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  • Kuuluvainen, Timo; Lindberg, Henrik; Vanha-Majamaa, Ilkka; Keto-Tokoi, Petri; Punttila, Pekka (Springer Berlin Heidelberg, 2019)
    Abstract In managed forests, leaving retention trees during final harvesting has globally become a common approach to reconciling the often conflicting goals of timber production and safeguarding biodiversity and delivery of several ecosystem services. In Finland, the dominant certification scheme requires leaving low levels of retention that can benefit some specific species. However, species responses are dependent on the level of retention and the current low amounts of retention clearly do not provide the habitat quality and continuity needed for declining and red-listed forest species which are dependent on old living trees and coarse woody debris. Several factors contribute to this situation. First, the ecological benefits of the current low retention levels are further diminished by monotonous standwise use of retention, resulting in low variability of retention habitat at the landscape scale. Second, the prevailing timber-oriented management thinking may regard retention trees as an external cost to be minimized, rather than as part of an integrated approach to managing the ecosystem for specific goals. Third, the main obstacles of development may still be institutional and policy-related. The development of retention practices in Finland indicates that the aim has not been to use ecological understanding to attain specific ecological sustainability goals, but rather to define the lowest level of retention that still allows access to the market. We conclude that prevailing retention practices in Finland currently lack ecological credibility in safeguarding biodiversity and they should urgently be developed based on current scientific knowledge to meet ecological sustainability goals.
  • Harrois, A.; Anstey, J. R; Taccone, F. S; Udy, A. A; Citerio, G.; Duranteau, J.; Ichai, C.; Badenes, R.; Prowle, J. R; Ercole, A.; Oddo, M.; Schneider, A.; van der Jagt, M.; Wolf, S.; Helbok, R.; Nelson, D. W; Skrifvars, M. B; Cooper, D. J; Bellomo, R. (Springer International Publishing, 2019)
    Following publication of the original article [1], we were notified that the collaborators’ names part of the “The TBI Collaborative” group has not been indexed in Pubmed. Below the collaborators names full list:
  • Rypdal, Veronika; Guzman, Jaime; Henrey, Andrew; Loughin, Thomas; Glerup, Mia; Arnstad, Ellen D; Aalto, Kristiina; Rygg, Marite; Nielsen, Susan; Herlin, Troels; Fasth, Anders; Berntson, Lillemor; Rypdal, Martin; Nordal, Ellen (BioMed Central, 2019)
    Abstract Background Models to predict disease course and long-term outcome based on clinical characteristics at disease onset may guide early treatment strategies in juvenile idiopathic arthritis (JIA). Before a prediction model can be recommended for use in clinical practice, it needs to be validated in a different cohort than the one used for building the model. The aim of the current study was to validate the predictive performance of the Canadian prediction model developed by Guzman et al. and the Nordic model derived from Rypdal et al. to predict severe disease course and non-achievement of remission in Nordic patients with JIA. Methods The Canadian and Nordic multivariable logistic regression models were evaluated in the Nordic JIA cohort for prediction of non-achievement of remission, and the data-driven outcome denoted severe disease course. A total of 440 patients in the Nordic cohort with a baseline visit and an 8-year visit were included. The Canadian prediction model was first externally validated exactly as published. Both the Nordic and Canadian models were subsequently evaluated with repeated fine-tuning of model coefficients in training sets and testing in disjoint validation sets. The predictive performances of the models were assessed with receiver operating characteristic curves and C-indices. A model with a C-index above 0.7 was considered useful for clinical prediction. Results The Canadian prediction model had excellent predictive ability and was comparable in performance to the Nordic model in predicting severe disease course in the Nordic JIA cohort. The Canadian model yielded a C-index of 0.85 (IQR 0.83–0.87) for prediction of severe disease course and a C-index of 0.66 (0.63–0.68) for prediction of non-achievement of remission when applied directly. The median C-indices after fine-tuning were 0.85 (0.80–0.89) and 0.69 (0.65–0.73), respectively. Internal validation of the Nordic model for prediction of severe disease course resulted in a median C-index of 0.90 (0.86–0.92). Conclusions External validation of the Canadian model and internal validation of the Nordic model with severe disease course as outcome confirm their predictive abilities. Our findings suggest that predicting long-term remission is more challenging than predicting severe disease course.
  • Leppänen, Marja H; Ray, Carola; Wennman, Heini; Alexandrou, Christina; Sääksjärvi, Katri; Koivusilta, Leena; Erkkola, Maijaliisa; Roos, Eva (BioMed Central, 2019)
    Abstract Background Recent 24-h movement guidelines for the early years established recommendations for physical activity (PA), screen time (ST), and sleep. To date, few studies have focused on compliance with meeting the guidelines and their associations with health outcomes. Thus, we aimed to investigate: 1) compliance with the 24-h movement guidelines, and 2) associations between compliance and anthropometry in Finnish preschoolers. Methods We utilized DAGIS survey data that were collected in 2015–2016 (N = 864). PA was assessed 24 h/day over 7 days using a waist-worn ActiGraph wGT3X-BT accelerometer. ST and sleep were reported by the parents during the same 7 days. Anthropometry was assessed using body mass index (BMI, kg/m2) and waist circumference (WC, cm). Children were classified as meeting the guidelines if they averaged ≥180 min/day of PA, which consisted of ≥60 min of moderate-to-vigorous intensity; ≤60 min/day of ST; and 10–13 h/day of sleep. In total, 778 children (51% boys, mean age: 4.7 ± 0.9 years) were included in the study. The compliance with meeting the 24-h movement guidelines was calculated for each behavior separately and in combinations. Adjusted linear regression analyses were applied to examine associations of compliance with BMI and WC. Results Children were physically active on average 390 (±46.2) min/day and spent 86 (±25.5) min/day in moderate-to-vigorous PA. They spent 76 (±37.4) min/day on ST and had on average 10:21 (±0:33) h:min/day of sleep. The compliance rate in meeting all three movement guidelines overall was 24%. The highest compliance rate was found for PA (85%), followed by sleep (76%) and ST (35%). Meeting guidelines separately for PA or sleep, or for both, were associated with lower WC (PA: B = -1.37, p < 0.001; Sleep: B = -0.72, p = 0.009; PA + Sleep: B = -1.03, p < 0.001). In addition, meeting guidelines for sleep or for both PA and sleep were associated with lower BMI (Sleep: B = -0.26, p = 0.027; PA + Sleep: B = -0.30, p = 0.007). There were no significant associations found regarding ST. Conclusions Meeting recommendations for PA and sleep may have an important role in supporting a healthy weight status in young children. However, there is still a need to improve compliance with the 24-h movement guidelines, especially for ST.
  • Toivo, Terhi; Airaksinen, Marja; Dimitrow, Maarit; Savela, Eeva; Pelkonen, Katariina; Kiuru, Valtteri; Suominen, Tuula; Uunimäki, Mira; Kivelä, Sirkka-Liisa; Leikola, Saija; Puustinen, Juha (BioMed Central, 2019)
    Abstract Background As populations are aging, a growing number of home care clients are frail and use multiple, complex medications. Combined with the lack of coordination of care this may pose uncontrolled polypharmacy and potential patient safety risks. The aim of this study was to assess the impact of a care coordination intervention on medication risks identified in drug regimens of older home care clients over a one-year period. Methods Two-arm, parallel, cluster randomized controlled trial with baseline and follow-up assessment at 12 months. The study was conducted in Primary Care in Lohja, Finland: all 5 home care units, the public healthcare center, and a private community pharmacy. Participants: All consented home care clients aged > 65 years, using at least one prescription medicine who were assessed at baseline and at 12 months. Intervention: Practical nurses were trained to make the preliminary medication risk assessment during home visits and report findings to the coordinating pharmacist. The coordinating pharmacist prepared the cases for the triage meeting with the physician and home care nurse to decide on further actions. Each patient’s physician made the final decisions on medication changes needed. Outcomes were measured as changes in medication risks: use of potentially inappropriate medications and psychotropics; anticholinergic and serotonergic load; drug-drug interactions. Results Participants (n = 129) characteristics: mean age 82.8 years, female 69.8%, mean number of prescription medicines in use 13.1. The intervention did not show an impact on the medication risks between the original intervention group and the control group in the intention to treat analysis, but the per protocol analysis indicated tendency for effectiveness, particularly in optimizing central nervous system medication use. Half (50.0%) of the participants with a potential need for medication changes, agreed on in the triage meeting, had none of the medication changes actually implemented. Conclusion The care coordination intervention used in this study indicated tendency for effectiveness when implemented as planned. Even though the outcome of the intervention was not optimal, the value of this paper is in discussing the real world experiences and challenges of implementing new practices in home care. Trial registration ClinicalTrials.gov (NCT02545257). Registered September 9 2015.
  • Kringel, Dario; Kaunisto, Mari A; Kalso, Eija; Lötsch, Jörn (BioMed Central, 2019)
    Abstract Background Glial cells in the central nervous system play a key role in neuroinflammation and subsequent central sensitization to pain. They are therefore involved in the development of persistent pain. One of the main sites of interaction of the immune system with persistent pain has been identified as neuro-immune crosstalk at the glial-opioid interface. The present study examined a potential association between the DNA methylation of two key players of glial/opioid intersection and persistent postoperative pain. Methods In a cohort of 140 women who had undergone breast cancer surgery, and were assigned based on a 3-year follow-up to either a persistent or non-persistent pain phenotype, the role of epigenetic regulation of key players in the glial-opioid interface was assessed. The methylation of genes coding for the Toll-like receptor 4 (TLR4) as a major mediator of glial contributions to persistent pain or for the μ-opioid receptor (OPRM1) was analyzed and its association with the pain phenotype was compared with that conferred by global genome-wide DNA methylation assessed via quantification of the methylation in the retrotransposon LINE1. Results Training of machine learning algorithms indicated that the global DNA methylation provided a similar diagnostic accuracy for persistent pain as previously established non-genetic predictors. However, the diagnosis can be based on a single DNA based marker. By contrast, the methylation of TLR4 or OPRM1 genes could not contribute further to the allocation of the patients to the pain-related phenotype groups. Conclusions While clearly supporting a predictive utility of epigenetic testing, the present analysis cannot provide support for specific epigenetic modulation of persistent postoperative pain via methylation of two key genes of the glial-opioid interface.
  • Ala-Kurikka, Eve; Munsterhjelm, Camilla; Bergman, Paula; Laine, Taina; Pekkarinen, Henna; Peltoniemi, Olli; Valros, Anna; Heinonen, Mari (BioMed Central, 2019)
    Abstract Background A high rate of euthanized and spontaneously dead sows causes production losses and likely indicates underlying welfare problems. Identification of predisposing factors to on-farm deaths requires a thorough understanding of the causes. Post-mortem examination is needed for a proper diagnosis. The aims of this descriptive study were to determine causes of spontaneous deaths and euthanasia in sows in a convenience sample of Finnish herds and to describe pathological findings in the locomotor system and in teeth and gums. Results This study described post-mortem findings in 65 sows found dead or euthanized on 15 farms. All but one of the sows presented with two or more pathological findings. The majority of primary pathologic-anatomic diagnoses (PAD-1) were inflammatory. The most prevalent diagnoses were arthritis and peritonitis (9% of sows each). The locomotor system was the body part most commonly affected by lesions. Findings in the locomotor system unassociated with death were present in 85% of the animals, additionally 29% of PAD-1 s concerned the locomotor system. The prevalence for both degenerative joint disease and tooth wear was 71%. Farmers had noted clinical signs within 30 days of death in every euthanized sow and in half of the spontaneously dead ones. The farmer’s impression of the cause of death agreed at least partly with the PAD-1 in 44% of the cases. Conclusion Multiple pathologies were the norm in the present animals. This may indicate an extended course of illness and therefore also an unnecessary delay in medical treatment or euthanasia. The prevalence and clinical relevance of the most common disorders, including degenerative joint disease and tooth wear, need to be elucidated.
  • Rajani, Rikesh M; Ratelade, Julien; Domenga-Denier, Valérie; Hase, Yoshiki; Kalimo, Hannu; Kalaria, Raj N; Joutel, Anne (BioMed Central, 2019)
    Abstract Cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL) is a genetic paradigm of small vessel disease (SVD) caused by NOTCH3 mutations that stereotypically lead to the vascular accumulation of NOTCH3 around smooth muscle cells and pericytes. White matter (WM) lesions (WMLs) are the earliest and most frequent abnormalities, and can be associated with lacunar infarcts and enlarged perivascular spaces (ePVS). The prevailing view is that blood brain barrier (BBB) leakage, possibly mediated by pericyte deficiency, plays a pivotal role in the formation of WMLs. Herein, we investigated the involvement of BBB leakage and pericyte loss in CADASIL WMLs. Using post-mortem brain tissue from 12 CADASIL patients and 10 age-matched controls, we found that WMLs are heterogeneous, and that BBB leakage reflects the heterogeneity. Specifically, while fibrinogen extravasation was significantly increased in WMLs surrounding ePVS and lacunes, levels of fibrinogen leakage were comparable in WMLs without other pathology (“pure” WMLs) to those seen in the normal appearing WM of patients and controls. In a mouse model of CADASIL, which develops WMLs but no lacunes or ePVS, we detected no extravasation of endogenous fibrinogen, nor of injected small or large tracers in WMLs. Moreover, there was no evidence of pericyte coverage modification in any type of WML in either CADASIL patients or mice. These data together indicate that WMLs in CADASIL encompass distinct classes of WM changes and argue against the prevailing hypothesis that pericyte coverage loss and BBB leakage are the primary drivers of WMLs. Our results also have important implications for the interpretation of studies on the BBB in living patients, which may misinterpret evidence of BBB leakage within WM hyperintensities as suggesting a BBB related mechanism for all WMLs, when in fact this may only apply to a subset of these lesions.
  • Hemilä, Harri; Friedrich, Jan O (BioMed Central, 2019)
    Abstract Background The relative scale adjusts for baseline variability and therefore may lead to findings that can be generalized more widely. It is routinely used for the analysis of binary outcomes but only rarely for continuous outcomes. Our objective was to compare relative vs absolute scale pooled outcomes using data from a recently published Cochrane systematic review that reported only absolute effects of inhaled β2-agonists on exercise-induced decline in forced-expiratory volumes in 1 s (FEV1). Methods From the Cochrane review, we selected placebo-controlled cross-over studies that reported individual participant data (IPD). Reversal in FEV1 decline after exercise was modeled as a mean uniform percentage point (pp) change (absolute effect) or average percent change (relative effect) using either intercept-only or slope-only, respectively, linear mixed-effect models. We also calculated the pooled relative effect estimates using standard random-effects, inverse-variance-weighting meta-analysis using study-level mean effects. Results Fourteen studies with 187 participants were identified for the IPD analysis. On the absolute scale, β2-agonists decreased the exercise-induced FEV1 decline by 28 pp., and on the relative scale, they decreased the FEV1 decline by 90%. The fit of the statistical model was significantly better with the relative 90% estimate compared with the absolute 28 pp. estimate. Furthermore, the median residuals (5.8 vs. 10.8 pp) were substantially smaller in the relative effect model than in the absolute effect model. Using standard study-level meta-analysis of the same 14 studies, β2-agonists reduced exercise-induced FEV1 decline on the relative scale by a similar amount: 83% or 90%, depending on the method of calculating the relative effect. Conclusions Compared with the absolute scale, the relative scale captures more effectively the variation in the effects of β2-agonists on exercise-induced FEV1-declines. The absolute scale has been used in the analysis of FEV1 changes and may have led to sub-optimal statistical analysis in some cases. The choice between the absolute and relative scale should be determined based on biological reasoning and empirical testing to identify the scale that leads to lower heterogeneity.
  • Zhou, Naihui; Jiang, Yuxiang; Bergquist, Timothy R; Lee, Alexandra J; Kacsoh, Balint Z; Crocker, Alex W; Lewis, Kimberley A; Georghiou, George; Nguyen, Huy N; Hamid, Md Nafiz; Davis, Larry; Dogan, Tunca; Atalay, Volkan; Rifaioglu, Ahmet S; Dalkıran, Alperen; Cetin Atalay, Rengul; Zhang, Chengxin; Hurto, Rebecca L; Freddolino, Peter L; Zhang, Yang; Bhat, Prajwal; Supek, Fran; Fernández, José M; Gemovic, Branislava; Perovic, Vladimir R; Davidović, Radoslav S; Sumonja, Neven; Veljkovic, Nevena; Asgari, Ehsaneddin; Mofrad, Mohammad R; Profiti, Giuseppe; Savojardo, Castrense; Martelli, Pier Luigi; Casadio, Rita; Boecker, Florian; Schoof, Heiko; Kahanda, Indika; Thurlby, Natalie; McHardy, Alice C; Renaux, Alexandre; Saidi, Rabie; Gough, Julian; Freitas, Alex A; Antczak, Magdalena; Fabris, Fabio; Wass, Mark N; Hou, Jie; Cheng, Jianlin; Wang, Zheng; Romero, Alfonso E; Paccanaro, Alberto; Yang, Haixuan; Goldberg, Tatyana; Zhao, Chenguang; Holm, Liisa; Törönen, Petri; Medlar, Alan J; Zosa, Elaine; Borukhov, Itamar; Novikov, Ilya; Wilkins, Angela; Lichtarge, Olivier; Chi, Po-Han; Tseng, Wei-Cheng; Linial, Michal; Rose, Peter W; Dessimoz, Christophe; Vidulin, Vedrana; Dzeroski, Saso; Sillitoe, Ian; Das, Sayoni; Lees, Jonathan Gill; Jones, David T; Wan, Cen; Cozzetto, Domenico; Fa, Rui; Torres, Mateo; Warwick Vesztrocy, Alex; Rodriguez, Jose Manuel; Tress, Michael L; Frasca, Marco; Notaro, Marco; Grossi, Giuliano; Petrini, Alessandro; Re, Matteo; Valentini, Giorgio; Mesiti, Marco; Roche, Daniel B; Reeb, Jonas; Ritchie, David W; Aridhi, Sabeur; Alborzi, Seyed Ziaeddin; Devignes, Marie-Dominique; Koo, Da Chen Emily; Bonneau, Richard; Gligorijević, Vladimir; Barot, Meet; Fang, Hai; Toppo, Stefano; Lavezzo, Enrico; Falda, Marco; Berselli, Michele; Tosatto, Silvio C; Carraro, Marco; Piovesan, Damiano; Ur Rehman, Hafeez; Mao, Qizhong; Zhang, Shanshan; Vucetic, Slobodan; Black, Gage S; Jo, Dane; Suh, Erica; Dayton, Jonathan B; Larsen, Dallas J; Omdahl, Ashton R; McGuffin, Liam J; Brackenridge, Danielle A; Babbitt, Patricia C; Yunes, Jeffrey M; Fontana, Paolo; Zhang, Feng; Zhu, Shanfeng; You, Ronghui; Zhang, Zihan; Dai, Suyang; Yao, Shuwei; Tian, Weidong; Cao, Renzhi; Chandler, Caleb; Amezola, Miguel; Johnson, Devon; Chang, Jia-Ming; Liao, Wen-Hung; Liu, Yi-Wei; Pascarelli, Stefano; Frank, Yotam; Hoehndorf, Robert; Kulmanov, Maxat; Boudellioua, Imane; Politano, Gianfranco; Di Carlo, Stefano; Benso, Alfredo; Hakala, Kai; Ginter, Filip; Mehryary, Farrokh; Kaewphan, Suwisa; Björne, Jari; Moen, Hans; Tolvanen, Martti E; Salakoski, Tapio; Kihara, Daisuke; Jain, Aashish; Šmuc, Tomislav; Altenhoff, Adrian; Ben-Hur, Asa; Rost, Burkhard; Brenner, Steven E; Orengo, Christine A; Jeffery, Constance J; Bosco, Giovanni; Hogan, Deborah A; Martin, Maria J; O’Donovan, Claire; Mooney, Sean D; Greene, Casey S; Radivojac, Predrag; Friedberg, Iddo (BioMed Central, 2019)
    Abstract Background The Critical Assessment of Functional Annotation (CAFA) is an ongoing, global, community-driven effort to evaluate and improve the computational annotation of protein function. Results Here, we report on the results of the third CAFA challenge, CAFA3, that featured an expanded analysis over the previous CAFA rounds, both in terms of volume of data analyzed and the types of analysis performed. In a novel and major new development, computational predictions and assessment goals drove some of the experimental assays, resulting in new functional annotations for more than 1000 genes. Specifically, we performed experimental whole-genome mutation screening in Candida albicans and Pseudomonas aureginosa genomes, which provided us with genome-wide experimental data for genes associated with biofilm formation and motility. We further performed targeted assays on selected genes in Drosophila melanogaster, which we suspected of being involved in long-term memory. Conclusion We conclude that while predictions of the molecular function and biological process annotations have slightly improved over time, those of the cellular component have not. Term-centric prediction of experimental annotations remains equally challenging; although the performance of the top methods is significantly better than the expectations set by baseline methods in C. albicans and D. melanogaster, it leaves considerable room and need for improvement. Finally, we report that the CAFA community now involves a broad range of participants with expertise in bioinformatics, biological experimentation, biocuration, and bio-ontologies, working together to improve functional annotation, computational function prediction, and our ability to manage big data in the era of large experimental screens.
  • Lyhs, Ulrike; Frandsen, Henrik; Andersen, Birgitte; Nonnemann, Bettina; Hjulsager, Charlotte; Pedersen, Karl; Chriél, Mariann (BioMed Central, 2019)
    Abstract Background The quality of mink feed and raw ingredients affect health and growth. The objectives of this study were to examine the microbiological quality of ready-to-eat mink feed and its raw ingredients, screen the plant part of the feed for mycotoxins, and determine the hygiene of the production environment in the feed processing facilities. The results of the study are important for identification of critical steps in the feed production and for formulation of recommendations for improvements of production processes to obtain better quality feed. Feed and swab samples were taken at three Danish mink feed producers October 2016 and May 2017, respectively. Viable counts, detection of methicillin-resistant Staphylococcus aureus (MRSA), influenza virus and filamentous fungi were performed together with qualitative chemical analyses for bioactive fungal metabolites and mycotoxins. Swab samples were analyzed for total viable counts. Results Viable counts varied between 7.2 × 102 and 9.3 × 107 cfu/g in raw ingredients and between 107 and 109 cfu/cm2 on different surfaces at the feed production facilities. A pork meat product, pork haemoglobin, pork liver and a poultry mix was found positive for MRSA, while monophasic Salmonella [4,5,12:i:-] was detected in a pork meat product. Neither MRSA nor Salmonella was detected in any ready-to-eat feed. Influenza A virus was not detected in any sample. Filamentous fungi were detected in all analysed samples of ready-to-eat feed while dihydro-demethyl-sterigmatocystin was found in almost 50% of all ready-to-eat feed samples and in 80% of the sugar beet pulp. Fumonisins and other Fusarium toxins were found especially in corn gluten meal and extruded barley and wheat. Conclusions Mink feed contained a cocktail of mycotoxins and bacteria, which may not per se cause clinical disease, but may affect organ function and animal performance and well-being.
  • Kiiski, A.; Airaksinen, M.; Mäntylä, A.; Desselle, S.; Kumpusalo-Vauhkonen, A.; Järvensivu, T.; Pohjanoksa-Mäntylä, M. (BioMed Central, 2019)
    Abstract Background Collaborative medication review (CMR) practices for older adults are evolving in many countries. Development has been under way in Finland for over a decade, but no inventory of evolved practices has been conducted. The aim of this study was to identify and describe CMR practices in Finland after 10 years of developement. Methods An inventory of CMR practices was conducted using a snowballing approach and an open call in the Finnish Medicines Agency’s website in 2015. Data were quantitatively analysed using descriptive statistics and qualitatively by inductive thematic content analysis. Clyne et al’s medication review typology was applied for evaluating comprehensiveness of the practices. Results In total, 43 practices were identified, of which 22 (51%) were designed for older adults in primary care. The majority (n = 30, 70%) of the practices were clinical CMRs, with 18 (42%) of them being in routine use. A checklist with criteria was used in 19 (44%) of the practices to identify patients with polypharmacy (n = 6), falls (n = 5), and renal dysfunction (n = 5) as the most common criteria for CMR. Patients were involved in 32 (74%) of the practices, mostly as a source of information via interview (n = 27, 63%). A medication care plan was discussed with the patient in 17 practices (40%), and it was established systematically as usual care to all or selected patient groups in 11 (26%) of the practices. All or selected patients’ medication lists were reconciled in 15 practices (35%). Nearly half of the practices (n = 19, 44%) lacked explicit methods for following up effects of medication changes. When reported, the effects were followed up as a routine control (n = 9, 21%) or in a follow-up appointment (n = 6, 14%). Conclusions Different MRs in varying settings were available and in routine use, the majority being comprehensive CMRs designed for primary outpatient care and for older adults. Even though practices might benefit from national standardization, flexibility in their customization according to context, medical and patient needs, and available resources is important.
  • Friman, Mari J; Eklund, Marjut H; Pitkälä, Anna H; Rajala-Schultz, Päivi J; Rantala, Merja H J (BioMed Central, 2019)
    Abstract Background Infection with Serratia spp. have been associated with mastitis outbreaks in dairy cattle herds. Environmental contamination or a point source, like a teat dip product, have often been observed to be potential sources of such outbreaks. We describe two Serratia marcescens associated mastitis outbreaks associated with a contaminated teat dip containing a tertiary alkyl amine, n,n-bis (3-aminopropyl) dodecylamine in two dairy cattle farms in Finland. S. marcescens strains isolated from milk and environmental samples were identified by the MALDI-TOF method. Results Six specimens (n = 19) on Herd 1 and all specimens (n = 9) on Herd 2 were positive for S. marcescens. Positive specimens were from mastitis milk and teat dip liquid and equipment. Bacteria were not isolated from the unopened teat dip canister. The same clone of S. marcescens was isolated from milk samples and teat dip samples within the farms. Pulsed field gel electrophoresis results to the S. marcescens isolates from these two different herds were tested with unweighted pair-group method using arithmetic average clustering analysis. The isolates were not same clone in both herds, because similarity in that test was only 75% when cut-off value to similarity is 85%. Conclusions Our investigation showed that the post milking teat dip and/or temporary containers were contaminated with S. marcescens and these were most likely the sources for new mastitis cases. The negative result from the unopened teat dip canister and positive results from refillable containers demonstrated that the product itself was not contaminated with S. marcescens at the production unit, but became contaminated at the farm level.
  • Liu, Fulu; Zhang, Yating; Qiao, Wanjin; Zhu, Duolong; Xu, Haijin; Saris, Per E J; Qiao, Mingqiang (BioMed Central, 2019)
    Abstract Background After 2.83% genome reduction in Lactococcus lactis NZ9000, a good candidate host for proteins production was obtained in our previous work. However, the gene deletion process was time consuming and laborious. Here, we proposed a convenient gene deletion method suitable for large-scale genome reduction in L. lactis NZ9000. Results Plasmid pNZ5417 containing a visually selectable marker PnisZ-lacZ was constructed, which allowed more efficient and convenient screening of gene deletion mutants. Using this plasmid, two large nonessential DNA regions, L-4A and L-5A, accounting for 1.25% of the chromosome were deleted stepwise in L. lactis 9k-3. When compared with the parent strain, the mutant L. lactis 9k-5A showed better growth characteristics, transformability, carbon metabolic capacity, and amino acids biosynthesis. Conclusions Thus, this study provides a convenient and efficient system for large-scale genome deletion in L. lactis through application of visually selectable marker, which could be helpful for rapid genome streamlining and generation of restructured L. lactis strains that can be used as cell factories.
  • Eerola, Sini K; Santio, Niina M; Rinne, Sanni; Kouvonen, Petri; Corthals, Garry L; Scaravilli, Mauro; Scala, Giovanni; Serra, Angela; Greco, Dario; Ruusuvuori, Pekka; Latonen, Leena; Rainio, Eeva-Marja; Visakorpi, Tapio; Koskinen, Päivi J (BioMed Central, 2019)
    Abstract Background Progression of prostate cancer from benign local tumors to metastatic carcinomas is a multistep process. Here we have investigated the signaling pathways that support migration and invasion of prostate cancer cells, focusing on the role of the NFATC1 transcription factor and its post-translational modifications. We have previously identified NFATC1 as a substrate for the PIM1 kinase and shown that PIM1-dependent phosphorylation increases NFATC1 activity without affecting its subcellular localization. Both PIM kinases and NFATC1 have been reported to promote cancer cell migration, invasion and angiogenesis, but it has remained unclear whether the effects of NFATC1 are phosphorylation-dependent and which downstream targets are involved. Methods We used mass spectrometry to identify PIM1 phosphorylation target sites in NFATC1, and analysed their functional roles in three prostate cancer cell lines by comparing phosphodeficient mutants to wild-type NFATC1. We used luciferase assays to determine effects of phosphorylation on NFAT-dependent transcriptional activity, and migration and invasion assays to evaluate effects on cell motility. We also performed a microarray analysis to identify novel PIM1/NFATC1 targets, and validated one of them with both cellular expression analyses and in silico in clinical prostate cancer data sets. Results Here we have identified ten PIM1 target sites in NFATC1 and found that prevention of their phosphorylation significantly decreases the transcriptional activity as well as the pro-migratory and pro-invasive effects of NFATC1 in prostate cancer cells. We observed that also PIM2 and PIM3 can phosphorylate NFATC1, and identified several novel putative PIM1/NFATC1 target genes. These include the ITGA5 integrin, which is differentially expressed in the presence of wild-type versus phosphorylation-deficient NFATC1, and which is coexpressed with PIM1 and NFATC1 in clinical prostate cancer specimens. Conclusions Based on our data, phosphorylation of PIM1 target sites stimulates NFATC1 activity and enhances its ability to promote prostate cancer cell migration and invasion. Therefore, inhibition of the interplay between PIM kinases and NFATC1 may have therapeutic implications for patients with metastatic forms of cancer.
  • Es-Haghi, Masoumeh; Godakumara, Kasun; Häling, Annika; Lättekivi, Freddy; Lavrits, Arina; Viil, Janeli; Andronowska, Aneta; Nafee, Tamer; James, Victoria; Jaakma, Ülle; Salumets, Andres; Fazeli, Alireza (BioMed Central, 2019)
    Abstract Background Successful establishment of pregnancy hinges on appropriate communication between the embryo and the uterus prior to implantation, but the nature of this communication remains poorly understood. Here, we tested the hypothesis that the endometrium is receptive to embryo-derived signals in the form of RNA. Methods We have utilized a non-contact co culture system to simulate the conditions of pre implantation environment of the uterus. We bioorthogonally tagged embryonic RNA and tracked the transferred transcripts to endometrium. Transferred transcripts were separated from endometrial transcripts and sequenced. Changes in endometrial transcripts were quantified using quantitative PCR. Results We show that three specific transcripts are transferred to endometrial cells. We subsequently demonstrate a role of extracellular vesicles (EVs) in this process, as EVs obtained from cultured trophoblast spheroids incubated with endometrial cells induced down-regulation of all the three identified transcripts in endometrial cells. Finally, we show that EVs/nanoparticles captured from conditioned culture media of viable embryos as opposed to degenerating embryos induce ZNF81 down-regulation in endometrial cells, hinting at the functional importance of this intercellular communication. Conclusion Ultimately, our findings demonstrate the existence of an RNA-based communication which may be of critical importance for the establishment of pregnancy.
  • Lahelma, Eero; Pietiläinen, Olli; Chandola, Tarani; Hyde, Martin; Rahkonen, Ossi; Lallukka, Tea (BioMed Central, 2019)
    Abstract Background Prior analyses of class differences in health trajectories among employees have often omitted women and transitions to retirement. We examined social class trajectories in physical functioning among Finnish female employees from midlife to retirement age, and whether transitions to retirement modified these trajectories. Methods Data were derived from mail surveys at Phases 1–3 (2000–2012) among employees of the City of Helsinki, Finland, aged 40–60 at baseline (n = 8960, 80% women, response rates 69–83%). We included respondents to any of the Phases 1–3 aged 40–72 (n = 6976). We distinguished higher and lower social classes, and employment statuses, i.e. employed, mandatorily retired and disability-retired. Short Form 36 physical component summary was used to measure physical functioning. Mixed-effect growth curve models were used to assess the association of social class and employment status with functioning over age. Results For employed women, physical functioning deteriorated faster in the lower than in the higher class, with class trajectories widening in ages 40–65. After mandatory retirement, functioning deteriorated in both classes, whereas after disability retirement, functioning improved. Across employment statuses, functioning converged at older ages, and the disability-retired caught up with the better functioning of the employed and mandatorily retired. Employment status modified the trajectories, as among the continuously employed and mandatorily retired women functioning deteriorated, but among the disability-retired, trajectories improved and reached a similar level with employed and mandatorily retired women. Social class inequalities remained in all employment status groups. Conclusions Overall, our results suggest evidence for the cumulative disadvantage model, with accumulating work exposures among lower classes potentially contributing to their trajectories of ill health.
  • Dobewall, Henrik; Lindfors, Pirjo; Karvonen, Sakari; Koivusilta, Leena; Vainikainen, Mari-Pauliina; Hotulainen, Risto; Rimpelä, Arja (BioMed Central, 2019)
    Abstract Background The health selection hypothesis suggests that poor health leads to low educational attainment during the life course. Adolescence is an important period as poor health might prevent students from making the best educational choices. We test if health in adolescence is associated with educational aspirations and whether these associations persist over and above sociodemographic background and academic achievement. Methods Using classroom surveys, a cohort of students (n = 5.614) from the Helsinki Metropolitan Region was followed from the 7th (12–13 years,) up to the 9th grade (15–16 years) when the choice between the academic and the vocational track is made in Finland. Health factors (Strengths and Difficulties Questionnaire (SDQ), self-rated health, daily health complaints, and long-term illness and medicine prescribed) and sociodemographic background were self-reported by the students. Students’ educational aspirations (applying for academic versus vocational track, or both) and their academic achievement were obtained from the Joint Application Registry held by the Finnish National Agency for Education. We conducted multilevel multinomial logistic regression analyses, taking into account that students are clustered within schools. Results All studied health factors were associated with adolescents’ educational aspirations. For the SDQ, daily health complaints, and self-rated health these associations persisted over and above sociodemographic background and academic achievement. Students with better health in adolescence were more likely to apply for the academic track, and those who were less healthy were more likely to apply for the vocational track. The health in the group of those students who had applied for both educational tracks was in between. Inconsistent results were observed for long-term illness. We also found robust associations between educational aspirations and worsening health from grade 7 to grade 9. Conclusions Our findings show that selection by health factors to different educational trajectories takes place at early teenage much before adolescents choose their educational track, thus supporting the health selection hypothesis in the creation of socioeconomic health inequalities. Our findings also show the importance of adolescence in this process. More studies are needed to reveal which measures would be effective in helping students with poor health to achieve their full educational potential.
  • Haahtela, Tari; von Hertzen, Leena; Anto, Josep M; Bai, Chunxue; Baigenzhin, Abay; Bateman, Eric D; Behera, Digambar; Bennoor, Kazi; Camargos, Paulo; Chavannes, Niels; de Sousa, Jaime C; Cruz, Alvaro; Do Céu Teixeira, Maria; Erhola, Marina; Furman, Eeva; Gemicioğlu, Bilun; Gonzalez Diaz, Sandra; Hellings, Peter W; Jousilahti, Pekka; Khaltaev, Nikolai; Kolek, Vitezslav; Kuna, Piotr; La Grutta, Stefania; Lan, Le T T; Maglakelidze, Tamaz; Masjedi, Mohamed R; Mihaltan, Florin; Mohammad, Yousser; Nunes, Elizabete; Nyberg, Arvid; Quel, Jorge; Rosado-Pinto, Jose; Sagara, Hironori; Samolinski, Boleslaw; Schraufnagel, Dean; Sooronbaev, Talant; Tag Eldin, Mohamed; To, Teresa; Valiulis, Arunas; Varghese, Cherian; Vasankari, Tuula; Viegi, Giovanni; Winders, Tonya; Yañez, Anahi; Yorgancioğlu, Arzu; Yusuf, Osman; Bousquet, Jean; Billo, Nils E (BioMed Central, 2019)
    Abstract Background The Nature Step to Respiratory Health was the overarching theme of the 12th General Meeting of the Global Alliance against Chronic Respiratory Diseases (GARD) in Helsinki, August 2018. New approaches are needed to improve respiratory health and reduce premature mortality of chronic diseases by 30% till 2030 (UN Sustainable Development Goals, SDGs). Planetary health is defined as the health of human civilization and the state of the natural systems on which it depends. Planetary health and human health are interconnected, and both need to be considered by individuals and governments while addressing several SDGs. Results The concept of the Nature Step has evolved from innovative research indicating, how changed lifestyle in urban surroundings reduces contact with biodiverse environments, impoverishes microbiota, affects immune regulation and increases risk of NCDs. The Nature Step calls for strengthening connections to nature. Physical activity in natural environments should be promoted, use of fresh vegetables, fruits and water increased, and consumption of sugary drinks, tobacco and alcohol restricted. Nature relatedness should be part of everyday life and especially emphasized in the care of children and the elderly. Taking “nature” to modern cities in a controlled way is possible but a challenge for urban planning, nature conservation, housing, traffic arrangements, energy production, and importantly for supplying and distributing food. Actions against the well-known respiratory risk factors, air pollution and smoking, should be taken simultaneously. Conclusions In Finland and elsewhere in Europe, successful programmes have been implemented to reduce the burden of respiratory disorders and other NCDs. Unhealthy behaviour can be changed by well-coordinated actions involving all stakeholders. The growing public health concern caused by NCDs in urban surroundings cannot be solved by health care alone; a multidisciplinary approach is mandatory.
  • Lallukka, Tea; Kronholm, Erkki; Pekkala, Johanna; Jäppinen, Sauli; Blomgren, Jenni; Pietiläinen, Olli; Lahelma, Eero; Rahkonen, Ossi (BioMed Central, 2019)
    Abstract Background Early exit from paid employment is a notable public health and societal challenge. Previous research has largely focused on the relationships among variables instead of the relationships among individuals with different work participation history. Person-oriented methods enable to identify latent groups of individuals who are likely to follow similar development in their work participation over time. We thus aimed to identify work participation trajectories during early and midlife careers and their social determinants using large nationally representative data comprising over 1 million initially employed individuals and a 10-year follow-up for their work participation. A further aim was to determine the cumulative incidence of sickness absence due to key diagnostic groups, mental disorders and musculoskeletal diseases within the trajectories. Methods Young (25–38 years at baseline, n = 495,663) and midlife (39–52 years at baseline, n = 603,085) Finnish people, all working in 2004, were followed up through 2013, with registers of the Social Insurance Institution, and the Statistics Finland. The registers provided data for work participation and its determinants, as well as for computing the cumulative incidence of sickness absence. Latent class growth analysis was used to identify trajectories. Results Three distinctive trajectories were identified: temporary exit, permanent exit, and continuously employed people. As compared to the other trajectories, those belonging to the permanent exit trajectory were more likely men, manual workers and had a lower income. The cumulative incidence of sickness absence due to mental disorders was highest in the permanent exit trajectory group. For musculoskeletal diseases, the cumulative incidence of sickness absence increased in the permanent exit trajectory mainly in the older age groups. Conclusion Distinct group-based trajectories of early work exit can be identified in a representative cohort of initially employed people. Focusing on the determinants of premature exit and early intervention to tackle increasing sickness absence may promote work participation particularly in the most vulnerable groups.

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