will also compare health-resource use associated with early diagnosis and intervention versus later diagnosis and intervention. ETHICS AND DISSEMINATION: The Children's Health Queensland Hospital and Health Service, The University of Queensland, University of Sydney, Monash University and Curtin University Human Research Ethics Committees have approved this study. Informed consent will be sought from the parent or legal guardian of every child invited to participate. Results will be disseminated in peer-reviewed journals, scientific conferences and professional organisations, and to people with lived experience of CP and their families. TRIAL REGISTRATION NUMBER: ACTRN12621001253897.

Growth Inhibitory Effects of Antimicrobial Natural Products against Cariogenic and Health-Associated Oral Bacterial Species.

PURPOSE: This study investigated whether selected natural products could specifically target the growth of a caries-associated bacterial species (Streptococcus mutans) without affecting the viability of a health-associated oral commensal bacterial species (Streptococcus sanguinis). MATERIALS AND METHODS: Agar diffusion assays were used to screen the natural products for bacterial-growth inhibitory effects and the diameters of the inhibitory zones for the two bacterial species compared. The minimum inhibitory concentrations (MIC) of the natural products that showed growth inhibitory effects were determined using the broth microdilution method. RESULTS: Except for the berry extracts (cranberry, wild blueberry, and strawberry), all the other selected natural products (peppermint, ginger, cinnamon, rosemary, liquorice, xanthorrrhizol, tt-farnesol, guaijaverin, and macelignan) exhibited varying degrees of bacterial growth inhibition. The MIC values ranged from as low as 4 µg/ml for xanthorrrhizol to 1000 µg/ml for guaijaverin. All the growth inhibitory natural agents tested showed similar inhibition for both S. mutans and S. sanguinis. CONCLUSIONS: Although several natural products exerted significant antibacterial effects, none had selective inhibitory action on the growth of S. mutans.

Prediction of childhood brain outcomes in infants born preterm using neonatal MRI and concurrent clinical biomarkers (PREBO-6): study protocol for a prospective cohort study.

INTRODUCTION: Infants born very preterm are at risk of adverse neurodevelopmental outcomes, including cognitive deficits, motor impairments and cerebral palsy. Earlier identification enables targeted early interventions to be implemented with the aim of improving outcomes. METHODS AND ANALYSIS: Protocol for 6-year follow-up of two cohorts of infants born <31 weeks gestational age (PPREMO: Prediction of Preterm Motor Outcomes; PREBO: Prediction of Preterm Brain Outcomes) and a small term-born reference sample in Brisbane, Australia. Both preterm cohorts underwent very early MRI and concurrent clinical assessment at 32 and 40 weeks postmenstrual age (PMA) and were followed up at 3, 12 and 24 months corrected age (CA). This study will perform MRI and electroencephalography (EEG). Primary outcomes include the Movement Assessment Battery for Children second edition and Full-Scale IQ score from the Wechsler Intelligence Scale for Children fifth edition (WISC-V). Secondary outcomes include the Gross Motor Function Classification System for children with cerebral palsy; executive function (Behavior Rating Inventory of Executive Function second edition, WISC-V Digit Span and Picture Span, Wisconsin Card Sorting Test 64 Card Version); attention (Test of Everyday Attention for Children second edition); language (Clinical Evaluation of Language Fundamentals fifth edition), academic achievement (Woodcock Johnson IV Tests of Achievement); mental health and quality of life (Development and Well-Being Assessment, Autism Spectrum Quotient-10 Items Child version and Child Health Utility-9D). AIMS: Examine the ability of early neonatal MRI, EEG and concurrent clinical measures at 32 weeks PMA to predict motor, cognitive, language, academic achievement and mental health outcomes at 6 years CA.Determine if early brain abnormalities persist and are evident on brain MRI at 6 years CA and the relationship to EEG and concurrent motor, cognitive, language, academic achievement and mental health outcomes. ETHICS AND DISSEMINATION: Ethical approval has been obtained from Human Research Ethics Committees at Children's Health Queensland (HREC/19/QCHQ/49800) and The University of Queensland (2019000426). Study findings will be presented at national and international conferences and published in peer-reviewed journals. TRIAL REGISTRATION NUMBER: ACTRN12619000155190p. WEB ADDRESS OF TRIAL: http://www.anzctr.org.au/Trial/Registration/TrialReview.aspx?ACTRN=12619000155190p.

Potential Role for Natural Products in Dental Caries Control.

PURPOSE: This paper discusses the cariostatic mechanisms of some of the most promising natural products and explores the research directions that are needed to translate the potential of natural products into commercial oral care products for dental caries control. MATERIALS AND METHODS: The search strategy for this narrative review involved performing a comprehensive literature search to capture all published studies (up to December 2017) specifically related to natural products with anticaries effects. The databases searched were Medline (via PubMed), Embase and Web of Science, using a combination of controlled vocabulary and text words. The reference list of all selected studies was also manually searched for additional relevant studies. RESULTS: In recent years there has been renewed interest in the anticariogenic properties of several natural products, especially those that have the ability to inhibit cariogenic virulence properties or bacterial adhesion without disrupting the key health benefits of the resident oral microbiome. Other cariostatic mechanisms identified for natural products include phytochemicals that can inhibit demineralisation and enhance remineralisation thereby beneficially rebalancing the caries equilibrium, and natural non-fermentable dietary sweeteners that can reduce the acidogenic challenge posed by sugar-laden foods or beverages. CONCLUSION: Natural phytochemicals hold enormous potential as adjunctive therapeutic agents against cariogenic bacteria in the prevention and control of dental caries. However, there are several significant challenges to which future research needs to be directed in order to translate the potential of cariostatic natural products into clinically relevant oral care products for dental caries control.

Casein Phosphopeptide-Amorphous Calcium Phosphate Attenuates Virulence and Modulates Microbial Ecology of Saliva-Derived Polymicrobial Biofilms.

BACKGROUND: Casein phosphopeptide-amorphous calcium phosphate (CPP-ACP) acts as a salivary biomimetic that provides bioavailable calcium and phosphate ions to augment fluoride-mediated remineralisation of early caries lesions. However, there are indications that it may also have beneficial ecological effects on the oral microbiome. OBJECTIVE: This in vitro study investigated whether CPP-ACP could influence microbial counts, acidogenicity, and the relative abundance of specific caries- and health-associated bacterial -species in polymicrobial biofilms. METHODS: Saliva-derived polymicrobial biofilms were grown for 96 h in a cariogenic environment and treated every 12 h with 2% CPP-ACP or vehicle control. Colony forming units (CFUs) and acidogenicity were estimated from the treated biofilms. Microbial ecological effects of CPP-ACP were assessed based on the relative abundance of 14 specific caries- and health-associated -bacterial species using a real-time quantitative PCR assay. -Results: CPP-ACP-treated biofilms showed relatively modest, but significant, reductions in microbial CFUs (21% reduction, p = 0.008) and acidogenicity (33% reduction, p < 0.001), compared to the control-treated biofilms. The CPP-ACP treated biofilms also exhibited significantly lower bacterial loads of cariogenic Scardovia wiggsiae (fold change 0.017, p < 0.001) and Prevotella denticola(fold change 0.005, p < 0.001), and higher bacterial loads of commensal Streptococcus sanguinis(fold change 30.22, p < 0.001), S. mitis/oralis(fold change 9.66, p = 0.012), and S. salivarius/thermophilus(fold change 89.35, p < 0.001) than the control-treated biofilms. CONCLUSIONS: The results indicate that CPP-ACP has virulence-attenuating attributes that can influence a beneficial microbial ecological change in the biofilm.

Effect of polyphenol-rich cranberry extracts on cariogenic biofilm properties and microbial composition of polymicrobial biofilms.

OBJECTIVE: To investigate the effect of cranberry extracts on saliva-derived polymicrobial biofilms with regards to biofilm biomass, acidogenicity, exopolysaccharide (EPS)/microbial biovolumes, colony forming unit (CFU) counts, and the relative abundance of specific caries- and health-associated bacteria. METHODS: Saliva-derived polymicrobial biofilms were grown for 96 h in a cariogenic environment and treated for 2 min every 12 h over the entire biofilm growth period with 500 µg/mL cranberry extract or vehicle control. The effect of the cranberry extract on biofilm behaviour was evaluated using different assays and its influence on key cariogenic and health-associated bacterial populations was assessed with a microarray real-time quantitative PCR method. RESULTS: Cranberry-treated biofilms showed significant drops in biomass (38% reduction, P < 0.001), acidogenicity (44% reduction, P < 0.001), EPS/microbial biovolume ratios (P = 0.033), and CFU counts (51% reduction, P = 0.001). Furthermore, the cranberry extracts effected a significantly lower relative abundance of caries-associated Streptococcus sobrinus (fold change 0.004, P = 0.002) and Provotella denticola (0.002, P < 0.001), and a significantly higher relative abundance of the health-associated Streptococcus sanguinis (fold change 90.715, P = 0.001). CONCLUSIONS: The cranberry extract lowered biofilm biomass, acidogenicity, EPS/microbial biovolumes, CFU counts, and modulated a beneficial microbial ecological change in saliva-derived polymicrobial biofilms.

Polyphenol-Rich Cranberry Extracts Modulate Virulence of Streptococcus mutans-Candida albicans Biofilms Implicated in the Pathogenesis of Early Childhood Caries.

Purpose: The purpose of this study was to investigate the effects of polyphenol-rich cranberry extracts on dual-species Streptococcus mutans-Candida. albicans biofilms implicated in contributing to the severity of early childhood caries. Methods: S. mutans-C. albicans biofilms were grown on saliva-coated hydroxyapatite discs (s-HA) mounted on the high-throughput Amsterdam Active Attachment model. The s-HA discs were treated with the cranberry extracts/vehicle control for five minutes just before biofilm growth and subsequently, for similar exposure times, after 12 hours and 24 hours of biofilm growth. The treated 24-hour-old biofilms were then assessed for acidogenicity, metabolic activity, exopolysaccharide (EPS)/microbial biovolumes, structural organization, and colony forming unit (CFU) counts. Results: Treatment with 500 to 1,000 µg/mL of the cranberry extracts produced significant reductions in acidogenicity and metabolic activity (P<0.0001) compared to the control-treated biofilms. A significant decrease in biovolumes of the EPS (P=0.003) and microbial biofilm components (P=0.007) was also seen. Qualitative assessment of confocal biofilm images revealed that the cranberry extract disrupted biofilm structural architecture. Finally, significantly fewer S. mutans (P=0.006) and C. albicans (P=0.036) CFUs were recovered from the cranberry-treated biofilms than from the control-treated bio-films. Conclusions: Cranberry extracts inhibited cariogenic virulence properties of S. mutans-C. albicans dual-species biofilms in an in vitro model.

Inhibitory effects of fruit berry extracts on Streptococcus mutans biofilms.

Dark-colored fruit berries are a rich source of polyphenols that could provide innovative bioactive molecules as natural weapons against dental caries. High-quality extracts of cranberry, blueberry, and strawberry, and a combination of the three berry extracts (Orophenol), were used to treat 24-h-old Streptococcus mutans biofilms. The grown biofilms were treated with the berry extracts at concentrations ranging from 62.5 to 500 µg ml-1 . Treated biofilms were assessed for metabolic activity, acidogenicity, biovolumes, structural organization, and bacterial viability. The biofilms treated with the cranberry and Orophenol extracts exhibited the most significant reductions in metabolic activity, acid production, and bacterial/exopolysaccharide (EPS) biovolumes, while their structural architecture appeared less compact than the control-treated biofilms. The blueberry extract produced significant reductions in metabolic activity and acidogenicity only at the highest concentration tested, without significantly affecting bacterial/EPS biovolumes or biofilm architecture. Strawberry extracts had no significant effects on S. mutans biofilms. None of the berry extracts were bactericidal for S. mutans. The results indicate that cranberry extract was the most effective extract in disrupting S. mutans virulence properties without significantly affecting bacterial viability. This suggests a potential ecological role for cranberry phenols as non-bactericidal agents capable of modulating pathogenicity of cariogenic biofilms.

Interference of Antimicrobial Activity of Combinations of Oral Antiseptics Against Streptococcus mutans, Streptococcus sanguinis, and Lactobacillus acidophilus.

PURPOSE: The purpose of this study was to compare the effects of combinations of sodium fluoride and antiseptic compounds on the growth of Streptococcus mutans, Streptococcus sanguinis, and Lactobacillus acidophilus. METHODS: The agar diffusion assay was used to determine bacterial growth inhibition. RESULTS: Of the combinations tested, 0.1 percent sodium fluoride and five percent povidone iodine produced synergistic antibacterial effects against S. mutans and S. sanguinis. The combination of 10 percent povidone iodine and 0.5 percent sodium hypochlorite produced additive antibacterial effects against L. acidophilus. Interference was seen in some combinations such as 0.01 percent chlorhexidine and 0.25 percent sodium lauryl sulphate, 0.5 percent sodium hypochlorite and 10 percent povidone iodine, and 0.01 percent cetyl pyridium chloride and 0.1 percent sodium fluoride. However, 0.1 percent sodium fluoride combined with 0.01 percent chlorhexidine did not interfere with the antibacterial effects of chlorhexidine against S. mutans or S. sanguinis. CONCLUSIONS: Combinations of common antiseptics and fluoride compounds can produce interference, synergistic, or additive effects. The combination of 0.1 percent sodium fluoride and five percent povidone iodine had the greatest potential for suppression of S. mutans.

Association of erosion with timing of detection and selected risk factors in primary dentition: a longitudinal study.

OBJECTIVE: The aims of this study were to determine the prevalence of erosion in a birth cohort at 24, 36, and 48 months and to investigate risk factors for erosion. METHODS: One hundred and fifty-four children from a birth cohort were followed at 24, 36, and 48 months of age. RESULTS: Of the 154 children examined, 0% (0/154), 7% (11/154), and 28% (40/154) had erosion detected for the first time at 24, 36, and 48 months, respectively (P < 0.001). A cumulative total of 51 (33%) children and 256 (8%) teeth had erosion by the age of 48 months. There were no significant associations between erosive lesions first detected at 36 months and oral hygiene behaviour, medical conditions, or dietary habits reported at the 24- or 36-month examinations (all P > 0.05). In contrast, erosive lesion first detected at 48 months was positively associated with the use of a feeding bottle reported at the 36-month examination (P = 0.026). CONCLUSIONS: The prevalence of dental erosion in young children increased with age, with clinically detectable lesions forming between 24 and 36 months of age. Erosive lesions first detected at 48 months were positively associated with the use of a feeding bottle reported at 36 months.

Local and systemic inflammatory responses to experimentally induced gingivitis.

This study profiled the local and systemic inflammatory responses to experimentally induced gingivitis. Eight females participated in a 21-day experimental gingivitis model followed by a 14-day resolution phase. Bleeding on probing and plaque index scores were assessed before, during, and after resolution of gingival inflammation, and samples of saliva, GCF, and plasma were collected. Samples were assessed for biomarkers of inflammation using the BioPlex platform and ELISA. There were no significant changes in GCF levels of cytokines during the experimental phase; however, individual variability in cytokine profiles was noted. During resolution, mean GCF levels of IL-2, IL-6, and TNF-α decreased and were significantly lower than baseline levels (P = 0.003, P = 0.025, and P = 0.007, resp.). Furthermore, changes in GCF levels of IL-2, IL-6, and TNF-α during resolution correlated with changes in plaque index scores (r = 0.88, P = 0.004; r = 0.72, P = 0.042; r = 0.79, P = 0.019, resp.). Plasma levels of sICAM-1 increased significantly during the experimental phase (P = 0.002) and remained elevated and significantly higher than baseline levels during resolution (P < 0.001). These results support the concept that gingivitis adds to the systemic inflammatory burden of an individual.

Periodontal pathogen load and increased antibody response to heat shock protein 60 in patients with cardiovascular disease.

AIM: To determine the relationship between periodontal pathogen load and anti-human heat shock protein 60 (hHSP60) antibodies in patients with established cardiovascular disease (CVD). MATERIALS AND METHODS: Participants were cardiovascular patients (n = 74) with a previous hospital admission for myocardial infarction. Concurrent periodontal pathogen load of Porphyromonas gingivalis, Fusobacterium nucleatum, Tannerella forsythia and Aggregatibacter actinomycetemcomitans was determined using quantitative real-time PCR. Serum antibodies to these pathogens, GroEL and hHSP60 were determined using an ELISA. RESULTS: There was a trend for increasing anti-hHSP60 antibody as the number of bacterial species increased. The strongest positive correlations were found between anti-hHSP60 levels and numbers of T. forsythia (r = 0.43; p < 0.001) and between anti-hHSP60 and anti-GroEL levels (r = 0.39; p = 0.001). Patients with extensive periodontal pocketing (≥4 mm) had higher numbers of P. gingivalis and T. forsythia (p < 0.05) and a higher subgingival pathogen load (p < 0.05) than patients with minimal pocketing (≤1 site ≥ 4 mm). They also had significantly elevated anti-hHSP60 levels (p < 0.05). Overall, the highest anti-hHSP60 levels were seen in patients with extensive periodontal pocketing and all four bacterial species. CONCLUSIONS: In cardiovascular patients, a greater burden of subgingival infection with increased levels of P. gingivalis and T. forsythia is associated with modestly higher anti-hHSP60 levels.

Cardiovascular disease and the role of oral bacteria.

In terms of the pathogenesis of cardiovascular disease (CVD) the focus has traditionally been on dyslipidemia. Over the decades our understanding of the pathogenesis of CVD has increased, and infections, including those caused by oral bacteria, are more likely involved in CVD progression than previously thought. While many studies have now shown an association between periodontal disease and CVD, the mechanisms underpinning this relationship remain unclear. This review gives a brief overview of the host-bacterial interactions in periodontal disease and virulence factors of oral bacteria before discussing the proposed mechanisms by which oral bacterial may facilitate the progression of CVD.