Assessing the suitability of fused deposition modeling to produce acrylic removable denture bases.

OBJECTIVE: To study the feasibility of using poly methyl methacrylate (PMMA) filament and fused deposition modeling (FDM) to manufacture denture bases via the development of a study that considers both conventional and additive-based manufacturing techniques. MATERIALS AND METHODS: Five sample groups were compared: heat and cold cured acrylic resins, CAD/CAM milled PMMA, 3D-printed PMMA (via FDM), and 3D-printed methacrylate resin (via stereolithography, SLA). All groups were subjected to mechanical testing (flexural strength, impact strength, and hardness), water sorption and solubility tests, a tooth bonding test, microbiological assessment, and accuracy of fit measurements. The performance of sample groups was referred to ISO 20795-1 and ISO/TS 19736. The data was analyzed using one-way ANOVA. RESULTS: Samples manufactured using FDM performed within ISO specifications for mechanical testing, water sorption, and solubility tests. However, the FDM group failed to achieve the ISO requirements for the tooth bonding test. FDM samples presented a rough surface finish which could ultimately encourage an undesirable high level of microbial adhesion. For accuracy of fit, FDM samples showed a lower degree of accuracy than existing materials. CONCLUSIONS: Although FDM samples were a cost-effective option and were able to be quickly manufactured in a reproducible manner, the results demonstrated that current recommended testing regimes for conventionally manufactured denture-based polymers are not directly applicable to additive-manufactured denture base polymers. Therefore, new standards should be developed to ensure the correct implementation of additive manufacturing techniques within denture-based fabrication workflow.

Entrapment and extraction of wheelchairs at flange gaps with and without flange gap fillers at pedestrian railway crossings.

PURPOSE: Where pedestrian crossings meet rail tracks, a flange gap allows the train wheel flanges to pass. This gap can be hazardous for wheelchair users as castor wheels may become trapped. While compressible gap fillers can eliminate the flange gap, fillers are subject to wear, pose a derailment hazard to light rail vehicles and can strip grease from passing wheels. These issues could be mitigated by partially filling the flange gap with a compressible filler. The aim was to investigate the risk of entrapment and ease of extraction of wheelchair castors from flange gaps fully and partially filled with compressible fillers, and assess ride quality. MATERIALS AND METHODS: Entrapment risk and ease of extraction for four wheelchairs were tested at various crossing angles with flange gap fillers. Twelve wheelchair users tested ease of extraction and ride quality for partially and fully filled flange gaps. RESULTS: It was found that risk of entrapment is low if a standards-compliant crossing with open flange gaps is traversed in a straight line. However, castors can become trapped if the user alters direction to avoid an obstacle or if the crossing surface is uneven. Once trapped, castors are extremely difficult to remove without external assistance. CONCLUSIONS: Flange gap fillers that reduce the gap to 10 mm or less eliminate entrapment while retaining acceptable ride quality. Filling flange gaps or leaving a residual gap depth of less than 10 mm is the best option to eliminate risk of entrapment and ensure good ride quality for wheelchair users.IMPLICATIONS FOR REHABILITATIONRail crossings flange gaps pose an entrapment hazard for wheelchair usersPartial or complete flange gap fillers may reduce entrapment but require researchRehabilitation professionals need to educate wheelchair users on techniques to cross flange gaps safelyConsumers and health professionals can consult rail operators to partially fill flange gaps.

Community-based education programmes in the context of dental education: A scoping review.

BACKGROUND: Community education programmes are vital tools for teaching skills, such as understanding the larger cultural, economic and social determinants of health and how these factors impact people's health. It is currently unclear whether community education programmes in the field of dentistry deliver adequate value. This review aims to scope, collate and analyse globally published evidence concerning community education programmes in dentistry from inception, to gain an understanding of the intentions for these programmes and establish whether outcomes have shifted over time from the original intentions. METHODS: Arksey and O'Malley's framework for scoping reviews was employed to guide the reviewers. A systematic search of electronic databases and the reference lists in key papers was conducted. RESULTS: A systematic search concerning community education in dentistry identified a total of 140 papers for full-text evaluations. After further exclusions, 115 articles were selected for data charting. There was a lack of clarity in the literature concerning programmes' definitions and strategies for achieving intentions. Origins, intentions and motivations of the programmes were identified. The literature largely focused on assessing students' clinical treatment skills, contradicting the programme's original idea and intentions. Only a few studies incorporated patient and community perspectives, and the majority of assessments were self-reported, primarily by students. CONCLUSIONS: There is broad interest in integrating community education into dental curricula to teach complex concepts, dental public health principles and to ensure professional skills development. We identified issues in the literature around programme definitions, strategies, measurement approaches and programme success requiring additional research.

Comparing direct anterior approach versus posterior approach or lateral approach in total hip arthroplasty: a systematic review and meta-analysis.

BACKGROUND: There are several approaches to THA, and each has their respective advantages and disadvantages. Previous meta-analysis included non-randomised studies that introduce further heterogeneity and bias to the evidence presented. This meta-analysis aims to present level I evidence by comparing functional outcomes, peri-operative parameters and complications of direct anterior approach (DAA) versus posterior approach (PA) or lateral approach (LA) in THA. PATIENTS AND METHODS: A comprehensive multi-database search (PubMed, OVID Medline, EMBASE) was conducted from date of database inception to 1st December 2020. Data from randomised controlled trials comparing outcomes of DAA versus PA or LA in THA were extracted and analysed. RESULTS: Twenty-four studies comprising 2010 patients were included in this meta-analysis. DAA has a longer operative time (MD = 17.38 min, 95%CI: 12.28, 22.47 min, P < 0.001) but a shorter length of stay compared to PA (MD = - 0.33 days, 95%CI: - 0.55, - 0.11 days, P = 0.003). There was no difference in operative time or length of stay when comparing DAA versus LA. DAA also had significantly better HHS than PA at 6 weeks (MD = 8.00, 95%CI: 5.85, 10.15, P < 0.001) and LA at 12 weeks (MD = 2.23, 95%CI: 0.31, 4.15, P = 0.02). There was no significant difference in risk of neurapraxia for DAA versus LA or in risk of dislocations, periprosthetic fractures or VTE between DAA and PA or DAA and LA. CONCLUSION: The DAA has better early functional outcomes with shorter mean length of stay but was associated with a longer operative time than PA. There was no difference in risk of dislocations, neurapraxias, periprosthetic fractures or VTE between approaches. Based on our results, choice of THA approach should ultimately be guided by surgeon experience, surgeon preference and patient factors. LEVEL OF EVIDENCE I: Meta-analysis of randomised controlled trials.

Profiling fatal and serious injury crashes in South Australia according to the Swedish transport administration model.

OBJECTIVES: This article describes a study examining fatal road crashes in South Australia (SA) according to the safety model developed by the Swedish Road Administration (STA). The STA model is based on the biomechanical limits that human beings can tolerate and specifies a number of elements that must be present for "compliance" with the model: driving at or below the speed limit, driver not intoxicated by alcohol or drugs, vehicle occupants wearing a seatbelt, car with a EuroNCAP rating of 5 stars, car equipped with electronic stability control, and a road with an EuroRAP rating of 4 stars. METHOD: The study used a sample of 105 fatal crashes in SA in 2010 and 2011 and a comparison sample of 136 serious injury crashes from 2014 to 2017. RESULTS: It was found that there were high levels of noncompliance with all elements of the STA model, with multiple forms of noncompliance in a clear majority of fatal cases. CONCLUSIONS: Considerable gains in safety could occur with greater penetration into the SA fleet of 5-star cars fitted with ESC and other vehicle safety technology, especially as the majority of both sets of crashes were of a type involving loss of vehicular control. It is also important to note that risky road user behavior was less common in the serious injury crashes and so a road safety strategy focusing on changing road user behavior will be ineffective for addressing the major factors contributing to non-fatal road trauma.

Evaluation of a warning system to reduce the risk of casualty crashes at rural junctions in South Australia.

OBJECTIVE: This study evaluated the effectiveness and potential safety benefits of a Rural Junction Active Warning System (RJAWS), which uses variable speed limit signs (VSLSs) to temporarily impose a reduced speed limit along the major road when another vehicle is approaching on the minor road or turning into the minor road from the far-side major leg. METHODS: The RJAWS was trialed at 4 3-leg rural junctions between 2-lane roads in South Australia. A quasi-experimental before-after analysis was conducted. The free-flow speed of vehicles along the junction major approaches was used as an indicator of the risk of a casualty crash with adjacent traffic. Events with activated and nonactivated VSLSs after the RJAWS installation were analyzed separately. Travel speed, speed limit compliance, and the relative risk of a casualty crash were compared. The potential risk of casualty crashes relative to traveling at the default speed limit was calculated based on a known relationship between travel speed and relative casualty risk for rural roads in South Australia. RESULTS: When the reduced speed limit signs are activated, the average travel speed along the major road is reduced between 11.3 and 22.1 km/h, with a consequent reduction of the expected average casualty risk between 42% and 65% compared to before the RJAWS installation. . Though compliance with the reduced posted speed limit was low, the RJAWS still proved effective in reducing travel speed because the majority of drivers traveled through the monitored junctions at speeds below the default speed limit when the sign was activated. CONCLUSIONS: This evaluation indicated that the trialed RJAWS can potentially reduce the risk of fatal and serious injuries at junctions under conditions that may present the opportunity for an adjacent-direction collision with another vehicle. Extending the RJAWS installation to additional junctions is strongly suggested. Further monitoring is needed to determine whether safety benefits are sustained over the long term.

Remote clinical consultations in restorative dentistry: a clinical service evaluation study.

Introduction Specialist consultant services in the UK NHS provide a decision-making support service to other health professionals. There is a drive to deliver this service in a more patient-centred, cost-effective and efficient manner. Remote clinical consultations (RCC), using secure, live, super-fast internet connectivity and high-resolution, multi-channel audio-visual streaming, has the potential for the delivery of this service.Aim To conduct a clinical service evaluation to assess the viability and efficiency of conducting a RCC for the management of primary care referrals in restorative dentistry, compared to an in-person consultation.Design A RCC was conducted for every participating patient and immediately followed with a 'verification' in-person consultation.Materials and method Twenty-three patients of even gender distribution participated in this study across the three specialisms of restorative dentistry. A thematic questionnaire was completed by each member of the study intervention team and the patient after each consultation.Results In all the cases, the consultant was able to conduct an effective and safe clinical consultation, not inferior to an in-person process, regardless of gender and age. The GDP, the nurse and the patient were able to participate effectively in the process and with each other.Conclusion This proof-of-concept study suggests that the RCC concept is a feasible way of delivering specialist consultations in restorative dentistry with high levels of patient acceptability and that it can be delivered in a practical and simple manner.

Evaluation of reproducibility of the chemical solubility of dental ceramics using ISO 6872:2015.

STATEMENT OF PROBLEM: The current chemical solubility method in the International Standards Organization (ISO) 6872 (2015) specifies only the total surface area of specimens for testing (≥30 cm2) but does not describe the morphology or geometry. This could impact the reproducibility of the test outcomes. PURPOSE: The purpose of this in vitro study was to investigate the factors influencing the reliability of the ISO 6872:2015 "Dentistry-Ceramic materials" test for chemical solubility. MATERIAL AND METHODS: Chemical solubility analysis of a range of materials and specimen geometries was performed in accordance with ISO 6872:2015. Yttria-stabilized tetragonal zirconia polycrystal (Y-TZP), VITABLOCS Mark II, IPS e.max Press, and IPS e.max ZirPress materials were formed into a range of cubic and spherical geometries to comply with the 30-cm2 minimum surface area requirement. The surface microstructure of the specimens was analyzed using a scanning electron microscope, inductively coupled plasma optical emission spectrometry (ICP-OES) was used to analyze the solutes, and surface hardness of the specimens was measured by using a Vickers hardness tester before and after testing. An optimized solubility test was devised, which eliminated specimen handling once the specimens had been ground and polished. This modified test was performed on VITABLOCS Mark II and Y-TZP. RESULTS: The results of the original chemical solubility method of ISO 6872:2015 showed significantly variable findings for each tested material, with a predictable relationship between geometry and chemical solubility. The hardness values decreased significantly after the solubility testing. The optimized method showed significantly improved reproducibility of the chemical solubility measurement compared with the original ISO 6872:2015 test. CONCLUSIONS: The results of the current chemical solubility standard method can be manipulated while still complying with the ISO 6872:2015 standard.

Conflicting demands that dentists and dental care professionals experience when using social media: a scoping review.

Introduction There are many conflicting demands for dentists and dental care professionals (DCPs) when using social media, for example between using social media for marketing and as professional provider of information. To gain a fuller understanding of how dentists/DCPs should optimally use social media, these conflicting demands need to be explored. The aim of this scoping review was to map out the current state of the literature describing the conflicting demands encountered by dentists and DCPs when using social media and the approaches used to manage these conflicting demands.Methods A scoping review was carried out. PubMed and Web of Science Core Collection were searched using inclusion and exclusion criteria. Data was extracted from the identified articles and analysed.Results The review identified 39 articles for inclusion. Conflicting demands were related to marketing and education with little information about how these conflicting demands can be managed.Conclusions The published literature on dentists'/DCPs' use of social media highlights that there are conflicting demands and little advice on management strategies. To gain an understanding of these conflicting demands, further research is required, including looking at the patient perspective, to inform future practice.

The dark side of technological advances in analysis of microbial ecosystems.

Recent technological advances mean that samples from animal experiments may be analysed more cheaply, more easily and with a much greater return of data than previously. Research groups are frequently faced with a choice of continuing to use established technology in which they may have made a significant investment of time and resources, and have significant amounts of reference data, or switching to new technology where reference data may be limited. Apart from cost, the choice needs to be based on a comparison between the increase in data available from future experiments by switching and the value of comparison with reference data from historical experiments analysed with earlier technology. One approach to this problem is to ensure that sufficient quantity and variety of samples are taken from each experiment and appropriately stored to allow re-establishment of a sufficiently large reference set and to avoid the need to repeat animal experiments. The establishment of 'biobanks' of experimental material will require funding for infrastructure, consistent storage of metadata and, importantly, horizon-scanning to ensure that samples are taken appropriately for techniques which will become accessible in future. Such biobanks are a recognised resource in human medicine, where the value of samples increases as more analysis is carried out and added to the metadata.

A scoping review of the use and application of virtual reality in pre-clinical dental education.

Introduction Virtual reality (VR) is gaining recognition as a valuable tool for training dental students and its use by dental schools around the world is growing. It is timely to review the literature relating to the use of VR in dental education, in order to ensure that educators are well-informed of current areas of inquiry, and those requiring further investigation, to enable appropriate decisions about whether to employ VR as a teaching tool. Method A scoping review using the method outlined by Arksey and O'Malley was conducted. Both Web of Science and ERIC databases were searched. Inclusion and exclusion criteria were established to filter results. The data were collected and categorised using a custom data collection spreadsheet. Results The review identified 68 relevant articles. Following review, four educational thematic areas relating to the 'simulation hardware', the 'realism of the simulation', 'scoring systems' and 'validation' of the systems emerged. Conclusion This paper summarises and draws out themes from the current areas of inquiry in the literature, uncovering a number of weaknesses and assumptions. It recommends areas where additional investigation is required in order to form a better evidence base for the utility of VR in dental education, as well as to inform its future development.

Development of Immune Cells in the Intestinal Mucosa Can Be Affected by Intensive and Extensive Farm Environments, and Antibiotic Use.

Epidemiological studies have demonstrated that exposure to farm environments during childhood can be linked to reductions in the incidence of immune disorders, but generating an appropriate model is difficult. 108 half-sibling piglets were born on either extensive (outdoor) or intensive (indoor) farms: at 1 day old, a subset of piglets from each litter were transferred to a high-hygiene isolator facility to create differences in rearing environment either during birth/first day or during the subsequent 56 days of life. Interactions between CD14, CD16, MHCIIDR, and capillary endothelium were assessed using four-color quantitative fluorescence immunohistology. Effects of birth and rearing environment on the antigen-presenting microenvironment of the proximal and distal jejunum (professional and stromal) were apparent at 5, 28, and 56 days after birth However, effects on CD4+CD25+Foxp3+ regulatory T-cells (Tregs) in the intestinal mucosa were apparent around weaning at 28 days but had disappeared by 56 days. These Tregs were reduced in the isolator piglets compared to their farm-reared siblings, but this effect was less marked in piglets born on the extensive farm and required administration of antibiotics. Our results suggest that there may be at least two windows of opportunity in which different farm environments were influencing immune development: one during the perinatal period (up to the first day of life), and one during later infancy. Furthermore, the differences on Tregs suggest that the effects of early life influences may be particularly critical around weaning.

Diagnostic accuracy of computed tomography-guided biopsy in pathological fractures.

BACKGROUND: Obtaining a histological diagnosis is essential for appropriate management of pathological fractures. Computed tomography (CT) is an accurate method of obtaining diagnosis for musculoskeletal tumours. We analysed whether diagnostic accuracy was maintained in the evaluation of pathological fractures. METHODS: A retrospective review of 101 consecutive patients presenting to our tertiary musculoskeletal tumour centre with pathological fracture was performed. Patients underwent core needle biopsy under CT guidance of pathological fractures diagnosed by plain radiography and either CT or magnetic resonance imaging. The histopathology of the CT-guided biopsy was compared with the sample obtained from open biopsy or definitive surgery to determine diagnostic accuracy. RESULTS: The mean age at diagnosis was 52 ± 20 years (range: 18-85) in a cohort of 46 men and 55 women. Diagnostic accuracy of CT-guided biopsy was 82.18%. There were 65 malignant and 36 benign tumours with diagnostic accuracy of 86.15% and 80.56%, respectively. The positive predictive value for a malignant tumour was 98.21% whilst it was 93.1% for benign tumours. The femur (53 cases) and humerus (25 cases) were the commonest bones fractured. The most frequent diagnoses were metastasis (20.79%), giant cell tumour (17.82%), osteosarcoma (9.90%) and myeloma (9.90%). There were no complications of CT-guided biopsy. CONCLUSION: Pathological fracture does not confound the diagnosis of musculoskeletal tumours. CT-guided biopsy is an accurate diagnostic tool in the evaluation of pathological fractures. Final diagnosis and management should be made in the context of appropriate anatomical and functional imaging using a multidisciplinary approach.

Patients presenting with fractures are likely to be vitamin D deficient: are we getting enough sun?

BACKGROUND: 25-Hydroxyvitamin D serves a crucial role in bone metabolism through its role on osteoclast and osteoblastic function. To assess the implication of vitamin D and its relationship to bone fracture and fracture force, we have examined vitamin D levels in patients requiring inpatient fracture management. METHODS: We performed serological testing of vitamin D levels, calcium, parathyroid hormone and liver function tests on patients admitted to our rural institution in southeastern Australia for inpatient fracture management. All participants completed a questionnaire designed to screen for potential contributing factors to bony fragility. Demographic data were also obtained including age, gender and body mass index. Fracture location and the type of inpatient management as well as the force of injury were included in our analysis. RESULTS: We recruited 100 patients to the study, with a median age of 72 (range 22-98) of whom 66 were women. Most had low-energy fractures (79%), treated by internal fixation (73%) or arthroplasty (9%) with 18 treated non-operatively. The majority of the patients were at best vitamin D insufficient, <75 nmol/L (77%), and 38% were vitamin D deficient (<50 nmol/L). Only 14 patients had a formal diagnosis of osteoporosis at presentation, with 63 patients claiming daily sun exposure in line with recommendations for vitamin D sufficiency. CONCLUSIONS: Our data suggest that the prevalence of vitamin D insufficiency and deficiency is common in patients presenting with fractures in southeastern Australia and is not confined to elderly patients. All patients with fractures should be assessed for vitamin D levels and treated in accordance with vitamin D deficiency guidelines.

Protective immunity against infection with Mycoplasma haemofelis.

Hemoplasmas are potentially zoonotic mycoplasmal pathogens, which are not consistently cleared by antibiotic therapy. Mycoplasma haemofelis is the most pathogenic feline hemoplasma species. The aim of this study was to determine how cats previously infected with M. haemofelis that had recovered reacted when rechallenged with M. haemofelis and to characterize the immune response following de novo M. haemofelis infection and rechallenge. Five specific-pathogen-free (SPF)-derived naive cats (group A) and five cats that had recovered from M. haemofelis infection (group B) were inoculated subcutaneously with M. haemofelis. Blood M. haemofelis loads were measured by quantitative PCR (qPCR), antibody response to heat shock protein 70 (DnaK) by enzyme-linked immunosorbent assay (ELISA), blood lymphocyte cell subtypes by flow cytometry, and cytokine mRNA levels by quantitative reverse transcriptase PCR. Group A cats all became infected with high bacterial loads and seroconverted, while group B cats were protected from reinfection, thus providing the unique opportunity to study the immunological parameters associated with this protective immune response against M. haemofelis. First, a strong humoral response to DnaK was only observed in group A, demonstrating that an antibody response to DnaK is not important for protective immunity. Second, proinflammatory cytokine interleukin-6 (IL-6) mRNA levels appeared to increase rapidly postinoculation in group B, indicating a possible role in protective immunity. Third, an increase in IL-12p35 and -p40 mRNA and decrease in the Th2/Th1 ratio observed in group A suggest that a Th1-type response is important in primary infection. This is the first study to demonstrate protective immunity against M. haemofelis reinfection, and it provides important information for potential future hemoplasma vaccine design.

The effect of ZrO2 and TiO 2 on solubility and strength of apatite-mullite glass-ceramics for dental applications.

The effect of ZrO2 and TiO2 on the chemical and mechanical properties of apatite-mullite glass-ceramics was investigated after sample preparation according to the ISO (2768:2008) recommendations for dental ceramics. All materials were characterized using differential thermal analysis, X-ray diffraction, scanning electron microscopy and energy dispersive spectroscopy. X-ray fluorescence spectroscopy was used to determine the concentrations of elements present in all materials produced. The chemical solubility test and the biaxial flexural strength (BFS) test were then carried out on all the samples. The best solubility value of 242 ± 61 µg/cm(2) was obtained when HG1T was heat-treated for 1 h at the glass transition temperature plus 20 °C (Tg + 20 °C) followed by 5 h at 1200 °C. The highest BFS value of 174 ± 38 MPa was achieved when HG1Z and HG1Z+T were heat-treated for 1 h at the Tg + 20 °C followed by 7 h at 1200 °C. The present study has demonstrated that the addition of TiO2 to the reference composition showed promise in both the glass and heat-treated samples. However, ZrO2 is an effective agent for developing the solubility or the mechanical properties of an apatite-mullite glass-ceramic separately but does not improve the solubility and the BFS simultaneously.

Chimeric anti-CD14 IGG2/4 Hybrid antibodies for therapeutic intervention in pig and human models of inflammation.

CD14 is a key recognition molecule of innate immune responses, interacting with several TLRs. TLR signaling cross-talks extensively with the complement system, and combined CD14 and complement inhibition has been proved effective in attenuating inflammatory responses. Pig models of human diseases have emerged as valuable tools to study therapeutic intervention, but suitable neutralizing Abs are rare. Undesired Fc-mediated functions, such as platelet activation and IL-8 release induced by the porcine CD14-specific clone Mil2, limit further studies. Therefore, an inert human IgG2/IgG4 hybrid C region was chosen for an rMil2. As revealed in ex vivo and in vivo pig experiments, rMil2 inhibited the CD14-mediated proinflammatory cytokine response similar to the original clone, but lacked the undesired Fc-effects, and inflammation was attenuated further by simultaneous complement inhibition. Moreover, rMil2 bound porcine FcRn, a regulator of t1/2 and biodistribution. Thus, rMil2, particularly combined with complement inhibitors, should be well suited for in vivo studies using porcine models of diseases, such as sepsis and ischemia-reperfusion injury. Similarly, the recombinant anti-human CD14 IgG2/4 Ab, r18D11, was generated with greatly reduced Fc-mediated effects and preserved inhibitory function ex vivo. Such Abs might be drug candidates for the treatment of innate immunity-mediated human diseases.

Effect of maternal intake of organically or conventionally produced feed on oral tolerance development in offspring rats.

The aim of this study was to investigate the effect of maternal consumption of organically or conventionally produced feed on immunological biomarkers and their offsprings' response to a novel dietary antigen. First-generation rats were fed plant-based diets from two different cultivation systems (organic or conventional) or a chow. Second-generation rats were exposed to ovalbumin (OVA) via their mother's milk and subsequently challenged with OVA after weaning onto the chow diet. In the chow diet group feeding the dams OVA resulted in suppression of the pups' anti-OVA antibody response to the OVA challenge (total OVA-specific IgG was 197 for the OVA-treated chow diet group and 823 for the control chow diet group (arbitrary ELISA units)). In contrast, OVA exposure of the dams from the plant-based dietary groups did not result in a similar suppression. Cultivation system had no effect on the immunological biomarkers, except for a higher spleen prostaglandin E2 (PGE2) concentration in pups originating from dams fed the conventional plant-based diet (223 ng/L) than from those fed the organic plant-based diet (189 ng/L).

Direct experimental evidence that early-life farm environment influences regulation of immune responses.

BACKGROUND: In mammals, early-life environmental variations appear to affect microbial colonization and therefore competent immune development, and exposure to farm environments in infants has been inversely correlated with allergy development. Modelling these effects using manipulation of neonatal rodents is difficult due to their dependency on the mother, but the relatively independent piglet is increasingly identified as a valuable translational model for humans. This study was designed to correlate immune regulation in piglets with early-life environment. METHODS: Piglets were nursed by their mother on a commercial farm, while isolator-reared siblings were formula fed. Fluorescence immunohistology was used to quantify T-reg and effector T-cell populations in the intestinal lamina propria and the systemic response to food proteins was quantified by capture ELISA. RESULTS: There was more CD4(+) and CD4(+) CD25(+) effector T-cell staining in the intestinal mucosa of the isolator-reared piglets compared with their farm-reared counterparts. In contrast, these isolator-reared piglets had a significantly reduced CD4(+) CD25(+) Foxp3(+) regulatory T-cell population compared to farm-reared littermates, resulting in a significantly higher T-reg-to-effector ratio in the farm animals. Consistent with these findings, isolator-reared piglets had an increased serum IgG anti-soya response to novel dietary soya protein relative to farm-reared piglets. CONCLUSION: Here, we provide the first direct evidence, derived from intervention, that components of the early-life environment present on farms profoundly affects both local development of regulatory components of the mucosal immune system and immune responses to food proteins at weaning. We propose that neonatal piglets provide a tractable model which allows maternal and treatment effects to be statistically separated.

Establishment of normal gut microbiota is compromised under excessive hygiene conditions.

BACKGROUND: Early gut colonization events are purported to have a major impact on the incidence of infectious, inflammatory and autoimmune diseases in later life. Hence, factors which influence this process may have important implications for both human and animal health. Previously, we demonstrated strong influences of early-life environment on gut microbiota composition in adult pigs. Here, we sought to further investigate the impact of limiting microbial exposure during early life on the development of the pig gut microbiota. METHODOLOGY/PRINCIPAL FINDINGS: Outdoor- and indoor-reared animals, exposed to the microbiota in their natural rearing environment for the first two days of life, were transferred to an isolator facility and adult gut microbial diversity was analyzed by 16S rRNA gene sequencing. From a total of 2,196 high-quality 16S rRNA gene sequences, 440 phylotypes were identified in the outdoor group and 431 phylotypes in the indoor group. The majority of clones were assigned to the four phyla Firmicutes (67.5% of all sequences), Proteobacteria (17.7%), Bacteroidetes (13.5%) and to a lesser extent, Actinobacteria (0.1%). Although the initial maternal and environmental microbial inoculum of isolator-reared animals was identical to that of their naturally-reared littermates, the microbial succession and stabilization events reported previously in naturally-reared outdoor animals did not occur. In contrast, the gut microbiota of isolator-reared animals remained highly diverse containing a large number of distinct phylotypes. CONCLUSIONS/SIGNIFICANCE: The results documented here indicate that establishment and development of the normal gut microbiota requires continuous microbial exposure during the early stages of life and this process is compromised under conditions of excessive hygiene.