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  • Vered, Marilena; Lehtonen, Meri; Hotakainen, Lari; Pirilä, Emma; Teppo, Susanna; Nyberg, Pia; Sormunen, Raija; Zlotogorski-Hurvitz, Ayelet; Salo, Tuula; Dayan, Dan (BioMed Central Ltd, 2015)
    Abstract Background Caveolin-1 (CAV1) may be upregulated by hypoxia and acts in a tumor-dependent manner. We investigated CAV1 in tongue squamous cell carcinoma (TSCC) and its association with clinical outcomes, and studied in vitro possible ways for CAV1 accumulation in the tumor microenvironment (TME). Methods TSCC cases (N = 64) were immunohistochemically stained for CAV1. Scores were separately assessed in the tumor and TME and plotted for association with recurrence and survival (univariate analysis with log-rank test). In vitro studies were performed on a 3D myoma organotypic model, a mimicker of TME. Prior to monoculturing HSC-3 tongue cancer cells, the model underwent modifications in oxygenation level (1%O2 hypoxia to upregulate CAV1) and/or in the amount of natural soluble factors [deleted by 14-day rinsing (rinsed myoma, RM), to allow only HSC-3-derived factors to act]. Controls included normoxia (21%O2) and naturally occurring soluble factors (intact myoma, IM). HSC-3 cells were also co-cultured with CaDEC12 cells (fibroblasts exposed to human tongue cancer). CAV1 expression and cellular distribution were examined in different cellular components in hypoxic and rinsed myoma assays. Twist served as a marker for the process of epithelial-mesenchymal transition (EMT). Exosomes isolated from HSC-3 media were investigated for containing CAV1. Results Expression of CAV1 in TSCC had a higher score in TME than in the tumor cells and a negative impact on recurrence (p = 0.01) and survival (p = 0.003). Monocultures of HSC-3 revealed expression of CAV1 mainly in the TME-like myoma assay, similar to TSCC. CAV1+, alpha-smooth muscle actin (αSMA) + and Twist + CAF-like cells were observed surrounding the invading HSC-3, possibly reflecting EMT. RM findings were similar to IM, inferring action of HSC-3 derived factors, and no differences were seen when hypoxia was induced. HSC-3-CaDEC12 co-cultures revealed CAV1+, αSMA+ and cytokeratin-negative CAF-like cells, raising the possibility of CaDEC12 cells gaining a CAF phenotype. HSC-3-derived exosomes were loaded with CAV1. Conclusions Accumulation of CAV1-TME in TSCC had a negative prognostic value. In vitro studies showed the presence of CAV1 in cancer cells undergoing EMT and in fibroblasts undergoing trans-differentiation to CAFs. CAV1 delivery to the TME involved cancer cell-derived exosomes.
  • Pohjola, Leena; Rossow, Laila; Huovilainen, Anita; Soveri, Timo; Hänninen, Marja-Liisa; Fredriksson-Ahomaa, Maria (BioMed Central Ltd, 2015)
    Abstract Background Although modern commercial poultry production today is based on large farms and intensive husbandry, keeping backyard poultry has regained popularity in industrialized countries. However, the health status of backyard flocks is still relatively poorly documented. A questionnaire was sent to the owners of 376 backyard poultry flocks (<500 birds) in order to study health management procedures and characterize backyard poultry populations in Finland. Information was also collected on the postmortem findings from non-commercial flocks using necropsy data from the Finnish Food Safety Authority (Evira). Results Backyard flocks in Finland are small in size (<50 birds), comprising mainly chickens. Based on the results of the questionnaire, the health of such flocks is good, mortality low and vaccinations are not commonly used. Most of the flocks were registered in the national poultry register. The standard biosecurity practices are not generally applied and contact with wild birds, pets and farm animals is frequent, which can make the flocks more prone to infectious diseases. We conducted an 11-year retrospective study of the postmortem necropsy findings of the Evira in order to document the diseases, which caused mortality in backyard chickens in Finland. Necropsy was performed on a total of 132 non-commercial laying hens during 2000 – 2011. The most common postmortem findings were Marek’s disease (27%) and colibacillosis (17%). Conclusions This study is the first to report data on characteristics of and management practices for backyard chicken flocks in Finland. Close connections with commercial flocks are rare and farms are usually distantly located suggesting that the risk that these backyard flocks pose to commercial poultry is low.
  • Kondadi, Pradeep K; Revez, Joana; Hänninen, Marja-Liisa; Rossi, Mirko (BioMed Central Ltd, 2015)
    Abstract Sialic acid in lipopolysaccharides (LPS) of mucosal pathogens is known to be an important virulence factor. Few strains of Helicobacter pylori express sialyl-Lewis-X and we have reported that human and canine Helicobacter bizzozeronii strains express sialyl-lactoseamine in their LPS. However, the role of sialyation of Helicobacter LPS in the interaction with the host cells is still unknown. In this study H. bizzozeronii LPS is shown to activate the TLR2 in a dose and strain dependent manner in the in vitro HEK-293 cells model expressing TLR2, but not the cells expressing TLR4. These results indicate that TLR2 is the specific receptor for H. bizzozzeronii LPS, as previously described for H. pylori. To further explore the role of sialylation of H. bizzozeronii LPS on TLR2 response, H. bizzozeronii Δhbs2 mutant strains deficient in sialyltransferase activity were constructed by homologous recombination. LPS from H. bizzozeronii Δhbs2 strains enhanced the NF-ĸB induction via TLR2 compared to the respective wild types, leading to the conclusion that the sialylation of H. bizzozeronii LPS in wild-type strains may modulate host immune response.
  • Kainulainen, Veera; Tang, Yurui; Spillmann, Thomas; Kilpinen, Susanne; Reunanen, Justus; Saris, Per EJ; Satokari, Reetta (BioMed Central Ltd, 2015)
    Abstract Background For a good probiotic candidate, the abilities to adhere to intestinal epithelium and to fortify barrier function are considered to be crucial for colonization and functionality of the strain. The strain Lactobacillus acidophilus LAB20 was isolated from the jejunum of a healthy dog, where it was found to be the most pre-dominant lactobacilli. In this study, the adhesion ability of LAB20 to intestinal epithelial cell (IECs) lines, IECs isolated from canine intestinal biopsies, and to canine, porcine and human intestinal mucus was investigated. Further, we studied the ability of LAB20 to fortify the epithelial cell monolayer and to reduce LPS-induced interleukin (IL-8) release from enterocytes. Results We found that LAB20 presented higher adhesion to canine colonic mucus as compared to mucus isolated from porcine colon. LAB20 showed adhesion to HT-29 and Caco-2 cell lines, and importantly also to canine IECs isolated from canine intestinal biopsies. In addition, LAB20 increased the transepithelial electrical resistance (TER) of enterocyte monolayers and thus strengthened the intestinal barrier function. The strain showed also anti-inflammatory capacity in being able to attenuate the LPS-induced IL-8 production of HT-29 cells. Conclusion In conclusion, canine indigenous strain LAB20 is a potential probiotic candidate for dogs adhering to the host epithelium and showing intestinal barrier fortifying and anti-inflammatory effects.
  • Roine, Ulrika; Salmi, Juha; Roine, Timo; Wendt, Taina Nieminen-von; Leppämäki, Sami; Rintahaka, Pertti; Tani, Pekka; Leemans, Alexander; Sams, Mikko (BioMed Central Ltd, 2015)
    Abstract Background The aim of this study was to investigate potential differences in neural structure in individuals with Asperger syndrome (AS), high-functioning individuals with autism spectrum disorder (ASD). The main symptoms of AS are severe impairments in social interactions and restricted or repetitive patterns of behaviors, interests or activities. Methods Diffusion weighted magnetic resonance imaging data were acquired for 14 adult males with AS and 19 age, sex and IQ-matched controls. Voxelwise group differences in fractional anisotropy (FA) were studied with tract-based spatial statistics (TBSS). Based on the results of TBSS, a tract-level comparison was performed with constrained spherical deconvolution (CSD)-based tractography, which is able to detect complex (for example, crossing) fiber configurations. In addition, to investigate the relationship between the microstructural changes and the severity of symptoms, we looked for correlations between FA and the Autism Spectrum Quotient (AQ), Empathy Quotient and Systemizing Quotient. Results TBSS revealed widely distributed local increases in FA bilaterally in individuals with AS, most prominent in the temporal part of the superior longitudinal fasciculus, corticospinal tract, splenium of corpus callosum, anterior thalamic radiation, inferior fronto-occipital fasciculus (IFO), posterior thalamic radiation, uncinate fasciculus and inferior longitudinal fasciculus (ILF). CSD-based tractography also showed increases in the FA in multiple tracts. However, only the difference in the left ILF was significant after a Bonferroni correction. These results were not explained by the complexity of microstructural organization, measured using the planar diffusion coefficient. In addition, we found a correlation between AQ and FA in the right IFO in the whole group. Conclusions Our results suggest that there are local and tract-level abnormalities in white matter (WM) microstructure in our homogenous and carefully characterized group of adults with AS, most prominent in the left ILF.
  • Seo, Seung Bum; Zeng, Xiangpei; King, Jonathan L; Larue, Bobby L; Assidi, Mourad; Al-Qahtani, Mohamed H; Sajantila, Antti; Budowle, Bruce (BioMed Central Ltd, 2015)
    Abstract Background Massively parallel sequencing (MPS) technologies have the capacity to sequence targeted regions or whole genomes of multiple nucleic acid samples with high coverage by sequencing millions of DNA fragments simultaneously. Compared with Sanger sequencing, MPS also can reduce labor and cost on a per nucleotide basis and indeed on a per sample basis. In this study, whole genomes of human mitochondria (mtGenome) were sequenced on the Personal Genome Machine (PGMTM) (Life Technologies, San Francisco, CA), the out data were assessed, and the results were compared with data previously generated on the MiSeqTM (Illumina, San Diego, CA). The objectives of this paper were to determine the feasibility, accuracy, and reliability of sequence data obtained from the PGM. Results 24 samples were multiplexed (in groups of six) and sequenced on the at least 10 megabase throughput 314 chip. The depth of coverage pattern was similar among all 24 samples; however the coverage across the genome varied. For strand bias, the average ratio of coverage between the forward and reverse strands at each nucleotide position indicated that two-thirds of the positions of the genome had ratios that were greater than 0.5. A few sites had more extreme strand bias. Another observation was that 156 positions had a false deletion rate greater than 0.15 in one or more individuals. There were 31-98 (SNP) mtGenome variants observed per sample for the 24 samples analyzed. The total 1237 (SNP) variants were concordant between the results from the PGM and MiSeq. The quality scores for haplogroup assignment for all 24 samples ranged between 88.8%-100%. Conclusions In this study, mtDNA sequence data generated from the PGM were analyzed and the output evaluated. Depth of coverage variation and strand bias were identified but generally were infrequent and did not impact reliability of variant calls. Multiplexing of samples was demonstrated which can improve throughput and reduce cost per sample analyzed. Overall, the results of this study, based on orthogonal concordance testing and phylogenetic scrutiny, supported that whole mtGenome sequence data with high accuracy can be obtained using the PGM platform.
  • Long, Georgina V; Atkinson, Victoria; Ascierto, Paolo A; Brady, Benjamin; Dutriaux, Caroline; Maio, Michele; Mortier, Laurent; Hassel, Jessica C; Rutkowski, Piotr; McNeil, Catriona; Kalinka-Warzocha, Ewa; Savage, Kerry J; Hernberg, Micaela; Lebbé, Celeste; Charles, Julie; Mihalcioiu, Catalin; Chiarion-Sileni, Vanna; Mauch, Cornelia; Schmidt, Henrik; Schadendorf, Dirk; Gogas, Helen; Horak, Christine; Sharkey, Brian; Waxman, Ian M; Robert, Caroline (BioMed Central Ltd, 2015)
  • Renggaman, Anriansyah; Choi, Hong L; Sudiarto, Sartika IA; Alasaarela, Laura; Nam, Ok S (BioMed Central Ltd, 2015)
    Abstract Background Due to increased interest in animal welfare, there is now a need for a comprehensive assessment protocol to be used in intensive pig farming systems. There are two current welfare assessment protocols for pigs: Welfare Quality® Assessment Protocols (applicable in the Europe Union), that mostly focuses on animal-based measures, and the Swine Welfare Assurance Program (applicable in the United States), that mostly focuses on management- and environment-based measures. In certain cases, however, animal-based measures might not be adequate for properly assessing pig welfare status. Similarly, welfare assessment that relies only on environment- and management-based measures might not represent the actual welfare status of pigs. Therefore, the objective of this paper was to develop a new welfare protocol by integrating animal-, environment-, and management-based measures. The background for selection of certain welfare criteria and modification of the scoring systems from existing welfare assessment protocols are described. Methods The developed pig welfare assessment protocol consists of 17 criteria that are related to four main principles of welfare (good feeding, good housing, good health, and appropriate behavior). Good feeding, good housing, and good health were assessed using a 3-point scale: 0 (good welfare), 1 (moderate welfare), and 2 (poor welfare). In certain cases, only a 2-point scale was used: 0 (certain condition is present) or 2 (certain condition is absent). Appropriate behavior was assessed by scan sampling of positive and negative social behaviors based on qualitative behavior assessment and human-animal relationship tests. Results Modification of the body condition score into a 3-point scale revealed pigs with a moderate body condition (score 1). Moreover, additional criteria such as feed quality confirmed that farms had moderate (score 1) or poor feed quality (score 2), especially those farms located in a high relative humidity region. Conclusions The developed protocol can be utilized to assess welfare status in an intensive pig farming system. Although further improvements are still needed, this study is a first step in developing a pig welfare assessment protocol that combines animal-, environment-, and management-based measures.
  • Korhonen, Anu (Transcript Verlag, 2015)
  • Stok, Marijn; König, Laura; Nurmi, Johanna; Müller, Andre Matthias (European Health Psychology Society, 2015)
  • Sajantila, Antti (BioMed Central Ltd, 2014)
    Abstract No abstract
  • Moilanen, Ulla; Kellock, Miriam; Várnai, Anikó; Andberg, Martina; Viikari, Liisa (BioMed Central Ltd, 2014)
    Abstract Background The recalcitrance of softwood to enzymatic hydrolysis is one of the major bottlenecks hindering its profitable use as a raw material for platform sugars. In softwood, the guaiacyl-type lignin is especially problematic, since it is known to bind hydrolytic enzymes non-specifically, rendering them inactive towards cellulose. One approach to improve hydrolysis yields is the modification of lignin and of cellulose structures by laccase-mediator treatments (LMTs). Results LMTs were studied to improve the hydrolysis of steam pre-treated spruce (SPS). Three mediators with three distinct reaction mechanisms (ABTS, HBT, and TEMPO) and one natural mediator (AS, that is, acetosyringone) were tested. Of the studied LMTs, laccase-ABTS treatment improved the degree of hydrolysis by 54%, while acetosyringone and TEMPO increased the hydrolysis yield by 49% and 36%, respectively. On the other hand, laccase-HBT treatment improved the degree of hydrolysis only by 22%, which was in the same order of magnitude as the increase induced by laccase treatment without added mediators (19%). The improvements were due to lignin modification that led to reduced adsorption of endoglucanase Cel5A and cellobiohydrolase Cel7A on lignin. TEMPO was the only mediator that modified cellulose structure by oxidizing hydroxyls at the C6 position to carbonyls and partially further to carboxyls. Oxidation of the reducing end C1 carbonyls was also observed. In contrast to lignin modification, oxidation of cellulose impaired enzymatic hydrolysis. Conclusions LMTs, in general, improved the enzymatic hydrolysis of SPS. The mechanism of the improvement was shown to be based on reduced adsorption of the main cellulases on SPS lignin rather than cellulose oxidation. In fact, at higher mediator concentrations the advantage of lignin modification in enzymatic saccharification was overcome by the negative effect of cellulose oxidation. For future applications, it would be beneficial to be able to understand and modify the binding properties of lignin in order to decrease unspecific enzyme binding and thus to increase the mobility, action, and recyclability of the hydrolytic enzymes.
  • Tikkinen, Kari AO; Agarwal, Arnav; Craigie, Samantha; Cartwright, Rufus; Gould, Michael K; Haukka, Jari; Naspro, Richard; Novara, Giacomo; Sandset, Per M; Siemieniuk, Reed A; Violette, Philippe D; Guyatt, Gordon H (BioMed Central Ltd, 2014)
    Abstract Background Pharmacological thromboprophylaxis in the peri-operative period involves a trade-off between reduction in venous thromboembolism (VTE) and an increase in bleeding. Baseline risks, in the absence of prophylaxis, for VTE and bleeding are known to vary widely between urological procedures, but their magnitude is highly uncertain. Systematic reviews and meta-analyses addressing baseline risks are uncommon, needed, and require methodological innovation. In this article, we describe the rationale and methods for a series of systematic reviews of the risks of symptomatic VTE and bleeding requiring reoperation in urological surgery. Methods/design We searched MEDLINE from January 1, 2000 until April 10, 2014 for observational studies reporting on symptomatic VTE or bleeding after urological procedures. Additional studies known to experts and studies cited in relevant review articles were added. Teams of two reviewers, independently assessed articles for eligibility, evaluated risk of bias, and abstracted data. We derived best estimates of risk from the median estimates among studies rated at the lowest risk of bias. The primary endpoints were 30-day post-operative risk estimates of symptomatic VTE and bleeding requiring reoperation, stratified by procedure and patient risk factors. Discussion This series of systematic reviews will inform clinicians and patients regarding the trade-off between VTE prevention and bleeding. Our work advances standards in systematic reviews of surgical complications, including assessment of risk of bias, criteria for arriving at best estimates of risk (including modeling of timing of events and dealing with suboptimal data reporting), dealing with subgroups at higher and lower risk of bias, and use of the Grading of Recommendations Assessment, Development and Evaluation (GRADE) approach to rate certainty in estimates of risk. The results will be incorporated in the upcoming European Association Urology Guideline on Thromboprophylaxis. Systematic review registration PROSPERO CRD42014010342.
  • Lappalainen, Anu K; Vaittinen, Elina; Junnila, Jouni; Laitinen-Vapaavuori, Outi (BioMed Central Ltd, 2014)
    Abstract Background Intervertebral disc disease (IDD) is a very common neurological disease, Dachshunds being the breed most often affected. In this breed, IDD has a hereditary background and is associated with intervertebral disc calcification (IDC), an indicator of severe intervertebral disc degeneration. In Finland, spinal radiography is used, when screening for IDC before breeding Dachshunds. We evaluated the association between IDC and IDD in Finnish Dachshunds radiographically screened for IDC. A questionnaire was sent to owners of 193 radiographically screened Dachshunds aged at least ten years. Clinical signs indicative of IDD were compared with IDC grade (grade 0 = no calcifications, grade 1 = 1 – 2 calcifications, grade 2 = 3 – 4 calcifications and grade 3 = 5 or more calcifications) and with age at the time of the radiographic examination. The diagnosis of IDD was confirmed by a veterinarian. Results IDD was common in the study population with 31% of dogs being affected. IDD and IDC were clearly connected (P < 0.001); IDD was rare in dogs with no calcifications (grade 0) and common in dogs with severe IDC (grade 3). The IDC grade was strongly positively associated with frequency of back pain periods (P < 0.001), and dogs with IDC grade 3 had frequent periods of pain. Reluctance to jump onto a sofa had a strong positive association with back pain. No association existed between age of the dog at the time of the radiographic examination and clinical signs indicative of IDD. Conclusions Radiographically detected IDC and IDD are common in Finnish Dachshunds and are strongly associated with one another. Spinal radiography is an appropriate screening tool for breeders attempting to diminish IDC and IDD in Dachshunds. A breeding program that screens dogs and selects against IDC can be expected to reduce the occurrence of IDD in future. Twenty-four to 48 months of age is a suitable age for screening.
  • Grote, Anne; Abbas, Mahmoud; Linder, Nina; Kreipe, Hans H; Lundin, Johan; Feuerhake, Friedrich (BioMed Central Ltd, 2014)
    Abstract Background Comprehensive spatial assessment of hormone receptor immunohistochemistry staining in digital whole slide images of breast cancer requires accurate detection of positive nuclei within biologically relevant regions of interest. Herein, we propose a combination of automated region labeling at low resolution and subsequent detailed tissue evaluation of subcellular structures in lobular structures adjacent to breast cancer, as a proof of concept for the approach to analyze estrogen and progesterone receptor expression in the spatial context of surrounding tissue. Methods Routinely processed paraffin sections of hormone receptor-negative ductal invasive breast cancer were stained for estrogen and progesterone receptor by immunohistochemistry. Digital whole slides were analyzed using commercially available image analysis software for advanced object-based analysis, applying textural, relational, and geometrical features. Mammary gland lobules were targeted as regions of interest for analysis at subcellular level in relation to their distance from coherent tumor as neighboring relevant tissue compartment. Lobule detection quality was evaluated visually by a pathologist. Results After rule set optimization in an estrogen receptor-stained training set, independent test sets (progesterone and estrogen receptor) showed acceptable detection quality in 33% of cases. Presence of disrupted lobular structures, either by brisk inflammatory infiltrate, or diffuse tumor infiltration, was common in cases with lower detection accuracy. Hormone receptor detection tended towards higher percentage of positively stained nuclei in lobules distant from the tumor border as compared to areas adjacent to the tumor. After adaptations of image analysis, corresponding evaluations were also feasible in hormone receptor positive breast cancer, with some limitations of automated separation of mammary epithelial cells from hormone receptor-positive tumor cells. Conclusions As a proof of concept for object-oriented detection of steroid hormone receptors in their spatial context, we show that lobular structures can be classified based on texture-based image features, unless brisk inflammatory infiltration disrupts the normal morphological structure of the tubular gland epithelium. We consider this approach as prototypic for detection and spatial analysis of nuclear markers in defined regions of interest. We conclude that advanced image analysis at this level of complexity requires adaptation to the individual tumor phenotypes and morphological characteristics of the tumor environment.
  • Kulhánová, Ivana; Menvielle, Gwenn; Bopp, Matthias; Borrell, Carme; Deboosere, Patrick; Eikemo, Terje A; Hoffmann, Rasmus; Leinsalu, Mall; Martikainen, Pekka; Regidor, Enrique; Rodríguez-Sanz, Maica; Rychtaříková, Jitka; Wojtyniak, Bogdan; Mackenbach, Johan P (BioMed Central Ltd, 2014)
    Abstract Background Cause-of-death data linked to information on socioeconomic position form one of the most important sources of information about health inequalities in many countries. The proportion of deaths from ill-defined conditions is one of the indicators of the quality of cause-of-death data. We investigated educational differences in the use of ill-defined causes of death in official mortality statistics. Methods Using age-standardized mortality rates from 16 European countries, we calculated the proportion of all deaths in each educational group that were classified as due to “Symptoms, signs and ill-defined conditions”. We tested if this proportion differed across educational groups using Chi-square tests. Results The proportion of ill-defined causes of death was lower than 6.5% among men and 4.5% among women in all European countries, without any clear geographical pattern. This proportion statistically significantly differed by educational groups in several countries with in most cases a higher proportion among less than secondary educated people compared with tertiary educated people. Conclusions We found evidence for educational differences in the distribution of ill-defined causes of death. However, the differences between educational groups were small suggesting that socioeconomic inequalities in cause-specific mortality in Europe are not likely to be biased.
  • Savanheimo, Nora; Vehkalahti, Miira M (BioMed Central Ltd, 2014)
    Abstract Background Dental general anesthesia (DGA) is part of public dental care in Finland, but the intention is to return the patient to routine dental care. The aims of this study were to describe the details of treatments under DGA given to generally healthy children and to explore the outcome of their dental care during a 5-year follow-up, with special focus on preventive care. In particular, we examined the return of the patients to routine dental care, of which, to our knowledge, little is known. Methods Our prospective 5-year follow-up of generally healthy children (aged 0–13 years) treated under DGA by the Helsinki Public Dental Service in 2004 was based on official dental and general anesthesia documents. The statistical analyses employed chi-square tests, t-tests, Pearson’s correlation coefficient (r), Fisher’s transformation to test r ≠ 0, and logistic regression modeling. Results The most common reason for DGA was uncooperation (82%), followed by dental fear (56%). Filling therapy predominated in the treatments given under anesthesia, and the mean number of treatments per patients was 9.5 (SD = 4.2). Throughout the follow-up, 54% of the patients continued to have co-operation problems and 53% expressed dental fear; 11% of the patients received repeat DGA. The mean follow-up time was 48 (median 52) months. The postoperative review visit was actualized within 1.5 (SD = 0.8) months and the first visit to the home dental clinic of the patients in 12.0 (SD = 11.8) months for the 0–5-year-olds and in 7.2 (SD = 5.9) months for the 6–13-year-olds (p < 0.001). The mean time elapsed to the first need for treatment was 18.5 (SD = 14.1) months. During the follow-up, the mean number of treatments per patient was 5.3 (SD = 4.9); almost all patients (97%) received preventive treatment at one of two visits, but the control of dental fear remained rare. Conclusions To return to routine dental care after DGA, most of the generally healthy children in our study still needed special attention due to their uncooperation and dental fear, thus calling for a renewal of practices to treat these patients.
  • Laurila, Kirsti; Autio, Reija; Kong, Lingjia; Närvä, Elisa; Hussein, Samer; Otonkoski, Timo; Lahesmaa, Riitta; Lähdesmäki, Harri (BioMed Central Ltd, 2014)
    Abstract Background Human genomic variations, including single nucleotide polymorphisms (SNPs) and copy number variations (CNVs), are associated with several phenotypic traits varying from mild features to hereditary diseases. Several genome-wide studies have reported genomic variants that correlate with gene expression levels in various tissue and cell types. Results We studied human embryonic stem cells (hESCs) and human induced pluripotent stem cells (hiPSCs) measuring the SNPs and CNVs with Affymetrix SNP 6 microarrays and expression values with Affymetrix Exon microarrays. We computed the linear relationships between SNPs and expression levels of exons, transcripts and genes, and the associations between gene CNVs and gene expression levels. Further, for a few of the resulted genes, the expression value was associated with both CNVs and SNPs. Our results revealed altogether 217 genes and 584 SNPs whose genomic alterations affect the transcriptome in the same cells. We analyzed the enriched pathways and gene ontologies within these groups of genes, and found out that the terms related to alternative splicing and development were enriched. Conclusions Our results revealed that in the human pluripotent stem cells, the expression values of several genes, transcripts and exons were affected due to the genomic variation.