Genetics, epigenetics, and environment may together affect the susceptibility for type 2 diabetes (T2D). Our aim was to dissect molecular mechanisms underlying T2D using genome-wide expression and ...DNA methylation data in adipose tissue from monozygotic twin pairs discordant for T2D and independent case-control cohorts. In adipose tissue from diabetic twins, we found decreased expression of genes involved in oxidative phosphorylation; carbohydrate, amino acid, and lipid metabolism; and increased expression of genes involved in inflammation and glycan degradation. The most differentially expressed genes included ELOVL6, GYS2, FADS1, SPP1 (OPN), CCL18, and IL1RN. We replicated these results in adipose tissue from an independent case-control cohort. Several candidate genes for obesity and T2D (e.g., IRS1 and VEGFA) were differentially expressed in discordant twins. We found a heritable contribution to the genome-wide DNA methylation variability in twins. Differences in methylation between monozygotic twin pairs discordant for T2D were subsequently modest. However, 15,627 sites, representing 7,046 genes including PPARG, KCNQ1, TCF7L2, and IRS1, showed differential DNA methylation in adipose tissue from unrelated subjects with T2D compared with control subjects. A total of 1,410 of these sites also showed differential DNA methylation in the twins discordant for T2D. For the differentially methylated sites, the heritability estimate was 0.28. We also identified copy number variants (CNVs) in monozygotic twin pairs discordant for T2D. Taken together, subjects with T2D exhibit multiple transcriptional and epigenetic changes in adipose tissue relevant to the development of the disease.
The bulk-filling of deep, wide dental cavities is faster and easier than traditional incremental restoration. However, the extent of cure at the bottom of the restoration should be carefully examined ...in combination with the polymerization contraction and gap formation that occur during the restorative procedure. The aim of this study, therefore, was to compare the depth of cure, polymerization contraction, and gap formation in bulk-fill resin composites with those of a conventional resin composite. To achieve this, the depth of cure was assessed in accordance with the International Organization for Standardization 4049 standard, and the polymerization contraction was determined using the bonded-disc method. The gap formation was measured at the dentin margin of Class II cavities. Five bulk-fill resin composites were investigated: two high-viscosity (Tetric EvoCeram Bulk Fill, SonicFill) and three low-viscosity (x-tra base, Venus Bulk Fill, SDR) materials. Compared with the conventional resin composite, the high-viscosity bulk-fill materials exhibited only a small increase (but significant for Tetric EvoCeram Bulk Fill) in depth of cure and polymerization contraction, whereas the low-viscosity bulk-fill materials produced a significantly larger depth of cure and polymerization contraction. Although most of the bulk-fill materials exhibited a gap formation similar to that of the conventional resin composite, two of the low-viscosity bulk-fill resin composites, x-tra base and Venus Bulk Fill, produced larger gaps.
For millions of years, our resident microbes have coevolved and coexisted with us in a mostly harmonious symbiotic relationship. We are not distinct entities from our microbiome, but together we form ...a 'superorganism' or holobiont, with the microbiome playing a significant role in our physiology and health. The mouth houses the second most diverse microbial community in the body, harbouring over 700 species of bacteria that colonise the hard surfaces of teeth and the soft tissues of the oral mucosa. Through recent advances in technology, we have started to unravel the complexities of the oral microbiome and gained new insights into its role during both health and disease. Perturbations of the oral microbiome through modern-day lifestyles can have detrimental consequences for our general and oral health. In dysbiosis, the finely-tuned equilibrium of the oral ecosystem is disrupted, allowing disease-promoting bacteria to manifest and cause conditions such as caries, gingivitis and periodontitis. For practitioners and patients alike, promoting a balanced microbiome is therefore important to effectively maintain or restore oral health. This article aims to give an update on our current knowledge of the oral microbiome in health and disease and to discuss implications for modern-day oral healthcare.
Trophic rewilding is an ecological restoration strategy that uses species introductions to restore top-down trophic interactions and associated trophic cascades to promote self-regulating biodiverse ...ecosystems. Given the importance of large animals in trophic cascades and their widespread losses and resulting trophic downgrading, it often focuses on restoring functional megafaunas. Trophic rewilding is increasingly being implemented for conservation, but remains controversial. Here, we provide a synthesis of its current scientific basis, highlighting trophic cascades as the key conceptual framework, discussing the main lessons learned from ongoing rewilding projects, systematically reviewing the current literature, and highlighting unintentional rewilding and spontaneous wildlife comebacks as underused sources of information. Together, these lines of evidence show that trophic cascades may be restored via species reintroductions and ecological replacements. It is clear, however, that megafauna effects may be affected by poorly understood trophic complexity effects and interactions with landscape settings, human activities, and other factors. Unfortunately, empirical research on trophic rewilding is still rare, fragmented, and geographically biased, with the literature dominated by essays and opinion pieces. We highlight the need for applied programs to include hypothesis testing and science-based monitoring, and outline priorities for future research, notably assessing the role of trophic complexity, interplay with landscape settings, land use, and climate change, as well as developing the global scope for rewilding and tools to optimize benefits and reduce human–wildlife conflicts. Finally, we recommend developing a decision framework for species selection, building on functional and phylogenetic information and with attention to the potential contribution from synthetic biology.
Reduced intake of n-3 long-chain polyunsaturated fatty acids (LCPUFAs) may be a contributing factor to the increasing prevalence of wheezing disorders. We assessed the effect of supplementation with ...n-3 LCPUFAs in pregnant women on the risk of persistent wheeze and asthma in their offspring.
We randomly assigned 736 pregnant women at 24 weeks of gestation to receive 2.4 g of n-3 LCPUFA (fish oil) or placebo (olive oil) per day. Their children formed the Copenhagen Prospective Studies on Asthma in Childhood
(COPSAC
) cohort and were followed prospectively with extensive clinical phenotyping. Neither the investigators nor the participants were aware of group assignments during follow-up for the first 3 years of the children's lives, after which there was a 2-year follow-up period during which only the investigators were unaware of group assignments. The primary end point was persistent wheeze or asthma, and the secondary end points included lower respiratory tract infections, asthma exacerbations, eczema, and allergic sensitization.
A total of 695 children were included in the trial, and 95.5% completed the 3-year, double-blind follow-up period. The risk of persistent wheeze or asthma in the treatment group was 16.9%, versus 23.7% in the control group (hazard ratio, 0.69; 95% confidence interval CI, 0.49 to 0.97; P=0.035), corresponding to a relative reduction of 30.7%. Prespecified subgroup analyses suggested that the effect was strongest in the children of women whose blood levels of eicosapentaenoic acid and docosahexaenoic acid were in the lowest third of the trial population at randomization: 17.5% versus 34.1% (hazard ratio, 0.46; 95% CI, 0.25 to 0.83; P=0.011). Analyses of secondary end points showed that supplementation with n-3 LCPUFA was associated with a reduced risk of infections of the lower respiratory tract (31.7% vs. 39.1%; hazard ratio, 0.75; 95% CI, 0.58 to 0.98; P=0.033), but there was no statistically significant association between supplementation and asthma exacerbations, eczema, or allergic sensitization.
Supplementation with n-3 LCPUFA in the third trimester of pregnancy reduced the absolute risk of persistent wheeze or asthma and infections of the lower respiratory tract in offspring by approximately 7 percentage points, or one third. (Funded by the Lundbeck Foundation and others; ClinicalTrials.gov number, NCT00798226 .).
Internationally, older patients (≥65 years) account for more than 40% of acute admissions. Older patients admitted to the emergency department (ED) are frequently malnourished and exposed to ...inappropriate medication prescribing, due in part to the inaccuracy of creatinine-based equations for estimated glomerular filtration rate (eGFR). The overall aims of this trial are to investigate: (1) the efficacy of a medication review (MED intervention) independent of nutritional status, (2) the accuracy of eGFR equations based on various biomarkers compared to measured GFR (mGFR) based on
Technetium-diethylenetriaminepentaacetic acid plasma clearance, and (3) the efficacy of an individualized multimodal and transitional nutritional intervention (MULTI-NUT-MED intervention) in older patients with or at risk of malnutrition in the ED.
The trial is a single-center block randomized, controlled, observer-blinded, superiority and explorative trial with two parallel groups. The population consists of 200 older patients admitted to the ED: 70 patients without malnutrition or risk of malnutrition and 130 patients with or at risk of malnutrition defined as a Mini Nutritional Assessment-Short Form score ≤11. All patients without the risk of malnutrition receive the MED intervention, which consists of a medication review by a pharmacist and geriatrician in the ED. Patients with or at risk of malnutrition receive the MULTI-NUT-MED intervention, which consists of the MED intervention in addition to, dietary counseling and individualized interventions based on the results of screening tests for dysphagia, problems with activities of daily living, low muscle strength in the lower extremities, depression, and problems with oral health. Baseline data are collected upon study inclusion, and follow-up data are collected at 8 and 16 weeks after discharge. The primary outcomes are (1) change in medication appropriateness index (MAI) score from baseline to 8 weeks after discharge, (2) accuracy of different eGFR equations compared to mGFR, and (3) change in health-related quality of life (measured with EuroQol-5D-5L) from baseline to 16 weeks after discharge.
The trial will provide new information on strategies to optimize the treatment of malnutrition and inappropriate medication prescribing among older patients admitted to the ED.
ClinicalTrials.gov NTC03741283 . Retrospectively registered on 14 November 2018.
A family history of schizophrenia is the strongest single indicator of individual schizophrenia risk. Bipolar affective disorder and schizo-affective disorders have been documented to occur more ...frequently in parents and siblings of schizophrenia patients, but the familial occurrence of the broader range of mental illnesses and their role as confounders have not been studied in large population-based samples.
All people born in Denmark between 1955 and 1991 (1.74 million) were followed for the development of schizophrenia (9324 cases) during 28 million person-years at risk. Information of schizophrenia in cohort members and psychiatric history in parents and siblings was established through linkage with the Danish Psychiatric Central Register. Data were analysed using log-linear Poisson regression.
Schizophrenia was, as expected, strongly associated with schizophrenia and related disorders among first-degree relatives. However, almost any other psychiatric disorder among first-degree relatives increased the individual's risk of schizophrenia. The population attributable risk associated with psychiatric family history in general was 27.1% whereas family histories including schizophrenia only accounted for 6.0%. The general psychiatric family history was a confounder of the association between schizophrenia and urbanization of place of birth.
Clinically diagnosed schizophrenia is associated with a much broader range of mental disorders in first-degree relatives than previously reported. This may suggest risk haplotypes shared across many disorders and/or shared environmental factors clustering in families. Failure to take the broad range of psychiatric family history into account may bias results of all risk-factor studies of schizophrenia.
The large-scale magnetic fields detected at the surface of about 10% of hot stars extend into the stellar interior, where they may alter the structure. Deep inner regions of stars are only observable ...using asteroseismology. Here, we investigate the pulsating magnetic B3.5V star HD 43317, infer its interior properties and assess whether the dipolar magnetic field with a surface strength of Bp = 1312 ± 332 G causes different properties compared to those of non-magnetic stars. We analyze the latest version of the star’s 150 d CoRoT light curve and extract 35 significant frequencies, 28 of which are found to be independent and not related to the known surface rotation period of Prot = 0.897673 d. We perform forward seismic modeling based on non-magnetic, non-rotating 1D MESA models and the adiabatic module of the pulsation code GYRE, using a grid-based approach. Our aim was to estimate the stellar mass, age, and convective core overshooting. The GYRE calculations were done for uniform rotation with Prot. This modeling is able to explain 16 of the 28 frequencies as gravity modes belonging to retrograde modes with (ℓ, m) = (1, −1) and (2, −1) period spacing patterns and one distinct prograde (2, +2) mode. The modeling resulted in a stellar mass M⋆ = 5.8−0.2+0.1 M⊙ M ⋆ = 5.8 − 0.2 + 0.1 M ⊙ $ M_\star=5.8_{-0.2}^{+0.1}M_\odot $ , a central hydrogen mass fraction Xc = 0.54−0.02+0.01 X c = 0.54 − 0.02 + 0.01 $ X_c=0.54_{-0.02}^{+0.01} $ , and exponential convective core overshooting parameter fov = 0.004−0.002+0.014 f ov = 0.004 − 0.002 + 0.014 $ f_\text{ov}=0.004_{-0.002}^{+0.014} $ . The low value for fov is compatible with the suppression of near-core mixing due to a magnetic field but the uncertainties are too large to pinpoint such suppression as the sole physical interpretation. We assess the frequency shifts of pulsation modes caused by the Lorentz and the Coriolis forces and find magnetism to have a lower impact than rotation for this star. Including magnetism in future pulsation computations would be highly relevant to exploit current and future photometric time series spanning at least one year, such as those assembled by the Kepler space telescope and expected from the TESS (Continuous Viewing Zone) and PLATO space missions.
Salivary secretion in health and disease Pedersen, A. M. L.; Sørensen, C. E.; Proctor, G. B. ...
Journal of oral rehabilitation,
September 2018, Letnik:
45, Številka:
9
Journal Article
Recenzirano
Odprti dostop
Summary
Saliva is a complex fluid produced by 3 pairs of major salivary glands and by hundreds of minor salivary glands. It comprises a large variety of constituents and physicochemical properties, ...which are important for the maintenance of oral health. Saliva not only protects the teeth and the oropharyngeal mucosa, it also facilitates articulation of speech, and is imperative for mastication and swallowing. Furthermore, saliva plays an important role in maintaining a balanced microbiota. Thus, the multiple functions provided by saliva are essential for proper protection and functioning of the body as a whole and for the general health. A large number of diseases and medications can affect salivary secretion through different mechanisms, leading to salivary gland dysfunction and associated oral problems, including xerostomia, dental caries and fungal infections. The first part of this review article provides an updated insight into our understanding of salivary gland structure, the neural regulation of salivary gland secretion, the mechanisms underlying the formation of saliva, the various functions of saliva and factors that influence salivary secretion under normal physiological conditions. The second part focuses on how various diseases and medical treatment including commonly prescribed medications and cancer therapies can affect salivary gland structure and function. We also provide a brief insight into how to diagnose salivary gland dysfunction.
Context. The evolution of stars born with a convective core is highly dependent on the efficiency and extent of near core mixing processes, which effectively increases both the core mass and ...main-sequence lifetime. These mixing processes remain poorly constrained and therefore result in large uncertainties in the stellar structure and evolution models of such stars. Aims. We investigate to what extent gravity-mode period spacings in slowly pulsating B-type stars observed by the Kepler mission can be used to constrain both the shape and extent of convective core overshoot and additional mixing in the radiative envelope. Methods. We compute grids of 1D stellar structure and evolution models for two different shapes of convective core overshooting and three shapes of radiative envelope mixing. The models in these grids are compared to a set of benchmark models to evaluate their capability of mimicking the dipole prograde g-modes of the benchmark models. Results. Through our model comparisons we find that at a central hydrogen content of Xc = 0.5, dipole prograde g-modes in the period range 0.8−3 d are capable of differentiating between step and exponential diffusive overshooting. This ability disappears towards the terminal age main sequence at X c = 0.1. Furthermore, the g-modes behave the same for the three different shapes of radiative envelope mixing considered. However, a constant envelope mixing requires a diffusion coefficient near the convective core five times higher than chemical mixing from internal gravity waves to obtain a surface nitrogen excess of ~ 0.5 dex within the main-sequence lifetime. Conclusions. Within the estimated frequency errors of the Kepler mission, the ability of g-modes to distinguish between step and exponential diffusive overshooting depends on the evolutionary stage. Combining information from the average period spacing and observed surface abundances, notably nitrogen, could potentially be used to constrain the shape of mixing in the radiative envelope of massive stars.