BioMed Central -artikkelit: Recent submissions

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  • Lopes, Alessandra; Feola, Sara; Ligot, Sophie; Fusciello, Manlio; Vandermeulen, Gaëlle; Préat, Véronique; Cerullo, Vincenzo (BioMed Central, 2019)
    Abstract Background DNA vaccines against cancer held great promises due to the generation of a specific and long-lasting immune response. However, when used as a single therapy, they are not able to drive the generated immune response into the tumor, because of the immunosuppressive microenvironment, thus limiting their use in humans. To enhance DNA vaccine efficacy, we combined a new poly-epitope DNA vaccine encoding melanoma tumor associated antigens and B16F1-specific neoantigens with an oncolytic virus administered intratumorally. Methods Genomic analysis were performed to find specific mutations in B16F1 melanoma cells. The antigen gene sequences were designed according to these mutations prior to the insertion in the plasmid vector. Mice were injected with B16F1 tumor cells (n = 7–9) and therapeutically vaccinated 2, 9 and 16 days after the tumor injection. The virus was administered intratumorally at day 10, 12 and 14. Immune cell infiltration analysis and cytokine production were performed by flow cytometry, PCR and ELISPOT in the tumor site and in the spleen of animals, 17 days after the tumor injection. Results The combination of DNA vaccine and oncolytic virus significantly increased the immune activity into the tumor. In particular, the local intratumoral viral therapy increased the NK infiltration, thus increasing the production of different cytokines, chemokines and enzymes involved in the adaptive immune system recruitment and cytotoxic activity. On the other side, the DNA vaccine generated antigen-specific T cells in the spleen, which migrated into the tumor when recalled by the local viral therapy. The complementarity between these strategies explains the dramatic tumor regression observed only in the combination group compared to all the other control groups. Conclusions This study explores the immunological mechanism of the combination between an oncolytic adenovirus and a DNA vaccine against melanoma. It demonstrates that the use of a rational combination therapy involving DNA vaccination could overcome its poor immunogenicity. In this way, it will be possible to exploit the great potential of DNA vaccination, thus allowing a larger use in the clinic.
  • Mali, Juha; Mentula, Panu; Leppäniemi, Ari; Sallinen, Ville (BioMed Central, 2019)
    Abstract Background Diverticular abscess diameter of 3–6 cm is generally accepted as a cutoff determining whether percutaneous drainage is recommended in addition to antibiotics, but this is not based on high-quality evidence. The aim of this study was to analyze the treatment choices and outcomes of patients with diverticular abscesses. Methods This was a retrospective cohort study conducted in an academic teaching hospital functioning as a secondary and tertiary referral center. Altogether, 241 patients with computer tomography-verified acute left-sided colonic diverticulitis with intra-abdominal abscess were collected from a database containing all patients treated for colonic diverticulitis in our institution during 2006–2013. The main measured outcomes were need of emergency surgery and 30-day mortality, and these were compared between antibiotics only and percutaneous drainage groups. Treatment choices, including surgery, were also analyzed for all patients. Results Abscesses under 40 mm were mostly treated with antibiotics alone with a high success rate (93 out of 107, 87%). In abscesses over 40 mm, the use of emergency surgery increased and the use of antibiotics alone decreased with increasing abscess size, but the proportion of successful drainage remained at 13–18% regardless of the abscess size. There were no differences in failure rate, 30-day mortality, the need of emergency surgery, permanent stoma, recurrence, or length of stay in patients treated with percutaneous drainage vs. antibiotics alone, even when groups were adjusted for potential confounders. Conclusions Percutaneous drainage as a treatment for large abscess does not seem to be superior to the treatment with only antibiotics.
  • Hägg-Holmberg, Stefanie; Dahlström, Emma H; Forsblom, Carol M; Harjutsalo, Valma; Liebkind, Ron; Putaala, Jukka; Tatlisumak, Turgut; Groop, Per-Henrik; Thorn, Lena M (BioMed Central, 2019)
    Abstract Background Hypertension is one of the strongest risk factors for stroke in the general population, while systolic blood pressure has been shown to independently increase the risk of stroke in type 1 diabetes. The aim of this study was to elucidate the association between different blood pressure variables and risk of stroke in type 1 diabetes, and to explore potential nonlinearity of this relationship. Methods We included 4105 individuals with type 1 diabetes without stroke at baseline, participating in the nationwide Finnish Diabetic Nephropathy Study. Mean age at baseline was 37.4 ± 11.9 years, median duration of diabetes 20.9 (interquartile range 11.5–30.4) years, and 52% were men. Office systolic blood pressure (SBP) and diastolic blood pressure (DBP) were measured. Based on these pulse pressure (PP) and mean arterial pressure (MAP) were calculated. Strokes were classified based on medical and autopsy records, as well as neuroimaging. Cox proportional hazard models were performed to study how the different blood pressure variables affected the risk of stroke and its subtypes. Results During median follow-up time of 11.9 (9.21–13.9) years, 202 (5%) individuals suffered an incident stroke; 145 (72%) were ischemic and 57 (28%) hemorrhagic. SBP, DBP, PP, and MAP all independently increased the risk of any stroke. SBP, PP, and MAP increased the risk of ischemic stroke, while SBP, DBP, and MAP increased the risk of hemorrhagic stroke. SBP was strongly associated with stroke with a hazard ratio of 1.20 (1.11–1.29)/10 mmHg. When variables were modeled using restricted cubic splines, the risk of stroke increased linearly for SBP, MAP, and PP, and non-linearly for DBP. Conclusions The different blood pressure variables are all independently associated with increased risk of stroke in individuals with type 1 diabetes. The risk of stroke, ischemic stroke, and hemorrhagic stroke increases linearly at blood pressure levels less than the current recommended treatment guidelines.
  • Numminen, Elina; Vaumourin, Elise; Parratt, Steven R; Poulin, Lucie; Laine, Anna-Liisa (BioMed Central, 2019)
    Abstract Background Understanding the mechanisms by which diversity is maintained in pathogen populations is critical for epidemiological predictions. Life-history trade-offs have been proposed as a hypothesis for explaining long-term maintenance of variation in pathogen populations, yet the empirical evidence supporting trade-offs has remained mixed. This is in part due to the challenges of documenting successive pathogen life-history stages in many pathosystems. Moreover, little is understood of the role of natural enemies of pathogens on their life-history evolution. Results We characterize life-history-trait variation and possible trade-offs in fungal pathogen Podosphaera plantaginis infecting the host plant Plantago lanceolata. We measured the timing of both asexual and sexual stages, as well as resistance to a hyperparasite of seven pathogen strains that vary in their prevalence in nature. We find significant variation among the strains in their life-history traits that constitute the infection cycle, but no evidence for trade-offs among pathogen development stages, apart from fast pathogen growth coninciding with fast hyperparasite growth. Also, the seemingly least fit pathogen strain was the most prevalent in the nature. Conclusions We conclude that in the nature environmental variation, and interactions with the antagonists of pathogens themselves may maintain variation in pathogen populations.
  • Kvist, Laura; Niskanen, Markku; Mannermaa, Kristiina; Wutke, Saskia; Aspi, Jouni (BioMed Central, 2019)
    Abstract Background The Finnhorse was established as a breed more than 110 years ago by combining local Finnish landraces. Since its foundation, the breed has experienced both strong directional selection, especially for size and colour, and severe population bottlenecks that are connected with its initial foundation and subsequent changes in agricultural and forestry practices. Here, we used sequences of the mitochondrial control region and genomic single nucleotide polymorphisms (SNPs) to estimate the genetic diversity and differentiation of the four Finnhorse breeding sections: trotters, pony-sized horses, draught horses and riding horses. Furthermore, we estimated inbreeding and effective population sizes over time to infer the history of this breed. Results We found a high level of mitochondrial genetic variation and identified 16 of the 18 haplogroups described in present-day horses. Interestingly, one of these detected haplogroups was previously reported only in the Przewalski’s horse. Female effective population sizes were in the thousands, but declines were evident at the times when the breed and its breeding sections were founded. By contrast, nuclear variation and effective population sizes were small (approximately 50). Nevertheless, inbreeding in Finnhorses was lower than in many other horse breeds. Based on nuclear SNP data, genetic differentiation among the four breeding sections was strongest between the draught horses and the three other sections (FST = 0.007–0.018), whereas based on mitochondrial DNA data, it was strongest between the trotters and the pony-sized and riding horses (ΦST = 0.054–0.068). Conclusions The existence of a Przewalski’s horse haplogroup in the Finnhorse provides new insights into the domestication of the horse, and this finding supports previous suggestions of a close relationship between the Finnhorse and eastern primitive breeds. The high level of mitochondrial DNA variation in the Finnhorse supports its domestication from a large number of mares but also reflects that its founding depended on many local landraces. Although inbreeding in Finnhorses was lower than in many other horse breeds, the small nuclear effective population sizes of each of its breeding sections can be considered as a warning sign, which warrants changes in breeding practices.
  • Ilves, Marit; Kinaret, Pia A S; Ndika, Joseph; Karisola, Piia; Marwah, Veer; Fortino, Vittorio; Fedutik, Yuri; Correia, Manuel; Ehrlich, Nicky; Loeschner, Katrin; Besinis, Alexandros; Vassallo, Joanne; Handy, Richard D; Wolff, Henrik; Savolainen, Kai; Greco, Dario; Alenius, Harri (BioMed Central, 2019)
    Abstract Background Copper oxide (CuO) nanomaterials are used in a wide range of industrial and commercial applications. These materials can be hazardous, especially if they are inhaled. As a result, the pulmonary effects of CuO nanomaterials have been studied in healthy subjects but limited knowledge exists today about their effects on lungs with allergic airway inflammation (AAI). The objective of this study was to investigate how pristine CuO modulates allergic lung inflammation and whether surface modifications can influence its reactivity. CuO and its carboxylated (CuO COOH), methylaminated (CuO NH3) and PEGylated (CuO PEG) derivatives were administered here on four consecutive days via oropharyngeal aspiration in a mouse model of AAI. Standard genome-wide gene expression profiling as well as conventional histopathological and immunological methods were used to investigate the modulatory effects of the nanomaterials on both healthy and compromised immune system. Results Our data demonstrates that although CuO materials did not considerably influence hallmarks of allergic airway inflammation, the materials exacerbated the existing lung inflammation by eliciting dramatic pulmonary neutrophilia. Transcriptomic analysis showed that CuO, CuO COOH and CuO NH3 commonly enriched neutrophil-related biological processes, especially in healthy mice. In sharp contrast, CuO PEG had a significantly lower potential in triggering changes in lungs of healthy and allergic mice revealing that surface PEGylation suppresses the effects triggered by the pristine material. Conclusions CuO as well as its functionalized forms worsen allergic airway inflammation by causing neutrophilia in the lungs, however, our results also show that surface PEGylation can be a promising approach for inhibiting the effects of pristine CuO. Our study provides information for health and safety assessment of modified CuO materials, and it can be useful in the development of nanomedical applications.
  • Heim, Anita; Paksi, Attila (BioMed Central, 2019)
    Abstract Objective Although the San in Namibia have been targeted by intensive development efforts, there is little knowledge available about San diet quality and nutritional status. The objective of this study is therefore to estimate and quantify the dietary diversity of a San group, and to investigate how socioeconomic characteristics affect dietary diversity. The dietary data (n = 200) for this cross-sectional study were collected as a part of a larger doctoral research investigating food environment, food choices, and dietary changes of the Khwe San in Bwabwata National Park East. Results The mean dietary diversity score (DDS) of the participants was 2.44 out of 10, with only two people having a DDS of 5. 87.5% of participants consumed only from 2 or 3 different food groups, mainly grains/roots and dark green leafy vegetables. DDS significantly correlated only with the level of education and with age. Due to their collinearity, the group with no education had the lowest DDS, but also belonged to the oldest age group. The overall dietary diversity of the Khwe is extremely low, indicating severe nutritional inadequacy. The small differences in DDS among the socioeconomic groups indicate the importance of other determining factors, such as cultural and food environmental characteristics.
  • Maiwald, Christian A; Annink, Kim V; Rüdiger, Mario; Benders, Manon J N L; van Bel, Frank; Allegaert, Karel; Naulaers, Gunnar; Bassler, Dirk; Klebermaß-Schrehof, Katrin; Vento, Maximo; Guimarães, Hercilia; Stiris, Tom; Cattarossi, Luigi; Metsäranta, Marjo; Vanhatalo, Sampsa; Mazela, Jan; Metsvaht, Tuuli; Jacobs, Yannique; Franz, Axel R (BioMed Central, 2019)
    Abstract Background Perinatal asphyxia and resulting hypoxic-ischemic encephalopathy is a major cause of death and long-term disability in term born neonates. Up to 20,000 infants each year are affected by HIE in Europe and even more in regions with lower level of perinatal care. The only established therapy to improve outcome in these infants is therapeutic hypothermia. Allopurinol is a xanthine oxidase inhibitor that reduces the production of oxygen radicals as superoxide, which contributes to secondary energy failure and apoptosis in neurons and glial cells after reperfusion of hypoxic brain tissue and may further improve outcome if administered in addition to therapeutic hypothermia. Methods This study on the effects of ALlopurinol in addition to hypothermia treatment for hypoxic-ischemic Brain Injury on Neurocognitive Outcome (ALBINO), is a European double-blinded randomized placebo-controlled parallel group multicenter trial (Phase III) to evaluate the effect of postnatal allopurinol administered in addition to standard of care (including therapeutic hypothermia if indicated) on the incidence of death and severe neurodevelopmental impairment at 24 months of age in newborns with perinatal hypoxic-ischemic insult and signs of potentially evolving encephalopathy. Allopurinol or placebo will be given in addition to therapeutic hypothermia (where indicated) to infants with a gestational age ≥ 36 weeks and a birth weight ≥ 2500 g, with severe perinatal asphyxia and potentially evolving encephalopathy. The primary endpoint of this study will be death or severe neurodevelopmental impairment versus survival without severe neurodevelopmental impairment at the age of two years. Effects on brain injury by magnetic resonance imaging and cerebral ultrasound, electric brain activity, concentrations of peroxidation products and S100B, will also be studied along with effects on heart function and pharmacokinetics of allopurinol after iv-infusion. Discussion This trial will provide data to assess the efficacy and safety of early postnatal allopurinol in term infants with evolving hypoxic-ischemic encephalopathy. If proven efficacious and safe, allopurinol could become part of a neuroprotective pharmacological treatment strategy in addition to therapeutic hypothermia in children with perinatal asphyxia. Trial registration NCT03162653, www.ClinicalTrials.gov , May 22, 2017.
  • Ortiz, Rebekka M; Scheperjans, Filip; Pekkonen, Eero (BioMed Central, 2019)
    Abstract Background Dystonia is a movement disorder substantially affecting the quality of life and the ability to work. A proportion of patients does not respond to first line pharmacotherapy. Deep brain stimulation (DBS) is established as a primary operative treatment option for severe drug resistant dystonia. We studied dystonia patients treated with DBS in Finland between the years 2007–2016 to evaluate the use and outcomes of DBS treatment. Methods We analysed the hospital records of dystonia patients, who underwent DBS operation during 2007–2016 in Finland. The clinical and technical parameters were recorded as well as preoperative assessments and treatments. The response to DBS was evaluated retrospectively using the Global Dystonia Rating Scale (GDS). Results Out of 585 dB implantations during the study period, 37 were done for dystonia. The clinical response improved significantly with time in the isolated focal dystonia group, and at 12 months, 22 of 32 patients had over 50% alleviation of the GDS score. There was only one subclinical intracerebral haemorrhage, and four infections leading to revision. Speech impairment and limb coordination problems were common stimulation- related adverse events and were mostly resolved or relieved with the adjustment of stimulation parameters. Conclusions DBS seems to be beneficial in dystonia. Although DBS is indicated for dystonia in Finland, the number of operations did not increase at the same rate as DBS operations in general. DBS appears to be a safe and effective treatment for focal as well as generalized dystonia.
  • Skaga, Erlend; Kulesskiy, Evgeny; Fayzullin, Artem; Sandberg, Cecilie J; Potdar, Swapnil; Kyttälä, Aija; Langmoen, Iver A; Laakso, Aki; Gaál-Paavola, Emília; Perola, Markus; Wennerberg, Krister; Vik-Mo, Einar O (BioMed Central, 2019)
    Abstract Background A major barrier to effective treatment of glioblastoma (GBM) is the large intertumoral heterogeneity at the genetic and cellular level. In early phase clinical trials, patient heterogeneity in response to therapy is commonly observed; however, how tumor heterogeneity is reflected in individual drug sensitivities in the treatment-naïve glioblastoma stem cells (GSC) is unclear. Methods We cultured 12 patient-derived primary GBMs as tumorspheres and validated tumor stem cell properties by functional assays. Using automated high-throughput screening (HTS), we evaluated sensitivity to 461 anticancer drugs in a collection covering most FDA-approved anticancer drugs and investigational compounds with a broad range of molecular targets. Statistical analyses were performed using one-way ANOVA and Spearman correlation. Results Although tumor stem cell properties were confirmed in GSC cultures, their in vitro and in vivo morphology and behavior displayed considerable tumor-to-tumor variability. Drug screening revealed significant differences in the sensitivity to anticancer drugs (p < 0.0001). The patient-specific vulnerabilities to anticancer drugs displayed a heterogeneous pattern. They represented a variety of mechanistic drug classes, including apoptotic modulators, conventional chemotherapies, and inhibitors of histone deacetylases, heat shock proteins, proteasomes and different kinases. However, the individual GSC cultures displayed high biological consistency in drug sensitivity patterns within a class of drugs. An independent laboratory confirmed individual drug responses. Conclusions This study demonstrates that patient-derived and treatment-naïve GSC cultures maintain patient-specific traits and display intertumoral heterogeneity in drug sensitivity to anticancer drugs. The heterogeneity in patient-specific drug responses highlights the difficulty in applying targeted treatment strategies at the population level to GBM patients. However, HTS can be applied to uncover patient-specific drug sensitivities for functional precision medicine.
  • Ruuskanen, Miia; Leivo, Ilmo; Minn, Heikki; Vahlberg, Tero; Haglund, Caj; Hagström, Jaana; Irjala, Heikki (BioMed Central, 2019)
    Abstract Background Nasopharyngeal carcinoma (NPC) is a malignant disease with an enigmatic etiology. NPC associates with Epstein-Barr virus (EBV) and human papillomaviruses (HPVs), while immunological factors also play a role in carcinogenesis. Toll-like receptors (TLRs) are pattern recognition receptors that participate in the immunological defence against pathogens, but their functions are also linked to cancer. Methods In our whole population-based study, we retrieved 150 Finnish NPC cases and studied their tumour samples for TLR1, TLR2, TLR4, TLR5, TLR7, and TLR9 expressions by immunohistochemistry, and for the presence of EBV and high-risk HPVs with EBV RNA and HPV E6/E7 mRNA in situ hybridizations. In addition, we analyzed the TLR expression patterns according to age, tumour histology, EBV/HPV status, and outcome. Results We found that all TLRs studied were highly expressed in NPC. Viral status of the tumours varied, and 62% of them were EBV-positive, 14% HPV-positive, and 24% virus-negative. The tumours with strong TLR2nucl or TLR5 expression were mostly virus-negative or HPV-positive keratinizing squamous cell carcinomas, and the patients with these tumours were significantly older than those with mild or negative TLR2nucl/TLR5 expression. In Kaplan-Meier analysis, the patients with strong TLR5 expression had worse survival compared to the patients with negative or mild TLR5 expression, but the results were linked to other patient and tumour characteristics. In multivariable-adjusted Cox regression analysis, the patients with positive TLR7 tumour expression had better overall survival than those with no TLR7 expression. The 5-year overall survival rates according to TLR7 expression were 66% (mild), 52% (moderate or strong), and 22% (negative). Conclusions TLRs are highly expressed in non-endemic NPC. Intensity of TLR2 and TLR5 expressions correlate with viral status, and TLR7 seems to be an independent prognostic factor of non-endemic NPC.
  • Tšuiko, Olga; Dmitrijeva, Tuuli; Kask, Katrin; Tammur, Pille; Tõnisson, Neeme; Salumets, Andres; Jatsenko, Tatjana (BioMed Central, 2019)
    Abstract Background Balanced translocation carriers are burdened with fertility issues due to improper chromosome segregation in gametes, resulting in either implantation failure, miscarriage or birth of a child with chromosomal disorders. At the same time, these individuals are typically healthy with no signs of developmental problems, hence they often are unaware of their condition. Yet, because of difficulties in conceiving, balanced translocation carriers often turn to assisted reproduction, some of whom may also undergo preimplantation genetic testing for aneuploidy (PGT-A) to improve the likelihood of achieving a successful pregnancy. Case report We describe a female patient, who pursued in vitro fertilization (IVF) treatment coupled with PGT-A following two consecutive miscarriages, unaware of her genetic condition. PGT-A was performed on blastocyst-stage embryos and the results of comprehensive chromosome screening from a first IVF cycle demonstrated reciprocal segmental aberrations on chromosome 7 and chromosome 10 in two out of four embryos. Due to distinct embryo profiles, the couple was then referred for genetic counselling and subsequent parental karyotyping revealed the presence of a previously undetected balanced translocation in the mother. Conclusions These results confirm previous reports that genome-wide PGT-A can facilitate the identification of balanced translocation carriers in IVF patients, providing explanation for poor reproductive outcome and allowing adjustments in treatment strategies.
  • Kinfe, Thomas M; Asif, Maria; Chakravarthy, Krishnan V; Deer, Timothy R; Kramer, Jeffery M; Yearwood, Thomas L; Hurlemann, Rene; Hussain, Muhammad S; Motameny, Susanne; Wagle, Prerana; Nürnberg, Peter; Gravius, Sascha; Randau, Thomas; Gravius, Nadine; Chaudhry, Shafqat R; Muhammad, Sajjad (BioMed Central, 2019)
    Abstract Background In our recent clinical trial, increased peripheral concentrations of pro-inflammatory molecular mediators were determined in complex regional pain syndrome (CRPS) patients. After 3 months adjunctive unilateral, selective L4 dorsal root ganglion stimulation (L4-DRGSTIM), significantly decreased serum IL-10 and increased saliva oxytocin levels were assessed along with an improved pain and functional state. The current study extended molecular profiling towards gene expression analysis of genes known to be involved in the gonadotropin releasing hormone receptor and neuroinflammatory (cytokines/chemokines) signaling pathways. Methods Blood samples were collected from 12 CRPS patients for whole-transcriptome profiling in order to assay 18,845 inflammation-associated genes from frozen blood at baseline and after 3 months L4-DRGSTIM using PANTHER™ pathway enrichment analysis tool. Results Pathway enrichment analyses tools (GOrilla™ and PANTHER™) showed predominant involvement of inflammation mediated by chemokines/cytokines and gonadotropin releasing hormone receptor pathways. Further, screening of differentially regulated genes showed changes in innate immune response related genes. Transcriptomic analysis showed that 21 genes (predominantly immunoinflammatory) were significantly changed after L4-DRGSTIM. Seven genes including TLR1, FFAR2, IL1RAP, ILRN, C5, PKB and IL18 were down regulated and fourteen genes including CXCL2, CCL11, IL36G, CRP, SCGB1A1, IL-17F, TNFRSF4, PLA2G2A, CREB3L3, ADAMTS12, IL1F10, NOX1, CHIA and BDKRB1 were upregulated. Conclusions In our sub-group analysis of L4-DRGSTIM treated CRPS patients, we found either upregulated or downregulated genes involved in immunoinflammatory circuits relevant for the pathophysiology of CRPS indicating a possible relation. However, large biobank-based approaches are recommended to establish genetic phenotyping as a quantitative outcome measure in CRPS patients. Trial registration The study protocol was registered at the 15.11.2016 on German Register for Clinical Trials (DRKS ID 00011267). https://www.drks.de/drks_web/navigate.do?navigationId=trial.HTML&TRIAL_ID=DRKS00011267
  • Peivastegan, Bahram; Hadizadeh, Iman; Nykyri, Johanna; Nielsen, Kåre L; Somervuo, Panu; Sipari, Nina; Tran, Cuong; Pirhonen, Minna (BioMed Central, 2019)
    Abstract Background Stored potato (Solanum tuberosum L.) tubers are sensitive to wet conditions that can cause rotting in long-term storage. To study the effect of water on the tuber surface during storage, microarray analysis, RNA-Seq profiling, qRT-PCR and phytohormone measurements were performed to study gene expression and hormone content in wet tubers incubated at two temperatures: 4 °C and 15 °C. The growth of the plants was also observed in a greenhouse after the incubation of tubers in wet conditions. Results Wet conditions induced a low-oxygen response, suggesting reduced oxygen availability in wet tubers at both temperatures when compared to that in the corresponding dry samples. Wet conditions induced genes coding for heat shock proteins, as well as proteins involved in fermentative energy production and defense against reactive oxygen species (ROS), which are transcripts that have been previously associated with low-oxygen stress in hypoxic or anoxic conditions. Wet treatment also induced senescence-related gene expression and genes involved in cell wall loosening, but downregulated genes encoding protease inhibitors and proteins involved in chloroplast functions and in the biosynthesis of secondary metabolites. Many genes involved in the production of phytohormones and signaling were also affected by wet conditions, suggesting altered regulation of growth by wet conditions. Hormone measurements after incubation showed increased salicylic acid (SA), abscisic acid (ABA) and auxin (IAA) concentrations as well as reduced production of jasmonate 12-oxo-phytodienoic acid (OPDA) in wet tubers. After incubation in wet conditions, the tubers produced fewer stems and more roots compared to controls incubated in dry conditions. Conclusions In wet conditions, tubers invest in ROS protection and defense against the abiotic stress caused by reduced oxygen due to excessive water. Changes in ABA, SA and IAA that are antagonistic to jasmonates affect growth and defenses, causing induction of root growth and rendering tubers susceptible to necrotrophic pathogens. Water on the tuber surface may function as a signal for growth, similar to germination of seeds.
  • Uusitalo, Liisa; Erkkola, Maijaliisa; Lintonen, Tomi; Rahkonen, Ossi; Nevalainen, Jaakko (BioMed Central, 2019)
    Abstract Background Alcohol consumption is a significant cause of disease, death and social harm, and it clusters with smoking tobacco and an unhealthy diet. Using automatically registered retail data for research purposes is a novel approach, which is not subject to underreporting bias. Based on loyalty card data (LoCard) obtained by a major Finnish retailer holding a market share of 47%, we examined alcohol expenditure and their associations with food and tobacco expenditures. Methods The data consisted of 1,527,217 shopping events in 2016 among 13,274 loyalty card holders from southern Finland. A K-means cluster analysis was applied to group the shopping baskets according to their content of alcoholic beverages. The differences in the absolute and relative means of food and tobacco between the clusters were tested by linear mixed models with the loyalty card holder as the random factor. Results By far, the most common basket type contained no alcoholic beverages, followed by baskets containing a small number of beers or ciders. The expenditure on food increased along with the expenditure on alcoholic beverages. The foods most consistently associated with alcohol purchases were sausages, soft drinks and snacks. The expenditure on cigarettes relative to total basket price peaked in the mid-price alcohol baskets. Conclusion Clustering of unhealthy choices occurred on the level of individual shopping events. People who bought many alcoholic beverages did not trim their food budget. Automatically registered purchase data provide valuable insight into the health behaviours of individuals and the population.
  • 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.