Articles from BioMed Central

 

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  • McLay, Lucy K; Hopkins, Juhani P; Wong, Bob B M; Candolin, Ulrika; Jones, Therésa M (BioMed Central, 2019)
    Abstract Background Artificial light at night (ALAN), has increased dramatically over the past two centuries and is linked to demonstrable shifts in a range of behaviours across diverse animal taxa. This systematic map will collate and synthesise the documented effects of ALAN on animal behaviour and fitness, identify gaps in the literature, inform future research and provide the basis for a decision-making tool for informing policy makers. Methods This systematic map will summarise and examine all available evidence on the effects of ALAN on animal behaviour and ensuing fitness effects. All documented changes to behaviour in animals (excluding humans), will be included and both peer reviewed primary and grey literature will be searched. Searches will be conducted in academic journal databases, online search engines, and specialist websites. Articles will be screened for inclusion in the systematic map at title, abstract and full-text levels and will then be critically appraised for study robustness and validity. Data from studies included in the review will then be extracted and coded according to categories informed by consultation with Stakeholders. Data will be summarised, where possible, in a quantitative manner, accompanied with a descriptive overview. Future avenues for research and specific questions suitable for a systematic literature review will be formulated.
  • Berger-Tal, Oded; Wong, Bob B M; Candolin, Ulrika; Barber, Jesse (BioMed Central, 2019)
    Abstract Background Noise pollution is an intense, widespread anthropogenic disturbance that can have highly detrimental impacts on natural populations, communities, and ecosystems across the globe. One major way through which noise can affect wildlife is by masking acoustic signals that animals rely on and, in doing so, hindering inter- and intraspecific communication among individuals. In response, many animals change their vocal behavior in an attempt to overcome the signal- and cue-masking effects of noisy environments. This can be done by changing the amplitude of the vocal output, shifting its frequency, or changing its temporal structure. However, to date, we still know very little about the ecological contexts of signal modifications in animals or their fitness consequences. We present a protocol for a systematic map aiming to collect and characterize all research done on animals’ signal modification in response to anthropogenic noise. The map will increase our understanding of the consequences of noise pollution on animal communication and may guide the development of new mitigation tools to alleviate any negative effects. The map will also allow us to identify gaps in the literature and highlight possible future research areas. Methods We will collect information about different types of acoustic modifications in response to noise as well as information about the noise’s source and properties. The map will also include the ecological context of the signal modification and the fitness consequences of the modification, if measured. We will search both commercially published literature and grey literature, and conduct the searches in academic journal databases, online search engines, and specialist websites. Articles will be screened for inclusion at title, abstract and full-text levels and will then be critically appraised for study robustness and validity. Data will then be extracted and coded according to categories informed by consultation with stakeholders. Data will be summarized in a quantitative manner, accompanied with a narrative review that will map our knowledge on how animals change their vocalizations in response to noise pollution as a function of their taxa, geographic location, noise pollution source, and vocalization type.
  • Taponen, Suvi; McGuinness, David; Hiitiö, Heidi; Simojoki, Heli; Zadoks, Ruth; Pyörälä, Satu (BioMed Central, 2019)
    Abstract The aim of this study was to analyze bacterial profiles of bovine mastitic milk samples and samples from healthy quarters using Next Generation Sequencing of amplicons from 16S rRNA genes and to compare results with microbiological results by PCR assays of the same samples. A total of 49 samples were collected from one single dairy herd during the same day. The samples were divided in two sample sets, which were used in this study. The DNA extraction as well as the library preparation and sequencing of these two sets were performed separately, and results of the two datasets were then compared. The vast majority of genera detected appeared with low read numbers and/or in only a few samples. Results of PCR and microbiome analyses of samples infected with major pathogens Staphylococcus aureus or Streptococcus uberis were consistent as these genera also covered the majority of reads detected in the microbiome analysis. Analysis of alpha diversity revealed a much higher species richness in set 1 than in set 2. The dominating bacterial genera with the highest read numbers clearly differed between datasets, especially in PCR negative samples and samples positive for minor pathogens. In addition to this, linear discriminant analysis (LDA) was conducted between the two sets to identify significantly different genera/family level microbes. The genus Methylobacterium was much more common in set 2 compared to set 1, and genus Streptococcus more common in set 1. Our results indicate amplification of contaminating bacteria in excess in samples with no or minor amounts of pathogen DNA in dataset 2. There is a need for critical assessment of results of milk microbiome analyses.
  • Stephen, Ruth; Liu, Yawu; Ngandu, Tiia; Antikainen, Riitta; Hulkkonen, Juha; Koikkalainen, Juha; Kemppainen, Nina; Lötjönen, Jyrki; Levälahti, Esko; Parkkola, Riitta; Pippola, Pauliina; Rinne, Juha; Strandberg, Timo; Tuomilehto, Jaakko; Vanninen, Ritva; Kivipelto, Miia; Soininen, Hilkka; Solomon, Alina (BioMed Central, 2019)
    Abstract Background The Finnish Geriatric Intervention Study to Prevent Cognitive Impairment and Disability (FINGER) was a multicenter randomized controlled trial that reported beneficial effects on cognition for a 2-year multimodal intervention (diet, exercise, cognitive training, vascular risk monitoring) versus control (general health advice). This study reports exploratory analyses of brain MRI measures. Methods FINGER targeted 1260 older individuals from the general Finnish population. Participants were 60–77 years old, at increased risk for dementia but without dementia/substantial cognitive impairment. Brain MRI scans were available for 132 participants (68 intervention, 64 control) at baseline and 112 participants (59 intervention, 53 control) at 2 years. MRI measures included regional brain volumes, cortical thickness, and white matter lesion (WML) volume. Cognition was assessed at baseline and 1- and 2-year visits using a comprehensive neuropsychological test battery. We investigated the (1) differences between the intervention and control groups in change in MRI outcomes (FreeSurfer 5.3) and (2) post hoc sub-group analyses of intervention effects on cognition in participants with more versus less pronounced structural brain changes at baseline (mixed-effects regression models, Stata 12). Results No significant differences between the intervention and control groups were found on the changes in MRI measures. Beneficial intervention effects on processing speed were more pronounced in individuals with higher baseline cortical thickness in Alzheimer’s disease signature areas (composite measure of entorhinal, inferior and middle temporal, and fusiform regions). The randomization group × time × cortical thickness interaction coefficient was 0.198 (p = 0.021). A similar trend was observed for higher hippocampal volume (group × time × hippocampus volume interaction coefficient 0.1149, p = 0.085). Conclusions The FINGER MRI exploratory sub-study did not show significant differences between the intervention and control groups on changes in regional brain volumes, regional cortical thicknesses, or WML volume after 2 years in at-risk elderly without substantial impairment. The cognitive benefits on processing speed of the FINGER intervention may be more pronounced in individuals with fewer structural brain changes on MRI at baseline. This suggests that preventive strategies may be more effective if started early, before the occurrence of more pronounced structural brain changes. Trial registration ClinicalTrials.gov, NCT01041989 . Registered January 5, 2010.
  • Fruchart, Jean-Charles; Santos, Raul D; Aguilar-Salinas, Carlos; Aikawa, Masanori; Al Rasadi, Khalid; Amarenco, Pierre; Barter, Philip J; Ceska, Richard; Corsini, Alberto; Després, Jean-Pierre; Duriez, Patrick; Eckel, Robert H; Ezhov, Marat V; Farnier, Michel; Ginsberg, Henry N; Hermans, Michel P; Ishibashi, Shun; Karpe, Fredrik; Kodama, Tatsuhiko; Koenig, Wolfgang; Krempf, Michel; Lim, Soo; Lorenzatti, Alberto J; McPherson, Ruth; Nuñez-Cortes, Jesus M; Nordestgaard, Børge G; Ogawa, Hisao; Packard, Chris J; Plutzky, Jorge; Ponte-Negretti, Carlos I; Pradhan, Aruna; Ray, Kausik K; Reiner, Željko; Ridker, Paul M; Ruscica, Massimiliano; Sadikot, Shaukat; Shimano, Hitoshi; Sritara, Piyamitr; Stock, Jane K; Su, Ta-Chen; Susekov, Andrey V; Tartar, André; Taskinen, Marja-Riitta; Tenenbaum, Alexander; Tokgözoğlu, Lale S; Tomlinson, Brian; Tybjærg-Hansen, Anne; Valensi, Paul; Vrablík, Michal; Wahli, Walter; Watts, Gerald F; Yamashita, Shizuya; Yokote, Koutaro; Zambon, Alberto; Libby, Peter (BioMed Central, 2019)
    Abstract In the era of precision medicine, treatments that target specific modifiable characteristics of high-risk patients have the potential to lower further the residual risk of atherosclerotic cardiovascular events. Correction of atherogenic dyslipidemia, however, remains a major unmet clinical need. Elevated plasma triglycerides, with or without low levels of high-density lipoprotein cholesterol (HDL-C), offer a key modifiable component of this common dyslipidemia, especially in insulin resistant conditions such as type 2 diabetes mellitus. The development of selective peroxisome proliferator-activated receptor alpha modulators (SPPARMα) offers an approach to address this treatment gap. This Joint Consensus Panel appraised evidence for the first SPPARMα agonist and concluded that this agent represents a novel therapeutic class, distinct from fibrates, based on pharmacological activity, and, importantly, a safe hepatic and renal profile. The ongoing PROMINENT cardiovascular outcomes trial is testing in 10,000 patients with type 2 diabetes mellitus, elevated triglycerides, and low levels of HDL-C whether treatment with this SPPARMα agonist safely reduces residual cardiovascular risk.
  • Niemelä, Tytti M; Tulamo, Riitta-Mari; Carmona, Jorge U; López, Catalina (BioMed Central, 2019)
    Abstract Background Inflammatory and degenerative activity inside the joint can be studied in vivo by analysis of synovial fluid biomarkers. In addition to pro-inflammatory mediators, several anabolic and anti-inflammatory substances are produced during the disease process. They counteract the catabolic effects of the pro-inflammatory cytokines and thus diminish the cartilage damage. The response of synovial fluid biomarkers after intra-articular hyaluronan injection, alone or in combination with other substances, has been examined only in a few equine studies. The effects of hyaluronan on some pro-inflammatory mediators, such as prostaglandin E2, have been documented but especially the effects on synovial fluid anti-inflammatory mediators are less studied. In animal models hyaluronan has been demonstrated to reduce pain via protecting nociceptive nerve endings and by blocking pain receptor channels. However, the results obtained for pain-relief of human osteoarthritis are contradictory. The aim of the study was to measure the synovial fluid IL-1ra, PDGF-BB, TGF-β1 and TNF-α concentrations before and after surgically induced cartilage defect, and following intra-articular hyaluronan injection in horses. Eight Standardbred horses underwent bilateral arthroscopic surgeries of their intercarpal joints under general anaesthesia, and cartilage defect was created on the dorsal edge of the third carpal bone of one randomly selected intercarpal joint of each horse. Five days post-surgery, one randomly selected intercarpal joint was injected intra-articular with 3 mL HA (20 mg/mL). Results Operation type had no significant effect on the synovial fluid IL-1ra, PDGF-BB, TGF-β1 and TNF-α concentrations but compared with baseline, synovial fluid IL-1ra and TNF-α concentrations increased. Intra-articular hyaluronan had no significant effect on the biomarker concentrations but a trend of mild improvement in the clinical signs of intra-articular inflammation was seen. Conclusions Creation of the cartilage defect and sham-operation lead to an increase of synovial fluid IL-1ra and TNF-α concentrations but changes in concentrations of anabolic growth factors TGF-β1 and PDGF-BB could not be documented 5 days after the arthroscopy. Intra-articular hyaluronan was well tolerated. Further research is needed to document possible treatment effects of intra-articular hyaluronan on the synovial fluid biomarkers of inflammation and cartilage metabolism.
  • Bergman, Paula; Munsterhjelm, Camilla; Virtala, Anna-Maija; Peltoniemi, Olli; Valros, Anna; Heinonen, Mari (BioMed Central, 2019)
    Abstract Background The main objectives of this observational, cross-sectional study were to characterize piglet producing farms in Finland and to investigate how farm profiles are associated with sow culling and mortality. The study was conducted on 43 farms during 2014. A questionnaire survey was administered in-person and supplemented with observations in the housing facilities. Annual removal figures and average monthly sow inventories were retrieved from a centralized animal data recording system (National Swine Registry) administered by the Finnish Food Authority. Multiple correspondence analysis and hierarchical clustering were used to explore the complex underlying data-driven patterns. Results Sow removal varied markedly between farms with an overall average culling percentage of 38.0% (95% CI 34.1–42.0) and a relatively high average mortality percentage 9.7% (95% CI 7.9–11.5). We identified three farm clusters, which differed both in their typologies and removal patterns. Cluster 1 included farms with features indicative of a semi-intensive or intensive kind of farming, such as larger herd and room sizes, higher stocking density and more sows per caretaker. Most of the cluster 1 farms exceeded the investigated cut-off levels for culling and mortality. Cluster 2 farms were estimated to have the best animal welfare among the sample farms based on a combination of environmental indicators (e.g. amount of bedding, rooting and nesting materials, space allowance, pen cleanliness) and the lowest level of sow mortality as an animal-based indicator. Cluster 3 farms followed a strategy of a rather non-intensified system based on the predominance of smaller herd size, lower stocking density and less sows per caretaker, combined breeding and gestation rooms and rare use of farrowing induction. This cluster showed the lowest culling levels within the sample. Conclusions This study captures the diversity among Finnish sow farms and provides a baseline assessment of their practices and facilities. Our results support the notion that farm typologies are associated with sow culling and mortality. In summary, the control of suboptimal sow removal cannot be based on single improvements only, because of other limitations within the individual farm resources.
  • Berk, Benjamin A; Packer, Rowena M A; Law, Tsz H; Wessmann, Annette; Bathen-Nöthen, Andrea; Jokinen, Tarja S; Knebel, Anna; Tipold, Andrea; Pelligand, Ludovic; Volk, Holger A (BioMed Central, 2019)
    Abstract Background Epilepsy is the most common brain disease in dogs. Recently, diets have been reported to have a positive impact on seizure activity and behaviour in various species including dogs with idiopathic epilepsy (IE). Historically, classic high fat ketogenic diets (KD) and medium chain triglycerides (MCT) KD have been successfully used to manage drug-resistant epilepsy. Similarly, an MCT enriched diet has been shown to improve seizure control and behavioural comorbidities in some dogs with IE. However, it is unknown whether an MCT dietary supplement (DS) may provide similar positive effects. Methods A 6-month prospective, randomised, double-blinded, placebo-controlled, crossover, multicentre dietary trial is designed comparing a 9% metabolic energy based calculated medium-chain triglyceride (MCT) oil supplement to a conventional ‘control’ DS. Only dogs which will have an International Veterinary Epilepsy Task Force Tier II level like diagnosis of IE which satisfied the following inclusion criteria are included: age between 6 months and ≤ 12 years; weighing between 4 and ≤ 65 kg; unremarkable interictal neurological examinations; no clinically significant findings on routine laboratory diagnostics; unremarkable brain MRI scan; have had at least 3 seizures in the previous 3 months prior to enrolment; treated with at least one ASD and being classified as resistant. All dogs are fed initially for 90 ± 2 days with either the control oil or the MCT oil alongside their normal diet, followed by 97 ± 2 days with the other supplement including a 7-day washout period. Overall, the aim is to recruit thirty-six patients at five different centres and to investigate the effect of MCTs as DS on seizure activity, tolerability, behavioural comorbidities and quality of life (QoL). Discussion Dietary interventions are rarely studied in a standardised form in veterinary medicine. The background diet, the cohort of animals and ASD received is standardised in this prospective diet trial to ensure representative data about the potential effect of MCT DS. If the study data confirms former findings, this would provide further evidence for the efficacy of MCTs as a management option for canine epilepsy. This publication should offer a repository of trial conditions and variable description with forecasted statistical analysis.
  • Karjalainen, Liisa; Tikkanen, Minna; Rantanen, Kirsi; Laivuori, Hannele; Gissler, Mika; Ijäs, Petra (BioMed Central, 2019)
    Abstract Background Pregnancy-associated stroke is a rare but life-threatening event, with an estimated incidence of 30/100000 deliveries. Data on the risk of stroke recurrence and the risk of other adverse pregnancy outcomes are essential for adequate counselling and surveillance in subsequent pregnancies. The aim of this systematic review is to describe the implications of a pregnancy-associated stroke for the future health of these women. Methods We searched Ovid Medline, PubMed, Cochrane Library and CINAHL for articles published in 1980–2018. Articles including women with pregnancy-associated stroke and information on at least one of the following outcomes were included: 1) recurrence of stroke during subsequent pregnancy, 2) number and course of subsequent pregnancies and their outcomes and 3) subsequent cardiovascular health. Results Twelve articles were included in the review, with six providing information on subsequent pregnancies, four on subsequent maternal health and two on both. The included articles varied greatly in terms of study design, length of follow up and reported outcomes. We found 252 women with pregnancy-associated stroke for whom the outcomes of interest were reported: 135 women with information on subsequent pregnancies and 123 women with information on future health. In total, 55 pregnancies after stroke were found. In the majority of studies, the incidence of pregnancy complications was comparable to that of the general population. The risk of stroke recurrence during pregnancy was 2%. Data on subsequent health of these women were limited, and the quality of the data varied between the studies. Conclusions Data on subsequent pregnancies and health of women with a history of pregnancy-associated stroke are limited. Further research on this topic is essential for adequate counselling and secondary prevention.
  • Mäkinen, Mari; Kuuskeri, Jaana; Laine, Pia; Smolander, Olli-Pekka; Kovalchuk, Andriy; Zeng, Zhen; Asiegbu, Fred O; Paulin, Lars; Auvinen, Petri; Lundell, Taina (BioMed Central, 2019)
    Abstract Background The white rot fungus Phlebia radiata, a type species of the genus Phlebia, is an efficient decomposer of plant cell wall polysaccharides, modifier of softwood and hardwood lignin, and is able to produce ethanol from various waste lignocellulose substrates. Thus, P. radiata is a promising organism for biotechnological applications aiming at sustainable utilization of plant biomass. Here we report the genome sequence of P. radiata isolate 79 originally isolated from decayed alder wood in South Finland. To better understand the evolution of wood decay mechanisms in this fungus and the Polyporales phlebioid clade, gene content and clustering of genes encoding specific carbohydrate-active enzymes (CAZymes) in seven closely related fungal species was investigated. In addition, other genes encoding proteins reflecting the fungal lifestyle including peptidases, transporters, small secreted proteins and genes involved in secondary metabolism were identified in the genome assembly of P. radiata. Results The PACBio sequenced nuclear genome of P. radiata was assembled to 93 contigs with 72X sequencing coverage and annotated, revealing a dense genome of 40.4 Mbp with approximately 14 082 predicted protein-coding genes. According to functional annotation, the genome harbors 209 glycoside hydrolase, 27 carbohydrate esterase, 8 polysaccharide lyase, and over 70 auxiliary redox enzyme-encoding genes. Comparisons with the genomes of other phlebioid fungi revealed shared and specific properties among the species with seemingly similar saprobic wood-decay lifestyles. Clustering of especially GH10 and AA9 enzyme-encoding genes according to genomic localization was discovered to be conserved among the phlebioid species. In P. radiata genome, a rich repertoire of genes involved in the production of secondary metabolites was recognized. In addition, 49 genes encoding predicted ABC proteins were identified in P. radiata genome together with 336 genes encoding peptidases, and 430 genes encoding small secreted proteins. Conclusions The genome assembly of P. radiata contains wide array of carbohydrate polymer attacking CAZyme and oxidoreductase genes in a composition identifiable for phlebioid white rot lifestyle in wood decomposition, and may thus serve as reference for further studies. Comparative genomics also contributed to enlightening fungal decay mechanisms in conversion and cycling of recalcitrant organic carbon in the forest ecosystems.
  • Kettunen, Eeva; Savukoski, Sauli; Salmenkivi, Kaisa; Böhling, Tom; Vanhala, Esa; Kuosma, Eeva; Anttila, Sisko; Wolff, Henrik (BioMed Central, 2019)
    Abstract Background Deletion of the CDKN2A locus is centrally involved in the development of several malignancies. In malignant pleural mesothelioma (MPM), it is one of the most frequently reported genomic alteration. MPM is strongly associated with a patients’ asbestos exposure. However, the status of CDKN2A and the expression of the corresponding protein, p16, in relation to MPM patient’s asbestos exposure is poorly known. Copy number alterations in 2p16, 9q33.1 and 19p13 have earlier been shown to accumulate in lung cancer in relation to asbestos exposure but their status in MPM is unclear. Methods We studied DNA copy numbers for CDKN2A using fluorescence in situ hybridization (FISH) and p16 expression by immunohistochemistry (IHC) in 92 MPM patients, 75 of which with known asbestos exposure status. We also studied, in MPM, copy number alterations in 2p16, 9q33.1 and 19p13 by FISH. Results We were unable to detect an association between p16 expression and pulmonary asbestos fiber count in MPM tumor cells. However, significantly more MPM patients with high pulmonary asbestos fiber count (> 1 million fibers per gram [f/g]) had stromal p16 immunoreactivity than MPM of patients with low exposure (≤ 0.5 million f/g) (51.4% vs 16.7%; p = 0.035, Chi-Square). We found that an abnormal copy number of CDKN2A in MPM tumor cells associated with a high pulmonary asbestos fiber count (p = 0.044, Fisher’s Exact test, two-tailed). In contrast to our earlier findings in asbestos associated lung cancer, DNA copy number changes in 2p16, 9q33 and 19p13 were not frequent in MPM although single cases with variable copy numbers on those regions were seen. Conclusions We found two instances where the gene locus CDKN2A or its corresponding protein expression, is associated with high asbestos exposure levels. This suggests that there may be biological differences between the mesotheliomas with high pulmonary asbestos fiber count and those with low fiber count.
  • L’opez, Sara C; Theelen, Bart; Manserra, Serena; Issak, Tedros Y; Rytioja, Johanna; Mäkelä, Miia R; de Vries, Ronald P (BioMed Central, 2017)
    Abstract Dichomitus squalens is a white-rot fungus that colonizes and grows mainly on softwood and is commonly found in the northern parts of Europe, North America, and Asia. We analyzed the genetic and physiological diversity of eight D. squalens monokaryons derived from a single dikaryon. In addition, an unrelated dikaryon and a newly established dikaryon from two of the studied monokaryons were included. Both growth and lignocellulose acting enzyme profiles were highly variable between the studied monokaryotic and dikaryotic strains, demonstrating a high level of diversity within the species.
  • Mustonen, Anne-Mari; Käkelä, Reijo; Lehenkari, Petri; Huhtakangas, Johanna; Turunen, Sanna; Joukainen, Antti; Kääriäinen, Tommi; Paakkonen, Tommi; Kröger, Heikki; Nieminen, Petteri (BioMed Central, 2019)
    Abstract Background Infrapatellar fat pad (IFP) has recently emerged as a potential source of inflammation in knee arthropathies. It has been proposed to be one source of adipocytokines, fatty acids (FA), and FA-derived lipid mediators that could contribute to the pathophysiological processes in the knee joint. Alterations in synovial fluid (SF) lipid composition have been linked to both osteoarthritis (OA) and rheumatoid arthritis (RA). The aim of the present study was to compare the FA signatures in the IFP and SF of RA and OA patients. Methods Pairs of IFP and SF samples were collected from the same knees of RA (n = 10) and OA patients (n = 10) undergoing total joint replacement surgery. Control SF samples (n = 6) were harvested during diagnostic or therapeutic arthroscopic knee surgery unrelated to RA or OA. The FA composition in the total lipids of IFP and SF was determined by gas chromatography with flame ionization and mass spectrometric detection. Results Arthropathies resulted in a significant reduction in the SF proportions of n-6 polyunsaturated FA (PUFA), more pronouncedly in OA than in RA. OA was also characterized with reduced percentages of 22:6n-3 and lower product/precursor ratios of n-3 PUFA. The proportions of total monounsaturated FA increased in both RA and OA SF. Regarding IFP, RA patients had lower proportions of 20:4n-6, total n-6 PUFA, and 22:6n-3, as well as lower product/precursor ratios of n-3 PUFA compared to OA patients. The average chain length of SF FA decreased in both diagnoses and the double bond index in OA. Conclusions The observed complex alterations in the FA signatures could have both contributed to but also limited the inflammatory processes and cartilage destruction in the RA and OA knees.
  • Place, Katariina; Kruit, Heidi; Tekay, Aydin; Heinonen, Seppo; Rahkonen, Leena (BioMed Central, 2019)
    Abstract Background The rates of cesarean section (CS) are increasing worldwide leading to an increased risk for maternal and neonatal complications in the subsequent pregnancy and labor. Previous studies have demonstrated that successful trial of labor after cesarean (TOLAC) is associated with the least maternal morbidity, but the risks of unsuccessful TOLAC exceed the risks of scheduled repeat CS. However, prediction of successful TOLAC is difficult, and only limited data on TOLAC in women with previous failed labor induction or labor dystocia exists. Our aim was to evaluate the success of TOLAC in women with a history of failed labor induction or labor dystocia, to compare the delivery outcomes according to stage of labor at time of previous CS, and to assess the risk factors for recurrent failed labor induction or labor dystocia. Methods This retrospective cohort study of 660 women with a prior CS for failed labor induction or labor dystocia undergoing TOLAC was carried out in Helsinki University Hospital, Finland, between 2013 and 2015. Data on the study population was obtained from the hospital database and analyzed using SPSS. Results The rate of vaginal delivery was 72.9% and the rate of repeat CS for failed induction or labor dystocia was 17.7%. The rate of successful TOLAC was 75.6% in women with a history of labor arrest in the first stage of labor, 73.1% in women with a history of labor arrest in the second stage of labor, and 59.0% in women with previous failed induction. The adjusted risk factors for recurrent failed induction or labor dystocia were maternal height < 160 cm (OR 1.9 95% CI 1.1–3.1), no prior vaginal delivery (OR 8.3 95% CI 3.5–19.8), type 1 or gestational diabetes (OR 1.8 95% CI 1.0–3.0), IOL for suspected non-diabetic fetal macrosomia (OR 10.8 95% CI 2.1–55.9) and birthweight ≥4500 g (OR 3.3 95% CI 1.3–7.9). Conclusions TOLAC is a feasible option to scheduled repeat CS in women with a history of failed induction or labor dystocia. However, women with no previous vaginal delivery, maternal height < 160 cm, diabetes or suspected neonatal macrosomia (≥4500 g) may be at increased risk for failed TOLAC.
  • Passov, Arie; Petäjä, Liisa; Pihlajoki, Marjut; Salminen, Ulla-Stina; Suojaranta, Raili; Vento, Antti; Andersson, Sture; Pettilä, Ville; Schramko, Alexey; Pesonen, Eero (BioMed Central, 2019)
    Abstract Background Acute kidney injury (AKI) is common after heart surgery. Neutrophil gelatinase-associated lipocalin (NGAL) is produced in injured kidney. NGAL has been used as an early plasma biomarker for AKI in patients undergoing heart surgery. Neutrophils contain all isoforms (25-kDa, 45-kDa and 145-kDa) but the kidney produces almost exclusively the 25-kDa isoform of NGAL. We investigated first, whether there is association between NGAL and neutrophil activation, and second whether activated neutrophils are a significant source of circulating NGAL in plasma in patients undergoing cardiac surgery. Methods Two separate patient cohorts were studied: 1) the “kinetic cohort” (n = 29) and 2) the “FINNAKI cohort” (n = 306). As NGAL is strictly co-localized with lactoferrin in neutrophils, NGAL and lactoferrin were measured with enzyme-linked immunosorbent assay in all patients. In sixty-one patients of the “FINNAKI cohort” Western blot was used to separate NGAL isoforms according to their molecular size. Mann-Whitney U, Kruskal-Wallis H, Pearson’s and Spearman’s tests were used as appropriate. Results There was strong intraoperative association between NGAL and lactoferrin at all four time-points in the “kinetic cohort”. In the “FINNAKI cohort”, NGAL and lactoferrin concentrations correlated preoperatively (R = 0.59, p < 0.001) and at admission to the intensive care unit (R = 0.69, p < 0.001). At admission to intensive care unit, concentrations of NGAL and lactoferrin were higher in AKI than in non-AKI patients (NGAL: p < 0.001; lactoferrin: p < 0.029). In Western blot analyses, neutrophil specific 45-kDa isoform (median 41% [IQR 33.3–53.1]) and mostly neutrophil derived 145-kDa isoform (median 53.5% [IQR 44.0–64.9%]) together represented over 90% of total NGAL in plasma. Potentially kidney derived NGAL isoform (25-kDa) accounted for only 0.9% (IQR 0.3 – 3.0%) of total NGAL in plasma. There were no statistically significant differences in the distribution of NGAL isomers between AKI and non-AKI patients. Conclusions Plasma NGAL during cardiac surgery is associated with neutrophil activation. Based on molecular size, the majority of circulating NGAL is derived from neutrophils. Neutrophil activation is a confounding factor when interpreting increased plasma NGAL in cardiac surgery.
  • Saraswat, Mayank; Nieminen, Heini; Joenvaara, Sakari; Tohmola, Tiialotta; Seppänen, Hanna; Ristimäki, Ari; Haglund, Caj; Renkonen, Risto (BioMed Central, 2019)
    Abstract Background Intraductal Papillary Mucinous Neoplasia (IPMN) are potentially malignant cystic tumors of the pancreas. IPMN can progress from low to moderate to high grade dysplasia and further to IPMN associated carcinoma. Often the difference between benign and malignant nature of the IPMN is not clear preoperatively. We aim to elucidate molecular expression patterns of various grades of IPMN and pancreatic carcinoma. Additionally we suggest potential novel biomarkers to differentiate IPMN from healthy individuals and pancreatic carcinoma to enable early detection as well as help in differential diagnosis in future. Methods We have performed retrospective label-free proteomic analysis of the serum samples from 44 patients with various grades of benign IPMN or IPMN associated carcinoma and 11 healthy controls. Proteomic data was further analyzed by various multivariate statistical methods. Four groups of samples (low-grade, high-grade IPMN, pancreatic carcinoma and age- and sex-matched healthy controls) were compared with ANOVA. Orthogonal projections to latent structures-discriminant analysis (OPLS-DA) modeling gave S-plot for feature selection. Stringently selected potential markers were further evaluated with ROC curve analysis and area under the curve was calculated. Differentially expressed proteins were used for pathway analysis. Linear trend analysis (Mann Kendall test) was used for identifying significant increasing or decreasing trends from healthy-low grade-high grade IPMN-pancreatic carcinoma. Results Based on protein expression (436 proteins quantified), PCA separated most sample groups from each other. S-Plot selected biomarker panels with moderate to very high AUC values for differentiating controls from Low-, High-Grade IPMN and carcinoma. Linear trend analysis identified 12 proteins which were consistently increasing or decreasing trend among the groups. We found potential biomarkers to differentiate healthy controls from different degrees of dysplasia and pancreatic carcinoma. These biomarkers can classify IPMN, carcinoma and healthy controls from each other which is an unmet clinical need. Data are available via ProteomeXchange with identifier PXD009139. Conclusion Kininogen-1 was able to differentiate healthy persons from low and high-grade IPMN. Retinol binding protein-4 could classify the low-grade IPMN from pancreatic carcinoma. Twelve proteins including apolipoproteins and complement proteins had significantly increasing or decreasing trends from healthy to low to high-grade IPMN to pancreatic carcinoma.
  • Jakkula, Pekka; Hästbacka, Johanna; Reinikainen, Matti; Pettilä, Ville; Loisa, Pekka; Tiainen, Marjaana; Wilkman, Erika; Bendel, Stepani; Birkelund, Thomas; Pulkkinen, Anni; Bäcklund, Minna; Heino, Sirkku; Karlsson, Sari; Kopponen, Hiski; Skrifvars, Markus B (BioMed Central, 2019)
    Abstract Background Cerebral hypoperfusion may aggravate neurological damage after cardiac arrest. Near-infrared spectroscopy (NIRS) provides information on cerebral oxygenation but its relevance during post-resuscitation care is undefined. We investigated whether cerebral oxygen saturation (rSO2) measured with NIRS correlates with the serum concentration of neuron-specific enolase (NSE), a marker of neurological injury, and with clinical outcome in out-of-hospital cardiac arrest (OHCA) patients. Methods We performed a post hoc analysis of a randomised clinical trial (COMACARE, NCT02698917) comparing two different levels of carbon dioxide, oxygen and arterial pressure after resuscitation from OHCA with ventricular fibrillation as the initial rhythm. We measured rSO2 in 118 OHCA patients with NIRS during the first 36 h of intensive care. We determined the NSE concentrations from serum samples at 48 h after cardiac arrest and assessed neurological outcome with the Cerebral Performance Category (CPC) scale at 6 months. We evaluated the association between rSO2 and serum NSE concentrations and the association between rSO2 and good (CPC 1–2) and poor (CPC 3–5) neurological outcome. Results The median (inter-quartile range (IQR)) NSE concentration at 48 h was 17.5 (13.4–25.0) μg/l in patients with good neurological outcome and 35.2 (22.6–95.8) μg/l in those with poor outcome, p < 0.001. We found no significant correlation between median rSO2 and NSE at 48 h, rs = − 0.08, p = 0.392. The median (IQR) rSO2 during the first 36 h of intensive care was 70.0% (63.5–77.0%) in patients with good outcome and 71.8% (63.3–74.0%) in patients with poor outcome, p = 0.943. There was no significant association between rSO2 over time and neurological outcome. In a binary logistic regression model, rSO2 was not a statistically significant predictor of good neurological outcome (odds ratio 0.99, 95% confidence interval 0.94–1.04, p = 0.635). Conclusions We found no association between cerebral oxygenation measured with NIRS and NSE concentrations or outcome in patients resuscitated from OHCA. Trial registration ClinicalTrials.gov, NCT02698917 . Registered on 26 January 2016.
  • Norri, Tuukka; Cazaux, Bastien; Kosolobov, Dmitry; Mäkinen, Veli (BioMed Central, 2019)
    Abstract Background  We study a preprocessing routine relevant in pan-genomic analyses: consider a set of aligned haplotype sequences of complete human chromosomes. Due to the enormous size of such data, one would like to represent this input set with a few founder sequences that retain as well as possible the contiguities of the original sequences. Such a smaller set gives a scalable way to exploit pan-genomic information in further analyses (e.g. read alignment and variant calling). Optimizing the founder set is an NP-hard problem, but there is a segmentation formulation that can be solved in polynomial time, defined as follows. Given a threshold L and a set $${\mathcal {R}} = \{R_1, \ldots , R_m\}$$ R = { R 1 , … , R m } of m strings (haplotype sequences), each having length n, the minimum segmentation problem for founder reconstruction is to partition [1, n] into set P of disjoint segments such that each segment $$[a,b] \in P$$ [ a , b ] ∈ P has length at least L and the number $$d(a,b)=|\{R_i[a,b] :1\le i \le m\}|$$ d ( a , b ) = | { R i [ a , b ] : 1 ≤ i ≤ m } | of distinct substrings at segment [a, b] is minimized over $$[a,b] \in P$$ [ a , b ] ∈ P . The distinct substrings in the segments represent founder blocks that can be concatenated to form $$\max \{ d(a,b) :[a,b] \in P \}$$ max { d ( a , b ) : [ a , b ] ∈ P } founder sequences representing the original $${\mathcal {R}}$$ R such that crossovers happen only at segment boundaries. Results  We give an O(mn) time (i.e. linear time in the input size) algorithm to solve the minimum segmentation problem for founder reconstruction, improving over an earlier $$O(mn^2)$$ O ( m n 2 ) . Conclusions  Our improvement enables to apply the formulation on an input of thousands of complete human chromosomes. We implemented the new algorithm and give experimental evidence on its practicality. The implementation is available in https://github.com/tsnorri/founder-sequences .
  • Tammiste, Triin; Kask, Keiu; Padrik, Peeter; Idla, Külli; Rosenstein, Karin; Jatsenko, Tatjana; Veerus, Piret; Salumets, Andres (BioMed Central, 2019)
    Abstract Background Ovarian insufficiency is a major concern for long-term cancer survivors. Although semen freezing is well established to preserve male fertility, the possibilities to secure post-cancer female fertility are mostly limited to oocyte or embryo freezing. These methods require time-consuming ovarian stimulation with or without in vitro fertilization (IVF) that evidently delays cancer therapy. Ovarian tissue cryopreservation and subsequent thawed tissue autotransplantation are considered the most promising alternative strategy for restoring the fertility of oncology patients, which has not yet received the full clinical acceptance. Therefore, all successful cases are needed to prove its reliability and safety. Case presentation Here we report a single case in Estonia, where a 28-year-old woman with malignant breast neoplasm had ovarian cortex cryopreserved before commencing gonadotoxic chemo- and radiotherapy. Two years after cancer therapy, the patient underwent heterotopic ovarian tissue transplantation into the lateral pelvic wall. The folliculogenesis was stimulated in the transplanted tissue by exogenous follicle-stimulating hormone and oocytes were collected under ultrasound guidance for IVF and embryo transfer. The healthy boy was born after full-term gestation in 2014, first in Eastern Europe. Conclusion Despite many countries have reported the first implementation of the ovarian tissue freezing and transplantation protocols, the data is still limited on the effectiveness of heterotopic ovarian transplant techniques. Thus, all case reports of heterotopic ovarian tissue transplantation and long-term follow-ups to describe the children’s health are valuable source of clinical experience.
  • Hietapakka, Laura; Elovainio, Marko; Wesolowska, Karolina; Aalto, Anna-Mari; Kaihlanen, Anu-Marja; Sinervo, Timo; Heponiemi, Tarja (BioMed Central, 2019)
    Abstract Background To test the validity of the Finnish version of the Bernhard et al.’s Cross-Cultural Competence instrument of Healthcare Professionals (CCCHP). Methods The study sample comprised registered nurses (N = 810) from the Finnish “Competent workforce for the future” -project (COPE). Exploratory factor analyses and structural equation modelling were applied to test structural validity of the CCCHP. Internal consistency of the sub-scales was evaluated using the Cronbach’s alphas. Criterion validity was explored in terms of received education for multicultural work, perceived difficulty of patients, and job satisfaction variables. Results The revised version of the instrument including four (motivation/curiosity, attitudes, skills and emotions/empathy) of the five original dimensions provided satisfactory psychometric properties (internal consistency, a good model fit of the data). Of the four remaining competence sub-scales, motivation/curiosity, attitudes and emotions/empathy were associated with the amount of received education for multicultural work, and all with perceived difficulty of patients, and all but attitudes with job satisfaction. Conclusion This revised Finnish version of the CCCHP provides a useful tool for studies focusing on the healthcare personnel’s cross-cultural competence in delivering effective and culturally sensitive healthcare services for patients from different cultures.

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