Articles from BioMed Central


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  • Mildh, Henriikka; Pettilä, Ville; Korhonen, Anna-Maija; Karlsson, Sari; Ala-Kokko, Tero; Reinikainen, Matti; Vaara, Suvi T (Springer Paris, 2016)
    Abstract Background The role of an episode of acute kidney injury (AKI) in long-term mortality among initial survivors of critical illness is controversial. We aimed to determine whether AKI is independently associated with decreased survival at 3 years among 30-day survivors of intensive care. Results We included 2336 30-day survivors of intensive care enrolled in the FINNAKI study conducted in seventeen medical–surgical ICUs in Finland during a 5-month period in 2011–2012. The incidence of AKI, defined by the Kidney Disease: Improving Global Outcomes criteria, was 34.6%, and 192 (8.3%) commenced RRT. The 3-year mortality among AKI patients was 23.5% (95% CI 20.6–26.4%) compared to 18.9% (17.0–20.9%) of patients without AKI, p = 0.01. However, after adjustments using Cox proportional hazards regression, AKI was not associated with decreased 3-year survival (HR 1.05; CI 95% 0.86–1.27), whereas advanced age, poor pre-morbid functional performance, and presence of several comorbidities were. Additionally, we matched AKI patients to non-AKI patients 1:1 according to age, gender, presence of severe sepsis, and a propensity score to develop AKI. In the well-balanced matched cohort, 3-year mortality among AKI patients was 136 of 662 (20.5%; 17.5–23.6%) and among matched non-AKI patients 143 of 662 (21.6%; 18.5–24.7%), p = 0.687. Neither AKI nor RRT was associated with decreased survival at 3 years in the sensitivity analyses that excluded patients (1) with chronic kidney disease, (2) with AKI not commenced renal replacement therapy (RRT), and (3) with estimated pre-admission creatinine, chronic kidney disease, or AKI stage 1. Conclusion AKI was not an independent risk factor for 3-year mortality among 30-day survivors. Increased 3-year mortality among patients with AKI who survive critical illness may not be related to AKI per se, but rather to advanced age and pre-existing comorbidities.
  • Okuneva, Olesya; Li, Zhilin; Körber, Inken; Tegelberg, Saara; Joensuu, Tarja; Tian, Li; Lehesjoki, Anna-Elina (BioMed Central, 2016)
    Abstract Progressive myoclonus epilepsy of Unverricht-Lundborg type (EPM1) is an autosomal recessively inherited childhood-onset neurodegenerative disorder, characterized by myoclonus, seizures, and ataxia. Mutations in the cystatin B gene (CSTB) underlie EPM1. The CSTB-deficient (Cstb −/− ) mouse model recapitulates key features of EPM1, including myoclonic seizures. The mice show early microglial activation that precedes seizure onset and neuronal loss and leads to neuroinflammation. We here characterized the inflammatory phenotype of Cstb −/− mice in more detail. We found higher concentrations of chemokines and pro-inflammatory cytokines in the serum of Cstb −/− mice and higher CXCL13 expression in activated microglia in Cstb −/− compared to control mouse brains. The elevated chemokine levels were not accompanied by blood-brain barrier disruption, despite increased brain vascularization. Macrophages in the spleen and brain of Cstb −/− mice were predominantly pro-inflammatory. Taken together, these data show that CXCL13 expression is a hallmark of microglial activation in Cstb −/− mice and that the brain inflammation is linked to peripheral inflammatory changes, which might contribute to the disease pathology of EPM1.
  • Roman-Viñas, Blanca; Chaput, Jean-Philippe; Katzmarzyk, Peter T; Fogelholm, Mikael; Lambert, Estelle V; Maher, Carol; Maia, Jose; Olds, Timothy; Onywera, Vincent; Sarmiento, Olga L; Standage, Martyn; Tudor-Locke, Catrine; Tremblay, Mark S (BioMed Central, 2016)
    Abstract Background The Canadian 24-h movement guidelines were developed with the hope of improving health and future health outcomes in children and youth. The purpose of this study was to evaluate adherence to the 3 recommendations most strongly associated with health outcomes in new 24-h movement guidelines and their relationship with adiposity (obesity and body mass index z-score) across countries participating in the International Study of Childhood Obesity, Lifestyle and the Environment (ISCOLE). Methods Cross-sectional results were based on 6128 children aged 9–11 years from the 12 countries of ISCOLE. Sleep duration and moderate-to-vigorous physical activity (MVPA) were assessed using accelerometry. Screen time was measured through self-report. Body weight and height were measured. Body mass index (BMI, kg · m−2) was calculated, and BMI z-scores were computed using age- and sex-specific reference data from the World Health Organization. Obesity was defined as a BMI z-score > +2 SD. Meeting the overall 24-h movement guidelines was defined as: 9 to 11 h/night of sleep, ≤2 h/day of screen time, and at least 60 min/day of MVPA. Age, sex, highest parental education and unhealthy diet pattern score were included as covariates in statistical models. Associations between meeting vs. not meeting each single recommendation (and combinations) with obesity were assessed with odds ratios calculated using generalized linear mixed models. A linear mixed model was used to examine the differences in BMI z-scores between children meeting vs. not meeting the different combinations of recommendations. Results The global prevalence of children meeting the overall recommendations (all three behaviors) was 7%, with children from Australia and Canada showing the highest adherence (15%). Children meeting the three recommendations had lower odds ratios for obesity compared to those meeting none of the recommendations (OR = 0.28, 95% CI 0.18–0.45). Compared to not meeting the 24-h movement recommendations either independently or combined, meeting them was significantly associated with a lower BMI z-score. Whenever the MVPA recommendation was included in the analysis the odds ratios for obesity were lower. Conclusions For ISCOLE participants meeting these 3 healthy movement recommendations the odds ratios of being obese or having high BMI z-scores were lower. However, only a small percentage of children met all recommendations. Future efforts should aim to find promising ways to increase daily physical activity, reduce screen time, and ensure an adequate night’s sleep in children. Trial registration The International Study of Childhood Obesity, Lifestyle and the Environment (ISCOLE) was registered at (Identifier NCT01722500) (October 29, 2012).
  • Keikkala, Elina; Koskinen, Sini; Vuorela, Piia; Laivuori, Hannele; Romppanen, Jarkko; Heinonen, Seppo; Stenman, Ulf-Håkan (BioMed Central, 2016)
    Abstract Background To study whether maternal serum hyperglycosylated human chorionic gonadotropin (hCG-h) improves first trimester prediction of pre-eclampsia when combined with placental growth factor (PlGF), pregnancy-associated plasma protein-A (PAPP-A) and maternal risk factors. Methods Gestational-age-adjusted concentrations of hCG, hCG-h, PlGF and PAPP-A were analysed in serum samples by time-resolved immunofluorometric assays at 8–13 weeks of gestation. The case–control study included 98 women who developed pre-eclampsia, 25 who developed gestational hypertension, 41 normotensive women with small-for-gestational-age (SGA) infants and 177 controls. Results Of 98 women with pre-eclampsia, 24 women developed preterm pre-eclampsia (diagnosis < 37 weeks of gestation) and 13 of them had early-onset pre-eclampsia (diagnosis < 34 weeks of gestation). They had lower concentrations of PlGF, PAPP-A and proportion of hCG-h to hCG (%hCG-h) than controls. In receiver-operating characteristics (ROC) curve analysis, the area under the curve (AUC) for the combination of PlGF, PAPP-A, %hCG-h, nulliparity and mean arterial blood pressure was 0.805 (95% confidence interval, CI, 0.699–0.912) for preterm pre-eclampsia and 0.870 (95% CI 0.750–0.988) for early-onset pre-eclampsia. Without %hCG-h the AUC values were 0.756 (95% CI 0.651–0.861) and 0.810 (95% CI 0.682–0.938) respectively. For prediction of gestational hypertension, the AUC for %hCG-h was 0.708 (95% CI 0.608–0.808), but for other markers the AUC values were not significant. None of the AUC values were significant for the prediction of SGA infants in normotensive women. Conclusions First trimester maternal serum %hCG-h tended to improve prediction of preterm and early-onset pre-eclampsia when combined with PlGF, PAPP-A and maternal risk factors.
  • Löfström, Erika (Springer Singapore, 2016)
    Abstract This article describes research-based role-play on academic integrity. In the role-play, doctoral students negotiated the revision of an institutional integrity policy representing different groups of academics and students. On the one hand, role-play as a teaching method and learning activity demonstrated the difficulty of accommodating different perspectives; on the other, it showed the power and necessity of negotiation in matters that involve value judgments. The role-play is described in detail along with its underlying pedagogical foundations and its contextualisation in a doctoral summer school where it took place. The purpose of the article is to describe how academic integrity was approached through role-play and to discuss theoretical and pedagogical foundations of role-play in teaching academic integrity. Although the article does not describe empirical research on role-play as a teaching method, it demonstrates how role-play in teaching academic integrity was developed based on prior research on the topic.
  • Castillo, Sandra; Barth, Dorothee; Arvas, Mikko; Pakula, Tiina M; Pitkänen, Esa; Blomberg, Peter; Seppanen-Laakso, Tuulikki; Nygren, Heli; Sivasiddarthan, Dhinakaran; Penttilä, Merja; Oja, Merja (BioMed Central, 2016)
    Abstract Background Trichoderma reesei is one of the main sources of biomass-hydrolyzing enzymes for the biotechnology industry. There is a need for improving its enzyme production efficiency. The use of metabolic modeling for the simulation and prediction of this organism’s metabolism is potentially a valuable tool for improving its capabilities. An accurate metabolic model is needed to perform metabolic modeling analysis. Results A whole-genome metabolic model of T. reesei has been reconstructed together with metabolic models of 55 related species using the metabolic model reconstruction algorithm CoReCo. The previously published CoReCo method has been improved to obtain better quality models. The main improvements are the creation of a unified database of reactions and compounds and the use of reaction directions as constraints in the gap-filling step of the algorithm. In addition, the biomass composition of T. reesei has been measured experimentally to build and include a specific biomass equation in the model. Conclusions The improvements presented in this work on the CoReCo pipeline for metabolic model reconstruction resulted in higher-quality metabolic models compared with previous versions. A metabolic model of T. reesei has been created and is publicly available in the BIOMODELS database. The model contains a biomass equation, reaction boundaries and uptake/export reactions which make it ready for simulation. To validate the model, we dem1onstrate that the model is able to predict biomass production accurately and no stoichiometrically infeasible yields are detected. The new T. reesei model is ready to be used for simulations of protein production processes.
  • Niskanen, Alina K; Kennedy, Lorna J; Lohi, Hannes; Aspi, Jouni; Pyhäjärvi, Tanja (BioMed Central, 2016)
    Abstract Background Despite decades of studying, the mechanisms maintaining high diversity in the genes of the Major Histocompatibility Complex (MHC) are still puzzling scientists. In addition to pathogen recognition and other functions, MHC molecules may act prenatally in mate choice and in maternal-foetal interactions. These interactions are potential selective mechanisms that increase genetic diversity in the MHC. During pregnancy, immune response has a dual role: the foetus represents foreign tissue compared to mother, but histo-incompatibility is required for successful pregnancy. We have studied the prenatal selection in MHC class II loci (DLA-DQA1, DLA-DQB1 and DLA-DRB1) in domestic dogs by comparing the observed and expected offspring genotype proportions in 110 dog families. Several potential selection targets were addressed, including the peptide-binding site, the MHC locus, three-locus haplotype and supertype levels. For the supertype analysis, the first canine supertype classification was created based on in silico analysis of peptide-binding amino-acid polymorphism. Results In most loci and levels, no deviation from the expected genotype frequencies was observed. However, one peptide-binding site in DLA-DRB1 had an excess of heterozygotes among the offspring. In addition, if the father shared a DLA-DRB1 allele with the mother, that allele was inherited by the offspring more frequently than expected, suggesting the selective advantage of a histo-compatible foetus, in contrast to our expectations. Conclusions We conclude that there is some evidence of post-copulatory selection at nucleotide site level in the MHC loci of pet dogs. But due to no indication of selection at locus, three-locus, or supertype levels, we estimated that the prenatal selection coefficient is less than 0.3 in domestic dogs and very likely other factors are more important in maintaining the genetic diversity in MHC loci.
  • Shrivastava, Paul; Raivio, Kari; Kasuga, Fumiko; Tewksbury, Joshua; Haines, Andy; Daszak, Peter (BioMed Central, 2016)
    Abstract Future Earth is an international research platform providing the knowledge and support to accelerate our transformations to a sustainable world. Future Earth 2025 Vision identified eight key focal challenges, and challenge #6 is to “Improve human health by elucidating, and finding responses to, the complex interactions amongst environmental change, pollution, pathogens, disease vectors, ecosystem services, and people’s livelihoods, nutrition and well-being.” Several studies, including the Rockefeller Foundation/Lancet Planetary Health Commission Report of 2015, the World Health Organization/Convention on Biological Diversity report and those by oneHEALTH (former ecoHEALTH), have been conducted over the last 30 years. Knowledge-Action Networks (KANs) are the frameworks to apply Future Earth principles of research to related activities that respond to societal challenges. Future Earth Health Knowledge-Action Network will connect health researchers with other natural and social scientists, health and environmental policy professionals and leaders in government, the private sector and civil society to provide research-based solutions based on better, integrated understanding of the complex interactions between a changing global environment and human health. It will build regional capacity to enhance resilience, protect the environment and avert serious threats to health and will also contribute to achieving Sustainable Development Goals. In addition to the initial partners, Future Earth Health Knowledge-Action Network will further nourish collaboration with other on-going, leading research programmes outside Future Earth, by encouraging them in active participation.
  • Ager, Casey; Reilley, Matthew; Nicholas, Courtney; Bartkowiak, Todd; Jaiswal, Ashvin; Curran, Michael; Albershardt, Tina C; Bajaj, Anshika; Archer, Jacob F; Reeves, Rebecca S; Ngo, Lisa Y; Berglund, Peter; ter Meulen, Jan; Denis, Caroline; Ghadially, Hormas; Arnoux, Thomas; Chanuc, Fabien; Fuseri, Nicolas; Wilkinson, Robert W; Wagtmann, Nicolai; Morel, Yannis; Andre, Pascale; Atkins, Michael B; Carlino, Matteo S; Ribas, Antoni; Thompson, John A; Choueiri, Toni K; Hodi, F. S; Hwu, Wen-Jen; McDermott, David F; Atkinson, Victoria; Cebon, Jonathan S; Fitzharris, Bernie; Jameson, Michael B; McNeil, Catriona; Hill, Andrew G; Mangin, Eric; Ahamadi, Malidi; van Vugt, Marianne; van Zutphen, Mariëlle; Ibrahim, Nageatte; Long, Georgina V; Gartrell, Robyn; Blake, Zoe; Simoes, Ines; Fu, Yichun; Saito, Takuro; Qian, Yingzhi; Lu, Yan; Saenger, Yvonne M; Budhu, Sadna; De Henau, Olivier; Zappasodi, Roberta; Schlunegger, Kyle; Freimark, Bruce; Hutchins, Jeff; Barker, Christopher A; Wolchok, Jedd D; Merghoub, Taha; Burova, Elena; Allbritton, Omaira; Hong, Peter; Dai, Jie; Pei, Jerry; Liu, Matt; Kantrowitz, Joel; Lai, Venus; Poueymirou, William; MacDonald, Douglas; Ioffe, Ella; Mohrs, Markus; Olson, William; Thurston, Gavin; Capasso, Cristian; Frascaro, Federica; Carpi, Sara; Tähtinen, Siri; Feola, Sara; Fusciello, Manlio; Peltonen, Karita; Martins, Beatriz; Sjöberg, Madeleine; Pesonen, Sari; Ranki, Tuuli; Kyruk, Lukasz; Ylösmäki, Erkko; Cerullo, Vincenzo; Cerignoli, Fabio; Xi, Biao; Guenther, Garret; Yu, Naichen; Muir, Lincoln; Zhao, Leyna; Abassi, Yama; Cervera-Carrascón, Víctor; Siurala, Mikko; Santos, João; Havunen, Riikka; Parviainen, Suvi; Hemminki, Akseli; Dalgleish, Angus; Mudan, Satvinder; DeBenedette, Mark; Plachco, Ana; Gamble, Alicia; Grogan, Elizabeth W; Krisko, John; Tcherepanova, Irina; Nicolette, Charles; Dhupkar, Pooja; Yu, Ling; Kleinerman, Eugenie S; Gordon, Nancy; Grenga, Italia; Lepone, Lauren; Gameiro, Sofia; Knudson, Karin M; Fantini, Massimo; Tsang, Kwong; Hodge, James; Donahue, Renee; Schlom, Jeffrey; Evans, Elizabeth; Bussler, Holm; Mallow, Crystal; Reilly, Christine; Torno, Sebold; Scrivens, Maria; Foster, Cathie; Howell, Alan; Balch, Leslie; Knapp, Alyssa; Leonard, John E; Paris, Mark; Fisher, Terry; Hu-Lieskovan, Siwen; Ribas, Antoni; Smith, Ernest; Zauderer, Maurice; Fogler, William; Franklin, Marilyn; Thayer, Matt; Saims, Dan; Magnani, John L; Gong, Jian; Gray, Michael; Hutchins, Jeff; Freimark, Bruce; Fromm, George; de Silva, Suresh; Giffin, Louise; Xu, Xin; Rose, Jason; Schreiber, Taylor H; Fantini, Massimo; Gameiro, Sofia R; Knudson, Karin M; Clavijo, Paul E; Allen, Clint T; Donahue, Renee; Lepone, Lauren; Grenga, Italia; Hodge, James W; Tsang, Kwong Y; Schlom, Jeffrey; Gray, Michael; Gong, Jian; Hutchins, Jeff; Freimark, Bruce; Grogan, Jane; Manieri, Nicholas; Chiang, Eugene; Caplazi, Patrick; Yadav, Mahesh; Hagner, Patrick; Chiu, Hsiling; Waldman, Michelle; Klippel, Anke; Thakurta, Anjan; Pourdehnad, Michael; Gandhi, Anita; Henrich, Ian; Quick, Laura; Young, Rob; Chou, Margaret; Hotson, Andrew; Willingham, Stephen; Ho, Po; Choy, Carmen; Laport, Ginna; McCaffery, Ian; Miller, Richard; Tipton, Kimberly A; Wong, Kenneth R; Singson, Victoria; Wong, Chihunt; Chan, Chanty; Huang, Yuanhiu; Liu, Shouchun; Richardson, Jennifer H; Kavanaugh, W. M; West, James; Irving, Bryan A; Tipton, Kimberly A; Wong, Kenneth R; Singson, Victoria; Wong, Chihunt; Chan, Chanty; Huang, Yuanhiu; Liu, Shouchun; Richardson, Jennifer H; Kavanaugh, W. M; West, James; Irving, Bryan A; Jaini, Ritika; Loya, Matthew; Eng, Charis; Johnson, Melissa L; Adjei, Alex A; Opyrchal, Mateusz; Ramalingam, Suresh; Janne, Pasi A; Dominguez, George; Gabrilovich, Dmitry; de Leon, Laura; Hasapidis, Jeannette; Diede, Scott J; Ordentlich, Peter; Cruickshank, Scott; Meyers, Michael L; Hellmann, Matthew D; Kalinski, Pawel; Zureikat, Amer; Edwards, Robert; Muthuswamy, Ravi; Obermajer, Nataša; Urban, Julie; Butterfield, Lisa H; Gooding, William; Zeh, Herbert; Bartlett, David; Zubkova, Olga; Agapova, Larissa; Kapralova, Marina; Krasovskaia, Liudmila; Ovsepyan, Armen; Lykov, Maxim; Eremeev, Artem; Bokovanov, Vladimir; Grigoryeva, Olga; Karpov, Andrey; Ruchko, Sergey; Nicolette, Charles; Shuster, Alexandr; Khalil, Danny N; Campesato, Luis F; Li, Yanyun; Merghoub, Taha; Wolchok, Jedd D; Lazorchak, Adam S; Patterson, Troy D; Ding, Yueyun; Sasikumar, Pottayil; Sudarshan, Naremaddepalli; Gowda, Nagaraj; Ramachandra, Raghuveer; Samiulla, Dodheri; Giri, Sanjeev; Eswarappa, Rajesh; Ramachandra, Murali; Tuck, David; Wyant, Timothy; Leshem, Jasmin; Liu, Xiu-fen; Bera, Tapan; Terabe, Masaki; Bossenmaier, Birgit; Niederfellner, Gerhard; Reiter, Yoram; Pastan, Ira; Xia, Leiming; Xia, Yang; Hu, Yangyang; Wang, Yi; Bao, Yangyi; Dai, Fu; Huang, Shiang; Hurt, Elaine; Hollingsworth, Robert E; Lum, Lawrence G; Chang, Alfred E; Wicha, Max S; Li, Qiao; Mace, Thomas; Makhijani, Neil; Talbert, Erin; Young, Gregory; Guttridge, Denis; Conwell, Darwin; Lesinski, Gregory B; Gonzales, Rodney J M; Huffman, Austin P; Wang, Ximi K; Reshef, Ran; MacKinnon, Andy; Chen, Jason; Gross, Matt; Marguier, Gisele; Shwonek, Peter; Sotirovska, Natalija; Steggerda, Susanne; Parlati, Francesco; Makkouk, Amani; Bennett, Mark K; Chen, Jason; Emberley, Ethan; Gross, Matt; Huang, Tony; Li, Weiqun; MacKinnon, Andy; Marguier, Gisele; Neou, Silinda; Pan, Alison; Zhang, Jing; Zhang, Winter; Parlati, Francesco; Marshall, Netonia; Marron, Thomas U; Agudo, Judith; Brown, Brian; Brody, Joshua; McQuinn, Christopher; Mace, Thomas; Farren, Matthew; Komar, Hannah; Shakya, Reena; Young, Gregory; Ludwug, Thomas; Lesinski, Gregory B; Morillon, Y. M; Hammond, Scott A; Schlom, Jeffrey; Greiner, John W; Nath, Pulak R; Schwartz, Anthony L; Maric, Dragan; Roberts, David D; Obermajer, Nataša; Bartlett, David; Kalinski, Pawel; Naing, Aung; Papadopoulos, Kyriakos P; Autio, Karen A; Wong, Deborah J; Patel, Manish; Falchook, Gerald; Pant, Shubham; Ott, Patrick A; Whiteside, Melinda; Patnaik, Amita; Mumm, John; Janku, Filip; Chan, Ivan; Bauer, Todd; Colen, Rivka; VanVlasselaer, Peter; Brown, Gail L; Tannir, Nizar M; Oft, Martin; Infante, Jeffrey; Lipson, Evan; Gopal, Ajay; Neelapu, Sattva S; Armand, Philippe; Spurgeon, Stephen; Leonard, John P; Hodi, F. S; Sanborn, Rachel E; Melero, Ignacio; Gajewski, Thomas F; Maurer, Matthew; Perna, Serena; Gutierrez, Andres A; Clynes, Raphael; Mitra, Priyam; Suryawanshi, Satyendra; Gladstone, Douglas; Callahan, Margaret K; Crooks, James; Brown, Sheila; Gauthier, Audrey; de Boisferon, Marc H; MacDonald, Andrew; Brunet, Laura R; Rothwell, William T; Bell, Peter; Wilson, James M; Sato-Kaneko, Fumi; Yao, Shiyin; Zhang, Shannon S; Carson, Dennis A; Guiducci, Cristina; Coffman, Robert L; Kitaura, Kazutaka; Matsutani, Takaji; Suzuki, Ryuji; Hayashi, Tomoko; Cohen, Ezra E W; Schaer, David; Li, Yanxia; Dobkin, Julie; Amatulli, Michael; Hall, Gerald; Doman, Thompson; Manro, Jason; Dorsey, Frank C; Sams, Lillian; Holmgaard, Rikke; Persaud, Krishnadatt; Ludwig, Dale; Surguladze, David; Kauh, John S; Novosiadly, Ruslan; Kalos, Michael; Driscoll, Kyla; Pandha, Hardev; Ralph, Christy; Harrington, Kevin; Curti, Brendan; Sanborn, Rachel E; Akerley, Wallace; Gupta, Sumati; Melcher, Alan; Mansfield, David; Kaufman, David R; Schmidt, Emmett; Grose, Mark; Davies, Bronwyn; Karpathy, Roberta; Shafren, Darren; Shamalov, Katerina; Cohen, Cyrille; Sharma, Naveen; Allison, James; Shekarian, Tala; Valsesia-Wittmann, Sandrine; Caux, Christophe; Marabelle, Aurelien; Slomovitz, Brian M; Moore, Kathleen M; Youssoufian, Hagop; Posner, Marshall; Tewary, Poonam; Brooks, Alan D; Xu, Ya-Ming; Wijeratne, Kithsiri; Gunatilaka, Leslie A A; Sayers, Thomas J; Vasilakos, John P; Alston, Tesha; Dovedi, Simon; Elvecrog, James; Grigsby, Iwen; Herbst, Ronald; Johnson, Karen; Moeckly, Craig; Mullins, Stefanie; Siebenaler, Kristen; SternJohn, Julius; Tilahun, Ashenafi; Tomai, Mark A; Vogel, Katharina; Wilkinson, Robert W; Vietsch, Eveline E; Wellstein, Anton; Wythes, Martin; Crosignani, Stefano; Tumang, Joseph; Alekar, Shilpa; Bingham, Patrick; Cauwenberghs, Sandra; Chaplin, Jenny; Dalvie, Deepak; Denies, Sofie; De Maeseneire, Coraline; Feng, JunLi; Frederix, Kim; Greasley, Samantha; Guo, Jie; Hardwick, James; Kaiser, Stephen; Jessen, Katti; Kindt, Erick; Letellier, Marie-Claire; Li, Wenlin; Maegley, Karen; Marillier, Reece; Miller, Nichol; Murray, Brion; Pirson, Romain; Preillon, Julie; Rabolli, Virginie; Ray, Chad; Ryan, Kevin; Scales, Stephanie; Srirangam, Jay; Solowiej, Jim; Stewart, Al; Streiner, Nicole; Torti, Vince; Tsaparikos, Konstantinos; Zheng, Xianxian; Driessens, Gregory; Gomes, Bruno; Kraus, Manfred; Xu, Chunxiao; Zhang, Yanping; Kradjian, Giorgio; Qin, Guozhong; Qi, Jin; Xu, Xiaomei; Marelli, Bo; Yu, Huakui; Guzman, Wilson; Tighe, Rober; Salazar, Rachel; Lo, Kin-Ming; English, Jessie; Radvanyi, Laszlo; Lan, Yan; Zappasodi, Roberta; Budhu, Sadna; Hellmann, Matthew D; Postow, Michael; Senbabaoglu, Yasin; Gasmi, Billel; Zhong, Hong; Li, Yanyun; Liu, Cailian; Hirschhorhn-Cymerman, Daniel; Wolchok, Jedd D; Merghoub, Taha; Zha, Yuanyuan; Malnassy, Gregory; Fulton, Noreen; Park, Jae-Hyun; Stock, Wendy; Nakamura, Yusuke; Gajewski, Thomas F; Liu, Hongtao; Ju, Xiaoming; Kosoff, Rachelle; Ramos, Kimberly; Coder, Brandon; Petit, Robert; Princiotta, Michael; Perry, Kyle; Zou, Jun; Arina, Ainhoa; Fernandez, Christian; Zheng, Wenxin; Beckett, Michael A; Mauceri, Helena J; Fu, Yang-Xin; Weichselbaum, Ralph R; DeBenedette, Mark; Lewis, Whitney; Gamble, Alicia; Nicolette, Charles; Han, Yanyan; Wu, Yeting; Yang, Chou; Huang, Jing; Wu, Dongyun; Li, Jin; Liang, Xiaoling; Zhou, Xiangjun; Hou, Jinlin; Hassan, Raffit; Jahan, Thierry; Antonia, Scott J; Kindler, Hedy L; Alley, Evan W; Honarmand, Somayeh; Liu, Weiqun; Leong, Meredith L; Whiting, Chan C; Nair, Nitya; Enstrom, Amanda; Lemmens, Edward E; Tsujikawa, Takahiro; Kumar, Sushil; Coussens, Lisa M; Murphy, Aimee L; Brockstedt, Dirk G; Koch, Sven D; Sebastian, Martin; Weiss, Christian; Früh, Martin; Pless, Miklos; Cathomas, Richard; Hilbe, Wolfgang; Pall, Georg; Wehler, Thomas; Alt, Jürgen; Bischoff, Helge; Geissler, Michael; Griesinger, Frank; Kollmeier, Jens; Papachristofilou, Alexandros; Doener, Fatma; Fotin-Mleczek, Mariola; Hipp, Madeleine; Hong, Henoch S; Kallen, Karl-Josef; Klinkhardt, Ute; Stosnach, Claudia; Scheel, Birgit; Schroeder, Andreas; Seibel, Tobias; Gnad-Vogt, Ulrike; Zippelius, Alfred; Park, Ha-Ram; Ahn, Yong-Oon; Kim, Tae M; Kim, Soyeon; Kim, Seulki; Lee, Yu S; Keam, Bhumsuk; Kim, Dong-Wan; Heo, Dae S; Pilon-Thomas, Shari; Weber, Amy; Morse, Jennifer; Kodumudi, Krithika; Liu, Hao; Mullinax, John; Sarnaik, Amod A; Pike, Luke; Bang, Andrew; Ott, Patrick A; Balboni, Tracy; Taylor, Allison; Spektor, Alexander; Wilhite, Tyler; Krishnan, Monica; Cagney, Daniel; Alexander, Brian; Aizer, Ayal; Buchbinder, Elizabeth; Awad, Mark; Ghandi, Leena; Hodi, F. S; Schoenfeld, Jonathan; Schwartz, Anthony L; Nath, Pulak R; Lessey-Morillon, Elizabeth; Ridnour, Lisa; Roberts, David D; Segal, Neil H; Sharma, Manish; Le, Dung T; Ott, Patrick A; Ferris, Robert L; Zelenetz, Andrew D; Neelapu, Sattva S; Levy, Ronald; Lossos, Izidore S; Jacobson, Caron; Ramchandren, Radhakrishnan; Godwin, John; Colevas, A. D; Meier, Roland; Krishnan, Suba; Gu, Xuemin; Neely, Jaclyn; Suryawanshi, Satyendra; Timmerman, John; Vanpouille-Box, Claire I; Formenti, Silvia C; Demaria, Sandra; Wennerberg, Erik; Mediero, Aranzazu; Cronstein, Bruce N; Formenti, Silvia C; Demaria, Sandra; Gustafson, Michael P; DiCostanzo, AriCeli; Wheatley, Courtney; Kim, Chul-Ho; Bornschlegl, Svetlana; Gastineau, Dennis A; Johnson, Bruce D; Dietz, Allan B; MacDonald, Cameron; Bucsek, Mark; Qiao, Guanxi; Hylander, Bonnie; Repasky, Elizabeth; Turbitt, William J; Xu, Yitong; Mastro, Andrea; Rogers, Connie J; Withers, Sita; Wang, Ziming; Khuat, Lam T; Dunai, Cordelia; Blazar, Bruce R; Longo, Dan; Rebhun, Robert; Grossenbacher, Steven K; Monjazeb, Arta; Murphy, William J; Rowlinson, Scott; Agnello, Giulia; Alters, Susan; Lowe, David; Scharping, Nicole; Menk, Ashley V; Whetstone, Ryan; Zeng, Xue; Delgoffe, Greg M; Santos, Patricia M; Menk, Ashley V; Shi, Jian; Delgoffe, Greg M; Butterfield, Lisa H; Whetstone, Ryan; Menk, Ashley V; Scharping, Nicole; Delgoffe, Greg; Nagasaka, Misako; Sukari, Ammar; Byrne-Steele, Miranda; Pan, Wenjing; Hou, Xiaohong; Brown, Brittany; Eisenhower, Mary; Han, Jian; Collins, Natalie; Manguso, Robert; Pope, Hans; Shrestha, Yashaswi; Boehm, Jesse; Haining, W. 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C; West, Brian; Coussens, Lisa M; Kunk, Paul R; Obeid, Joseph M; Winters, Kevin; Pramoonjago, Patcharin; Smolkin, Mark E; Stelow, Edward B; Bauer, Todd W; Slingluff, Craig L; Rahma, Osama E; Lamble, Adam; Kosaka, Yoko; Huang, Fei; Saser, Kate A; Adams, Homer; Tognon, Christina E; Laderas, Ted; McWeeney, Shannon; Loriaux, Marc; Tyner, Jeffery W; Druker, Brian J; Lind, Evan F; Liu, Zhuqing; Lu, Shanhong; Kane, Lawrence P; Ferris, Robert L; Liu, Zhuqing; Shayan, Gulidanna; Lu, Shanhong; Ferris, Robert L; Femel, Julia; Tsujikawa, Takahiro; Lane, Ryan; Booth, Jamie; Lund, Amanda W; Melssen, Marit; Rodriguez, Anthony; Slingluff, Craig L; Engelhard, Victor H; Metelli, Alessandra; Wu, Bill X; Fugle, Caroline W; Saleh, Rachidi; Sun, Shaoli; Wu, Jennifer; Liu, Bei; Li, Zihai; Morris, Zachary S; Guy, Emily I; Heinze, Clinton; Kler, Jasdeep; Gressett, Monica M; Werner, Lauryn R; Gillies, Stephen D; Korman, Alan J; Loibner, Hans; Hank, Jacquelyn A; Rakhmilevich, Alexander L; Harari, Paul M; Sondel, Paul M; Newman, Jenna; Zloza, Andrew; Huelsmann, Erica; Broucek, Joseph; Kaufman, Howard L; Brech, Dorothee; Straub, Tobias; Irmler, Martin; Beckers, Johannes; Buettner, Florian; Schaeffeler, Elke; Schwab, Matthias; Noessner, Elfriede; Anand, Snjezana; McDaniel, Amanda; Cha, John; Uecker, Darrin; Nuccitelli, Richard; Ordentlich, Peter; Wolfreys, Alison; Da Costa, Andre; Silva, John; Crosby, Andrea; Staelens, Ludovicus; Craggs, Graham; Cauvin, Annick; Mason, Sean; Paterson, Alison M; Lake, Andrew C; Armet, Caroline M; O’Connor, Rachel W; Hill, Jonathan A; Normant, Emmanuel; Adam, Ammar; Biniszkiewicz, Detlev M; Chappel, Scott C; Palombella, Vito J; Holland, Pamela M; Powers, Jay P; Becker, Annette; Chen, Ada; Leleti, Manmohan R; Newcomb, Eric; Sexton, Holly; Schindler, Ulrike; Tan, Joanne B L; Young, Steve W; Jaen, Juan C; Rapisuwon, Suthee; Radfar, Arash; Gardner, Kellie; Gibney, Geoffrey; Atkins, Michael; Rennier, Keith R; Crowder, Robert; Wang, Ping; Pachynski, Russell K; Carrero, Rosa M S; Rivas, Sarai; Beceren-Braun, Figen; Anthony, Scott; Schluns, Kimberly S; Sawant, Deepali; Chikina, Maria; Yano, Hiroshi; Workman, Creg; Vignali, Dario; Salerno, Elise; Bedognetti, Davide; Mauldin, Ileana; Deacon, Donna; Shea, Sofia; Pinczewski, Joel; Obeid, Joseph M; Coukos, George; Wang, Ena; Gajewski, Thomas; Marincola, Franco M; Slingluff, Craig L; Spranger, Stefani; Horton, Brendan; Gajewski, Thomas F; Suzuki, Akiko; Leland, Pamela; Joshi, Bharat H; Puri, Raj K; Sweis, Randy F; Bao, Riyue; Luke, Jason; Gajewski, Thomas F; Theodoraki, Marie-Nicole; Mogundo, Frances-Mary; Edwards, Robert P; Kalinski, Pawel; Won, Haejung; Moreira, Dayson; Gao, Chan; Zhao, Xingli; Duttagupta, Priyanka; Jones, Jeremy; D’Apuzzo, Massimo; Pal, Sumanta; Kortylewski, Marcin (BioMed Central, 2016)
  • Terho, Petra M; Leppäniemi, Ari K; Mentula, Panu J (BioMed Central, 2016)
    Abstract Background The purpose of the study was to identify risk factors for conversion of laparoscopic cholecystectomy and risk factors for postoperative complications in acute calculous cholecystitis. The most common complications arising from cholecystectomy were also to be identified. Methods A total of 499 consecutive patients, who had undergone emergent cholecystectomy with diagnosis of cholecystitis in Meilahti Hospital in 2013–2014, were identified from the hospital database. Of the identified patients, 400 had acute calculous cholecystitis of which 27 patients with surgery initiated as open cholecystectomy were excluded, resulting in 373 patients for the final analysis. The Clavien-Dindo classification of surgical complications was used. Results Laparoscopic cholecystectomy was initiated in 373 patients of which 84 (22.5%) were converted to open surgery. Multivariate logistic regression identified C-reactive protein (CRP) over 150 mg/l, age over 65 years, diabetes, gangrene of the gallbladder and an abscess as risk factors for conversion. Complications were experienced by 67 (18.0%) patients. Multivariate logistic regression identified age over 65 years, male gender, impaired renal function and conversion as risk factors for complications. Conclusions Advanced cholecystitis with high CRP, gangrene or an abscess increase the risk of conversion. The risk of postoperative complications is higher after conversion. Early identification and treatment of acute calculous cholecystitis might reduce the number of patients with advanced cholecystitis and thus improve outcomes.
  • Lahelma, Eero; Pietiläinen, Olli; Rahkonen, Ossi; Lahti, Jouni; Lallukka, Tea (BioMed Central, 2016)
    Abstract Background Mental symptoms are prevalent among populations, but their associations with premature mortality are inadequately understood. We examined whether mental symptoms contribute to cause-specific mortality among midlife employees, while considering key covariates. Methods Baseline mail survey data from 2000–02 included employees, aged 40–60, of the City of Helsinki, Finland (n = 8960, 80 % women, response rate 67 %). Mental symptoms were measured by the General Health Questionnaire 12-item version (GHQ-12) and the Short Form 36 mental component summary (MCS). Covariates included sex, marital status, social support, health behaviours, occupational social class and limiting long-standing illness. Causes of death by the end of 2013 were obtained from Statistics Finland (n = 242) and linked individually to survey data pending consent (n = 6605). Hazard ratios (HR) and 95 % confidence intervals (95 % CI) were calculated using Cox regression analysis. Results For all-cause mortality, only MCS showed a weak association before adjustments. For natural mortality, no associations were found. For unnatural mortality (n = 21), there was a sex adjusted association with GHQ (HR = 1.96, 95 % CI = 1.45–2.64) and MCS (2.30, 95 % CI = 1.72–3.08). Among unnatural causes of death suicidal mortality (n = 11) was associated with both GHQ (2.20, 95 % CI = 1.47–3.29) and MCS (2.68, 95 % CI = 1.80–3.99). Of the covariates limiting long-standing illness modestly attenuated the associations. Conclusions Two established measures of mental symptoms, i.e. GHQ-12 and SF-36 MCS, were both associated with subsequent unnatural, i.e. accidental and violent, as well as suicidal mortality. No associations were found for natural mortality due to diseases. These findings need to be corroborated in further populations. Supporting mental health through workplace measures may help counteract subsequent suicidal and other unnatural mortality among midlife employees.
  • Raj, Rahul; Bendel, Stepani; Reinikainen, Matti; Hoppu, Sanna; Luoto, Teemu; Ala-Kokko, Tero; Tetri, Sami; Laitio, Ruut; Koivisto, Timo; Rinne, Jaakko; Kivisaari, Riku; Siironen, Jari; Skrifvars, Markus B (BioMed Central, 2016)
    Abstract Background Differences in outcomes after traumatic brain injury (TBI) between neurosurgical centers exist, although the reasons for this are not clear. Thus, our aim was to assess the association between the annual volume of TBI patients and mortality in neurosurgical intensive care units (NICUs). Methods We collected data on all patients treated in the five Finnish university hospitals to examine all patients with TBI treated in NICUs in Finland from 2009 to 2012. We used a random effect logistic regression model to adjust for important prognostic factors to assess the independent effect of ICU volume on 6-month mortality. Subgroup analyses were performed for patients with severe TBI, moderate-to-severe TBI, and those who were undergoing mechanical ventilation or intracranial pressure monitoring. Results Altogether 2,328 TBI patients were treated during the study period in five NICUs. The annual TBI patient volume ranged from 61 to 206 patients between the NICUs. Univariate analysis, showed no association between the NICUs’ annual TBI patient volume and 6-month mortality (p = 0.063). The random effect model showed no independent association between the NICUs’ annual TBI patient volume and 6-month mortality (OR = 1.000, 95% CI = 0.996–1.004, p = 0.876). None of the pre-defined subgroup analyses indicated any association between NICU volume and patient mortality (p > 0.05 for all). Discussion and Conclusion We did not find any association between annual TBI patient volume and 6-month mortality in NICUs. These findings should be interpreted taking into account that we only included NICUs, which by international standards all treated high volumes of TBI patients, and that we were not able to study the effect of NICU volume on neurological outcome.
  • Chaguza, Chrispin; Cornick, Jennifer E; Harris, Simon R; Andam, Cheryl P; Bricio-Moreno, Laura; Yang, Marie; Yalcin, Feyruz; Ousmane, Sani; Govindpersad, Shanil; Senghore, Madikay; Ebruke, Chinelo; Du Plessis, Mignon; Kiran, Anmol M; Pluschke, Gerd; Sigauque, Betuel; McGee, Lesley; Klugman, Keith P; Turner, Paul; Corander, Jukka; Parkhill, Julian; Collard, Jean-Marc; Antonio, Martin; von Gottberg, Anne; Heyderman, Robert S; French, Neil; Kadioglu, Aras; Hanage, William P; Everett, Dean B; Bentley, Stephen D (BioMed Central, 2016)
    Abstract Background Pneumococcus kills over one million children annually and over 90 % of these deaths occur in low-income countries especially in Sub-Saharan Africa (SSA) where HIV exacerbates the disease burden. In SSA, serotype 1 pneumococci particularly the endemic ST217 clone, causes majority of the pneumococcal disease burden. To understand the evolution of the virulent ST217 clone, we analysed ST217 whole genomes from isolates sampled from African and Asian countries. Methods We analysed 226 whole genome sequences from the ST217 lineage sampled from 9 African and 4 Asian countries. We constructed a whole genome alignment and used it for phylogenetic and coalescent analyses. We also screened the genomes to determine presence of antibiotic resistance conferring genes. Results Population structure analysis grouped the ST217 isolates into five sequence clusters (SCs), which were highly associated with different geographical regions and showed limited intracontinental and intercontinental spread. The SCs showed lower than expected genomic sequence, which suggested strong purifying selection and small population sizes caused by bottlenecks. Recombination rates varied between the SCs but were lower than in other successful clones such as PMEN1. African isolates showed higher prevalence of antibiotic resistance genes than Asian isolates. Interestingly, certain West African isolates harbored a defective chloramphenicol and tetracycline resistance-conferring element (Tn5253) with a deletion in the loci encoding the chloramphenicol resistance gene (cat pC194), which caused lower chloramphenicol than tetracycline resistance. Furthermore, certain genes that promote colonisation were absent in the isolates, which may contribute to serotype 1’s rarity in carriage and consequently its lower recombination rates. Conclusions The high phylogeographic diversity of the ST217 clone shows that this clone has been in circulation globally for a long time, which allowed its diversification and adaptation in different geographical regions. Such geographic adaptation reflects local variations in selection pressures in different locales. Further studies will be required to fully understand the biological mechanisms which makes the ST217 clone highly invasive but unable to successfully colonise the human nasopharynx for long durations which results in lower recombination rates.
  • Dilokpimol, Adiphol; Mäkelä, Miia R; Aguilar-Pontes, Maria V; Benoit-Gelber, Isabelle; Hildén, Kristiina S.; de Vries, Ronald P (BioMed Central, 2016)
    Abstract Feruloyl esterases (FAEs) represent a diverse group of carboxyl esterases that specifically catalyze the hydrolysis of ester bonds between ferulic (hydroxycinnamic) acid and plant cell wall polysaccharides. Therefore, FAEs act as accessory enzymes to assist xylanolytic and pectinolytic enzymes in gaining access to their site of action during biomass conversion. Their ability to release ferulic acid and other hydroxycinnamic acids from plant biomass makes FAEs potential biocatalysts in a wide variety of applications such as in biofuel, food and feed, pulp and paper, cosmetics, and pharmaceutical industries. This review provides an updated overview of the knowledge on fungal FAEs, in particular describing their role in plant biomass degradation, diversity of their biochemical properties and substrate specificities, their regulation and conditions needed for their induction. Furthermore, the discovery of new FAEs using genome mining and phylogenetic analysis of current publicly accessible fungal genomes will also be presented. This has led to a new subfamily classification of fungal FAEs that takes into account both phylogeny and substrate specificity.
  • Virtanen, Elina; Pietilä, Tuuli; Nieminen, Pekka; Qian, Kui; Auvinen, Eeva (Springer International Publishing, 2016)
    Abstract Using small RNA sequencing of libraries established from cervical samples and cervical cancer cell lines, we have previously reported identification of nine and validation of five putative microRNA species encoded by human papillomaviruses (HPV) including five microRNAs encoded by HPV 16. Here we have studied the expression of HPV 16 encoded microRNAs in cervical samples and in HPV 16 containing cell lines. Different sample matrices were collected for the study: 20 paraffin embedded cervical tissue samples, 16 liquid cytology samples, and 16 cervical cell samples from women attending colposcopy due to cervical abnormalities, as well as four HPV 16 containing cell lines. Total RNA was extracted, the samples were spiked with small synthetic control RNAs, and the expression of five HPV 16 encoded microRNAs was assessed by real-time PCR amplification. HPV encoded microRNAs could be frequently detected, albeit at high cycle counts. HPV16-miR-H1 was detected in 3.6 %, HPV16-miR-H3 in 23.6 %, HPV16-miR-H5 in 7.3 %, and HPV16-miR-H6 in 18.2 % of all valid samples. True positive signals for HPV16-miR-H2 could not be detected in any of the samples. Viral microRNAs were detected most frequently in paraffin-embedded samples: in one sample representing normal squamous epithelium, in one cervical intraepithelial neoplasia (CIN) grade 1, one CIN2, three CIN3, two squamous cell carcinoma, three adenocarcinoma in situ, and two adenocarcinoma samples. One liquid cytology sample from a patient with CIN3 as well as all four cell lines were positive for HPV16-miR-H3. In all cases HPV encoded microRNAs were expressed at low levels.