An evolutionary epigenetic clock in plants.

Molecular clocks are the basis for dating the divergence between lineages over macroevolutionary timescales (~105 to 108 years). However, classical DNA-based clocks tick too slowly to inform us about the recent past. Here, we demonstrate that stochastic DNA methylation changes at a subset of cytosines in plant genomes display a clocklike behavior. This "epimutation clock" is orders of magnitude faster than DNA-based clocks and enables phylogenetic explorations on a scale of years to centuries. We show experimentally that epimutation clocks recapitulate known topologies and branching times of intraspecies phylogenetic trees in the self-fertilizing plant Arabidopsis thaliana and the clonal seagrass Zostera marina, which represent two major modes of plant reproduction. This discovery will open new possibilities for high-resolution temporal studies of plant biodiversity.

An evolutionary epigenetic clock in plants.

Molecular clocks are the basis for dating the divergence between lineages over macro-evolutionary timescales (~10 5 -10 8 years). However, classical DNA-based clocks tick too slowly to inform us about the recent past. Here, we demonstrate that stochastic DNA methylation changes at a subset of cytosines in plant genomes possess a clock-like behavior. This 'epimutation-clock' is orders of magnitude faster than DNA-based clocks and enables phylogenetic explorations on a scale of years to centuries. We show experimentally that epimutation-clocks recapitulate known topologies and branching times of intra-species phylogenetic trees in the selfing plant A. thaliana and the clonal seagrass Z. marina , which represent two major modes of plant reproduction. This discovery will open new possibilities for high-resolution temporal studies of plant biodiversity.

Review: Smart agri-systems for the pig industry.

The projected rise in the global human population and the anticipated increase in demand for meat and animal products, albeit with a greatly reduced environmental footprint, offers a difficult set of challenges to the livestock sector. Primarily, how do we produce more, but in a way that is healthier for the animals, public, and the environment? Implementing a smart agri-systems approach, utilising multiplatform precision technologies, internet of things, data analytics, machine learning, digital twinning and other emerging technologies can support a more informed decision-making and forecasting position that will allow us to move towards greater sustainability in future. If we look to precision agronomy, there are a wide range of technologies available and examples of how digitalisation and integration of platform outputs can lead to advances in understanding the agricultural system and forecasting upcoming events and performance that have hitherto been impossible to achieve. There is much for the livestock sector and animal scientists to learn from the developments of precision technologies and smart agri-system approaches in the arable and horticultural contexts. However, there are several barriers the livestock sector must overcome: (i) the development and implementation of precision livestock farming technologies that can be easily integrated and analysed without the support of a dedicated data analyst in house; (ii) the lack of extensive validation of many developed and available precision livestock farming technologies means that reliability and accuracy are likely to be compromised when applied in commercial practice; (iii) the best smart agri-systems approaches are reliant on large quantities of data from across a wide variety of conditions, but at present the complications of data sharing, commercial sensitivities, data ownership, and permissions make it challenging to obtain or knit together data from different parts of the system into a comprehensive picture; and (iv) the high level of investment needed to develop and scale these technologies is substantial and represents significant risk for companies when a technology is emerging. Using a case study of the National Pig Centre (a flagship pig research facility in the UK) we discuss how a smart agri-systems approach can be applied in practice to investigate alternative future systems for production, and enable monitoring of these systems as a commercial demonstrator site for future pork production.

Reference range for 24-h urine calcium, calcium/creatinine ratio, and correlations with calcium absorption and serum vitamin D metabolites in normal women.

A study of 959 black and white women shows that the normal range for 24-h urine calcium excretion in white women is 30-300 mg and 10-285 mg in black women. Clinical laboratories use a normal range for 24-h urine calcium excretion of 100-300 mg; there is a need for them to update their age- and race-specific ranges. INTRODUCTION: Recommendations for a normal range for 24-h urine calcium vary from a low of 50 mg to a high of 400 mg; most "laboratory normal ranges" based on older literature are incorrect. The objective of this analysis is to define a normal range for young women age 25-45 years and older women age 55-90 years, white and black, for 24-h urine calcium and calcium/creatinine ratio, and to examine the relationship between 24-h urine calcium, calcium absorption, and vitamin D metabolites. METHODS: Data from 3 studies was collected on 959 normal black and white women, ages 25-87 years, for 24-h urine calcium, creatinine, calcium intake, serum 25-hydroxyvitamin D (25OHD),1,25 dihydroxyvitamin D (1,25(OH)2D), and calcium absorption. Urine calcium and creatinine were measured on an auto-analyzer. Calcium absorption was measured by a single isotope method. Serum 25OHD and 1,25(OH)2D were measured by competitive protein binding assay or radioimmunoassay. Because 24-h urine calcium did not fit a normal distribution, non-parametric methods were used to determine the 95% reference interval (RI) and 90% non-parametric confidence intervals (CI) calculated for groups. RESULTS: The 95% reference intervals for 24-h urine calcium for women were as follows: black older 7-225 mg, black younger 8-285 mg; white older 37-275 mg, and white younger 23-287 mg. In older white women, 24-h urine calcium was significantly correlated with serum 1,25(OH)2 D, r = 0.23, p < 0.001, calcium intake r = 0.12, p = 0.001, and calcium absorption r = 0.18, p = 0.003, but not serum 25OHD r = 0.07, p = 0.06. CONCLUSIONS: The normal reference interval for 24-h urine calcium for black women is lower than white women. Twenty-four-hour urine calcium was correlated with serum 1,25(OH)2 D calcium intake and calcium absorption, but not serum 25OHD. This range will be useful clinically for defining hypercalciuria and for following patients on vitamin D and calcium treatment.

Projecting effects of land use change on human well-being through changes in ecosystem services.

Changing patterns of land use, temperature, and precipitation are expected to impact ecosystem services, including water quality and quantity, buffering of extreme events, soil quality, and biodiversity. Scenario analyses that link such impacts on ecosystem services to human well-being may be valuable in anticipating potential consequences of change that are meaningful to people living in a community. Ecosystem services provide numerous benefits to community well-being, including living standards, health, cultural fulfillment, education, and connection to nature. Yet assessments of impacts of ecosystem services on human well-being have largely focused on human health or monetary benefits (e.g. market values). This study applies a human well-being modelling framework to demonstrate the potential impacts of alternative land use scenarios on multi-faceted components of human well-being through changes in ecosystem services (i.e., ecological benefits functions). The modelling framework quantitatively defines these relationships in a way that can be used to project the influence of ecosystem service flows on indicators of human well-being, alongside social service flows and economic service flows. Land use changes are linked to changing indicators of ecosystem services through the application of ecological production functions. The approach is demonstrated for two future land use scenarios in a Florida watershed, representing different degrees of population growth and environmental resource protection. Increasing rates of land development were almost universally associated with declines in ecosystem services indicators and associated indicators of well-being, as natural ecosystems were replaced by impervious surfaces that depleted the ability of ecosystems to buffer air pollutants, provide habitat for biodiversity, and retain rainwater. Scenarios with increases in indicators of ecosystem services, however, did not necessarily translate into increases in indicators of well-being, due to covarying changes in social and economic services indicators. The approach is broadly transferable to other communities or decision scenarios and serves to illustrate the potential impacts of changing land use on ecosystem services and human well-being.

Effect of vitamin D supplementation on total and free 25 hydroxyvitamin D and parathyroid hormone. An analysis of two randomized controlled trials.

BACKGROUND: It is questionable as to whether total serum 25 hydroxyvitamin D (T25D) levels are lower in African Americans. We measured serum T25D, free 25hydroxyvitamin D (F25D) and serum parathyroid hormone (PTH) in African American and Caucasian women and studied the effect of vitamin D dosing to determine if differences by race or age occur. METHODS: Healthy young and older Caucasian and African American women who were vitamin D insufficient were randomized in two clinical trials to escalating daily doses of vitamin D from 400 to 4800 IU and placebo for 12 months. RESULTS: Baseline F25D and T25D were significantly lower in young but not older African American compared to Caucasian women. At baseline, the rate of change, or slope, in F25D with T25D was significantly greater in younger women than in older women, but difference in the rate of change in F25D with T25D is similar in African American and Caucasian women. After vitamin D supplementation, there was an increase in F25D, and the dose response was not significantly different by age or race. The ratio of F25D/T25D decreased in all groups once T25D exceeded ~60 nmol L-1 . There was a progressive decrease in serum PTH with increasing vitamin D doses and the per cent change was similar for F25D and T25D. CONCLUSION: Serum F25D and T25D are lower in younger African American women, and since dietary vitamin D is similar in the groups, it is likely that the cause of low serum 25OHD in African American women is due to reduced UV exposure and reduced skin production of vitamin D.

Feeding activity of the cayenne pompano Trachinotus cayennensis (Cuvier 1832) (Perciformes, Carangidae) in estuaries on the western coast of the state of Maranhão, Brazil / Atividade alimentar do pampo Trachinotus cayennensis (Cuvier 1832) (Perciformes, Carangidae) em estuários do litoral ocidental do Estado do Maranhão, Brasil

Abstract The present paper addresses the feeding activity of Trachinotus cayennensis, collected in Lençóis Bay (1°18'S - 1°19'S; 44°51'W - 44°53'W) on the western coast of the state of Maranhão, Brazil. Sampling was conducted between June 2012 and June 2013 using driftnets with stretch mesh sizes from 95 to 100 mm. A total of 205 individuals (114 females and 91 males) were analyzed. Statistically significant differences in the sex ratio were found in June, September and December 2012. Food items were analyzed based on frequency of occurrence and volumetric method, with the subsequent calculation of the alimentary importance index. Three size groups were defined to determine possible ontogenetic changes in eating habits based on the size range of the individuals collected: I (˂ 29 cm), II (29.1 to 37.0) and III (≥ 37.1). Eleven food item categories were identified: mollusks, polychaetes, crustaceans, nematodes, insects, algae, bryozoans, ophiuroids, fishes, vegetal matter and sediments. The variety of items in the diet of T. cayennensis indicates considerable feeding plasticity and opportunistic behavior. Seasonal variations influenced the feeding pattern of the species, with greater feeding activity in the dry season. The considerable availability of resources in estuarine habitats of the western coast of Maranhão constitutes another factor that influences the feeding behavior of this species.

Resumo Atividade alimentar do pampo Trachinotus cayennensis (Cuvier 1832) (Perciformes, Carangidae) em estuários na costa ocidental do Maranhão, Brasil. O presente trabalho descreve a atividade alimentar do Trachinotus cayennensis , coletado na Baía de Lençóis (1°18'S - 1°19'S; 44°51'W - 44°53'W) na costa oeste do Maranhão. Amostragens foram realizadas entre junho de 2012 e junho de 2013, utilizando redes de emalhar à deriva com tamanho de malha de 95 a 100 mm. Foram analisados ​​205 indivíduos (114 fêmeas e 91 machos). Encontraram-se diferenças estatisticamente significativas na proporção sexual nos meses de junho, setembro e dezembro de 2012. Os itens alimentares foram analisados ​​com base na frequência de ocorrência e utilizando o método volumétrico, com o subsequente cálculo do índice de importância alimentar. Três grupos de tamanho foram definidos para determinar possíveis mudanças ontogenéticas nos hábitos alimentares com base na faixa de tamanho dos indivíduos coletados: I (˂ 29 cm), II (29,1 a 37,0) e III (≥ 37,1). Foram identificadas 11 categorias de alimentos: moluscos, poliquetas, crustáceos, nematoides, insetos, algas, briozoários, ophiuro, peixes, matéria vegetal e sedimentos. A variedade de itens na dieta de T. cayennensis indica uma plasticidade alimentar considerável e um comportamento oportunista. As variações sazonais influenciaram o padrão alimentar da espécie, com maior atividade de alimentação na estação seca. A considerável disponibilidade de recursos nos habitats estuarinos da costa oeste do Maranhão constitui outro fator que exerce influência sobre o comportamento alimentar desta espécie.

SHH pathway inhibition is protumourigenic in adamantinomatous craniopharyngioma.

Pharmacological inhibition of the sonic hedgehog (SHH) pathway can be beneficial against certain cancers but detrimental in others. Adamantinomatous craniopharyngioma (ACP) is a relevant pituitary tumour, affecting children and adults, that is associated with high morbidity and increased mortality in long-term follow-up. We have previously demonstrated overactivation of the SHH pathway in both human and mouse ACP. Here, we show that this activation is ligand dependent and induced by the expression of SHH protein in a small proportion of tumour cells. We investigate the functional relevance of SHH signalling in ACP through MRI-guided preclinical studies using an ACP mouse model. Treatment with vismodegib, a clinically approved SHH pathway inhibitor, results in a significant reduction in median survival due to premature development of highly proliferative and vascularised undifferentiated tumours. Reinforcing the mouse data, SHH pathway inhibition in human ACP leads to a significant increase in tumour cell proliferation both ex vivo, in explant cultures, and in vivo, in a patient-derived xenograft model. Together, our results demonstrate a protumourigenic effect of vismodegib-mediated SHH pathway inhibition in ACP.

Feeding activity of the cayenne pompano Trachinotus cayennensis (Cuvier 1832) (Perciformes, Carangidae) in estuaries on the western coast of the state of Maranhão, Brazil.

The present paper addresses the feeding activity of Trachinotus cayennensis, collected in Lençóis Bay (1°18'S - 1°19'S; 44°51'W - 44°53'W) on the western coast of the state of Maranhão, Brazil. Sampling was conducted between June 2012 and June 2013 using driftnets with stretch mesh sizes from 95 to 100 mm. A total of 205 individuals (114 females and 91 males) were analyzed. Statistically significant differences in the sex ratio were found in June, September and December 2012. Food items were analyzed based on frequency of occurrence and volumetric method, with the subsequent calculation of the alimentary importance index. Three size groups were defined to determine possible ontogenetic changes in eating habits based on the size range of the individuals collected: I (˂ 29 cm), II (29.1 to 37.0) and III (≥ 37.1). Eleven food item categories were identified: mollusks, polychaetes, crustaceans, nematodes, insects, algae, bryozoans, ophiuroids, fishes, vegetal matter and sediments. The variety of items in the diet of T. cayennensis indicates considerable feeding plasticity and opportunistic behavior. Seasonal variations influenced the feeding pattern of the species, with greater feeding activity in the dry season. The considerable availability of resources in estuarine habitats of the western coast of Maranhão constitutes another factor that influences the feeding behavior of this species.

Effect of increasing doses of vitamin D on bone mineral density and serum N-terminal telopeptide in elderly women: a randomized controlled trial.

BACKGROUND: There are few controlled studies of the effect of different doses of vitamin D3 on bone mineral density (BMD). OBJECTIVES: We conducted a randomized placebo-controlled trial of increasing doses of vitamin D3 in 163 Caucasian and 31 African American women with serum 25-hydroxyvitamin D (25OHD) ≤50 nmol/L. This is an analysis of secondary outcome BMD to see if there is an association between percent change in BMD and dose of vitamin D3. METHODS: Participants were randomly assigned to placebo, vitamin D3 400, 800, 1600, 2400, 3200, 4000, or 4800 IU/day; calcium supplements, average 600mg, were given to provide a total calcium intake of 1200 mg/d. The primary outcome was 12-month serum 25OHD level. Analysis methods include ANOVA and Pearson correlations. RESULTS: The mean percent increase (±SD) in BMD at 12 months for all women was small; total body, 0.62% (± 2.72), femoral neck 0.59% (±3.58) and spine 0.43% (±2.80). There was no difference in BMD or serum N-telopeptide in response to vitamin D by dose or race. The increase in total body, spine and hip BMD in elderly women given vitamin D doses between 400 and 4800 IU daily and calcium supplementation is small, unrelated to dose or 12-month serum 25OHD, free 25OHD or 1,25(OH)2D. There was no evidence of a threshold change in BMD with increasing serum 25OHD or free 25OHD in this population. CONCLUSIONS: We found no significant effect of daily vitamin D dose ranging from 400 to 4800 IU/day on BMD or serum N-terminal telopeptides in elderly women with initially low serum 25OHD.

Characterizing the experience of auditory verbal hallucinations and accompanying delusions in individuals with a diagnosis of bipolar disorder: A systematic review.

OBJECTIVES: The aim of the current study was to inform ongoing attempts to identify clinically meaningful subcategories of auditory verbal hallucination (AVH), and to evaluate evidence that might pertain to the suitability of current psychological interventions for people with bipolar disorder (BD) who experience psychotic symptoms. METHODS: A comprehensive synthesis of findings on the phenomenology of AVH and delusions in BD is included, alongside a critical review of clinical and cognitive correlates. Studies published in the previous 20 years, until December 2016, were retrieved from the following databases: Embase, CINAHL, MEDLINE, PsycINFO and Web of Science. Thirty-two articles were reviewed after applying a set of predetermined inclusion criteria. RESULTS: Psychotic symptoms were common in both manic and depressive phases, although higher frequencies were indicated in mania. Few detailed characterizations of AVH phenomenology were identified. Delusions with persecutory, grandiose and referential themes were the most common in BD. AVHs were associated with delusions and there was evidence to suggest that delusion subtype may vary according to mood state and type of AVH. Data on clinical correlates of AVH in BD were sparse. However, the results indicated that cognitive appraisals or interpretations of voices might be different in BD from those established to be predictive of clinical outcomes in schizophrenia spectrum disorders. CONCLUSIONS: Clear gaps exist in our current understanding of the first-person experience of AVH in BD and the potential relationship to co-occurring symptoms, including delusions. Further research into cognitive interpretations of AVH in BD might inform adapted psychological interventions for psychotic symptoms in this population.

Population structure of an orchid mycorrhizal fungus with genus-wide specificity.

Fundamental life history processes of mycorrhizal fungi with inconspicuous fruiting bodies can be difficult to elucidate. In this study we investigated the species identities and life history of the orchid mycorrhizal Tulasnella fungi, which associate with the south eastern Australia orchid genus Chiloglottis. Tulasnella prima was the primary partner and was found to be associated with all 17 Chiloglottis species across a range of >1000 km, and to occur in the two edaphic conditions investigated (soil and sphagnum hammocks). Another Tulasnella species (T. sphagneti) appears to be restricted to moist conditions of alpine sphagnum hammocks. The population genetic structure of the widespread species T. prima, was investigated at 10 simple sequence repeat (SSR) markers and at four cross-amplified SSR loci for T. sphagneti. For both taxa, no sharing of multilocus genotypes was found between sites, but clones were found within sites. Evidence for inbreeding within T. prima was found at 3 of 5 sites. Significant genetic differentiation was found within and between taxa. Significant local positive spatial genetic autocorrelation was detected among non-clonal isolates at the scale of two metres. Overall, the population genetic patterns indicated that in Tulasnella mating occurs by inbreeding and dispersal is typically restricted to short-distances.

Epistatic effect of TLR-1, -6 and -10 polymorphisms on organic dust-mediated cytokine response.

Exposure to organic dust from agricultural environments is associated with inflammatory respiratory conditions. The putative causal agents in organic dust include viral, microbial and fungal components, which are recognized by the family of Toll-like receptors (TLRs) and drive host innate and adaptive responses. Our aim in this study was to determine whether responsiveness to organic dust among agricultural workers was dependent on polymorphisms in the TLR10-TLR1-TLR6 gene cluster. We stimulated whole blood from 509 agricultural workers with organic dust, triacyl lipopeptide N-palmitoyl-S-dipalmitoylglyceryl Cys-Ser-(Lys)4 (Pam3CSK4) and the diacyl-lipopeptide peptidoglycan. Several of the tagging polymorphisms and haplotypes conferred hyper-responsiveness to organic dust with an increase in interleukin-6 (IL-6; P<0.005), but not tumor necrosis factor-α (TNF-α), secretion. We conclude that genetic variation in the TLR10-TLR1-TLR6 gene cluster mediates responsiveness to organic dust, but indicates different signaling pathways for IL-6 and TNF-α. These studies provide new insight into the role of the TLR10-TLR1-TLR6 gene cluster and the innate immune response to organic dust.

Role of Akt2 in regulation of metastasis suppressor 1 expression and colorectal cancer metastasis.

Survival signaling is critical for the metastatic program of cancer cells. The current study investigated the role of Akt survival proteins in colorectal cancer (CRC) metastasis and explored potential mechanisms of Akt-mediated metastasis regulation. Using an orthotopic implantation model in mice, which uniquely recapitulates the entire multistep process of CRC metastasis, combined with an inducible system of short hairpin RNA-mediated Akt isoform knockdown in human CRC cells, our studies confirm a role of Akt2 in CRC cell dissemination to distant organs in vivo. Akt2 deficiency profoundly inhibited the development of liver lesions in mice, whereas Akt1 had no effect under the experimental conditions used in the study. Array analysis of human metastatic genes identified the scaffolding protein metastasis suppressor 1 (MTSS1) as a novel Akt2-regulated gene. Inducible loss of Akt2 in CRC cells robustly upregulated MTSS1 at the messenger RNA and protein level, and the accumulated protein was functionally active as shown by its ability to engage an MTSS1-Src-cortactin inhibitory axis. MTSS1 expression led to a marked reduction in levels of functional cortacin (pcortactin Y421), an actin nucleation-promoting factor that has a crucial role in cancer cell invasion and metastasis. MTSS1 was also shown to mediate suppressive effects of Akt2 deficiency on CRC cell viability, survival, migration and actin polymerization in vitro. The relevance of these findings to human CRC is supported by analysis of The Cancer Genome Atlas (TCGA) and NCBI GEO data sets, which demonstrated inverse changes in expression of Akt2 and MTSS1 during CRC progression. Taken together, the data identify MTSS1 as a new Akt2-regulated gene, and point to suppression of MTSS1 as a key step in the metastasis-promoting effects of Akt2 in CRC cells.

Oral Health in Young Australian Aboriginal Children: Qualitative Research on Parents' Perspectives.

Despite dedicated government funding, Aboriginal Australians, including children, experience more dental disease than other Australians, despite it being seen as mostly preventable. The ongoing legacy of colonization and discrimination against Aboriginal Australians persists, even in health services. Current neoliberal discourse often holds individuals responsible for the state of their health, rather than the structural factors beyond individual control. While presenting a balanced view of Aboriginal health is important and attests to Indigenous peoples' resilience when faced with persistent adversity, calling to account those structural factors affecting the ability of Aboriginal people to make favorable oral health choices is also important. A decolonizing approach informed by Indigenous methodologies and whiteness studies guides this article to explore the perceptions and experiences of Aboriginal parents ( N = 52) of young children, mainly mothers, in Perth, Western Australia, as they relate to the oral health. Two researchers, 1 Aboriginal and 1 non-Aboriginal, conducted 9 focus group discussions with 51 Aboriginal participants, as well as 1 interview with the remaining individual, and independently analyzed responses to identify themes underpinning barriers and enablers to oral health. These were compared, discussed, and revised under key themes and interpreted for meanings attributed to participants' perspectives. Findings indicated that oral health is important yet often compromised by structural factors, including policy and organizational practices that adversely preclude participants from making optimal oral health choices: limited education about prevention, prohibitive cost of services, intensive marketing of sugary products, and discrimination from health providers resulting in reluctance to attend services. Current government intentions center on Aboriginal-non-Aboriginal partnerships, access to flexible services, and health care that is free of racism and proactively seeks and welcomes Aboriginal people. The challenge is whether these good intentions are matched by policies and practices that translate into sustained improvements to oral health for Aboriginal Australians. Knowledge Transfer Statement: Slow progress in reducing persistent oral health disparities between Aboriginal and non-Aboriginal Australians calls for a new approach to this seemingly intractable problem. Findings from our qualitative research identified that structural factors-such as cost of services, little or no education on preventing oral disease, and discrimination by health providers-compromised Aboriginal people's optimum oral health choices and access to services. The results from this study can be used to recommend changes to policies and practices that promote rather than undermine Aboriginal health and well-being and involve Aboriginal people in decisions about their health care.

Oral health interventions in Australian Aboriginal communities: a review of the literature.

Aboriginal Australians experience significant disparities in oral health with even poorer outcomes reported in rural and remote areas. The high rates of preventable dental disease in Aboriginal communities are a serious concern from a social standpoint and in terms of service provision and health care expenditure. In this review, primary research literature was comprehensively reviewed. Papers were selected if they reported designing or implementing an intervention or oral health programme specific to the needs of Aboriginal communities. Twenty-one publications fulfilled the inclusion criteria with 19 different interventions being described. Interventions were categorized using a classification adapted from the work of Whitehead (2002). The review identified interventions that aimed to reduce early childhood caries, increase services to remote communities, develop the role of Aboriginal health workers, improve oral health literacy, establish water fluoridation and provide periodontal therapy. Implementing successful oral health interventions in Aboriginal communities is a challenge that is compounded by the complex interplay between psychosocial and cultural determinants. Even interventions that follow a rigorous and consultative design have a high failure rate in Aboriginal communities if upstream determinants of health are not adequately understood and addressed.

Compliance of post-radiation therapy head and neck cancer patients with caries preventive protocols.

BACKGROUND: Caries prevention is paramount in safeguarding the life quality of head and neck cancer patients and is dependent on patient compliance with caries preventive protocols. The purpose of this study was to examine this compliance. METHODS: All records of patients referred to one public oral medicine clinic servicing a head and neck oncology unit of one major Western Australian hospital, between January 2005 and December 2011, were examined. Data extracted included patient and cancer characteristics and compliance with dietary advice, dental care, oral hygiene instruction and fluoride use over a follow-up period of at least 12 months. Compliance was assessed against various oral health outcomes and patient characteristics. RESULTS: Of the 116 participants, 75.9% complied with all caries preventive measures over a mean follow-up period of 45 months. Non-compliance with regular dental attendance (P = 0.004), oral hygiene instruction (P = 0.009), dietary advice (P = 0.034) and daily fluoride use (P = 0.018) were associated with the development of dental caries post-treatment. The presence of dental caries at the time of cancer diagnosis was predictive of poorer compliance. CONCLUSIONS: High compliance with caries preventive measures is attainable in the head and neck cancer patient group. Factors other than fluoride use seem important in caries prevention.

Striatal mRNA expression patterns underlying peak dose L-DOPA-induced dyskinesia in the 6-OHDA hemiparkinsonian rat.

L-DOPA is the primary pharmacological treatment for relief of the motor symptoms of Parkinson's disease (PD). With prolonged treatment (⩾5 years) the majority of patients will develop abnormal involuntary movements as a result of L-DOPA treatment, known as L-DOPA-induced dyskinesia. Understanding the underlying mechanisms of dyskinesia is a crucial step toward developing treatments for this debilitating side effect. We used the 6-hydroxydopamine (6-OHDA) rat model of PD treated with a three-week dosing regimen of L-DOPA plus the dopa decarboxylase inhibitor benserazide (4 mg/kg and 7.5 mg/kgs.c., respectively) to induce dyskinesia in 50% of individuals. We then used RNA-seq to investigate the differences in mRNA expression in the striatum of dyskinetic animals, non-dyskinetic animals, and untreated parkinsonian controls at the peak of dyskinesia expression, 60 min after L-DOPA administration. Overall, 255 genes were differentially expressed; with significant differences in mRNA expression observed between all three groups. In dyskinetic animals 129 genes were more highly expressed and 14 less highly expressed when compared with non-dyskinetic and untreated parkinsonian controls. In L-DOPA treated animals 42 genes were more highly expressed and 95 less highly expressed when compared with untreated parkinsonian controls. Gene set cluster analysis revealed an increase in expression of genes associated with the cytoskeleton and phosphoproteins in dyskinetic animals compared with non-dyskinetic animals, which is consistent with recent studies documenting an increase in synapses in dyskinetic animals. These genes may be potential targets for drugs to ameliorate L-DOPA-induced dyskinesia or as an adjunct treatment to prevent their occurrence.

Mice deficient in Muc4 are resistant to experimental colitis and colitis-associated colorectal cancer.

MUC4, a large transmembrane mucin normally expressed in the small and large intestine, is differentially expressed during inflammatory and malignant conditions of the colon. However, the expression pattern and the role of MUC4 in colitis and colorectal cancer (CRC) are inconclusive. Therefore, the aim of this study was to understand the role of Muc4 during inflammatory and malignant conditions of the colon. Here, we generated Muc4(-/-) mice and addressed its role in colitis and colitis-associated CRC using dextran sodium sulfate (DSS) and azoxymethane (AOM)-DSS experimental models, respectively. Muc4(-/-) mice were viable, fertile with no apparent defects. Muc4(-/-) mice displayed increased resistance to DSS-induced colitis compared with wild-type (WT) littermates that was evaluated by survival rate, body weight loss, diarrhea and fecal blood score, and histological score. Reduced infiltration of inflammatory cells, that is, CD3(+) lymphocytes and F4/80(+) macrophages was observed in the inflamed mucosa along with reduction in the mRNA levels of inflammatory cytokines interleukin (IL)-1ß and tumor necrosis factor (TNF)-α and anti-microbial genes Lysozyme M and SLPI in the colon of Muc4(-/-) mice compared with WT littermates. Compensatory upregulation of Muc2 and Muc3 mucins under basal and DSS treatment conditions partly explains the resistance observed in Muc4(-/-) mice. Accordingly, Muc4(-/-) mice exhibited significantly reduced tumor burden compared with WT mice assessed in a colitis-induced tumor model using AOM/DSS. An increased percentage of Ki67(+) nuclei was observed in the tumors from WT compared with Muc4(-/-) mice suggesting Muc4 to be critical in intestinal cell proliferation during tumorigenesis. Taken together, we conclusively demonstrate for the first time the role of Muc4 in driving intestinal inflammation and inflammation-associated tumorigenesis using a novel Muc4(-/-) mouse model.

Impact of variation in structure of condensed tannins from sainfoin (Onobrychis viciifolia) on in vitro ruminal methane production and fermentation characteristics.

Our study investigated the effects of condensed tannins (CT) on rumen in vitro methane (CH4 ) production and fermentation characteristics by incubating lucerne in buffered rumen fluid in combination with different CT extracts at 0 (control), 40, 80 and 120 g CT/kg of substrate DM. Condensed tannins were extracted from four sainfoin accessions: Rees 'A', CPI63763, Cotswold Common and CPI63767. Gas production (GP) was measured using a fully automated GP apparatus with CH4 measured at distinct time points. Condensed tannins differed substantially in terms of polymer size and varied from 13 (Rees 'A') to 73 (CPI63767) mean degree of polymerization, but had relatively similar characteristics in terms of CT content, procyanidin: prodelphinidin (PC: PD) and cis:trans ratios. Compared to control, addition of CT from CPI63767 and CPI63763 at 80 and 120 g CT/kg of substrate DM reduced CH4 by 43% and 65%, and by 23% and 57%, respectively, after 24-h incubation. Similarly, CT from Rees 'A' and Cotswold Common reduced CH4 by 26% and 46%, and by 28% and 46% respectively. Addition of increasing level of CT linearly reduced the maximum rates of GP and CH4 production, and the estimated in vitro organic matter digestibility. There was a negative linear and quadratic (p < 0.01) relation between CT concentration and total volatile fatty acid (VFA) production. Inclusion of 80 and 120 g CT/kg of substrate DM reduced (p < 0.001) branched-chain VFA production and acetate: propionate ratio and was lowest for CPI63767. A decrease in proteolytic activity as indirectly shown by a change in VFA composition favouring a shift towards propionate and reduction in branched-chain VFA production varied with type of CT and was highest for CPI63767. In conclusion, these results suggest that tannin polymer size is an important factor affecting in vitro CH4 production which may be linked to the CT interaction with dietary substrate or microbial cells.