Atopic asthma after rhinovirus-induced wheezing is associated with DNA methylation change in the SMAD3 gene promoter.

Children with rhinovirus-induced severe early wheezing have an increased risk of developing asthma later in life. The exact molecular mechanisms for this association are still mostly unknown. To identify potential changes in the transcriptional and epigenetic regulation in rhinovirus-associated atopic or nonatopic asthma, we analyzed a cohort of 5-year-old children (n = 45) according to the virus etiology of the first severe wheezing episode at the mean age of 13 months and to 5-year asthma outcome. The development of atopic asthma in children with early rhinovirus-induced wheezing was associated with DNA methylation changes at several genomic sites in chromosomal regions previously linked to asthma. The strongest changes in atopic asthma were detected in the promoter region of SMAD3 gene at chr 15q22.33 and introns of DDO/METTL24 genes at 6q21. These changes were validated to be present also at the average age of 8 years.

Tracking of body mass index from 7 to 69 years of age.

BACKGROUND: Heavy children have an increased risk of being overweight young adults. Whether this risk remains in late adulthood is not well-understood. We investigated body mass index (BMI; kg m(-2)) tracking from childhood to late adulthood. METHODS: From the Copenhagen School Health Records Register, 72 959 men and 25 252 women born between 1930 and 1989 with BMI values at 7 and/or 13 years and as adults were included. Using a meta-regression approach, age- and sex-specific partial correlation analyses and logistic regressions were performed. RESULTS: Correlations between BMI at 7 years and young adult ages (18-19 years) were r=0.55 for men and r=0.55 for women. At late ages (60-69 years) these were r=0.28 for men and r=0.26 for women. The correlations did not differ by birth years. Compared with normal-weight 7-year-olds, overweight children had a higher odds of overweight at 18-19 years; odds ratio (OR)=14.02 (95% confidence interval (CI): 12.14-16.19) for men and 10.46 (95% CI: 4.82-22.70) for women. At ages 60-69 years ORs were 5.46 (95% CI: 0.95-31.36) for men and 1.61 (95% CI: 0.83-3.15) for women. Correlations and ORs were stronger at age 13 years than age 7 years as expected, but the overall patterns were similar. CONCLUSIONS: BMI tracking was weaker at late adult ages than at young adult ages. Although BMI tracks across the life course, childhood BMI is relatively poor at identifying later adult overweight or obesity at ages when chronic diseases generally emerge.

Association of physical workload and leisure time physical activity with incident mobility limitations: a follow-up study.

OBJECTIVES: To examine individual as well as joint associations of physical workload and leisure time physical activity with incident mobility limitations in initially well-functioning middle-aged workers. METHODS: This study is based on 6-year follow-up data of the Danish Longitudinal Study on Work, Unemployment and Health. Physical workload was reported at baseline and categorised as light, moderate or heavy. Baseline leisure time physical activity level was categorised as sedentary or active following the current recommendations on physical activity. Incidence of mobility limitations in climbing stairs and running among initially well-functioning workers (n=3202 and n=2821, respectively) was assessed during follow-up. RESULTS: Higher workload increased whereas active leisure time decreased the risk of developing mobility limitations. The incidence of limitations increased progressively with higher workload regardless of level of leisure time physical activity, although the risks tended to be higher among those with sedentary leisure time compared with their active counterparts. All in all, the risk for onset of mobility limitations was highest among those with heavy workload combined with sedentary leisure time and lowest among those with light workload combined with active leisure time. CONCLUSIONS: Although leisure time physical activity prevents development of mobility decline, high workload seems to accelerate the progression of mobility limitations among both those with active and sedentary leisure time. Therefore, efforts should be made to recommend people to engage in physical activity regardless of their physical workload.

Self-etching dental adhesive containing a natural essential oil: anti-biofouling performance and mechanical properties.

This study assessed the anti-biofouling performance of an experimental adhesive system containing a naturally occurring essential vegetable oil and examined the following physical and mechanical properties: water sorption (WS) and solubility (SL), microtensile bond strength to dentin (µTBS), and degree of conversion. The following six groups were tested: a self-etching experimental adhesive containing refined essential oil from the seeds of the Butia capitata tree (EAO); an oil-free version of the experimental adhesive (EANO); one group without adhesive as the control (C); and the three following commercial self-etching adhesives: Clearfil Protect Bond (CPB), Clearfil SE Bond, and Adper SE Plus. The antibacterial effect was estimated by microbiological culture on selective/non-selective media, and the results expressed as colony-forming units per unit weight of dry biofilm (CFU mg(-1)). The data were submitted to ANOVA and Tukey's post hoc test (α = 0.05). After 24 h, pH changes were similar in the storage medium of all tested adhesive systems. EAO showed similar levels of antimicrobial activity in a model biofilm microcosm as the commercial self-etching adhesive CPB. Both were effective against total microorganisms, aciduric bacteria, lactobacilli, and Streptococcus mutans. WS and SL were not affected by the presence of the essential oil; the values of EAO were similar to or less than those of commercial equivalents. The incorporation of an essential oil into an experimental adhesive did not influence its monomer conversion result. Immediate µTBS values of EAO and EANO were similar and were greater than those of commercial equivalents. After storage for 6 months, the µTBS of the EAO decreased significantly and became similar to the values of commercial equivalents, while the strength of the EANO was not affected.

Antifungal susceptibility, exoenzyme production and cytotoxicity of novel oximes against Candida.

Novel oximes were synthesized, their in vitro antifungal activity against Candida was evaluated and their cytotoxicity was determined. The procedure used for the synthesis of the oximes is aligned with the current green chemistry trend; water is employed as the solvent in this reaction. The minimum inhibitory and minimum fungicidal concentrations of the oximes were evaluated using the CLSI M27-A3 method. The influence of these compounds on the inhibition of the production of hydrolytic enzymes, phospholipase and proteinase by Candida was also investigated. The compounds showed a good ability to inhibit phospholipase, with a 50 % reduction in most cases. However, the tested compounds did not affect proteinase. The current results showed a substantial reduction in the phospholipase production, which suggests that compounds of this class may interfere with host infection and disease progression. The oximes examined showed lower fungicidal activities than fluconazole but interfered significantly with the expression of phospholipase. Some of the oximes included in this study could be a suitable matrix for the development of novel antifungal compounds.

Transition kinetics of mixed lipid:photosurfactant assemblies studied by time-resolved small angle X-ray scattering.

HYPOTHESIS: Photoswitchable surfactants are used in the design of many light-responsive colloids and/or self-assemblies. Photo-isomerization enables to control molecular equilibrium, and triggers transient reorganizations with possibly out-of-equilibrium intermediate states that have been overlooked. Here, we address this question by an in depth structural investigation of intermediate lipid-surfactant assemblies that occur during fast isothermal photo-triggered transition in lipid:surfactant mixtures. EXPERIMENTS: The structural parameters of mixed assemblies of azobenzene-containing cationic surfactant (AzoTMA) and dioleoylphosphatidylcholine (DOPC) lipids were studied by light scattering and time-resolved small angle X-ray scattering. Structural and compositional information about the assemblies and unimers in bulk were determined at the photostationary states, as well as at intermediate kinetic states formed during UV or blue light illumination. FINDINGS: DOPC:AzoTMA systems form mixed assemblies representative of phospholipid:cationic surfactant mixtures, that evolve from spheroid, to rod-like micelles, and vesicles with increasing DOPC fraction. Transient assemblies detected during the photo-triggered kinetics are similar to the ones found in stationary states. But changes of AzoTMA unimers in bulk can be considerably faster than mass reorganizations of the mixed assemblies, suggesting that out-of-equilibrium conditions are transiently reached. Mass reorganization of the surfactant-enriched assemblies is much faster than in the lipid enriched ones, providing insight into the role of lipids in a slow reorganization of the assemblies.

An in vitro biofilm model for enamel demineralization and antimicrobial dose-response studies.

Microcosm biofilms formed in microplates have demonstrated complex community dynamics similar to natural dental biofilm. No simplified microcosm models to evaluate enamel demineralization and dose-response effect to anticariogenic therapies have yet been established, thus this study was designed to develop a pre-clinical model fulfilling this purpose. Experiments were carried out to establish the time of biofilm formation and the sucrose concentration and exposure regimen. Biofilms were initiated from saliva and grown for up to 10 days on bovine enamel discs in 24-well plates, with a saliva analogue medium. Data were collected as pH readings and the percentage enamel surface hardness change. A dose-response evaluation was performed with chlorhexidine, which significantly affected the pH and mineral loss. Overall, the established model parameters, 5 days of biofilm growth with intermittent 1% sucrose exposure of 6 h per day, was suitable as a pre-clinical model for enamel demineralization and dose-response studies.

Associations of loneliness and social isolation with physical and mental health among adolescents and young adults.

AIMS: The present study investigates whether loneliness and social isolation are associated with poor physical and mental health among adolescents and young adults, and whether age and gender play a role in the associations of loneliness and social isolation with mental and physical health. METHODS: This study used cross-sectional self-report data from the 2017 Danish Health and Morbidity Surveys titled 'How are you?' (N = 19,890, M = 22.6 years). RESULTS: Logistic regression analyses showed that loneliness and social isolation were independently associated with poor physical and mental health. Loneliness was associated with increased odds of asthma, migraine, osteoarthritis, rheumatoid arthritis, hypertension, slipped disc/back pain, tinnitus, long-term mental illness, depressive symptomatology, anxiety symptomatology and alcohol problems. Social isolation was associated with decreased odds of having migraine, osteoarthritis and alcohol problems, and an increased risk of long-term mental illness and depressive symptomatology. Small age and gender differences were detected. CONCLUSIONS: In adolescents and young adults, loneliness and social isolation were associated with poor mental health and loneliness with poor physical health. These findings highlight the need for targeted prevention and intervention initiatives to alleviate loneliness and social isolation.

Self-rated health in individuals with and without disease is associated with multiple biomarkers representing multiple biological domains.

Self-rated health (SRH) is one of the most frequently used indicators in health and social research. Its robust association with mortality in very different populations implies that it is a comprehensive measure of health status and may even reflect the condition of the human organism beyond clinical diagnoses. Yet the biological basis of SRH is poorly understood. We used data from three independent European population samples (N approx. 15,000) to investigate the associations of SRH with 150 biomolecules in blood or urine (biomarkers). Altogether 57 biomarkers representing different organ systems were associated with SRH. In almost half of the cases the association was independent of disease and physical functioning. Biomarkers weakened but did not remove the association between SRH and mortality. We propose three potential pathways through which biomarkers may be incorporated into an individual's subjective health assessment, including (1) their role in clinical diseases; (2) their association with health-related lifestyles; and (3) their potential to stimulate physical sensations through interoceptive mechanisms. Our findings indicate that SRH has a solid biological basis and it is a valid but non-specific indicator of the biological condition of the human organism.

Human adult bone marrow-derived somatic cells rescue vision in a rodent model of retinal degeneration.

Visual impairment associated with photoreceptor degeneration is a largely untreatable condition affecting millions of people worldwide. Cellular therapies offer an attractive alternative for the treatment of retinal degeneration. Human adult bone marrow-derived somatic cells (hABM-SCs) present particular advantages for interventional therapy to the eye because they are non-immunogenic, effective at low dose, maintain a stable phenotype and secrete factors known to promote photoreceptor cell survival. Here we assess the potential of hABM-SCs (developed by Garnet BioTherapeutics) to sustain vision in a rodent model of human retinal disease-the Royal College of Surgeons (RCS) rat. A cell suspension of 5 x 10(4) cells in 2 microl carrying medium was injected into the subretinal space of RCS rats at P21, control animals received medium alone and untreated. Animals were maintained with/without oral cyclosporine A through the experimental period. Visual functions including optokinetic response (OKR) and luminance threshold recording were conducted in both cell-treated and control animals. Histological study was performed afterward to examine donor cell survival and photoreceptor rescue. OKR measured at P60 and P90 in cell-injected groups with/without immunosuppression was significantly better than controls (P<0.01). Luminance threshold recordings around P90-100 also showed much lower threshold in cell-injected eyes with best result of 0.8 log units above background (compared with 0.4 log units in wild type retina), while sham-injected and untreated eyes gave values of 2.7 and 3.5 log units respectively. Histological examination revealed that there were 3-6 layers of photoreceptors in cell-injected eyes at P100; but only one layer in sham-injected and untreated controls. There was no evidence of unwanted pathology. This study has demonstrated that a human cell product that can be manufactured under conditions acceptable for clinical use and in quantities sufficient for treating large numbers of patients can rescue photoreceptors and sustain substantial visual function when injected into the subretinal space of a rodent model for retinal degeneration. Furthermore, we have shown that achieving a therapeutic benefit does not require the cells to persist and does not require immunosuppression.

Sensitivity to antifungals by Candida spp samples isolated from cases of chronic atrophic candidiasis (CAC).

The treatment of choice for chronic atrophic candidiasis (CAC), also known as denture stomatitis, is topical antifungal therapy. This study aimed to isolate, identify, and assess the antifungal susceptibility of Candida species from mucosal sites in denture wearers with a diagnosis of CAC and determine the prevalence of associated variables. The sample consisted of 44 patients wearing complete or partial dentures who had a clinical diagnosis of CAC. Using sterile cotton swabs, specimens were collected from the oral mucosa of all patients and grown at 30ºC for 48 h in CHROMagar Candida, as a means of isolating and screening the species. The complementary identification of the species was performed using the VITEK 2 automated system (BioMérieux), as well as the determination of their susceptibility to antifungal agents. Data were analyzed using the chi-square test. STATA 13.1 was used for statistical analysis (α = 5%). Of 44 patients with CAC, 33 (75%) had lesions classified as Newton type II. Yeasts were isolated in 38 cases. The most prevalent species was Candida albicans. None of the isolates were resistant to the antifungals tested. Our findings suggest that current indications for antifungal agents are appropriate. Also, antifungal susceptibility testing and proper fungal identification can help dentists to determine the optimal course of treatment for CAC.

Plasma cell-free DNA methylation marks for episodic memory impairment: a pilot twin study.

Decline in episodic memory performance usually causes the first clinical symptoms of Alzheimer's disease. At present, Alzheimer's disease can only be diagnosed at a very late stage when neurodegeneration and cognitive impairment is already irreversible. New early disease markers are needed for earlier and more efficient Alzheimer's disease intervention. To identify early disease markers, we implemented a genome-wide bisulphite sequencing method for the analysis of plasma cell-free DNA methylation profiles and compared differences associated with episodic memory performance in Finnish twin pairs. A noticeable amount of cell-free DNA was present in plasma, however, the amounts as well as the genomic coverage of these fragments varied substantially between individuals. We found no significant markers associated with episodic memory performance in the twins' plasma cell-free DNA methylation profiles. Furthermore, our results indicate that due to the low genomic coverage of cell-free DNA fragments and the variety in these fragments between individuals, the implemented genome-wide bisulphite sequencing method is not optimal for comparing cell-free DNA methylation differences between large groups of individuals.

The impact of social relations on the incidence of severe depressive symptoms among infertile women and men.

BACKGROUND: The present study investigates anticipated support and perceived appreciation as well as perceived negative aspects of social relations as determinants of the incidence of severe depressive symptoms among women and men in unsuccessful fertility treatment. METHODS: A prospective cohort study of consecutively recruited, new couples in fertility treatment completed questionnaires immediately before initiating treatment (T1) and at 1-year follow-up (T2) (response rates 80%, 88%). The study population included 695 participants (355 women and 340 men) who had no severe depressive symptoms at T1, who had no child together at T1 and whose treatment had failed. We measured severe depressive symptoms with Mental Health Inventory 5 from Short-Form 36, functional aspects of general social relations and of infertility-specific social relations. RESULTS: Fifteen per cent of women and 6% of men in unsuccessful treatment reported severe depressive symptoms at T2. Among men, low emotional support, low appreciation and high excessive demands from the partner were significant determinants of the incidence of severe depressive symptoms. Among women and men, low appreciation from the family, many conflicts and high excessive demands from family, friends and neighbours were significant determinants of severe depressive symptoms. The analyses were controlled for gender. Duration of infertility, infertility diagnosis and socio-economic position did not confound the associations. CONCLUSIONS: More women than men report severe depressive symptoms after 1 year of unsuccessful treatment. It is important to be aware of the possible negative impact of relational strain among fertility patients in unsuccessful treatment.

Viviparity and intrauterine feeding in a new holocephalan fish from the lower carboniferous of montana.

A new species of Lower Carboniferous holocephalan chondrichthyan, Delphyodontos dacriformes, is described from two fetal specimens. The well-developed slashing and piercing dentition, enlargement of the abdominal region, and fecal material indicate the probable evolution of intrauterine oophagy and viviparity in Paleozoic Chondrichthyes.

Intermuscular Bones in Pholidophorus bechei from the Lower Lias of England.

Intermuscular bones, considered the one neomorph which decisively separates the pholidophoroids from the teleosts, have been found in a specimen of Pholidophorus bechei Agassiz, from the Lower Lias of England. It is suggested that intermuscular bones were prevalent among the pholidophoroids.

Neurofibrils and the Nauta method.

When the pretreatment stages are omitted, the Nauta method for degenerating axons stains neurofibrils. Under the electron microscope the stain is closely related to neurofilaments. When one uses the comnplete Nauta technique, the stain is specific for mnembrane structures.

Development of the rat's uncrossed retinotectal pathway and its relation to plasticity studies.

In the normal newborn rat the retinotectal pathway from each eye distributes across the whole area of both the ipsilateral and contralateral superior colliculus. Most of the ipsilateral projection retracts during the first ten postnatal days to produce the normal adult pattern, but retraction fails to occur if one eye is removed at birth.

Synaptic adjustment after deafferentation of the superior colliculus of the rat.

Eyes were removed from rats shortly after birth, when there are few formed synapses in the colliculus. It was found that synaptogenesis continues to give a near-normal ratio of terminals containing either spheroidal or flattened vesicles. After eye removal in adult rats, however, reinvasion of synaptic sites vacated by degenerate optic terminals occurs, with an incomplete return toward a normal proportion of synaptic types.

Transplanted neural tissue develops connections with host rat brain.

Superior collicular fragments transplanted from fetal to newborn rat brains develop complex internal organization and receive visual afferents from the host providing they lie sufficiently close to the host visual pathways. This system allows investigation in vivo of special affinities between cells of the mammalian central nervous system.

A Randomized Double-blind Clinical Trial of Dentin Surface Treatments for Composite Restorations in Noncarious Cervical Lesions: A 36-month Evaluation.

OBJECTIVE:: This randomized, double-blind clinical trial aimed to evaluate the influence of different dentin surface treatments in noncarious cervical lesions (NCCLs). METHODS AND MATERIALS:: Twenty-nine patients participated in this study. One hundred sixty-five NCCLs were selected and randomly assigned to three groups: G0 (control group) with phosphoric acid etching for 15 seconds; G1: phosphoric acid etching for 30 seconds; and G2: ultrasound probe applied for 30 seconds on the dentin surface. Class V composite resin restorations were performed (Z350, 3M ESPE, St Paul, MN, USA). The restorations were evaluated at baseline and at six, 12, 24, and 36 months according to the World Dental Federation criteria. Survival curves were obtained using the Kaplan-Meier method and the log-rank test. Comparisons between groups and times were performed using the McNemar and Chi-square tests (α =0.05). RESULTS:: The presence of failures due to retention was statistically different among the groups ( p=0.012), and G0 and G2 showed better clinical performance than did G1. Sensitivity decreased over time in all groups. Marginal discoloration, postoperative sensitivity, and marginal adaptation were not different among the groups ( p>0.05). CONCLUSIONS:: The studied dentin surface treatments showed similar clinical performance to the conventional technique at 36 months in terms of marginal discoloration, marginal adaptation, and postoperative sensitivity. In contrast, increased acid-etching time resulted in a higher risk of failure due to retention over time in composite Class V restorations.