Maternal vitamin D status in pregnancy and molar incisor hypomineralisation and hypomineralised second primary molars in the offspring at 7-9 years of age: a longitudinal study.

PURPOSE: The study aimed to investigate associations between maternal vitamin D status during pregnancy and molar incisor hypomineralisation (MIH) and hypomineralised second primary molars (HSPM) among children. METHODS: The study had a longitudinal design using prospectively collected data from 176 mother and child pairs. Mothers were initially recruited in a randomised controlled trial to assess a pregnancy exercise programme. Along with the 7-year follow-up, we invited the children to a dental examination. The exposure variable was maternal serum 25-hydroxyvitamin D in gestational weeks 18-22 and 32-36, categorised as insufficient (< 50 nmol/l) and sufficient (≥ 50 nmol/l). Negative binomial hurdle models were used to analyse potential associations between the exposure variables and MIH or HSPM. The models were adjusted for potential confounders. RESULTS: Among the children (7-9 years old), 32% and 22% had at least one tooth with MIH or HSPM, respectively. A significant association was found between insufficient maternal vitamin D measured in gestational weeks 18-22 and the number of affected teeth among those with MIH at 7-9 years (adjusted RR = 1.82, 95% CI 1.13-2.93). CONCLUSION: Considering any limitations of the present study, it has been shown that insufficient maternal serum vitamin D at mid-pregnancy was associated with a higher number of affected teeth among the offspring with MIH at 7-9 years of age. Further prospective studies are needed to investigate whether this finding is replicable and to clarify the role of maternal vitamin D status during pregnancy and MIH, as well as HSPM, in children.

Parents' experiences of participating in health-promoting activities at a family centre for preschool children in Sweden.

In Sweden, the family centre is a meeting place for families in a neighbourhood. It is a place for families to meet and exchange experiences and is a confidence-filled place for preschool children to play and develop. The staff at the family centre collaborate on early prevention strategies to promote health. Since 2014, the Public Dental Health Service in Södra Ryd, Skövde, has been a collaborative partner with the family centre. OBJECTIVES: To explore and describe the parents' experiences of participating in health-promoting activities at the family centre. BASIC RESEARCH DESIGN: A qualitative design based on interviews, analysed using a phenomenograpic approach. PARTICIPANTS: Six focus groups with two to six participants in each group. RESULTS: Three themes, all describing parents' experiences of visiting the family centre, emerged in the analysis. The themes were as follows; "Social fellowship", "A secure place" and "A learning environment". Each theme contained three categories, which represent the parents' different conceptions. CONCLUSIONS: The present study showed that the parents who visit the family centre found that the collaboration is perceived as positive and has many benefits. The participants found that the family centre is an institution that increases social interaction. Furthermore, meeting dental professionals in an arena outside the clinic creates confidence and makes people feel secure. Parents also learn both from the staff and from each other. According to these findings, the family centre is a suitable arena to work on health-promotion activities.

Vitamin D and stress urinary incontinence in pregnancy: a cross-sectional study.

OBJECTIVE: To assess the association between levels of vitamin D and urinary incontinence (UI) in pregnancy. DESIGN: A cross-sectional study. Secondary analysis of a randomised controlled trial. SETTING: Two university hospitals in Norway. POPULATION: A total of 851 healthy, pregnant women >18 years in gestational weeks 18-22 with a singleton live fetus. METHODS: Data on UI were collected from a questionnaire at inclusion and serum analysis of 25-hydroxy vitamin D (25(OH)D) was performed. Univariable and multivariable logistic regression analyses were applied to study associations between exposure and outcomes. MAIN OUTCOME MEASURES: Prevalence of self-reported UI, stress (SUI) and urge (UUI) or mixed UI. RESULTS: In total, 230/851 (27%) of the participants were vitamin D insufficient (25(OH)D <50 nmol/l) and 42% reported to have any UI. Women with 25(OH)D <50 nmol/l were more likely to report any UI (P = 0.03) and SUI (P < 0.01) compared with women with 25(OH)D ≥50 nmol/l. In a univariable logistic regression analysis, serum levels of 25(OH)D <50 nmol/l was associated with increased risk of any UI (odds ratio [OR] 1.5 with 95% CI 1.0-2.1), SUI only (OR 1.7, 95% CI 1.2-2.4), but not mixed UI or UUI only (OR 0.8, 95% CI 0.5-1.5). In a multivariable logistic regression model, serum levels of 25(OH)D <50 nmol/l were associated with a higher risk of experiencing SUI only (OR 1.5, 95% CI 1.1-2.2). CONCLUSIONS: Serum 25(OH)D <50 nmol/l was associated with increased risk of any UI, and SUI in particular. TWEETABLE ABSTRACT: Low levels of vitamin D are associated with increased risk of urinary incontinence in pregnancy.

Quasi-Herglotz functions and convex optimization.

We introduce the set of quasi-Herglotz functions and demonstrate that it has properties useful in the modelling of non-passive systems. The linear space of quasi-Herglotz functions constitutes a natural extension of the convex cone of Herglotz functions. It consists of differences of Herglotz functions and we show that several of the important properties and modelling perspectives are inherited by the new set of quasi-Herglotz functions. In particular, this applies to their integral representations, the associated integral identities or sum rules (with adequate additional assumptions), their boundary values on the real axis and the associated approximation theory. Numerical examples are included to demonstrate the modelling of a non-passive gain medium formulated as a convex optimization problem, where the generating measure is modelled by using a finite expansion of B-splines and point masses.

Inhalation toxicity profiles of particulate matter: a comparison between brake wear with other sources of emission.

Objective: There is substantial evidence that exposure to airborne particulate matter (PM) from road traffic is associated with adverse health outcomes. Although it is often assumed to be caused by vehicle exhaust emissions such as soot, other components may also contribute to detrimental effects. The toxicity of fine PM (PM2.5; <2.5 µm mass median aerodynamic diameter) released from brake pads was compared to PM from other sources. Materials and methods: PM2.5 of different types of brake pads (low-metallic, semi-metallic, NAO and ECE-NAO hybrid), tires and road pavement, poultry as well as the combustion of diesel fuel and wood (modern and old-fashioned stove technologies) were collected as suspensions in water. These were subsequently aerosolized for inhalation exposures. Female BALB/cOlaHsd mice were exposed for 1.5, 3, or 6 hours by nose-only inhalation up to 9 mg/m3. Results: Neither cytotoxicity nor oxidative stress was observed after exposure to any of the re-aerosolized PM2.5 samples. Though, at similar PM mass concentrations the potency to induce inflammatory responses was strongly dependent on the emission source. Exposure to most examined PM2.5 sources provoked inflammation including those derived from the poultry farm, wear emissions of the NAO and ECE-NAO hybrid brake pads as well as diesel and wood combustion, as indicated by neutrophil chemoattractant, KC and MIP-2 and lung neutrophil influx. Discussion and conclusions: Our study revealed considerable variability in the toxic potency of brake wear particles. Understanding of sources that are most harmful to health can provide valuable information for risk management strategies and could help decision-makers to develop more targeted air pollution regulation.

Signal, noise and resolution in linear and nonlinear structured-illumination microscopy.

Structured-illumination microscopy allows widefield fluorescence imaging with resolution beyond the classical diffraction limit. Its linear form extends resolution by a factor of two, and its nonlinear form by an in-principle infinite factor, the effective resolution in practice being determined by noise. In this paper, we analyse the noise properties and achievable resolution of linear and nonlinear 1D and 2D patterned SIM from a frequency-space perspective. We develop an analytical theory for a general case of linear or nonlinear fluorescent imaging, and verify the analytical calculations with numerical simulation for a special case where nonlinearity is produced by photoswitching of fluorescent labels. We compare the performance of two alternative implementations, using either two-dimensional (2D) illumination patterns or sequentially rotated one-dimensional (ID) patterns. We show that 1D patterns are advantageous in the linear case, and that in the nonlinear case 2D patterns provide a slight signal-to-noise advantage under idealised conditions, but perform worse than 1D patterns in the presence of nonswitchable fluorescent background. LAY DESCRIPTION: Structured-illumination microscopy (SIM) is a high-resolution light microscopy technique that allows imaging of fluorescence at a resolution about twice the classical diffraction limit. There are various ways that the illumination can be structured, but it is not obvious how the choice of illumination pattern affects the final image quality, especially in view of the noise. We present a detailed performance analysis considering two illumination techniques: sequential illumination with line-gratings that are shifted and rotated during image acquisition and two-dimensional (2D) illumination structures requiring only shift operations. Our analysis is based on analytical theory, supported by simulations of images considering noise. We also extend our analysis to a nonlinear variant of SIM, with which enhanced resolution can be achieved, limited only by noise. This includes nonlinear SIM based on the light-induced switching of the fluorescent molecules between a bright and a dark state. We find sequential illumination with line-gratings to be advantageous in ordinary (linear) SIM, whereas 2D patterns provides a slight signal-to-noise advantage under idealised conditions in nonlinear SIM if there is no nonswitching background.

Novel Genetic Variants in BAG3 and TNNT2 in a Swedish Family with a History of Dilated Cardiomyopathy and Sudden Cardiac Death.

Familial dilated cardiomyopathy is a rare cause of dilated cardiomyopathy (DCM), especially in childhood. Our aim was to describe the clinical course and the genetic variants in a family where the proband was a four-month-old infant presenting with respiratory problems due to DCM. In the family, there was a strong family history of DCM and sudden cardiac death in four generations. DNA was analyzed initially from the deceased girl using next-generation sequencing including 50 genes involved in cardiomyopathy. A cascade family screening was performed in the family after identification of the TNNT2 and the BAG3 variants in the proband. The first-degree relatives underwent clinical examination including biochemistry panel, cardiac ultrasound, Holter ECG, exercise stress test, and targeted genetic testing. The index patient presented with advanced DCM. After a severe clinical course, the baby had external left ventricular assist as a bridge to heart transplantation. 1.5 months after transplantation, the baby suffered sudden cardiac death (SCD) despite maximal treatment in the pediatric intensive care unit. The patient was shown to carry two heterozygous genetic variants in the TNNT2 gene [TNNT2 c.518G>A(p.Arg173Gln)] and BAG3 [BAG3 c.785C>T(p.Ala262Val)]. Two of the screened individuals (two females) appeared to carry both the familial variants. All the individuals carrying the TNNT2 variant presented with DCM, the two adult patients had mild or moderate symptoms of heart failure and reported palpitations but no syncope or presyncopal attacks prior to the genetic diagnosis. The female carriers of TNNT2 and BAG3 variants had more advanced DCM. In the family history, there were three additional cases of SCD due to DCM, diagnosed by autopsy, but no genetic analysis was possible in these cases. Our findings suggest that the variants in TNNT2 and BAG3 are associated with a high propensity to life-threatening cardiomyopathy presenting from childhood and young adulthood.

Dental attendance patterns among older people: a retrospective review of records in public and private dental care in Sweden.

OBJECTIVES: Nowadays, older people retain their natural teeth more frequently and so are at increased risk of oral disease. At the same time, discontinued contacts with dental services prevent access to preventive care and increase the risk of undetected disease. This study aims to evaluate how often older people discontinue regular dental visits and to establish the reasons. METHODS: This study is a retrospective review of records of patients aged ≥75 years from seven Swedish clinics, three in the public dental service (PuDS) and four in the private (PrDS). All patients were examined in 2010, and their dental attendance records from 2010 to 2014 studied. Data included gender, dental insurance system, last performed planned examination, emergency visits, registrations in the recall system, cause of discontinued care and number of teeth and implants. RESULTS: In total, 993 records were studied, 303 in PuDS and 690 in PrDS. In both groups, 10% of patients had no complete dental examinations between 2010 and 2014 after baseline examination in 2010. One-quarter were not registered in the recall system after their last examinations, and this was more common in PrDS than PuDS. In many cases, no reason for discontinued regular visits were described in the records. The mean number of natural teeth was 19.0 in both groups, but there were more implants in the PrDS group. CONCLUSIONS: A large proportion of the participants risked losing regular contact with dental services. Dental services appeared to lack strategies for maintaining regular dental care for elderly patients.

Older people's description of factors that facilitate and impede regular dental care - a qualitative interview study.

OBJECTIVES: The aim of this study was to achieve an understanding of older people's view of the benefits of regular dental care and investigate factors that facilitate and impede regular dental care. METHODS: A qualitative research method was used. To gain a deeper understanding of the elderly people's views, individual interviews were conducted. Fifteen respondents, eleven women and four men aged between 65 and 95, participated, all recruited from senior social centres. All interviews were tape-recorded and transcribed verbatim, and the content analysis method was then used. Meaning units were identified and condensed into codes which were labelled and grouped into categories and subcategories. RESULTS: Findings were grouped into three categories: experiences of dental care, obstacles and facilitators to dental care and about oral health and responsibility. The elderly had experience of both regular and irregular dental care. Obstacles to visiting dental services included high costs and complicated dental insurance, other practical obstacles, lack of confidence in dentistry and seeing no benefits of dental care at their age. Views of the importance of oral health varied, and some people thought poor teeth were shameful. Some expressed that oral health was your own responsibility, while others thought that oral health was the responsibility of the dental services. CONCLUSIONS: Several factors which hamper regular dental care have been identified, and taken together, these obstacles often became unsurmountable. However, individuals taking their own responsibility for their dental status and dental services making certain adaptations, both encourage people to seek regular dental care.

Combination screening in vitro identifies synergistically acting KP372-1 and cytarabine against acute myeloid leukemia.

Cytogenetic lesions often alter kinase signaling in acute myeloid leukemia (AML) and the addition of kinase inhibitors to the treatment arsenal is of interest. We have screened a kinase inhibitor library and performed combination testing to find promising drug-combinations for synergistic killing of AML cells. Cytotoxicity of 160 compounds in the library InhibitorSelect™ 384-Well Protein Kinase Inhibitor I was measured using the fluorometric microculture cytotoxicity assay (FMCA) in three AML cell lines. The 15 most potent substances were evaluated for dose-response. The 6 most cytotoxic compounds underwent combination synergy analysis based on the FMCA readouts after either simultaneous or sequential drug addition in AML cell lines. The 4 combinations showing the highest level of synergy were evaluated in 5 primary AML samples. Synergistic calculations were performed using the combination interaction analysis package COMBIA, written in R, using the Bliss independence model. Based on obtained results, an iterative combination search was performed using the therapeutic algorithmic combinatorial screen (TACS) algorithm. Of 160 substances, cell survival was ⩽50% at <0.5µM for Cdk/Crk inhibitor, KP372-1, synthetic fascaplysin, herbimycin A, PDGF receptor tyrosine kinase inhibitor IV and reference-drug cytarabine. KP372-1, synthetic fascaplysin or herbimycin A obtained synergy when combined with cytarabine in AML cell lines MV4-11 and HL-60. KP372-1 added 24h before cytarabine gave similar results in patient cells. The iterative search gave further improved synergy between cytarabine and KP372-1. In conclusion, our in vitro studies suggest that combining KP372-1 and cytarabine is a potent and synergistic drug combination in AML.

The effects of an exercise programme during pregnancy on health-related quality of life in pregnant women: a Norwegian randomised controlled trial.

OBJECTIVE: To investigate whether a customised exercise programme influences pregnant women's psychological wellbeing and general health perception reflecting health-related quality of life (HRQoL) in late pregnancy. DESIGN: A two-armed, two-centred randomised controlled trial. SETTING: Trondheim and Stavanger University Hospitals, Norway. POPULATION: A total of 855 healthy Caucasian pregnant women. METHODS: The intervention group was offered a 12-week exercise programme between 20 and 36 weeks of pregnancy. One weekly group session was led by physiotherapists, in addition women were encouraged to follow a home exercise programme at least twice a week. The exercise programme followed standard recommendations and included both aerobic and strength training. The control group received regular antenatal care. Pretests and post-tests were performed at 18-22 and 32-36 weeks of pregnancy. MAIN OUTCOME MEASURES: In the original study primary outcome was gestational diabetes mellitus, but in this report the primary outcome is HRQoL. The questionnaire Psychological General Wellbeing Index (PGWBI) was used to assess psychological wellbeing and self-perceived general health before and after the intervention. PGWBI contains six subscales and it is also possible to summarise all items to a global score. RESULTS: No association between antenatal exercise programme allocation and PGWBI (global score and subscales) was found. The study population was homogeneous and had high educational level. CONCLUSIONS: The results indicate that offering women an exercise programme during pregnancy does not seem to influence healthy pregnant women's psychological wellbeing and self-perceived general health. Further research is needed to investigate the effects of exercise in pregnancy on psychological wellbeing and self-perceived general health among women from different sociocultural subgroups. TWEETABLE ABSTRACT: Exercise in pregnancy does not influence healthy pregnant women's health-related quality of life.

In vitro discovery of promising anti-cancer drug combinations using iterative maximisation of a therapeutic index.

In vitro-based search for promising anti-cancer drug combinations may provide important leads to improved cancer therapies. Currently there are no integrated computational-experimental methods specifically designed to search for combinations, maximizing a predefined therapeutic index (TI) defined in terms of appropriate model systems. Here, such a pipeline is presented allowing the search for optimal combinations among an arbitrary number of drugs while also taking experimental variability into account. The TI optimized is the cytotoxicity difference (in vitro) between a target model and an adverse side effect model. Focusing on colorectal carcinoma (CRC), the pipeline provided several combinations that are effective in six different CRC models with limited cytotoxicity in normal cell models. Herein we describe the identification of the combination (Trichostatin A, Afungin, 17-AAG) and present results from subsequent characterisations, including efficacy in primary cultures of tumour cells from CRC patients. We hypothesize that its effect derives from potentiation of the proteotoxic action of 17-AAG by Trichostatin A and Afungin. The discovered drug combinations against CRC are significant findings themselves and also indicate that the proposed strategy has great potential for suggesting drug combination treatments suitable for other cancer types as well as for other complex diseases.

Sublingual immunotherapy alters expression of IL-4 and its soluble and membrane-bound receptors.

Seasonal allergic rhinitis (SAR) is a disease of increasing prevalence, which results from an inappropriate T helper cell, type 2 (Th2) response to pollen. Specific immunotherapy (SIT) involves repeated treatment with small doses of pollen and can result in complete and lasting reversal of SAR. Here, we assayed the key Th2 cytokine, IL-4, and its soluble and membrane-bound receptor in patients with SAR before and after SIT. Using allergen-challenge assays, we found that SIT treatment decreased IL-4 cytokine levels, as previously reported. We also observed a significant decrease in the IL-4 membrane-bound receptor (mIL4R) at the level of both mRNA and protein. SIT treatment resulted in a significant increase in the inhibitory soluble IL-4 receptor (sIL4R). Reciprocal changes in mIL4R and sIL4R were also observed in patient serum. Altered mIL4R and sIL4R is a novel explanation for the positive effects of immunotherapy with potential basic and clinical research implications.

The Allergic Airway Inflammation Repository--a user-friendly, curated resource of mRNA expression levels in studies of allergic airways.

Public microarray databases allow analysis of expression levels of candidate genes in different contexts. However, finding relevant microarray data is complicated by the large number of available studies. We have compiled a user-friendly, open-access database of mRNA microarray experiments relevant to allergic airway inflammation, the Allergic Airway Inflammation Repository (AAIR, http://aair.cimed.ike.liu.se/). The aim is to allow allergy researchers to determine the expression profile of their genes of interest in multiple clinical data sets and several experimental systems quickly and intuitively. AAIR also provides quick links to other relevant information such as experimental protocols, related literature and raw data files.

Challenges of conducting experimental studies within a clinical nursing context.

In recent years, several distinguished scholars have advocated for nursing research that may carry strong evidence for practice. Their advocacy have highlighted that nursing science has reached a point where as nurse researchers we need to develop the questions we ask and design studies that have the power to produce solid, translational, evidence-based knowledge. To do so, we need to carry out experimental tests on complex, everyday nursing interventions and activities. We also need to create public space to present accounts of our endeavours pursuing this type of design in clinical practice. This paper will discuss some of the most important insights gained from conducting a quasi-experimental study in which the aim was to investigate the effect of a theory-based intervention, targeting knowledge and attitudes among registered nurses regarding cancer pain management. The importance of careful practical and methodological planning is emphasised, and the need for participation-friendly interventions is discussed.

Nonequilibrium probing of two-level charge fluctuators using the step response of a single-electron transistor.

We report a new method to study two-level fluctuators (TLFs) by measuring the offset charge induced after applying a sudden step voltage to the gate electrode of a single-electron transistor. The offset charge is measured for more than 20 h for samples made on three different substrates. We find that the offset charge drift follows a logarithmic increase over 4 orders of magnitude in time and that the logarithmic slope increases linearly with the step voltage. The charge drift is independent of temperature, ruling out thermally activated TLFs and demonstrating that the charge fluctuations involve tunneling. These observations are in agreement with expectations for an ensemble of TLFs driven out of equilibrium. From our model, we extract the density of TLFs assuming either a volume density or a surface density.

Spontaneous Electrical Activity and Spikes in the Tail of Marine Cercariae.

Spontaneous electrical activity is recorded in two species of marine cercariae, Cryptocotyle lingua and Himasthla elongata, with different types of swimming-by glass microelectrode recordings. Slow local field potentials (sLFPs) of low amplitude and fast high amplitude action potentials (APs) are found. The shape of the sLFPs is different in the species and correlates with the type of swimming. Fast high amplitude APs are recorded for the first time in cercariae. The limited number of APs included in the swimming pattern of larva suggests a key role for the spiking neurons in initiating the motility pattern in the cercaria and needs further research.

Interferometer-based structured-illumination microscopy utilizing complementary phase relationship through constructive and destructive image detection by two cameras.

In an interferometer-based fluorescence microscope, a beam splitter is often used to combine two emission wavefronts interferometrically. There are two perpendicular paths along which the interference fringes can propagate and normally only one is used for imaging. However, the other path also contains useful information. Here we introduced a second camera to our interferometer-based three-dimensional structured-illumination microscope (I(5)S) to capture the fringes along the normally unused path, which are out of phase by π relative to the fringes along the other path. Based on this complementary phase relationship and the well-defined phase interrelationships among the I(5)S data components, we can deduce and then computationally eliminate the path length errors within the interferometer loop using the simultaneously recorded fringes along the two imaging paths. This self-correction capability can greatly relax the requirement for eliminating the path length differences before and maintaining that status during each imaging session, which are practically challenging tasks. Experimental data is shown to support the theory.

Monozygotic twins discordant for intermittent allergic rhinitis differ in mRNA and protein levels.

Monozygotic (MZ) twins discordant for complex diseases may help to find disease mechanisms that are not due to genetic variants. Intermittent allergic rhinitis (IAR) is an optimal disease model because it occurs at defined time points each year, owing to known external antigens. We hypothesized that MZ twins discordant for IAR could help to find gene expression differences that are not dependent on genetic variants. We collected blood outside of the season from MZ twins discordant for IAR, challenged their peripheral blood mononuclear cells (PBMC) with pollen allergen in vitro, collected supernatants and isolated CD4+ T cells. We identified disease-relevant mRNAs and proteins that differed between the discordant MZ twins. By contrast, no differences in microRNA expression were found. Our results indicate that MZ twins discordant for IAR is an optimal model to identify disease mechanisms that are not due to genetic variants.

Cytokine mapping in cerebrospinal fluid and blood in multiple sclerosis patients without oligoclonal bands.

OBJECTIVE: Since there are clinical and genetic differences between MS patients with intrathecal oligoclonal bands (OCB+) in the cerebrospinal fluid (CSF) compared with those without (OCB-), the aim was to find out if OCB- patients showed a different pattern of cytokine immune activation compared with OCB+ patients. METHODS: The study included 25 MS patients (10 OCB- and 15 OCB+) and 13 controls. A panel of cytokines was measured; IL-1ß, IL-6, IL-8/CXCL8, IL-10, TNF and GM-CSF in serum, CSF and in supernatants from polyclonally stimulated blood mononuclear cells, where also levels of IL-12p40, IL-13, IL-15, IL-17 and IFN-γ were measured. The concentrations of soluble (s) VCAM-1 and sCD14 were measured in serum and CSF. RESULTS: In general, there were no extensive differences in cytokine concentrations between the OCB- and OCB+ groups. CONCLUSION: OCB- MS patients do not seem to constitute a separate entity concerning inflammatory parameters measured as cytokine concentrations in CSF and blood.