Longitudinal evaluation of periodontitis and tooth loss among older adults.

AIM: To evaluate pattern of change in periodontal variables and tooth loss in a twelve-year follow-up study of older adults living in Sweden. METHODS: In a prospective population study of older adults, a clinical examination and radiographic dental examination were performed at baseline (2001-2003) and after 12 years (2013-2015). In 375 individuals, the number and proportion of sites with a distance ≥4 mm and ≥5 mm from cemento-enamel junction to the bone level, the number and proportion of teeth with pockets ≥5 mm and number of teeth lost were calculated. Dental caries was registered. Periodontitis was defined as having ≥2 sites with ≥5 mm distance from cemento-enamel junction to the marginal bone level and ≥1 tooth with pockets ≥5 mm. RESULTS: A diagnosis of periodontitis was evident in 39% of the individuals, and 23% of the individuals lost ≥3 teeth over the study period. The proportion of sites with ≥4 mm and ≥5 mm bone loss increased with age, while the proportion of teeth with pockets remained stable. Periodontitis was the strongest predictor for losing ≥3 teeth, OR 2.9 (p < .001) in the final model. CONCLUSIONS: Periodontitis is a risk factor for future tooth loss among older adults.

Longitudinal evaluation of periodontitis and development of cognitive decline among older adults.

AIM: To determine whether having periodontitis is associated with cognitive decline among older adults. MATERIAL AND METHODS: A prospective population study of older adults, Swedish National Study on Ageing and Care, (SNAC) provided repeated registrations of cognitive functions. Cognitive decline was defined as ≥3-points deterioration from a predetermined level at baseline, using the Mini-Mental State Examination (MMSE). Between 2001 and 2003, 715 individuals had a medical as well as a clinical and radiographic dental examination. The individuals were re-examined after 6 years. Periodontitis was defined as ≥4 mm bone loss at ≥30% of tooth sites. Social variables were captured from questionnaires. RESULTS: The multivariate logistic regression analysis demonstrated a statistically significant association between prevalence of periodontitis and cognitive decline after adjustments of confounding factors of importance. CONCLUSIONS: A history of periodontitis may be of importance for cognitive functions among older adults.

Epidemiology of Adult Ankle Fractures: 1756 cases identified in Norrbotten County during 2009-2013 and classified according to AO/OTA.

BACKGROUND: The ankle fracture is one of the most common fractures, increasing in an ageing population, but not generally seen as an osteoporotic fracture. The aim of this study was to examine the relationship between different AO/OTA classes of ankle fractures, age, sex and type of trauma. METHODS: Ankle fractures, treated at any of the hospitals in Norrbotten County in Sweden between 2009 and 2013, were retrospectively identified and classified according to the AO/OTA-classification system. Information about the trauma mechanism was also obtained. RESULTS: In Norrbotten County, 1756 ankle fractures in 1735 patients aged 20 years or older were identified. This gave an incidence in the county of 179 per 100,000 person-years. Of these patients, 34.6% were 65 years or older, 58.4% were women and 68.2% of the trauma leading to a fracture was defined as low-energy. In 1.5% of the cases the fractures were open. Incidences of type B fractures increased substantially with age, from 62 (95% CI 50-77) at 30-39 years of age to 158 (95% CI 131-190) in patients older than 80 years of age per 100,000 person-years. Type B fractures showed a slightly higher proportion of low-energy trauma while type C showed a lower mean age and proportion of women. CONCLUSIONS: This study shows an incidence of 179 adult ankle fractures annually per 100,000 persons. More than two thirds of the fractures were caused by a low-energy trauma and ankle fractures are more frequent among females. Females generally have an increased incidence during their life, mainly between the ages of 30 and 60. This is in contrast to men who have more of an even distribution throughout their life. Classification according to AO/OTA reveals some heterogeneity among the classes of ankle fractures in age and gender as well as the energy involved in the trauma.

Periodontitis, tooth loss and cognitive functions among older adults.

OBJECTIVE: This study aims to evaluate the potential association between periodontitis, the number of teeth and cognitive functions in a cohort of older adults in Sweden. MATERIAL AND METHODS: In total, 775 individuals from 60 to 99 years of age were selected for the study. A clinical and radiographic examination was performed. The number of teeth and prevalence of periodontal pockets and bone loss was calculated and categorised. Cognitive functions were assessed using the Mini-Mental State Examination (MMSE) and clock test. The education level was obtained from a questionnaire. Data were analysed using chi-square tests and multivariate logistic regression. RESULTS: Age and gender were associated with the prevalence of bone loss. Age and education were associated with lower number of teeth. Gender was also associated with the presence of pockets. The multivariate logistic regression analysis demonstrated a statistically significant association between prevalence of bone loss, the number of teeth and the outcome on MMSE test. This association remained even after adjustment for age, education and gender. Tooth loss was also associated with lower outcome on clock test. Presence of periodontal pockets ≥ 5 mm was not associated with cognitive test outcome. CONCLUSIONS: A history of periodontitis and tooth loss may be of importance for cognitive functions among older adults. CLINICAL RELEVANCE: Diseases with and inflammatory profile may have an impact on cognitive decline.

Anti-apoptotic quinolinate phosphoribosyltransferase (QPRT) is a target gene of Wilms' tumor gene 1 (WT1) protein in leukemic cells.

Wilms' tumor gene 1 (WT1) is a zinc finger transcription factor that has been implicated as an oncogene in leukemia and several other malignancies. When investigating possible gene expression network partners of WT1 in a large acute myeloid leukemia (AML) patient cohort, one of the genes with the highest correlation to WT1 was quinolinate phosphoribosyltransferase (QPRT), a key enzyme in the de novo nicotinamide adenine dinucleotide (NAD+) synthesis pathway. To investigate the possible relationship between WT1 and QPRT, we overexpressed WT1 in hematopoietic progenitor cells and cell lines, resulting in an increase of QPRT expression. WT1 knock-down gave a corresponding decrease in QPRT gene and protein expression. Chromatin-immunoprecipitation revealed WT1 binding to a conserved site in the first intron of the QPRT gene. Upon overexpression in leukemic K562 cells, QPRT conferred partial resistance to the anti-leukemic drug imatinib, indicating possible anti-apoptotic functions, consistent with previous reports on glioma cells. Interestingly, the rescue effect of QPRT overexpression was not correlated to increased NAD + levels, suggesting NAD + independent mechanisms. We conclude that QPRT, encoding a protein with anti-apoptotic properties, is a novel and direct target gene of WT1 in leukemic cells.

Distinct global binding patterns of the Wilms tumor gene 1 (WT1) -KTS and +KTS isoforms in leukemic cells.

The zinc finger transcription factor Wilms tumor gene 1 (WT1) acts as an oncogene in acute myeloid leukemia. A naturally occurring alternative splice event between zinc fingers three and four, removing or retaining three amino acids (±KTS), is believed to change the DNA binding affinity of WT1, although there are conflicting data regarding the binding affinity and motifs of the different isoforms. Increased expression of the WT1 -KTS isoform at the expense of the WT1 +KTS isoform is associated with poor prognosis in acute myeloid leukemia. We determined the genome-wide binding pattern of WT1 -KTS and WT1 +KTS in leukemic K562 cells by chromatin immunoprecipitation and deep sequencing. We discovered that the WT1 -KTS isoform predominantly binds close to transcription start sites and to enhancers, in a similar fashion to other transcription factors, whereas WT1 +KTS binding is enriched within gene bodies. We observed a significant overlap between WT1 -KTS and WT1 +KTS target genes, despite the binding sites being distinct. Motif discovery revealed distinct binding motifs for the isoforms, some of which have been previously reported as WT1 binding sites. Additional analyses showed that both WT1 -KTS and WT1 +KTS target genes are more likely to be transcribed than non-targets, and are involved in cell proliferation, cell death, and development. Our study provides evidence that WT1 -KTS and WT1 +KTS share target genes yet still bind distinct locations, indicating isoform-specific regulation in transcription of genes related to cell proliferation and differentiation, consistent with the involvement of WT1 in acute myeloid leukemia.

Contribution of Direct and Indirect Exposure to Human Serum Concentrations of Perfluorooctanoic Acid in an Occupationally Exposed Group of Ski Waxers.

The contribution of direct (i.e., uptake of perfluorooctanoic acid (PFOA) itself) and indirect (i.e., uptake of 8:2 fluorotelomer alcohol (FTOH) and metabolism to PFOA) exposure to PFOA serum concentrations was investigated using a dynamic one-compartment pharmacokinetic (PK) model. The PK model was applied to six occupationally exposed ski waxers for whom direct and indirect exposures via inhalation were characterized using multiple measurements with personal air sampling devices. The model was able to predict the diverging individual temporal trends of PFOA in serum with correlation coefficients of 0.82-0.94. For the four technicians with high initial concentrations of PFOA in serum (250-1050 ng/mL), the ongoing occupational exposure (both direct and indirect) was of minor importance and net depuration of PFOA was observed throughout the ski season. An estimated average intrinsic elimination half-life of 2.4 years (1.8-3.1 years accounting for variation between technicians and model uncertainty) was derived for these technicians. The remaining two technicians, who had much lower initial serum concentrations (10-17 ng/mL), were strongly influenced by exposure during the ski season with indirect exposure contributing to 45% of PFOA serum concentrations. On the basis of these model simulations, an average metabolism yield of 0.003 (molar concentration basis; uncertainty range of 0.0006-0.01) was derived for transformation of 8:2 FTOH to PFOA. An uncertainty analysis was performed, and it was determined that the input parameters quantifying the intake of PFOA were mainly responsible for the uncertainty of the metabolism yield and the initial concentration of PFOA in serum was mainly contributing to the uncertainty of estimated serum half-lives.

Tooth loss and cognitive functions among older adults.

OBJECTIVE: To evaluate the association between the number of teeth and cognitive functions adjusted for age and education level in a cohort of older adults living in Sweden. MATERIALS AND METHODS: The study employed a cross-sectional design in which 1147 individuals between 60-96 years underwent a clinical oral examination. The cognitive functions were assessed using Mini-Mental State Examination (MMSE) and Clock-test. The level of education was obtained from a questionnaire. Data were subjected to Chi-square tests and multivariate logistic regression analyses were employed, grouping the different variables into pre-determined categories. RESULTS: The co-variables age and education were significantly associated with the number of teeth (p < 0.05). The multivariate logistic regression analysis revealed that the association between the number of teeth and the cognitive functions persisted even after adjusting for age and level of education. CONCLUSIONS: The findings suggest that the presence of teeth may be of importance for cognitive abilities in older adults.

Inhalation exposure to fluorotelomer alcohols yield perfluorocarboxylates in human blood?

Levels of perfluorinated carboxylates (PFCAs) in different environmental and biological compartments have been known for some time, but the routes of exposure still remain unclear. The opinions are divergent whether the exposure to general populations occurs mainly indirect through precursor compounds or direct via PFCAs. Previous results showed elevated blood levels of PFCAs in ski wax technicians compared to a general population. The objective of this follow-up study was to determine concentrations of PFCAs, perfluorosulfonates (PFSAs), and fluorotelomer alcohols (FTOHs), precursor compounds that are known to degrade to PFCAs, in air collected in the breathing zone of ski wax technicians during work. We collected air samples by using ISOLUTE ENV+ cartridges connected to portable air pumps with an air flow of 2.0 L min(-1). PFCAs C5-C11 and PFSAs C4, C6, C8, and C10 were analyzed using LC-MS/MS and FTOHs 6:2, 8:2, and 10:2 with GC-MS/MS. The results show daily inhalation exposure of 8:2 FTOH in µg/m(3) air which is up to 800 times higher than levels of PFOA with individual levels ranging between 830-255000 ng/m(3) air. This suggests internal exposure of PFOA through biotransformation of 8:2 FTOH to PFOA and PFNA in humans.

The use of commercial alcohol products to sterilize bones prior to DNA sampling.

In disaster situations it is not always possible to maintain an adequate supply of standard equipment and sterilizing solutions. We have compared bone samples from cadavers cleaned in commercial white alcohol to samples from the same individuals cleaned with 95% surgical spirit. We have found that it is possible to use a commercial, white spirit to clean specimens taken from human cadavers femoral diaphysis collected for DNA analysis.

Microplastics in sea-surface waters surrounding Sweden sampled by manta trawl and in-situ pump.

Microplastics were sampled in open surface waters by using a manta trawl and an in-situ filtering pump. A total of 24 trawl samples and 11 pump samples were taken at 12 locations around Sweden. Overall, the concentration of microplastic particles was higher in pump samples compared to trawl samples. The median microplastic particle concentration was 0.04 particles per m-3 for manta trawl samples and 0.10 particles per m-3 in pump samples taken with a mesh size of 0.3 mm. The highest concentrations were recorded on the west coast of Sweden. Fibers were found in all samples and were also more frequent in the pump samples. Even higher concentrations of fibers and particles were found on the 0.05 mm pump filters. Using near-infrared hyperspectral imaging the majority of the particles were identified as polyethylene followed by polypropylene.

Enhanced complexity and catalytic efficiency in the hydrolysis of phosphate diesters by rationally designed helix-loop-helix motifs.

HJ1, a 42-residue peptide that folds into a helix-loop-helix motif and dimerizes to form a four-helix bundle, successfully catalyzes the cleavage of "early stage" DNA model substrates in an aqueous solution at pH 7.0, with a rate enhancement in the hydrolysis of heptyl 4-nitrophenyl phosphate of over three orders of magnitude over that of the imidazole-catalyzed reaction, k(2)(HJ1)/k(2)(Im) = 3135. The second-order rate constant, k(2)(HJ1) was determined to be 1.58x10(-4) M(-1) s(-1). The catalyst successfully assembles residues that in a single elementary reaction step are capable of general-acid and general-base catalysis as well as transition state stabilization and proximity effects. The reactivity achieved with the HJ1 polypeptide, rationally designed to catalyze the hydrolysis of phosphodiesters, is based on two histidine residues flanked by four arginines and two adjacent tyrosine residues, all located on the surface of a helix-loop-helix motif. The introduction of Tyr residues close to the catalytic site improves efficiency, in the cleavage of activated aryl alkyl phosphates as well as less activated dialkyl phosphates. HJ1 is also effective in the cleavage of an RNA-mimic substrate, uridine-3'-2,2,2-trichloroethyl phosphate (leaving group pK(a) = 12.3) with a second-order rate constant of 8.23x10(-4) M(-1) s(-1) in aqueous solution at pH 7.0, some 500 times faster than the reaction catalyzed by imidazole, k(2)(HJ1)/k(2)(Im) = 496.

Catalysis of the cleavage of uridine 3'-2,2,2-trichloroethylphosphate by a designed helix-loop-helix motif peptide.

A 42-residue peptide that folds into a helix-loop-helix motif and dimerizes to form a four-helix bundle has been designed to catalyze the hydrolysis of phosphodiesters. The active site on the surface of the folded catalyst is composed of two histidine and four arginine residues, with the capacity to provide general acid, general base, and/or nucleophilic catalysis as well as transition state stabilization. Uridine 3'-2,2,2 trichloroethylphosphate (2) is a mimic of RNA with a leaving group pKa of 12.3. Its hydrolysis is energetically less favorable than that of commonly used model substrates with p-nitrophenyl leaving groups and therefore a more realistic model for the design of catalysts capable of cleaving RNA. The second-order rate constant for the hydrolysis of 2 at pH 7.0 by the polypeptide catalyst was 418 x 10(-6) M-1 s-1, and that of the imidazole catalyzed reaction was 1.66 x 10(-6) M-1 s-1. The pH dependence suggested that catalysis is due to the unprotonated form of a residue with a pKa of around 5.3, and the observed kinetic solvent isotope effect of 1.9 showed that there is significant hydrogen bonding in the transition state, consistent with general acid-base catalysis. The rate constant ratio k2(Pep)/k2(Im) of 252 is probably due to a combination of nucleophilic and general acid-base catalysis, as well as transition state stabilization. Substrate binding was weak since no sign of saturation kinetics was observed for substrate concentrations in the range from 5 to 40 mM. The results provide a platform for the further development of catalysts for RNA cleavage with a potential role in the development of drugs.

The transcriptional coregulator NAB2 is a target gene for the Wilms' tumor gene 1 protein (WT1) in leukemic cells.

The Wilms' tumor gene 1 (WT1) is recurrently mutated in acute myeloid leukemia. Mutations and high expression of WT1 associate with a poor prognosis. In mice, WT1 cooperates with the RUNX1/RUNX1T1 (AML1/ETO) fusion gene in the induction of acute leukemia, further emphasizing a role for WT1 in leukemia development. Molecular mechanisms for WT1 are, however, incompletely understood. Here, we identify the transcriptional coregulator NAB2 as a target gene of WT1. Analysis of gene expression profiles of leukemic samples revealed a positive correlation between the expression of WT1 and NAB2, as well as a non-zero partial correlation. Overexpression of WT1 in hematopoietic cells resulted in increased NAB2 levels, while suppression of WT1 decreased NAB2 expression. WT1 bound and transactivated the proximal NAB2 promoter, as shown by ChIP and reporter experiments, respectively. ChIP experiments also revealed that WT1 can recruit NAB2 to the IRF8 promoter, thus modulating the transcriptional activity of WT1, as shown by reporter experiments. Our results implicate NAB2 as a previously unreported target gene of WT1 and that NAB2 acts as a transcriptional cofactor of WT1.

Y-chromosome STR haplotypes in Sweden.

A total of 708 men, with Swedish names, from different parts of Sweden have been typed for the Y-chromosome minimal haplotype STR markers DYS19, DYS389I, DYS389II, DYS390, DYS391, DYS392, DYS393 and DYS385. Of these, 403 men were of geographically undefined Swedish origin and the rest, 305, from seven defined geographical regions. PCR-products were detected by ABI377 using sequenced allelic ladders. An evaluation of the 708 chromosomes revealed 423 different haplotypes. Only 100 of the haplotypes were found more than once. The over all haplotype diversity was 0.994. The haplotype 14, 12, 28, 23, 10, 11, 13, 14-14 has the highest frequency of 5.79% and is significantly Swedish, when compared to other European populations.

The hematopoietic tumor suppressor interferon regulatory factor 8 (IRF8) is upregulated by the antimetabolite cytarabine in leukemic cells involving the zinc finger protein ZNF224, acting as a cofactor of the Wilms' tumor gene 1 (WT1) protein.

The transcription factor interferon regulatory factor-8 (IRF8) is highly expressed in myeloid progenitors, while most myeloid leukemias show low or absent expression. Loss of IRF8 in mice leads to a myeloproliferative disorder, indicating a tumor-suppressive role of IRF8. The Wilms tumor gene 1 (WT1) protein represses the IRF8-promoter. The zinc finger protein ZNF224 can act as a transcriptional co-factor of WT1 and potentiate the cytotoxic response to the cytostatic drug cytarabine. We hypothesized that cytarabine upregulates IRF8 and that transcriptional control of IRF8 involves WT1 and ZNF224. Treatment of leukemic K562 cells with cytarabine upregulated IRF8 protein and mRNA, which was correlated to increased expression of ZNF224. Knock down of ZNF224 with shRNA suppressed both basal and cytarabine-induced IRF8 expression. While ZNF224 alone did not affect IRF8 promoter activity, ZNF224 partially reversed the suppressive effect of WT1 on the IRF8 promoter, as judged by luciferase reporter experiments. Coprecipitation revealed nuclear binding of WT1 and ZNF224, and by chromatin immunoprecipitation (ChIP) experiments it was demonstrated that WT1 recruits ZNF224 to the IRF8 promoter. We conclude that cytarabine-induced upregulation of the IRF8 in leukemic cells involves increased levels of ZNF224, which can counteract the repressive activity of WT1 on the IRF8-promoter.

Collaborative EDNAP exercise on the IrisPlex system for DNA-based prediction of human eye colour.

The IrisPlex system is a DNA-based test system for the prediction of human eye colour from biological samples and consists of a single forensically validated multiplex genotyping assay together with a statistical prediction model that is based on genotypes and phenotypes from thousands of individuals. IrisPlex predicts blue and brown human eye colour with, on average, >94% precision accuracy using six of the currently most eye colour informative single nucleotide polymorphisms (HERC2 rs12913832, OCA2 rs1800407, SLC24A4 rs12896399, SLC45A2 (MATP) rs16891982, TYR rs1393350, and IRF4 rs12203592) according to a previous study, while the accuracy in predicting non-blue and non-brown eye colours is considerably lower. In an effort to vigorously assess the IrisPlex system at the international level, testing was performed by 21 laboratories in the context of a collaborative exercise divided into three tasks and organised by the European DNA Profiling (EDNAP) Group of the International Society of Forensic Genetics (ISFG). Task 1 involved the assessment of 10 blood and saliva samples provided on FTA cards by the organising laboratory together with eye colour phenotypes; 99.4% of the genotypes were correctly reported and 99% of the eye colour phenotypes were correctly predicted. Task 2 involved the assessment of 5 DNA samples extracted by the host laboratory from simulated casework samples, artificially degraded, and provided to the participants in varying DNA concentrations. For this task, 98.7% of the genotypes were correctly determined and 96.2% of eye colour phenotypes were correctly inferred. For Tasks 1 and 2 together, 99.2% (1875) of the 1890 genotypes were correctly generated and of the 15 (0.8%) incorrect genotype calls, only 2 (0.1%) resulted in incorrect eye colour phenotypes. The voluntary Task 3 involved participants choosing their own test subjects for IrisPlex genotyping and eye colour phenotype inference, while eye photographs were provided to the organising laboratory and judged; 96% of the eye colour phenotypes were inferred correctly across 100 samples and 19 laboratories. The high success rates in genotyping and eye colour phenotyping clearly demonstrate the reproducibility and the robustness of the IrisPlex assay as well as the accuracy of the IrisPlex model to predict blue and brown eye colour from DNA. Additionally, this study demonstrates the ease with which the IrisPlex system is implementable and applicable across forensic laboratories around the world with varying pre-existing experiences.

The public's perception of prehospital emergency care in the County of Skane, southern Sweden.

INTRODUCTION: The prehospital emergency care has had a rapid progress in Sweden in terms of technology, treatments and personnel education demands. In the County of Skane there is at least one specialized nurse in every ambulance. Possible misuses of the resources by the public have been acknowledged. AIM: To investigate the public's use, knowledge and expectations of the prehospital emergency care in Skane, southern Sweden. METHOD: A cross sectional descriptive survey, using a stratified sampling. Inclusion criteria were: 18 year or older and currently living in Skane. RESULTS: Of 735 people who were asked 54.4% (n=400) chose to participate in the study. 44.0% of the respondents had been transported with ambulance. 34.5% of the respondents believed that the lowest educated personnel responsible for the patient was the paramedic. The results show that the respondents trust the personnel's knowledge and work skills. Older informants expected faster treatment by a physician when arriving by ambulance to the hospital, regardless of medical condition. CONCLUSION: The public had confidence in the ambulance personnel's knowledge, ability to make assessment and give treatment despite not being updated on the current competence of the personnel. A positive experience of contact with the ambulance service was distinct.

Elimination kinetics of perfluorohexanoic acid in humans and comparison with mouse, rat and monkey.

Major fluorinated chemical manufacturers have developed new short-chain per- and polyfluorinated substances with more favorable environmental, health and safety profiles. This study provides the first evaluation of the elimination half-life of perfluorohexanoic acid (PFHxA) from the blood of humans. PFHxA biomonitoring data were obtained from a recently published study of professional ski wax technicians. These data were analyzed to provide estimates of the apparent half-life of PFHxA from humans, and comparisons were made with kinetic studies of PFHxA elimination from mice, rats and monkeys. The apparent elimination half-life of PFHxA in highly exposed humans ranged between 14 and 49 d with a geomean of 32 d. The half-lives of PFHxA in mice, rats, monkeys and humans were proportional to body weight with no differences observed between genders, indicating similar volumes of distribution and similar elimination mechanisms among mammalian species. Compared to long-chain perfluoroalkyl acid analogs, PFHxA is rapidly cleared from biota. The consistent weight-normalized elimination half-lives for PFHxA in mammalian species indicates that results obtained from animal models are suitable for establishment of PFHxA benchmark dose and reference dose hazard endpoints for use in human risk assessments.