Comparing the responses of grain-fed feedlot cattle under moderate heat load and during subsequent recovery with those of feed-restricted thermoneutral counterparts: blood cells and inflammatory markers.

Given the climate projections for livestock rearing regions globally, understanding the inflammatory status of livestock under various heat loads will be informative to animal welfare and management. A survey of plasma inflammatory markers was conducted, and blood leucocyte counts followed to investigate the capacity of the ~ 500 kg grain fed Black Angus steer to respond to and recover from a moderate heat load challenge. Two sequential cohorts of 12 steers were housed in climate-controlled rooms (CCR) for 18 days. A thermally challenged (TC) group (n = 2 × 6) experienced five consecutive periods: PreChallenge, Challenge, and Recovery within the CCR, and 40 days in outdoor pens (PENS and Late PENS). PreChallenge (5 days) and Recovery (7 days) delivered thermoneutral conditions, whereas in Challenge the TC steers experienced a diurnal temperature range of 28-35 °C. A feed-restricted thermoneutral (FRTN) treatment (n = 2 × 6) was run concurrently to differentiate between responses to reduced feed intake alone and moderate heat stress. Blood neutrophil counts were particularly sensitive to moderate heat load with higher numbers during Challlenge and in PENs. The plasma concentrations of TNFα and IL-1ß were depressed in the TC group compared to the FRTN counterparts and remained so for 40 days after Challenge. Linear relationships of the concentrations of IL-1ß, IL-10, and haptoglobin with rumen temperature or dry matter intake detected in the FRTN group were altered or absent in the TC group. The findings suggest significant impacts of moderate heat load on the inflammatory status of feedlot cattle.

Risk factors for excessive gestational weight gain in a UK population: a biopsychosocial model approach.

BACKGROUND: Gestational weight gain (GWG) can have implications for the health of both mother and child. However, the contributing factors remain unclear. Despite the advantages of using a biopsychosocial approach, this approach has not been applied to study GWG in the UK. This study aimed to investigate the risk factors of excessive GWG in a UK population, employing a biopsychosocial model. METHODS: This study utilised data from the longitudinal Grown in Wales (GiW) cohort, which recruited women in late pregnancy in South Wales. Specifically, data was collected from midwife recorded notes and an extensive questionnaire completed prior to an elective caesarean section (ELCS) delivery. GWG was categorised according to Institute of Medicine (IOM) guidelines. The analysis was undertaken for 275 participants. RESULTS: In this population 56.0% of women had excessive GWG. Increased prenatal depression symptoms (Exp(B)=1.10, p=.019) and an overweight (Exp(B)=4.16, p<.001) or obese (Exp(B)=4.20, p=.010) pre-pregnancy BMI, consuming alcohol in pregnancy (Exp(B)=.37, p=.005) and an income of less than £18,000 (Exp(B)=.24, p=.043) and £25-43,000 (Exp(B)=.25, p=.002) were associated with excessive GWG. CONCLUSION: GWG is complex and influenced by a range of biopsychosocial factors, with the high prevalence of excessive weight gain in this population a cause for concern. Women in the UK may benefit from a revised approach toward GWG within the National Health Service (NHS), such as tracking weight gain throughout pregnancy. Additionally, this research provides evidence for potential targets for future interventions, and potentially at-risk populations to target, to improve GWG outcomes.

Grandmothers' mental health is associated with grandchildren's emotional and behavioral development: a three-generation prospective study in Brazil.

BACKGROUND: Maternal mental health is associated with an increased risk of emotional and behavioural problems in children, and the risk is partly explained by the negative impact of maternal depression on caregiving. The role of mental health in other family members, who in many contexts also provide substantial caregiving, has received far less attention. We examined the impact of grandmothers' emotional symptoms, whose role in child care is increasing across the world, on internalizing and externalizing symptoms in grandchildren from a three-generation birth cohort study. METHODS: Prospective data from three generations in two birth cohorts 22 years apart (1982 and 2004) in Pelotas, Brazil, were used (n = 92). Mental health in grandmothers and parents was assessed using the Self-Reported Questionnaire (SRQ-20). Grandchildren were members of the 2004 birth cohort, and behavioural and emotional problems were measured using the Child-Behaviour Checklist (CBCL) at age 4 years. RESULTS: Grandmothers' symptoms were associated with more emotional and behavioural problems in grandchildren after adjustment for confounding factors. The size of the associations between grandmothers' and grandchildren mental health symptoms was comparable to the associations between maternal emotional symptoms and children emotional and behavioural problems. There was no evidence for associations with paternal symptoms. These effects were substantially stronger for maternal compared to paternal grandmothers. CONCLUSIONS: In some contexts, grandmothers' mental health may be as important to grandchild emotional and behavioural development as maternal mental health. Interventions to improve the mental health of grandmothers, as well as parents, may be important to child mental health.

Transition to parenthood and mental health at 30 years: a prospective comparison of mothers and fathers in a large Brazilian birth cohort.

Parenthood represents a major biological, social and environmental life change. Mental health disorders are common in parents and impact both the parent and their offspring. However, the relationship between parenthood and mental health and the direction of these effects are poorly understood. Longitudinal data from the Pelotas 1982 birth cohort, Southern Brazil, on 3701 individuals was used to investigate the association between number of children by age 30 years and mental health disorders using DSM-IV diagnoses at age 30 years, suicidal risk and the change in symptoms using repeated measures (using the SRQ-20) from age 19 to 30 years. Mothers, but not fathers, with higher number of children by age 30 years, were at a substantially increased risk of a wide range of mental health disorders compared to women with no children. There was evidence that motherhood was associated with an increase in symptoms over time rather than higher symptoms at baseline. Younger age at first child was also a risk factor for mental health disorders. Mothers, particularly those with multiple children, are at risk of a wide range of mental health disorders. The mechanisms to explain these risks are yet to be elucidated; however, the risk of mental health disorders was not replicated in fathers, which would be expected if residual confounding explained observed associations. Thus, multiparous mothers represent a high-risk group and should be prioritised for supportive interventions.

Impact of dysfunctional maternal personality traits on risk of offspring depression, anxiety and self-harm at age 18 years: a population-based longitudinal study.

BACKGROUND: The impact of underlying parental psychological vulnerability on the future mental health of offspring is not fully understood. Using a prospective cohort design, we investigated the association between dysfunctional parental personality traits and risks of offspring self-harm, depression and anxiety. METHODS: The association between dysfunctional parental personality traits (monotony avoidance, impulsivity, anger, suspicion, and detachment), measured in both mothers and fathers when offspring were age 9 years, and risk of offspring depression, anxiety and self-harm at age 18 years, was investigated in a population-based cohort (ALSPAC) from over 8000 parents and children. RESULTS: Higher levels of dysfunctional maternal, but not paternal, personality traits were associated with an increased risk of self-harm, depression, and anxiety in offspring. Maternal associations were best explained by the accumulation of dysfunctional traits. Associations were strongest for offspring depression: Offspring of mothers with three or more dysfunctional personality traits were 2.27 (1.45-3.54, p < 0.001) times as likely to be depressed, compared with offspring of mothers with no dysfunctional personality traits, independently of maternal depression and other variables. CONCLUSIONS: The accumulation of dysfunctional maternal personality traits is associated with the risk of self-harm, depression, anxiety in offspring independently of maternal depression and other confounding variables. The absence of associations for equivalent paternal traits makes a genetic explanation for the findings unlikely. Further research is required to elucidate the underlying mechanism. Mothers with high levels of dysfunctional personality traits may benefit from additional support to reduce the risk of adverse psychological outcomes occurring in their offspring.

Restoration of vision after transplantation of photoreceptors.

Cell transplantation is a potential strategy for treating blindness caused by the loss of photoreceptors. Although transplanted rod-precursor cells are able to migrate into the adult retina and differentiate to acquire the specialized morphological features of mature photoreceptor cells, the fundamental question remains whether transplantation of photoreceptor cells can actually improve vision. Here we provide evidence of functional rod-mediated vision after photoreceptor transplantation in adult Gnat1−/− mice, which lack rod function and are a model of congenital stationary night blindness. We show that transplanted rod precursors form classic triad synaptic connections with second-order bipolar and horizontal cells in the recipient retina. The newly integrated photoreceptor cells are light-responsive with dim-flash kinetics similar to adult wild-type photoreceptors. By using intrinsic imaging under scotopic conditions we demonstrate that visual signals generated by transplanted rods are projected to higher visual areas, including V1. Moreover, these cells are capable of driving optokinetic head tracking and visually guided behaviour in the Gnat1−/− mouse under scotopic conditions. Together, these results demonstrate the feasibility of photoreceptor transplantation as a therapeutic strategy for restoring vision after retinal degeneration.

The association between maternal postnatal depressive symptoms and offspring sleep problems in adolescence.

BACKGROUND: Sleep problems are associated with increased risk of physical and mental illness. Identifying risk factors is an important method of reducing public health impact. We examined the association between maternal postnatal depression (PND) and offspring adolescent sleep problems. METHOD: The sample was derived from Avon Longitudinal Study of Parents and Children (ALSPAC) participants. A sample with complete data across all variables was used, with four outcome variables. A sensitivity analysis imputing for missing data was conducted (n = 9633). RESULTS: PND was associated with increased risk of sleep problems in offspring at ages 16 and 18 years. The most robust effects were sleep problems at 18 years [adjusted odds ratio (OR) for a 1 s.d. increase in PND, 1.26, 95% confidence interval (CI) 1.15-1.39, p < 0.001] and waking more often (adjusted OR 1.14, 95% CI 1.05-1.25, p = 0.003). This remained after controlling for confounding variables including antenatal depression and early sleep problems in infancy. CONCLUSIONS: PND is associated with adolescent offspring sleep problems. Maternal interventions should consider the child's increased risk. Early sleep screening and interventions could be introduced within this group.

Understanding the culture of antimicrobial prescribing in agriculture: a qualitative study of UK pig veterinary surgeons.

OBJECTIVES: The use of antimicrobials in food-producing animals has been linked with the emergence of antimicrobial resistance in bacterial populations, with consequences for animal and public health. This study explored the underpinning drivers, motivators and reasoning behind prescribing decisions made by veterinary surgeons working in the UK pig industry. METHODS: A qualitative interview study was conducted with 21 veterinary surgeons purposively selected from all UK pig veterinary surgeons. Thematic analysis was used to analyse transcripts. RESULTS: Ensuring optimum pig health and welfare was described as a driver for antimicrobial use by many veterinary surgeons and was considered a professional and moral obligation. Veterinary surgeons also exhibited a strong sense of social responsibility over the need to ensure that antimicrobial use was responsible. A close relationship between management practices, health and economics was evident, with improvements in management commonly identified as being potential routes to reduce antimicrobial usage; however, these were not always considered economically viable. The relationship with clients was identified as being a source of professional stress for practitioners due to pressure from farmers requesting antimicrobial prescriptions, and concern over poor compliance of antimicrobial administration by some farmers. CONCLUSIONS: The drivers behind prescribing decisions by veterinary surgeons were complex and diverse. A combination of education, improving communication between veterinary surgeons and farmers, and changes in regulations, in farm management and in consumer/retailer demands may all be needed to ensure that antimicrobial prescribing is optimal and to achieve significant reductions in use.

Symptoms of generalized anxiety disorder but not panic disorder at age 15 years increase the risk of depression at 18 years in the Avon Longitudinal Study of Parents and Children (ALSPAC) cohort study.

BACKGROUND: Generalized anxiety disorder (GAD) and panic disorder (PD) differ in their biology and co-morbidities. We hypothesized that GAD but not PD symptoms at the age of 15 years are associated with depression diagnosis at 18 years. METHOD: Using longitudinal data from the Avon Longitudinal Study of Parents and Children (ALSPAC) birth cohort we examined relationships of GAD and PD symptoms (measured by the Development and Well-Being Assessment) at 15 years with depression at 18 years (by the Clinical Interview Schedule - Revised) using logistic regression. We excluded adolescents already depressed at 15 years and adjusted for social class, maternal education, birth order, gender, alcohol intake and smoking. We repeated these analyses following multiple imputation for missing data. RESULTS: In the sample with complete data (n = 2835), high and moderate GAD symptoms in adolescents not depressed at 15 years were associated with increased risk of depression at 18 years both in unadjusted analyses and adjusting for PD symptoms at 15 years and the above potential confounders. The adjusted odds ratio (OR) for depression at 18 years in adolescents with high relative to low GAD scores was 5.2 [95% confidence interval (CI) 3.0-9.1, overall p < 0.0001]. There were no associations between PD symptoms and depression at 18 years in any model (high relative to low PD scores, adjusted OR = 1.3, 95% CI 0.3-4.8, overall p = 0.737). Missing data imputation strengthened the relationship of GAD symptoms with depression (high relative to low GAD scores, OR = 6.2, 95% CI 3.9-9.9) but those for PD became weaker. CONCLUSIONS: Symptoms of GAD but not PD at 15 years are associated with depression at 18 years. Clinicians should be aware that adolescents with GAD symptoms may develop depression.

Maternal depression and anxiety predicts the pattern of offspring symptoms during their transition to adulthood.

BACKGROUND: Episodes of depression and anxiety (D&A) during the transition from late adolescence to adulthood, particularly when persistent, are predictive of long-term disorders and associated public health burden. Understanding risk factors at this time is important to guide intervention. The current objective was to investigate the associations between maternal symptoms of D&A with offspring symptoms during their transition to adulthood. METHOD: Data from a large population-based birth cohort study, in South Brazil, were used. Prospective associations between maternal D&A and offspring risk of these symptoms during the transition to adulthood (18/19, 24 and 30 years) were estimated. RESULTS: Maternal D&A in adolescence was associated with offspring symptoms across the transition to adulthood, associations were consistently stronger for females than for males. Daughters whose mothers reported D&A were 4.6 times (95% confidence interval 2.71-7.84) as likely to report D&A at all three time-points, than daughters of symptom-free mothers. CONCLUSIONS: Maternal D&A is associated with persistent D&A during the daughter's transition to adulthood. Intervention strategies should consider the mother's mental health.

Changing mothers' perception of infant emotion: a pilot study.

Cognitive bias modification (CBM) techniques, which experimentally retrain abnormal processing of affective stimuli, are becoming established for various psychiatric disorders. Such techniques have not yet been applied to maternal processing of infant emotion, which is affected by various psychiatric disorders. In a pilot study, mothers of children under 3 years old (n = 2) were recruited and randomly allocated to one of three training exercises, aiming either to increase or decrease their threshold of perceiving distress in a morphed continuum of 15 infant facial images. Differences between pre- and post-training threshold were analysed between and within subjects. Compared to baseline thresholds, the threshold for perceiving infant distress decreased in the lowered threshold group (mean difference -1.7 frames, 95 % confidence intervals (CI) -3.1 to -0.3, p = 0.02), increased in the raised threshold group (1.3 frames, 95 % CI 0.6 to 2.1, p < 0.01) and was unchanged in the control group (0.1 frames, 95 % CI -0.8 to 1.1, p = 0.80). Between-group differences were similarly robust in regression models and were not attenuated by potential confounders. The findings suggest that it is possible to change the threshold at which mothers perceive ambiguous infant faces as distressed, either to increase or decrease sensitivity to distress. This small study was intended to provide proof of concept (i.e. that it is possible to alter a mother's perception of infant distress). Questions remain as to whether the effects persist beyond the immediate experimental session, have an impact on maternal behaviour and could be used in clinical samples to improve maternal sensitivity and child outcomes.

THE IMPACT OF DEPRESSION ON MATERNAL RESPONSES TO INFANT FACES IN PREGNANCY.

Research has suggested that prenatal depression may be associated with disrupted maternal responses to infant stimuli, with depressed pregnant women not showing the bias toward distressed infants as that observed in nondepressed pregnant women. The current study examined the effects of depression on self- reported responses to infant stimuli, in early pregnancy. Women with clinical depression (n = 38), and nondepressed women (n = 67) were recruited from a wider cognitive behavioral therapy trial. They completed Maternal Response Scales in which they were presented with images of distressed, neutral, and happy infant faces, with no time limit. The women rated their responses to these images along three dimensions--wanting to comfort, wanting to turn away, and feelings of anxiety--using Likert scales via a computerized task. There was evidence that women with depression in pregnancy showed different responses than did women without depression. Women with depression were substantially more likely to be in the highest quartile for ratings of wanting to turn away, odds (OR) ratio = 4.15, 95% confidence intervals (CIs) = 1.63-10.5, p = .003, and also were substantially less likely to be in the highest quartile for wanting to comfort a distressed infant face, OR = 0.22, 95% CIs = 0.09-0.54, p < .001. Findings are consistent with there being both a heightened avoidant and a reduced comforting response toward distressed infants in depressed pregnant women, providing some support that depression disrupts maternal preparations at a conscious level.

Dysregulation of RNA polymerase I transcription during disease.

Transcription of the ribosomal RNA genes by the dedicated RNA polymerase I enzyme and subsequent processing of the ribosomal RNA are fundamental control steps in the synthesis of functional ribosomes. Dysregulation of Pol I transcription and ribosome biogenesis is linked to the etiology of a broad range of human diseases. Diseases caused by loss of function mutations in the molecular constituents of the ribosome, or factors intimately associated with RNA polymerase I transcription and processing are collectively termed ribosomopathies. Ribosomopathies are generally rare and treatment options are extremely limited tending to be more palliative than curative. Other more common diseases are associated with profound changes in cellular growth such as cardiac hypertrophy, atrophy or cancer. In contrast to ribosomopathies, altered RNA polymerase I transcriptional activity in these diseases largely results from dysregulated upstream oncogenic pathways or by direct modulation by oncogenes or tumor suppressors at the level of the RNA polymerase I transcription apparatus itself. Ribosomopathies associated with mutations in ribosomal proteins and ribosomal RNA processing or assembly factors have been covered by recent excellent reviews. In contrast, here we review our current knowledge of human diseases specifically associated with dysregulation of RNA polymerase I transcription and its associated regulatory apparatus, including some cases where this dysregulation is directly causative in disease. We will also provide insight into and discussion of possible therapeutic approaches to treat patients with dysregulated RNA polymerase I transcription. This article is part of a Special Issue entitled: Transcription by Odd Pols.

Cloning, recombinant expression and inhibitor profiles of dihydrofolate reductase from the Australian sheep blow fly, Lucilia cuprina.

While dihydrofolate reductase (DHFR) is an important drug target in mammals, bacteria and protozoa, no inhibitors of this enzyme have been developed as commercial insecticides. We therefore examined the potential of this enzyme as a drug target in an important ectoparasite of livestock, the Australian sheep blow fly, Lucilia cuprina (Diptera: Calliphoridae) (Wiedemann). The non-specific DHFR inhibitors aminopterin and methotrexate significantly inhibited the growth of L. cuprina larvae, with IC50 values at µg levels. Trimethoprim and pyrimethamine were 5-30-fold less active. Relative IC50 values for the inhibition of recombinant L. cuprina DHFR by various inhibitors were in accordance with their relative effects on larval growth. The active-site amino acid residues of L. cuprina DHFR differed by between 34% and 50% when compared with two mammalian species, as well as two bacteria and two protozoa. There were significant charge and size differences in specific residues between the blow fly and human DHFR enzymes, notably the L. cuprina Asn21, Lys31 and Lys63 residues. This study provides bioassay evidence to highlight the potential of blow fly DHFR as an insecticide target, and describes differences in active site residues between blow flies and other organisms which could be exploited in the design of blow fly control chemicals.

The effects of estuarine outflows on coastal marine ecosystems in New South Wales, Australia.

In the state of New South Wales (NSW), Australia, recent legislative action has focused on identifying key threats to the marine estate. We used a systematic literature review to evaluate the knowledge status of the effects of estuarine outflows on coastal marine ecosystems, within the environmental, hydrological, and physicochemical context of NSW waters. Results focussed on studies that measured outcomes for marine biota (n = 56). Trace elements and organochlorines were the most frequently studied contaminant types, with reported biological concentrations often below guideline values but detected at the highest concentrations adjacent to urban sources. Few studies measured the impacts of legacy and emerging contaminants to animal health, or the flow on effects to marine ecosystems in NSW. Our review highlights key biological and geographical data gaps in estuarine outflow research in NSW, particularly of the impact on ecosystems of exported carbon and nutrients to the oligotrophic waters of NSW.

Cardiac SABR: Image matching techniques for accurate treatment delivery.

BACKGROUND: Ventricular tachycardia is an irregular heartbeat conventionally treated using invasive cardiac catheter ablation and medication. However, when standard treatments have been exhausted, cardiac SABR provides a final treatment option to this high-mortality condition. Complex diagnostic mapping and planning scans enable multi-disciplinary target delineation for a 25Gy single fraction. However, organs at risk (OAR) near the target make this treatment challenging to plan and deliver. Publications from cardiologists report the efficacy of cardiac SABR, however there is limited data on the treatment delivery and image matching of this complex procedure. METHODS: Four specialist therapeutic radiographers experienced in cardiac SABR reviewed 40 CBCTs from 10 patients treated in the UK. Each therapeutic radiographer conducted five image matches: a manual match (manual), an automatic match to the heart structure (auto) and the auto match followed by manual adjustment to the PTV (PTV), all using three degrees of freedom (DoF) only. The auto and PTV matches were also repeated using 6DoF. Inter-observer variability was quantified using 95% limits of agreement from a modified Bland-Altman analysis. RESULTS: The limits of agreement were smallest in the automatic matches suggesting the algorithm is reliable. A manual adjustment from the auto match to the PTV is clinically appropriate to optimise target coverage. The limits of agreement were smaller in the 6DoF PTV match 1.06 mm, 1.24 mm, 1.68 mm than the 3DoF PTV match 1.57 mm, 2.06 mm, 2.11 mm (lateral, vertical, longitudinal). CONCLUSION: The 6DoF CBCT image match has less variability and therefore suggest using a 6DoF couch for treatment delivery. IMPLICATIONS FOR PRACTICE: Cardiac SABR CBCT image matching at treatment delivery is complex, optimisation of CBCT acquisition parameters and therapeutic radiographer training is essential prior to implementation.

From pelvic radiation to social isolation: a qualitative study of survivors' experiences of chronic bowel symptoms after pelvic radiotherapy.

PURPOSE: We explored survivors' experiences of chronic bowel symptoms following pelvic radiotherapy, strategies employed in living with these symptoms, effects on daily activities, and roles at home and in the workplace. METHODS: Semi-structured interviews were conducted with 28 individuals (10 gynaecological, 14 prostate, four anal/rectal cancer survivors) who had completed pelvic radiotherapy at least six months prior to data collection and who had experience of bowel symptoms during this post-treatment period. Reflexive thematic analysis was undertaken. RESULTS: We propose four themes describing a process leading from experience of symptoms to withdrawal from activities and roles. These are (1) losing control (the experience of unintended anal leakage or discharge); (2) experiencing embarrassment and fear (the experience of embarrassment or fear of embarrassment as a result of discharge becoming public); (3) managing and reacting (acting to reduce the likelihood of discharge or to prevent this becoming public); and (4) restriction and withdrawal (avoiding specific activities or situations so as to reduce or remove the risk of embarrassment). Returning to the workplace presented additional challenges across these themes. CONCLUSIONS: Impacts of chronic bowel symptoms can be severe. Survivors employ a variety of methods and strategies in living with their symptoms. Some of these support continued role fulfilment but some constitute a withdrawal from pre-treatment roles. Current healthcare provision and statutory protections fail to fully meet needs following pelvic radiotherapy. IMPLICATIONS FOR CANCER SURVIVORS: There is a need to develop and implement evidence-based services and supported self-management programmes for survivors experiencing chronic bowel problems post-radiotherapy.

Ecological divergence and speciation between lemur (Eulemur) sister species in Madagascar.

Understanding ecological niche evolution over evolutionary timescales is crucial to elucidating the biogeographic history of organisms. Here, we used, for the first time, climate-based ecological niche models (ENMs) to test hypotheses about ecological divergence and speciation processes between sister species pairs of lemurs (genus Eulemur) in Madagascar. We produced ENMs for eight species, all of which had significant validation support. Among the four sister species pairs, we found nonequivalent niches between sisters, varying degrees of niche overlap in ecological and geographic space, and support for multiple divergence processes. Specifically, three sister-pair comparisons supported the null model that niches are no more divergent than the available background region. These findings are consistent with an allopatric speciation model, and for two sister pairs (E. collaris-E. cinereiceps and E. rufus-E. rufifrons), a riverine barrier has been previously proposed for driving allopatric speciation. However, for the fourth sister pair E. flavifrons-E. macaco, we found support for significant niche divergence, and consistent with their parapatric distribution on an ecotone and the lack of obvious geographic barriers, these findings most strongly support a parapatric model of speciation. These analyses thus suggest that various speciation processes have led to diversification among closely related Eulemur species.

Outside-the-(cavity-prep)-box thinking.

Direct placement restorative materials must interface with tooth structures that are often compromised by caries or trauma. The material must seal the interface while providing sufficient strength and wear resistance to assure function of the tooth for, ideally, the lifetime of the patient. Needed are direct restorative materials that are less technique-sensitive than current resin-based composite systems while having improved properties. The ideal material could be successfully used in areas of the world with limited infrastructure. Advances in our understanding of the interface between the restoration adhesive system and the stages of carious dentin can be used to promote remineralization. Application of fracture mechanics to adhesion at the tooth-restoration interface can provide insights for improvement. Research in polymer systems suggests alternatives to current composite resin matrix systems to overcome technique sensitivity, while advances in nano- and mesoparticle reinforcement and alignment in composite systems can increase material strength, toughness, and wear resistance, foreshadowing dental application.