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The syntheses of a series of copper(II) porphyrins and their dimers linked by palladium(II) or platinum(II) are reported. Their electronic properties and their magnetic properties were studied. In particular, the effect of the linking unit on these properties was evaluated. It was discovered that three factors influence the electronic and magnetic interactions between the two metalloporphyrins: the nature of the linking metal ion, the nature of the external coordination site of the porphyrin, and also the nature of the metal ion present in the central core of the aromatic macrocycle.

Abstract Background The aims of our study were two-fold. Firstly, to determine if there is an association between gout and OSA in a representative Australian adult population. Secondly, to explore associations between gout and patient reported sleep outcomes. Methods A cross-sectional national online survey of a representative sample of Australian adults > 18 years assessed self-reported doctor-diagnosed OSA, insomnia and patient reported sleep outcomes. Possible undiagnosed OSA was estimated using self-reported frequent loud snoring and witnessed apnoeas. Participants self-reported physician-diagnosed gout and other health conditions. Multivariable logistic regression analyses were performed for both objectives. Odds ratios with 95% confidence intervals were reported. Results There were 1948 participants of whom 126 (6.5%) had gout and 124 (6.4%) had diagnosed sleep apnoea. After adjusting for age, body mass index (BMI), sex, alcohol intake and the presence of arthritis, those with obstructive sleep apnoea diagnosed on polysomnography were twice as likely to report having gout compared to those without. (OR = 2.6, 95% CI 1.5–4.6). Additionally, participants with symptoms suggestive of sleep apnoea were also twice as likely to have gout compared to those without (OR = 2.8, 95%CI 1.6–5.1). There was also a higher likelihood of restless legs syndrome, insomnia and worry about sleep in patients with gout. Conclusion Diagnosed and suspected OSA are associated with higher likelihood of gout. Participants with gout are also more likely to report suffering from restless legs syndrome, insomnia and worry about their sleep. Given the morbidity associated with sleep problems, we should be vigilant regarding sleep health in our patients with gout.

In this study, a series of new heteroleptic copper(I) bis(diimine) complexes are described. Using one highly hindered phenanthroline ligand and a second less-hindered diimine ligand led to unexpected results. Following a two-step one-pot method to obtain heteroleptic copper(I) complexes, an almost perfect tetrahedral coordination geometry around the copper(I) ion was obtained in several cases, despite the fact that at least one ligand was not sterically encumbered near the coordination site (at the position α to the nitrogen atoms of the ligand). This was demonstrated in the solid state by resolution of crystal structures, and these findings, corroborated by calculations, showed that the non-covalent interactions between the two diimine ligands present in these complexes were governing these structural features. The electronic properties of all complexes were also determined and the fluorescence lifetimes of two complexes were compared.

Abstract: There is a conflict in the literature regarding the association between serum uric acid (SUA) levels and glycemic status. Therefore, we evaluated the association between SUA level and glycemic status - impaired fasting glucose (IFG), impaired glucose tolerance (IGT), and diabetes mellitus - and insulin resistance, in a large Brazilian study. This is a cross-sectional, observational study with 13,207 participants aged 35-74 years, at baseline (2008-2010) of the Brazilian Longitudinal Study of Adult Health (ELSA-Brasil). A multinomial regression analysis was performed to test the association between SUA and glycemic status (IFG, IGT, and newly diagnosed type 2 diabetes at the cohort baseline) after adjustments by age, sex, skin color, body mass index, physical activity, smoking, alcohol consumption, comorbidities, and medicines use. Logistic regression model was used to evaluate the association between SUA and insulin resistance by HOMA-IR. Stratified analyses by sex were performed. The mean age (standard deviation) was 51.4 (8.9) years, 55.2% of participants were women. There were 1,439 newly diagnosed diabetes. After all adjustments, higher SUA was associated with IFG, IGT, and diabetes, with odds ratio (OR) = 1.15 (95%CI: 1.06; 1.25), 1.23 (95%CI: 1.14; 1.33), and 1.37 (95%CI: 1.24; 1.51), respectively. There was association between SUA levels and insulin resistance with OR = 1.24 (95%CI: 1.13; 1.36). In analysis stratified by sex, higher SUA persisted independently associated with impaired glycemic status. Our results suggest that a higher SUA levels were significantly associated with glycemic status in a large Latin American population, mainly among women.

Background On-call research and guidance materials typically focus on ‘traditional’ on-call work (e.g., emergency services, healthcare). However, given the increasing prevalence of non-standard employment arrangements (e.g., gig work and casualisation), it is likely that a proportion of individuals who describe themselves as being on-call are not included in current on-call literature. This study therefore aimed to describe the current sociodemographic and work characteristics of Australian on-call workers. Methods A survey of 2044 adults assessed sociodemographic and work arrangements. Of this population, 1057 individuals were workforce participants, who were asked to provide information regarding any on-call work they performed over the last three months, occupation type, weekly work hours, and the presence or absence of non-standard work conditions. Results Of respondents who were working, 45.5% reported working at least one day on-call in the previous month. There was a high prevalence of on-call work in younger respondents (63.1% of participants aged 18–24 years), and those who worked multiple jobs and more weekly work hours. Additionally, high prevalence rates of on-call work were reported by machinery operators, drivers, community and personal service workers, sales workers, and high-level managers. Conclusions These data suggest that on-call work is more prevalent than previously recorded and is likely to refer to a broad set of employment arrangements. Current classification systems may therefore be inadequate for population-level research. A taxonomy for the classification of on-call work is proposed, incorporating traditional on-call work, gig economy work, relief, or unscheduled work, and out of hours work.

Objectives: To validate novel non-contacting Confocal-Laser-Scanning-Microscopy (CLSM) methodology with conventional Contacting Profilometry (CP) measures investigating brushing or dab-on of stannous-fluoride dentifrice on early aggressive dentine erosion. Methods: 75 polished human dentine samples were prepared and eroded in agitated 6% citric acid then randomly allocated into 5 intervention groups; artificial saliva control (1); controlled use of a pressure sensitive counter-rotating oscillatory powered toothbrush with sodium-fluoride NaF (2) or stannous-fluoride SnF2 (3), and dab-on application of NaF (4) or SnF2 (5). Samples underwent three cycles of intervention and 2-min agitated 6 % citric acid challenges. CLSM images were taken and 3D reconstructions produced of step height using a developed software algorithm. In addition, 20 % samples were randomised and profiled using CP to measure step height and surface roughness. Vickers's diamond micro-hardness testing was carried out on all samples. Results: Comparing CLSM and CP; Pearson correlation was 0.77 and Intra-class correlation 0.81 (p = 0.01). There were no significant statistical differences in step height between groups using both CLSM and CP. From baseline, SnF2 brushing (3) increased micro-hardness more than control (1) (p = 0.03), NaF (4) and SnF2 dab-on (5) (p ≤ 0.001), and increased surface roughness more than control (p = 0.02), NaF brushing (2) and NaF dab-on (4) (p ≤ 0.017). Dab-on of SnF2 (5) produced rougher surfaces than control (1) (p = 0.014) and reduced hardness compared with NaF brushing (p = 0.04). Conclusions: Good agreement and correlation exists between CLSM and CP measures in dentine. There were no significant differences in surface loss after interventions between groups. Compared with control, SnF2 application increased dentine surface roughness and SnF2 controlled powered brushing application increased dentine hardness, likely caused by exposure of uneroded dentine. Clinical significance: Isosurfaces produced using CLSM can be used to represent dentine step height loss. They show good correlation and agreement with conventional CP measures, following early aggressive erosion-abrasion cycles of dentine. The CLSM and computer algorithm therefore provides an accurate, standalone and non-contacting three-dimensional measurement of early dentine wear. Stannous-fluoride brushing, and dab-on application offer no benefits following early aggressive erosion in dentine. To reduce dentine wear, limiting erosive challenges and avoiding brushing post-erosion is advised.

IntroductionStudies examining potential factors of all-cause mortality comprehensively at community level are rare. Using long-term community-based follow-up study, we examined the association of sociodemographic and behavioural characteristics, metabolic and chronic conditions, and medication and health service utilisation with all-cause mortality.MethodsWe followed 4056 participants, aged 18–90 years, for 18 years in the North West Adelaide Health Study (NWAHS). Mortality data were obtained from South Australian (SA) public hospitals and registries including SA births, deaths and marriages, the National Death Index and the NWAHS follow-up. Predictors of all-cause mortality were explored using Cox proportional hazard model, adjusting for potential confounders. We performed subgroup analyses by sex and age.ResultsMean (SD) age at baseline was 50.4 (16.4) years. Less than half (47.8%) of the participants were men. A total of 64 689.7 person-years from 4033 participants with 18.7 years of follow-up were generated. The median follow-up time was 17.7 years; 614 deaths were recorded. The overall crude death rate was 9.6 (95% CI 8.9 to 10.4) per 1000 person-years. After adjusting for potential confounders, a reduced risk of mortality was significantly associated with being separated or divorced, being in the highest Socioeconomic Indexes for Areas quintile, engaging in moderate exercise, being overweight (body mass index: 25.0–29.9 kg/m2) and per 10% increase in per cent predicted forced expiratory volume in 1 s. We found that the most important predictors of all-cause mortality were sociodemographic and behavioural characteristics. Sociodemographic factors were more important predictors of all-cause mortality in young age bracket compared with older people.ConclusionsSocioeconomic factors were found to be the most important predictors of all-cause mortality. The study highlights the need to address the social inequalities and strengthen behavioural interventions for different subgroups of population to prevent premature deaths.

The crypts of the intestinal epithelium house the stem cells that ensure the continual renewal of the epithelial cells that line the intestinal tract. Crypt number increases by a process called crypt fission, the division of a single crypt into two daughter crypts. Fission drives normal tissue growth and maintenance. Correspondingly, it becomes less frequent in adulthood. Importantly, fission is reactivated to drive adenoma growth. The mechanisms governing fission are poorly understood. However, only by knowing how normal fission operates can cancer-associated changes be elucidated. We studied normal fission in tissue in three dimensions using high-resolution imaging and used intestinal organoids to identify underlying mechanisms. We discovered that both the number and relative position of Paneth cells and Lgr5+ cells are important for fission. Furthermore, the higher stiffness and increased adhesion of Paneth cells are involved in determining the site of fission. Formation of a cluster of Lgr5+ cells between at least two Paneth-cell-rich domains establishes the site for the upward invagination that initiates fission.

SUMMARY Nonsense mutations that result in the expression of truncated, N-terminal, fragments of the adenomatous polyposis coli (APC) tumour suppressor protein are found in most sporadic and some hereditary colorectal cancers. These mutations can cause tumorigenesis by eliminating β-catenin-binding sites from APC, which leads to upregulation of β-catenin and thereby results in the induction of oncogenes such as MYC. Here we show that, in three distinct experimental model systems, expression of an N-terminal fragment of APC (N-APC) results in loss of directionality, but not speed, of cell motility independently of changes in β-catenin regulation. We developed a system to culture and fluorescently label live pieces of gut tissue to record high-resolution three-dimensional time-lapse movies of cells in situ. This revealed an unexpected complexity of normal gut cell migration, a key process in gut epithelial maintenance, with cells moving with spatial and temporal discontinuity. Quantitative comparison of gut tissue from wild-type mice and APC heterozygotes (APCMin/+; multiple intestinal neoplasia model) demonstrated that cells in precancerous epithelia lack directional preference when moving along the crypt-villus axis. This effect was reproduced in diverse experimental systems: in developing chicken embryos, mesoderm cells expressing N-APC failed to migrate normally; in amoeboid Dictyostelium, which lack endogenous APC, expressing an N-APC fragment maintained cell motility, but the cells failed to perform directional chemotaxis; and multicellular Dictyostelium slug aggregates similarly failed to perform phototaxis. We propose that N-terminal fragments of APC represent a gain-of-function mutation that causes cells within tissue to fail to migrate directionally in response to relevant guidance cues. Consistent with this idea, crypts in histologically normal tissues of APCMin/+ intestines are overpopulated with cells, suggesting that a lack of migration might cause cell accumulation in a precancerous state.

Robert J Adams1, Sarah L Appleton1, Antonia Cole2, Tiffany K Gill3, Anne W Taylor3, Catherine L Hill11The Health Observatory, 2Rheumatology Unit, 3Population Research and Outcomes Unit, SA Health, The University of Adelaide Discipline of Medicine, Queen Elizabeth Hospital, Woodville, AustraliaObjectives: To determine whether chronic conditions and patient factors, such as risk perception and decision-making preferences, are associated with complementary medicine and alternative practitioner use in a representative longitudinal population cohort.Participants and setting: Analysis of data from Stage 2 of the North West Adelaide Health Study of 3161 adults who attended a study clinic visit in 2004–2006. The main outcome measures were the medications brought by participants to the study clinic visit, chronic health conditions, attitudes to risk, levels of satisfaction with conventional medicine, and preferred decision-making style.Results: At least one oral complementary medicine was used by 27.9% of participants, and 7.3% were visiting alternative practitioners (naturopath, osteopath). Oral complementary medicine use was significantly associated with arthritis, osteoporosis, and mental health conditions, but not with other chronic conditions. Any pattern of complementary medicine use was generally significantly associated with female gender, age at least 45 years, patient-driven decision-making preferences (odds ratio [OR] 1.38, 95% confidence interval [CI]: 1.08–1.77), and frequent general practitioner visits (>five per year; OR 3.62, 95% CI: 2.13–6.17). Alternative practitioner visitors were younger, with higher levels of education (diploma/trade [OR 1.88, 95% CI: 1.28–2.76], bachelor’s degree [OR 1.77, 95% CI: 1.11–2.82], income > $80,000 (OR 2.28, 95% CI: 1.26–4.11), female gender (OR 3.15, 95% CI: 2.19–4.52), joint pain not diagnosed as arthritis (OR 1.68, 95% CI: 1.17–2.41), moderate to severe depressive symptoms (OR 2.15, 95% CI: 1.04–4.46), and risk-taking behavior (3.26, 1.80–5.92), or low-to-moderate risk aversion (OR 2.08, 95% CI: 1.26–4.11).Conclusion: Although there is widespread use of complementary medicines in the Australian community, there are differing patterns of use between those using oral complementary medicines and those using alternative practitioners.Keywords: complementary medicine, chronic disease, risk attitudes, population study

Biomedical research and drug development increasingly involve the extraction of quantitative data from digital microscope images, such as those obtained using fluorescence microscopy. Here, we describe a novel approach for both managing and analyzing such images. The Open Microscopy Environment (OME) is a sophisticated open-source scientific image management database that coordinates the organization, storage, and analysis of the large volumes of image data typically generated by modern imaging methods. We describe FindSpots, a powerful image-analysis package integrated in OME that will be of use to those who wish to identify and measure objects within microscope images or time-lapse movies. The algorithm used in FindSpots is in fact only one of many possible segmentation (object detection) algorithms, and the underlying data model used by OME to capture and store its results can also be used to store results from other segmentation algorithms. In this report, we illustrate how image segmentation can be achieved in OME using one such implementation of a segmentation algorithm, and how this output subsequently can be displayed graphically or processed numerically using a spreadsheet.

Studies on long-term exposure to foods/nutrients and its associations with fracture risk are scarce. Using data from the China Health and Nutrition Survey (CHNS), we determined the prospective association of dietary and nutrient patterns with fractures. Data from 15,572 adults aged ≥18 years were analyzed. Fracture occurrence was self-reported and dietary intake data were collected using a 24-h recall method for three consecutive days, for each individual across nine waves (1989–2011). We used cumulative and overall mean, recent and baseline dietary and nutrient exposures. Hazard ratios (HR) were used to determine the associations. Two dietary (traditional and modern) and two nutrient (plant- and animal-sourced) patterns were identified. After adjusting for potential confounders, study participants in the third tertiles (highest intake) of the modern dietary and animal-sourced nutrient patterns’ cumulative scores had a 34% (HR = 1.34; 95% CI: 1.06–1.71) and 37% (HR = 1.37; 95% CI: 1.08–1.72) increase in fracture risks compared to those in the first tertiles, respectively. While the overall mean factor scores of dietary and nutrient patterns had a similar (or stronger) pattern of association as the cumulative scores, no association between recent and baseline scores and fracture was found. Greater adherence to a modern dietary and/or an animal-sourced nutrient pattern is associated with a higher risk of total fractures. This suggests that a modern animal based diet is related to bone fragility. A repeated three-day 24-h recall dietary assessment provides a stronger association with fracture compared to a recent or baseline exposure.

Laboratory studies have demonstrated that experimental manipulations of oral processing can have a marked effect on energy intake. Here, we explored whether variations in oral processing across a range of unmodified everyday meals could affect post-meal fullness and meal size. In Study 1, female participants (N = 12) attended the laboratory over 20 lunchtime sessions to consume a 400-kcal portion of a different commercially available pre-packaged meal. Prior to consumption, expected satiation was assessed. During each meal, oral processing was characterised using: (i) video-recordings of the mouth and (ii) real-time measures of plate weight. Hunger and fullness ratings were elicited pre- and post-consumption, and for a further three hours. Foods that were eaten slowly had higher expected satiation and delivered more satiation and satiety. Building on these findings, in Study 2 we selected two meals (identical energy density) from Study 1 that were equally liked but maximised differences in oral processing. On separate days, male and female participants (N = 24) consumed a 400-kcal portion of either the “fast” or “slow” meal followed by an ad libitum meal (either the same food or a dessert). When continuing with the same food, participants consumed less of the slow meal. Further, differences in food intake during the ad libitum meal were not compensated at a subsequent snacking opportunity an hour later. Together, these findings suggest that variations in oral processing across a range of unmodified everyday meals can affect fullness after consuming a fixed portion and can also impact meal size. Modifying food form to encourage increased oral processing (albeit to a lesser extent than in experimental manipulations) might represent a viable target for food manufacturers to help to nudge consumers to manage their weight.

The role of the basement membrane is vital in maintaining the integrity and structure of an epithelial layer, acting as both a mechanical support and forming the physical interface between epithelial cells and the surrounding connective tissue. The function of this membrane is explored here in the context of the epithelial monolayer that lines the colonic crypt, test-tube shaped invaginations that punctuate the lining of the intestine and coordinate a regular turnover of cells to replenish the epithelial layer every few days. To investigate the consequence of genetic mutations that perturb the system dynamics and can lead to colorectal cancer, it must be possible to track the emerging tissue level changes that arise in the crypt. To that end, a theoretical crypt model with a realistic, deformable geometry is required. A new discrete crypt model is presented, which focuses on the interaction between cell- and tissue-level behaviour, while incorporating key subcellular components. The model contains a novel description of the role of the surrounding tissue and musculature, based upon experimental observations of the tissue structure of the crypt, which are also reported. A two-dimensional (2D) cross-sectional geometry is considered, and the shape of the crypt is allowed to evolve and deform. Simulation results reveal how the shape of the crypt may contribute mechanically to the asymmetric division events typically associated with the stem cells at the base. The model predicts that epithelial cell migration may arise due to feedback between cell loss at the crypt collar and density-dependent cell division, an hypothesis which can be investigated in a wet lab. This work forms the basis for investigation of the deformation of the crypt structure that can occur due to proliferation of cells exhibiting mutant phenotypes, experiments that would not be possible in vivo or in vitro.

Blue oaks were planted on a Tuolumne County hardwood rangeland site to assess low-input, low-cost regeneration technology on seedling establishment. After three growing seasons, approximately 22% of the planting spots had a surviving seedling. Costs ranged from $1.88 to $32.58 per surviving tree.