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  • 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.
  • Hemilä, Harri; Al-Biltagi, Mohammed; Baset, Ahmed A (BioMed Central Ltd, 2012)
    AbstractWe reported that the effect of vitamin C on asthma in Egyptian children was modified by age, exposure to dampness and the severity of asthma, Clinical & Translational Allergy 2011, 1:9. After our paper was published, we found out severe problems in the data set. There were 60 children in the study. The ages were by accident duplicated between the upper and lower halves of the database. Thus, the ages for the first 30 children in the data set were identical and in the same order with the ages for the second set of 30 children. Similar duplication was also found for C-ACT and FEV1 measurements after vitamin C supplementation and for exposure to dampness. This duplication thus directly invalidates the second part of the data set, and thus the reported outcome. We have not been able to sort out the reason for this duplication. The files with the original data are not available any more, making it impossible to reconstruct a valid data set for reanalysis. Therefore we have to retract our paper. The authors deeply regret the inconvenience this has caused to the journal and the scientific community.
  • Castellsagué, Xavier; Paavonen, Jorma; Jaisamrarn, Unnop; Wheeler, Cosette M; Skinner, S Rachel; Lehtinen, Matti; Naud, Paulo; Chow, Song-Nan; Del Rosario-Raymundo, Maria R; Teixeira, Julio C; Palmroth, Johanna; de Carvalho, Newton S; Germar, Maria JV; Peters, Klaus; Garland, Suzanne M; Szarewski, Anne; Poppe, Willy AJ; Romanowski, Barbara; Schwarz, Tino F; Tjalma, Wiebren AA; Bosch, F X; Bozonnat, Marie-Cecile; Struyf, Frank; Dubin, Gary; Rosillon, Dominique; Baril, Laurence; for the HPV PATRICIA Study Group (BioMed Central Ltd, 2014)
    Abstract Background More information is needed about time between sexual initiation and human papillomavirus (HPV) infection and development of cervical precancer. Methods The objectives were to investigate the time between first sexual activity and detection of first cervical HPV infection or development of first cervical intraepithelial neoplasia (CIN), and associated factors in women from the double-blind, multinational, 4-year PATRICIA trial. PATRICIA enroled women aged 15–25 years with no more than 6 lifetime sexual partners. Women were randomized 1:1 to the HPV-16/18 AS04-adjuvanted vaccine or to control, but only women from the control arm who began sexual intercourse during the study or within 6 months before enrolment, and had no HPV infection detected before the recorded date of their first sexual intercourse, were included in the present analysis. The time between onset of sexual activity and detection of the first cervical HPV infection or development of the first CIN lesion was analyzed using Kaplan-Meier and univariate and multivariable Cox proportional-hazards models. Results A total of 9337 women were enroled in the control arm of PATRICIA of whom 982 fulfilled the required inclusion criteria for analysis. A cumulative total of 28%, 44%, and 62% of the subjects had HPV infection within 12, 24, and 48 months, respectively. The overall incidence rate was 27.08 per 100 person-years. The most common oncogenic types associated with 6-month persistent infection were HPV-16 (incidence rate: 2.74 per 100 person-years), HPV-51 (2.70), HPV-52 (1.66), HPV-66 (1.14), and HPV-18 (1.09). Increased infection risk was associated with more lifetime sexual partners, being single, Chlamydia trachomatis history, and duration of hormone use. CIN1+ and CIN2+ lesions were most commonly associated with HPV-16, with an overall incidence rate of 1.87 and 1.07 per 100 person-years, respectively. Previous cervical HPV infection was most strongly associated with CIN development. Conclusions More than 25% of women were infected with HPV within 1 year of beginning sexual activity. Without underestimating the value of vaccination at older ages, our findings emphasize its importance before sexual initiation. Trial registration clinicaltrials.gov: NCT00122681.
  • Sidoroff, Marianne; Kolho, Kaija-Leena (BioMed Central Ltd, 2014)
    Abstract Background Pharmacological doses of corticoids may result in adrenal suppression but with individual sensitivity. In paediatric inflammatory bowel disease (IBD), glucocorticoids are needed in the majority of the patients but there are less studies related to tapering off the drugs. The objective of this study was to estimate the frequency of adrenal insufficiency in children with IBD that were at the end of their systemic glucocorticoid therapy course. Methods The study was a retrospective case series of 59 consecutive paediatric IBD patients (median age 14.1 years; Crohn’s disease n = 22, ulcerative colitis n = 26, unclassified colitis n = 11) that were on oral prednisolone therapy about to be discontinued. The study patients were treated in a tertiary university hospital setting. Serum morning cortisol was measured with Immulite 2000 cortisol kit. Values < 20 nmol/l are undetectable and indicate adrenal suppression, values > 69 nmol/l are considered to represent normal basal secretion. Results The morning cortisol was below the reference range in 20% of the patients and undetectable in 10%. Low cortisol levels associated with higher daily glucocorticoid doses (median 7.2 mg/m2 vs. 3.0 mg/m2 in patients with normal cortisol levels, p < 0.05) and with the long duration of the treatment (median 11 months vs. 4 months, p < 0.05). Patients with undetectable cortisol levels recovered within few weeks (median 5.6 weeks). Conclusions In paediatric IBD prolonged courses of glucocorticoids are frequent due to the steroid-dependent nature of the disease in a considerable proportion of patients. Adrenal suppression may occur in at least one fifth of the patients despite slowly tapering off the glucocorticoids. Notably, this is based on a set of serum cortisol measurements by request of experienced clinicians. All paediatric IBD patients receiving conventional doses of oral glucocorticoids should be subjected to screening for adrenal suppression when anticipated discontinuation of the drug.
  • Kim, Jinsil; Stirling, Kara J; Cooper, Margaret E; Ascoli, Mario; Momany, Allison M; McDonald, Erin L; Ryckman, Kelli K; Rhea, Lindsey; Schaa, Kendra L; Cosentino, Viviana; Gadow, Enrique; Saleme, Cesar; Shi, Min; Hallman, Mikko; Plunkett, Jevon; Teramo, Kari A; Muglia, Louis J; Feenstra, Bjarke; Geller, Frank; Boyd, Heather A; Melbye, Mads; Marazita, Mary L; Dagle, John M; Murray, Jeffrey C (BioMed Central Ltd, 2013)
    Abstract Background Preterm birth (PTB) is a complex disorder associated with significant neonatal mortality and morbidity and long-term adverse health consequences. Multiple lines of evidence suggest that genetic factors play an important role in its etiology. This study was designed to identify genetic variation associated with PTB in oxytocin pathway genes whose role in parturition is well known. Methods To identify common genetic variants predisposing to PTB, we genotyped 16 single nucleotide polymorphisms (SNPs) in the oxytocin (OXT), oxytocin receptor (OXTR), and leucyl/cystinyl aminopeptidase (LNPEP) genes in 651 case infants from the U.S. and one or both of their parents. In addition, we examined the role of rare genetic variation in susceptibility to PTB by conducting direct sequence analysis of OXTR in 1394 cases and 1112 controls from the U.S., Argentina, Denmark, and Finland. This study was further extended to maternal triads (maternal grandparents-mother of a case infant, N=309). We also performed in vitro analysis of selected rare OXTR missense variants to evaluate their functional importance. Results Maternal genetic effect analysis of the SNP genotype data revealed four SNPs in LNPEP that show significant association with prematurity. In our case–control sequence analysis, we detected fourteen coding variants in exon 3 of OXTR, all but four of which were found in cases only. Of the fourteen variants, three were previously unreported novel rare variants. When the sequence data from the maternal triads were analyzed using the transmission disequilibrium test, two common missense SNPs (rs4686302 and rs237902) in OXTR showed suggestive association for three gestational age subgroups. In vitro functional assays showed a significant difference in ligand binding between wild-type and two mutant receptors. Conclusions Our study suggests an association between maternal common polymorphisms in LNPEP and susceptibility to PTB. Maternal OXTR missense SNPs rs4686302 and rs237902 may have gestational age-dependent effects on prematurity. Most of the OXTR rare variants identified do not appear to significantly contribute to the risk of PTB, but those shown to affect receptor function in our in vitro study warrant further investigation. Future studies with larger sample sizes are needed to confirm the findings of this study.
  • Werner, Stefan; Apolinário, José A Jr.; Diniz, Paulo SR (Springer, 2007)
    Proportionate adaptive filters can improve the convergence speed for the identification of sparse systems as compared to their conventional counterparts. In this paper, the idea of proportionate adaptation is combined with the framework of set-membership filtering (SMF) in an attempt to derive novel computationally efficient algorithms. The resulting algorithms attain an attractive faster converge for both situations of sparse and dispersive channels while decreasing the average computational complexity due to the data discerning feature of the SMF approach. In addition, we propose a rule that allows us to automatically adjust the number of past data pairs employed in the update. This leads to a set-membership proportionate affine projection algorithm (SM-PAPA) having a variable data-reuse factor allowing a significant reduction in the overall complexity when compared with a fixed data-reuse factor. Reduced-complexity implementations of the proposed algorithms are also considered that reduce the dimensions of the matrix inversions involved in the update. Simulations show good results in terms of reduced number of updates, speed of convergence, and final mean-squared error.
  • 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.
  • 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.
  • Plug, Iris; Hoffmann, Rasmus; Artnik, Barbara; Bopp, Matthias; Borrell, Carme; Costa, Giuseppe; Deboosere, Patrick; Esnaola, Santi; Kalediene, Ramune; Leinsalu, Mall; Lundberg, Olle; Martikainen, Pekka; Regidor, Enrique; Rychtarikova, Jitka; Strand, Björn H; Wojtyniak, Bogdan; Mackenbach, Johan P (BioMed Central Ltd, 2012)
    AbstractBackgroundPrevious studies have reported large socioeconomic inequalities in mortality from conditions amenable to medical intervention, but it is unclear whether these can be attributed to inequalities in access or quality of health care, or to confounding influences such as inequalities in background risk of diseases. We therefore studied whether inequalities in mortality from conditions amenable to medical intervention vary between countries in patterns which differ from those observed for other (non-amenable) causes of death. More specifically, we hypothesized that, as compared to non-amenable causes, inequalities in mortality from amenable causes are more strongly associated with inequalities in health care use and less strongly with inequalities in common risk factors for disease such as smoking.MethodsCause-specific mortality data for people aged 30–74 years were obtained for 14 countries, and were analysed by calculating age-standardized mortality rates and relative risks comparing a lower with a higher educational group. Survey data on health care use and behavioural risk factors for people aged 30–74 years were obtained for 12 countries, and were analysed by calculating age-and sex-adjusted odds ratios comparing a low with a higher educational group. Patterns of association were explored by calculating correlation coefficients.ResultsIn most countries and for most amenable causes of death substantial inequalities in mortality were observed, but inequalities in mortality from amenable causes did not vary between countries in patterns that are different from those seen for inequalities in non-amenable mortality. As compared to non-amenable causes, inequalities in mortality from amenable causes are not more strongly associated with inequalities in health care use. Inequalities in mortality from amenable causes are also not less strongly associated with common risk factors such as smoking.ConclusionsWe did not find evidence that inequalities in mortality from amenable conditions are related to inequalities in access or quality of health care. Further research is needed to find the causes of socio-economic inequalities in mortality from amenable conditions, and caution should be exercised in interpreting these inequalities as indicating health care deficiencies.
  • 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.
  • 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.
  • van Raalte, Alyson A; Kunst, Anton E; Lundberg, Olle; Leinsalu, Mall; Martikainen, Pekka; Artnik, Barbara; Deboosere, Patrick; Stirbu, Irina; Wojtyniak, Bogdan; Mackenbach, Johan P (BioMed Central Ltd, 2012)
    Abstract Background Studies of socioeconomic inequalities in mortality consistently point to higher death rates in lower socioeconomic groups. Yet how these between-group differences relate to the total variation in mortality risk between individuals is unknown. Methods We used data assembled and harmonized as part of the Eurothine project, which includes census-based mortality data from 11 European countries. We matched this to national data from the Human Mortality Database and constructed life tables by gender and educational level. We measured variation in age at death using Theil's entropy index, and decomposed this measure into its between- and within-group components. Results The least-educated groups lived between three and 15 years fewer than the highest-educated groups, the latter having a more similar age at death in all countries. Differences between educational groups contributed between 0.6% and 2.7% to total variation in age at death between individuals in Western European countries and between 1.2% and 10.9% in Central and Eastern European countries. Variation in age at death is larger and differs more between countries among the least-educated groups. Conclusions At the individual level, many known and unknown factors are causing enormous variation in age at death, socioeconomic position being only one of them. Reducing variations in age at death among less-educated people by providing protection to the vulnerable may help to reduce inequalities in mortality between socioeconomic groups.
  • Hemilä, Harri (BioMed Central Ltd, 2014)
    Abstract Physical activity increases oxidative stress and therefore the antioxidant effects of vitamin C administration might become evident in people undertaking vigorous exercise. Vitamin C is involved in the metabolism of histamine, prostaglandins, and cysteinyl leukotrienes, all of which appear to be mediators in the pathogenesis of exercise-induced bronchoconstriction (EIB). Three studies assessing the effect of vitamin C on patients with EIB were subjected to a meta-analysis and revealed that vitamin C reduced postexercise FEV1 decline by 48% (95% CI: 33% to 64%). The correlation between postexercise FEV1 decline and respiratory symptoms associated with exercise is poor, yet symptoms are the most relevant to patients. Five other studies examined subjects who were under short-term, heavy physical stress and revealed that vitamin C reduced the incidence of respiratory symptoms by 52% (95% CI: 36% to 65%). Another trial reported that vitamin C halved the duration of the respiratory symptoms in male adolescent competitive swimmers. Although FEV1 is the standard outcome for assessing EIB, other outcomes may provide additional information. In particular, the mean postexercise decline of FEF50 is twice the decline of FEV1. Schachter and Schlesinger (1982) reported the effect of vitamin C on exercise-induced FEF60 levels in 12 patients suffering from EIB and their data are analyzed in this paper. The postexercise FEF60 decline was greater than 60% for five participants and such a dramatic decline indicates that the absolute postexercise FEF60 level becomes an important outcome in its own right. Vitamin C increased postexercise FEF60 levels by 50% to 150% in those five participants, but had no significant effect in the other seven participants. Thus, future research on the effects of vitamin C on EIB should not be restricted to measuring only FEV1. Vitamin C is inexpensive and safe, and further study on those people who have EIB or respiratory symptoms associated with exercise is warranted.
  • Karkamo, Veera; Kaistinen, Anu; Näreaho, Anu; Dillard, Kati; Vainio-Siukola, Katri; Vidgrén, Gabriele; Tuoresmäki, Niina; Anttila, Marjukka (BioMed Central Ltd, 2014)
    Abstract Background Leishmania spp. are zoonotic protozoans that infect humans and other mammals such as dogs. The most significant causative species in dogs is L. infantum. In dogs, leishmaniosis is a potentially progressive, chronic disease with varying clinical outcomes. Autochthonous cases of canine leishmaniosis have not previously been reported in the Nordic countries. Results In this report we describe the first diagnosed autochthonous cases of canine leishmaniosis in Finland, in which transmission via a suitable arthropod vector was absent. Two Finnish boxers that had never been in endemic areas of Leishmania spp., had never received blood transfusions, nor were infested by ectoparasites were diagnosed with leishmaniosis. Another dog was found with elevated Leishmania antibodies. A fourth boxer dog that had been in Spain was considered to be the source of these infections. Transmission occurred through biting wounds and semen, however, transplacental infection in one of the dogs could not be ruled out. Two of the infected dogs developed a serious disease and were euthanized and sent for necropsy. The first one suffered from membranoproliferative glomerulonephritis and the second one had a chronic systemic disease. Leishmania sp. was detected from tissues by PCR and/or IHC in both dogs. The third infected dog was serologically positive for Leishmania sp. but remained free of clinical signs. Conclusions This case report shows that imported Leishmania-infected dogs may pose a risk for domestic dogs, even without suitable local arthropod vectors.
  • Oksanen, Antti; Åsbakk, Kjetil; Raekallio, Marja; Nieminen, Mauri (BioMed Central Ltd, 2014)
    Abstract Background Overwintering (breeding) reindeer (Rangifer tarandus tarandus) are commonly treated with ivermectin against parasitic infestations once yearly in autumn-winter roundups. The only preparations registered to reindeer are those for subcutaneous injection. However, also oral extra-label ivermectin administration is used. Twenty-six, 8-month-old reindeer calves were randomly allocated into three groups. Group 1 (n = 9) received oral ivermectin mixture (Ivomec® vet mixt. 0.8 mg/ml, oral ovine liquid drench formulation), Group 2 (n = 9) oral ivermectin paste (Ivomec® vet 18.7 mg/g equine paste), and Group 3 (n = 8) subcutaneous injection of ivermectin (Ivomec® 10 mg/ml vet inj.), each group at a dose of 200 μg/kg body weight. Blood samples were collected at treatment and at days 1, 2, 3, 6, 9 and 16 post treatment. Plasma concentrations of ivermectin were determined by high-pressure liquid chromatography (HPLC) with fluorescence detection. Results The peak plasma concentration (Cmax) was reached by 2 days after each treatment. The Cmax and Area Under Curve (AUC) differed significantly between the groups: Cmax was 30.2 ± 3.9, 14.9 ± 5.7 and 63.1 ± 13.1 ng/ml, and AUC∞ was 2881 ± 462, 1299 ± 342 and 6718 ± 1620 ng*h/ml for groups 1, 2 and 3, respectively (mean ± standard deviation). Conclusions The differences in plasma concentrations of ivermectin are concomitant with earlier observed differences in antiparasitic efficacy, which discounts the use of the equine paste in reindeer in favour of the oral ovine liquid drench formulation, or preferably, the reindeer-registered subcutaneous injection formulation.
  • Piirilä, Päivi L; Hodgson, Ulla; Wuorimaa, Tomi; Smith, Hans-Jürgen; Sovijärvi, Anssi RA (BioMed Central Ltd, 2014)
    Abstract Background Dynamic gas compression during forced expiration has an influence on conventional flow-volume spirometry results. The extent of gas compression in different pulmonary disorders remains obscure. Utilizing a flow plethysmograph we determined the difference between thoracic and mouth flows during forced expiration as an indication of thoracic gas compression in subjects with different pulmonary diseases characterized by limitations in pulmonary mechanics. Methods Patients with emphysema (N = 16), interstitial lung disease (ILD) (N = 15), obesity (N = 15) and healthy controls (N = 16) were included. Compressed expiratory flow-volume curves (at mouth) and corresponding compression-free curves (thoracic) were recorded. Peak flow (PEF) and maximal flows at 75%, 50% and 25% of remaining forced vital capacity (MEF75, MEF50 and MEF25) were derived from both recordings. Their respective difference was assessed as an indicator of gas compression. Results In all groups, significant differences between thoracic and mouth flows were found at MEF50 (p < 0.01). In controls, a significant difference was also measured at MEF75 (p <0.005), in emphysema subjects, at PEF and MEF75 (p < 0.05, p < 0.005) and in obese subjects at MEF75 (p <0.005) and MEF25 (p < 0.01). ILD patients showed the lowest difference between thoracic and mouth flows at MEF75 relative to controls and emphysema patients (p < 0.005, p < 0.001). Obese subjects did not differ from controls, however, the difference between thoracic and mouth flows was significantly higher than in patients with emphysema at MEF50 (p < 0.001) and MEF25 (p < 0.005). Conclusions Alveolar gas compression distorts the forced expiratory flow volume curve in all studied groups at the middle fraction of forced expiratory flow. Consequently, mouth flows are underestimated and the reduction of flow measured at 75% and 50% of vital capacity is often considerable. However, gas compression profiles in stiff lungs, in patients with decreased elastic recoil in emphysema and in obesity differ; the difference between thoracic and mouth flows in forced expiration was minimal in ILD at the first part of forced expiration and was higher in obesity than in emphysema at the middle and last parts of forced expiration.
  • 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.
  • Myllärniemi, Marjukka; Tikkanen, Jussi; Hulmi, Juha J; Pasternack, Arja; Sutinen, Eva; Rönty, Mikko; Leppäranta, Outi; Ma, Hongqiang; Ritvos, Olli; Koli, Katri (BioMed Central Ltd, 2014)
    Abstract Background Activins are members of the TGF-ß superfamily of growth factors. First, we identified by expression array screening that activin-B and follistatin are upregulated in human idiopathic pulmonary fibrosis (IPF). Next, we wanted to clarify their specific role in lung fibrosis formation. Methods We used specific antibodies for activin-A and -B subunits and follistatin to measure and localize their levels in idiopathic pulmonary fibrosis and control lung biopsies. To inhibit activin signaling, we used soluble activin type IIB receptor fused to the Fc portion of human IgG1 (sActRIIB-Fc) in two different mouse models of pulmonary fibrosis. Results Activin-B and follistatin mRNA levels were elevated in the human IPF lung. Immunoreactivity to activin-A, -B and follistatin localized predominantly to the hyperplastic, activated alveolar epithelium, but was also seen in inflammatory cells. Mice treated with sActRIIB-Fc showed increased skeletal muscle mass and a clear reduction in alveolar cell counts in bronchoalveolar lavage fluid, but no significant antifibrotic effect in the lung was observed. Conclusions The upregulation of activin-B and follistatin in IPF is a novel finding. Our results indicate that activin inhibition is not an efficient tool for antifibrotic therapy, but could be useful in reducing alveolar cellular response to injury. Activin-B and follistatin levels may be useful as biomarkers of IPF.
  • van de Bunt, Bert; Bron, Peter A; Sijtsma, Lolke; de Vos, Willem M; Hugenholtz, Jeroen (BioMed Central Ltd, 2014)
    Abstract Background Lactococcus lactis is a lactic acid bacterium that has been used for centuries in the production of a variety of cheeses, as these bacteria rapidly acidify milk and greatly contribute to the flavour of the fermentation end-products. After a short growth phase during cheese ripening L. lactis enters an extended non-growing state whilst still strongly contributing to amino acid-derived flavour formation. Here, a research approach is presented that allows investigation of strain- and amino acid-specific flavour formation during the non-growing state. Results Non-growing cells of five selected L. lactis strains were demonstrated to degrade amino acids into flavour compounds that are relevant in food fermentations and differs greatly from production of flavour compounds using growing cells. As observed earlier in other research set-ups and with other microorganisms, addition of NADH, α-ketoglutarate and pyridoxal-5-phosphate was demonstrated to be essential for optimal flavour formation, suggesting that intracellular pools of these substrates are too low for the significant production of the flavour compounds. Production of flavours during the non-growing phase strongly depends on the individual amino acids that were supplied, on the presence of other amino acids (mixtures versus single compounds), and on the strain used. Moreover, we observed that the plasmid-free model strains L. lactis MG1363 and IL1403 produce relatively low amounts of flavour components under the various conditions tested. Conclusions By using this simplified and rapid approach to study flavour formation by non-growing lactic acid bacteria, lengthy ripening periods are no longer required to assess the capacity of strains to produce flavours in the long, non-growing state of dairy fermentation. In addition, this method also provides insight into the conversion of single amino acids versus the conversion of a mixture of amino acids as produced during protein degradation. The generated results are complementary to earlier generated datasets using growing cells, allowing assessment of the full flavour forming potential of strains used as starter cultures in industrial food fermentation processes.
  • Hemminki, Elina; Virtanen, Jorma I; Veerus, Piret (BioMed Central Ltd, 2014)
    Abstract Background To present empirical data on how the variation in regulating clinical research and patient care was perceived in Finland between 2009 and 2012. Methods Notes of interviews with 22 research ethics committee (REC) chairpersons were analyzed to identify whether differences in the regulation of clinical research and patient care were addressed. REC chairpersons’ opinions on three imaginary cases of clinical research projects challenging current research ethics rules (vignettes) were requested with a questionnaire; 18 of the 22 interviewed chairpersons responded. Results Based on REC chairpersons’ interviews, the differences between care and research regulation were not considered important issues in Finland. In the vignettes, REC chairpersons’ assumptions on how their REC would decide varied in regard to allowing research without informed consent, while solutions that are not allowed by current law were even anticipated. Mostly, but not always, the chairpersons’ own personal view agreed with their REC. Conclusions The distinction between care and research regulation has not been publicly challenged by Finnish RECs, even though it is a challenge when research relevant to health care is carried out. There is a need for debate and changes in laws and practices.