Browsing by Subject "DISEASES"

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  • Halonen, Jaana I.; Erhola, Marina; Furman, Eeva; Haahtela, Tari; Jousilahti, Pekka; Barouki, Robert; Bergman, Åke; Billo, Nils E.; Fuller, Richard; Haines, Andrew; Kogevinas, Manolis; Kolossa-Gehring, Marike; Krauze, Kinga; Lanki, Timo; Vicente, Joana Lobo; Messerli, Peter; Nieuwenhuijsen, Mark; Paloniemi, Riikka; Peters, Annette; Posch, Karl-Heinz; Timonen, Pekka; Vermeulen, Roel; Virtanen, Suvi M.; Bousquet, Jean; Antó, Josep M. (2021)
    In 2015, the Rockefeller Foundation-Lancet Commission launched a report introducing a novel approach called Planetary Health and proposed a concept, a strategy and a course of action. To discuss the concept of Planetary Health in the context of Europe, a conference entitled: “Europe That Protects: Safeguarding Our Planet, Safeguarding Our Health” was held in Helsinki in December 2019. The conference participants concluded with a need for action to support Planetary Health during the 2020s. The Helsinki Declaration emphasizes the urgency to act as scientific evidence shows that human activities are causing climate change, biodiversity loss, land degradation, overuse of natural resources and pollution. They threaten the health and safety of human kind. Global, regional, national, local and individual initiatives are called for and multidisciplinary and multisectorial actions and measures are needed. A framework for an action plan is suggested that can be modified for local needs. Accordingly, a shift from fragmented approaches to policy and practice towards systematic actions will promote human health and health of the planet. Systems thinking will feed into conserving nature and biodiversity, and into halting climate change. The Planetary Health paradigm ‒ the health of human civilization and the state of natural systems on which it depends ‒ must become the driver for all policies.
  • Siikamäki, Heli; Kivela, Pia; Fotopoulos, Mikael; Kantele, Anu (2017)
    Background: Although infections represent the most common health problem of travellers abroad, data on morbidity and incidences of various infections are scarce. Method: Data on infections of Finnish travellers during 2010-2012 were retrieved from the database of SOS International, an assistance organization covering 95% of Finns requiring aid abroad. The study included 30,086 cases. For incidence calculation, the data were linked to the numbers of Finns visiting these regions during the same period as recorded by the Official Statistics of Finland. Results: The incidence of infections was particularly high in Africa, southern Europe plus the eastern Mediterranean, and Asia plus Oceania. The most frequent diagnoses were acute gastroenteritis (38.0%) and respiratory-tract infections (RTI) (34.5%), followed by infections of the ear (12.6%), skin or subcutaneous tissue (5.1%), urogenital tract (4.2%), eye (3.1%), and systemic febrile infections (2.2%). Vaccinepreventable diseases (VPD) accounted for 0.8% of cases, with varicella as most (49%) and influenza as second-most (27%) common. Conclusions: Incidence of infections was higher in southern than in eastern and western Europe. Gastroenteritis and RTI proved the most frequent diagnoses, whereas systemic febrile infections were uncommon. Despite pre-travel immunizations, VPDs still occurred; pre-travel consultation should cover both varicella and influenza. (C) 2016 Elsevier Ltd. All rights reserved.
  • Drug-Induced Liver Injury Network; Int DILI Consortium iDILIC; Cirulli, Elizabeth T.; Nicoletti, Paola; Laitinen, Tarja (2019)
    BACKGROUND & AIMS: We performed genetic analyses of a multiethnic cohort of patients with idiosyncratic drug-induced liver injury (DILI) to identify variants associated with susceptibility. METHODS: We performed a genome-wide association study of 2048 individuals with DILI (cases) and 12,429 individuals without (controls). Our analysis included subjects of European (1806 cases and 10,397 controls), African American (133 cases and 1,314 controls), and Hispanic (109 cases and 718 controls) ancestry. We analyzed DNA from 113 Icelandic cases and 239,304 controls to validate our findings. RESULTS: We associated idiosyncratic DILI with rs2476601, a nonsynonymous polymorphism that encodes a substitution of tryptophan with arginine in the protein tyrosine phosphatase, nonreceptor type 22 gene (PTPN22) (odds ratio [OR] 1.44; 95% confidence interval [CI] 1.28-1.62; P = 1.2 x 10(-9) and replicated the finding in the validation set (OR 1.48; 95% CI 1.09-1.99; P =.01). The minor allele frequency showed the same effect size (OR > 1) among ethnic groups. The strongest association was with amoxicillin and clavulanate-associated DILI in persons of European ancestry (OR 1.62; 95% CI 1.32-1.98; P = 4.0 x 10(-6); allele frequency = 13.3%), but the polymorphism was associated with DILI of other causes (OR 1.37; 95% CI 1.21-1.56; P = 1.5 x 10(-6); allele frequency = 11.5%). Among amoxicillin-and clavulanate-associated cases of European ancestry, rs2476601 doubled the risk for DILI among those with the HLA risk alleles A* 02: 01 and DRB1* 15: 01. CONCLUSIONS: In a genome-wide association study, we identified rs2476601 in PTPN22 as a non-HLA variant that associates with risk of liver injury caused by multiple drugs and validated our finding in a separate cohort. This variant has been associated with increased risk of autoimmune diseases, providing support for the concept that alterations in immune regulation contribute to idiosyncratic DILI.
  • Jackson, Christopher B.; Hahn, Dagmar; Schroter, Barbara; Richter, Uwe; Battersby, Brendan J.; Schmitt-Mechelke, Thomas; Marttinen, Paula; Nuoffer, Jean-Marc; Schaller, Andre (2017)
    We describe a novel frameshift mutation in the mitochondrial ATP6 gene in a 4-year-old girl associated with ataxia, microcephaly, developmental delay and intellectual disability. A heteroplasmic frameshift mutation in the MT-ATP6 gene was confirmed in the patient's skeletal muscle and blood. The mutation was not detectable in the mother's DNA extracted from blood or buccal cells. Enzymatic and oxymetric analysis of the mitochondrial respiratory system in the patients' skeletal muscle and skin fibroblasts demonstrated an isolated complex V deficiency. Native PAGE with subsequent immunoblotting for complex V revealed impaired complex V assembly and accumulation of ATPase subcomplexes. Whilst northern blotting confirmed equal presence of ATP8/6 mRNA, metabolic S-35-labelling of mitochondrial translation products showed a severe depletion of the ATP6 protein together with aberrant translation product accumulation. In conclusion, this novel isolated complex V defect expands the clinical and genetic spectrum of mitochondrial defects of complex V deficiency. Furthermore, this work confirms the benefit of native PAGE as an additional diagnostic method for the identification of OXPHOS defects, as the presence of complex V subcomplexes is associated with pathogenic mutations of mtDNA. (C) 2017 Elsevier Masson SAS. All rights reserved.
  • Jokela, Johanna; Tapiovaara, Laura; Lundberg, Marie; Haapaniemi, Aaro; Bäck, Leif; Saarinen, Riitta (2018)
    Objectives. To evaluate the incidence and nature of complications associated with diagnostic and interventional sialendoscopies and to report intervention failures in a prospective setup. Study Design. Prospective observational study. Setting. Academic tertiary care university hospital. Subjects and Methods. Patients who underwent diagnostic or interventional sialendoscopy between October 2015 and December 2016 were prospectively enrolled. Patient data, operation-related factors, treatment failures, and complications were recorded into a database and analyzed. Results. A total of 140 sialendoscopies were attempted or performed on 118 patients; 67 (48%) were for a parotid gland and 73 (52%) for a submandibular gland. The sialendoscopy was interventional in 81 cases (58%), diagnostic in 56 (40%), and not possible to perform in 3 (2.1%). A total of 21 complications were registered for 21 sialendoscopies (15%) and 21 patients (18%). The most common complication was infection, in 9 cases (6.4%). Other observed complications were salivary duct perforation (4 cases), prolonged glandular swelling (3 cases), transient lingual nerve analgesia (2 cases), basket entrapment (2 cases), and transient weakness in the marginal branch of the facial nerve (1 case). All complications were related to interventional procedures or papilla dilatation. Failure to treat occurred in 21 (15%) sialendoscopies: sialendoscopy itself was unsuccessful in 3 cases, and an intended intervention failed in 18 cases. Conclusion. Complications in sialendoscopy are usually related to interventional procedures. The complications are mainly minor and temporary but lead to additional follow-up visits, further treatments, and sometimes hospitalization. Sialendoscopic procedures are safe but not free of complications.
  • Hiltunen, Kaija; Mäntylä, Päivi; Vehkalahti, Miira M (2021)
    Background: Population aging will likely have an impact on oral health care trends. The aim of this study was to describe age-and time-related trends in oral health care in people ages 60 and older in Public Oral Health Services (POHS) in Helsinki, Finland. Materials and methods: Material for the study comprised the electronic documentation of oral health care procedures performed on patients 60 years and older (N = 282,143) in POHS during 2007-2017. Patients were aggregated into 5-year age groups. The 5 most common treatment categories, restorations, periodontal treatment, extractions, endodontics, and prosthetics, were selected for analysis. Changes by time (calendar year) and differences by age group were shown as percentages and percentage points; corresponding trends were assessed by applying linear regression models to the data. Results: The attendance rate for these patients increased from 14.5% in 2007 to 23.1% in 2017, with the total number of visits increasing by 76.4% in the 11-year period. The average number of visits per patient decreased from 3.5 visits in 2007 to 3.0 visits in 2017. In 2007, 60.5% of patients received restorative treatment and 41.3% received periodontal care. In 2017, the corresponding figures were 55.5% and 49.8%, respectively. The older the patient, the fewer the visits and restorative, periodontal, and endodontic treatments and the greater the rate of tooth extractions and prosthetics. Conclusion: A declining age group-related trend was recognized for restorative, periodontal, and endodontic treatments. Owing to ongoing population growth, POHS will be facing huge challenges in providing treatment for all individuals seeking services. (c) 2020 The Authors. Published by Elsevier Inc. on behalf of FDI World Dental Federation. This is an open access article under the CC BY-NC-ND license (
  • Blein, Sophie; Bardel, Claire; Danjean, Vincent; McGuffog, Lesley; Healey, Sue; Barrowdale, Daniel; Lee, Andrew; Dennis, Joe; Kuchenbaecker, Karoline B.; Soucy, Penny; Terry, Mary Beth; Chung, Wendy K.; Goldgar, David E.; Buys, Saundra S.; Janavicius, Ramunas; Tihomirova, Laima; Tung, Nadine; Dorfling, Cecilia M.; van Rensburg, Elizabeth J.; Neuhausen, Susan L.; Ding, Yuan Chun; Gerdes, Anne-Marie; Ejlertsen, Bent; Nielsen, Finn C.; Hansen, Thomas V. O.; Osorio, Ana; Benitez, Javier; Andres Conejero, Raquel; Segota, Ena; Weitzel, Jeffrey N.; Thelander, Margo; Peterlongo, Paolo; Radice, Paolo; Pensotti, Valeria; Dolcetti, Riccardo; Bonanni, Bernardo; Peissel, Bernard; Zaffaroni, Daniela; Scuvera, Giulietta; Manoukian, Siranoush; Varesco, Liliana; Capone, Gabriele L.; Papi, Laura; Ottini, Laura; Yannoukakos, Drakoulis; Konstantopoulou, Irene; Garber, Judy; Hamann, Ute; Donaldson, Alan; Brady, Angela; Brewer, Carole; Foo, Claire; Evans, D. Gareth; Frost, Debra; Eccles, Diana; Douglas, Fiona; Cook, Jackie; Adlard, Julian; Barwell, Julian; Walker, Lisa; Izatt, Louise; Side, Lucy E.; Kennedy, M. John; Tischkowitz, Marc; Rogers, Mark T.; Porteous, Mary E.; Morrison, Patrick J.; Platte, Radka; Eeles, Ros; Davidson, Rosemarie; Hodgson, Shirley; Cole, Trevor; Godwin, Andrew K.; Isaacs, Claudine; Claes, Kathleen; De Leeneer, Kim; Meindl, Alfons; Gehrig, Andrea; Wappenschmidt, Barbara; Sutter, Christian; Engel, Christoph; Niederacher, Dieter; Steinemann, Doris; Plendl, Hansjoerg; Kast, Karin; Rhiem, Kerstin; Ditsch, Nina; Arnold, Norbert; Varon-Mateeva, Raymonda; Schmutzler, Rita K.; Preisler-Adams, Sabine; Markov, Nadja Bogdanova; Wang-Gohrke, Shan; de Pauw, Antoine; Lefol, Cedrick; Lasset, Christine; Leroux, Dominique; Rouleau, Etienne; Damiola, Francesca; Dreyfus, Helene; Barjhoux, Laure; Golmard, Lisa; Uhrhammer, Nancy; Bonadona, Valerie; Sornin, Valerie; Bignon, Yves-Jean; Carter, Jonathan; Van Le, Linda; Piedmonte, Marion; DiSilvestro, Paul A.; de la Hoya, Miguel; Caldes, Trinidad; Nevanlinna, Heli; Aittomaki, Kristiina; Jager, Agnes; van den Ouweland, Ans M. W.; Kets, Carolien M.; Aalfs, Cora M.; van Leeuwen, Flora E.; Hogervorst, Frans B. L.; Meijers-Heijboer, Hanne E. J.; Oosterwijk, Jan C.; van Roozendaal, Kees E. P.; Rookus, Matti A.; Devilee, Peter; van der Luijt, Rob B.; Olah, Edith; Diez, Orland; Teule, Alex; Lazaro, Conxi; Blanco, Ignacio; Del Valle, Jesus; Jakubowska, Anna; Sukiennicki, Grzegorz; Gronwald, Jacek; Lubinski, Jan; Durda, Katarzyna; Jaworska-Bieniek, Katarzyna; Agnarsson, Bjarni A.; Maugard, Christine; Amadori, Alberto; Montagna, Marco; Teixeira, Manuel R.; Spurdle, Amanda B.; Foulkes, William; Olswold, Curtis; Lindor, Noralane M.; Pankratz, Vernon S.; Szabo, Csilla I.; Lincoln, Anne; Jacobs, Lauren; Corines, Marina; Robson, Mark; Vijai, Joseph; Berger, Andreas; Fink-Retter, Anneliese; Singer, Christian F.; Rappaport, Christine; Kaulich, Daphne Geschwantler; Pfeiler, Georg; Tea, Muy-Kheng; Greene, Mark H.; Mai, Phuong L.; Rennert, Gad; Imyanitov, Evgeny N.; Mulligan, Anna Marie; Glendon, Gord; Andrulis, Irene L.; Tchatchou, Sandrine; Toland, Amanda Ewart; Pedersen, Inge Sokilde; Thomassen, Mads; Kruse, Torben A.; Jensen, Uffe Birk; Caligo, Maria A.; Friedman, Eitan; Zidan, Jamal; Laitman, Yael; Lindblom, Annika; Melin, Beatrice; Arver, Brita; Loman, Niklas; Rosenquist, Richard; Olopade, Olufunmilayo I.; Nussbaum, Robert L.; Ramus, Susan J.; Nathanson, Katherine L.; Domchek, Susan M.; Rebbeck, Timothy R.; Arun, Banu K.; Mitchell, Gillian; Karlan, Beth Y.; Lester, Jenny; Orsulic, Sandra; Stoppa-Lyonnet, Dominique; Thomas, Gilles; Simard, Jacques; Couch, Fergus J.; Offit, Kenneth; Easton, Douglas F.; Chenevix-Trench, Georgia; Antoniou, Antonis C.; Mazoyer, Sylvie; Phelan, Catherine M.; Sinilnikova, Olga M.; Cox, David G.; Breast Canc Family Registry; EMBRACE; GEMO Study Collaborators; HEBON (2015)
    Introduction: Individuals carrying pathogenic mutations in the BRCA1 and BRCA2 genes have a high lifetime risk of breast cancer. BRCA1 and BRCA2 are involved in DNA double-strand break repair, DNA alterations that can be caused by exposure to reactive oxygen species, a main source of which are mitochondria. Mitochondrial genome variations affect electron transport chain efficiency and reactive oxygen species production. Individuals with different mitochondrial haplogroups differ in their metabolism and sensitivity to oxidative stress. Variability in mitochondrial genetic background can alter reactive oxygen species production, leading to cancer risk. In the present study, we tested the hypothesis that mitochondrial haplogroups modify breast cancer risk in BRCA1/2 mutation carriers. Methods: We genotyped 22,214 (11,421 affected, 10,793 unaffected) mutation carriers belonging to the Consortium of Investigators of Modifiers of BRCA1/2 for 129 mitochondrial polymorphisms using the iCOGS array. Haplogroup inference and association detection were performed using a phylogenetic approach. ALTree was applied to explore the reference mitochondrial evolutionary tree and detect subclades enriched in affected or unaffected individuals. Results: We discovered that subclade T1a1 was depleted in affected BRCA2 mutation carriers compared with the rest of clade T (hazard ratio (HR) = 0.55; 95% confidence interval (CI), 0.34 to 0.88; P = 0.01). Compared with the most frequent haplogroup in the general population (that is, H and T clades), the T1a1 haplogroup has a HR of 0.62 (95% CI, 0.40 to 0.95; P = 0.03). We also identified three potential susceptibility loci, including G13708A/rs28359178, which has demonstrated an inverse association with familial breast cancer risk. Conclusions: This study illustrates how original approaches such as the phylogeny-based method we used can empower classical molecular epidemiological studies aimed at identifying association or risk modification effects.
  • Lassen, Brian; Geldhof, Peter; Hälli, Outi; Vlaminck, Johnny; Oliviero, Claudio; Orro, Toomas; Heinonen, Mari (2019)
    During their migration through the pig's body, Ascaris suum larvae cause significant damage to the lungs. Little is known about the actual impact of this tissue damage on the occurrence and severity of respiratory problems in industrial pig fattening farms. In this study, we evaluated the link between the serological response to two different A. suum antigen preparations and respiratory or meat inspection outcomes. Two different serological tests were used that measure antibodies against either the A. suum haemoglobin molecule or complete homogenate of the 3rd stage larva that migrate through the lungs. Firstly, serum samples were analysed that were collected from 19 herds in which the cause of acute clinical respiratory symptoms was either Actinobacillus pleuropneumoniae, A. suum, or a miscellaneous cause. This was done to test whether serological results could confirm pathological findings. Secondly, serum samples from 60 herds of finishing pigs with a history of high or low frequency of pleuritis at meat inspection (MI), but without acute respiratory symptoms at the time of sampling, were also submitted for serological evaluation using both tests. Regression models were used to search for potential associations between the proportion of pigs testing seropositive with MI results, in particular pathological changes related to the lungs. The results of both ELISAs were strongly associated (P <0.001) with pigs belonging to a herd where the respiratory problems could be attributed to A. swim by histology, indicating that both tests can be used to diagnose clinical respiratory outbreaks due to A. suum. In the herds without acute clinical respiratory symptoms, a positive association was found between the proportion of pigs testing seropositive and the percentage of livers rejected due to milk spots and with whole carcass condemnations. No association was found between Ascaris serology and lung pathology (pneumonia and pleuritis) registered at MI, however, challenging the likely involvement of Ascaris in the development of these lesions.
  • Vahermo, Mikko; Krogerus, Sara; Nasereddin, Abdelmajeed; Kaiser, Marcel; Brun, Reto; Jaffe, Charles L.; Yli-Kauhaluoma, Jari; Moreira, Vânia M. (2016)
    Derivatives of dehydroabietic acid bearing different amino acids scaffolds have potent antiprotozoal activity against Leishmania donovani and Trypanosoma cruzi, with good to high selectivity, and can therefore be regarded as good models for further development into new drugs to fight leishmaniasis and Chagas disease. Several of the tested compounds were able to kill parasites residing inside cells, with IC50 values ranging from 2.3 to 9 mu M (L. donovani) and 1.4 to 5.8 mu M (T. cruzi), reflecting their ability to fight these infections at the relevant stage responsible for disease. One of the compounds, bearing a 3-pyridyl-Dalanine side chain, was 1.5-fold more potent against T. cruzi amastigotes residing in L6 cells than the reference compound benznidazole.
  • Mahil, Satveer K.; Twelves, Sophie; Farkas, Katalin; Setta-Kaffetzi, Niovi; Burden, A. David; Gach, Joanna E.; Irvine, Alan D.; Kepiro, Laszlo; Mockenhaupt, Maja; Oon, Hazel H.; Pinner, Jason; Ranki, Annamari; Seyger, Marieke M. B.; Soler-Palacin, Pere; Storan, Eoin R.; Tan, Eugene S.; Valeyrie-Allanore, Laurence; Young, Helen S.; Trembath, Richard C.; Choon, Siew-Eng; Szell, Marta; Bata-Csorgo, Zsuzsanna; Smith, Catherine H.; Di Meglio, Paola; Barker, Jonathan N.; Capon, Francesca (2016)
    Prominent skin involvement is a defining characteristic of autoinflammatory disorders caused by abnormal IL-1 signaling. However, the pathways and cell types that drive cutaneous autoinflammatory features remain poorly understood. We sought to address this issue by investigating the pathogenesis of pustular psoriasis, a model of autoinflammatory disorders with predominant cutaneous manifestations. We specifically characterized the impact of mutations affecting AP1S3, a disease gene previously identified by our group and validated here in a newly ascertained patient resource. We first showed that AP1S3 expression is distinctively elevated in keratinocytes. Because AP1S3 encodes a protein implicated in autophagosome formation, we next investigated the effects of gene silencing on this pathway. We found that AP1S3 knockout disrupts keratinocyte autophagy, causing abnormal accumulation of p62, an adaptor protein mediating NF-kappa B activation. We showed that as a consequence, AP1S3-deficient cells up-regulate IL-1 signaling and overexpress IL-36 alpha, a cytokine that is emerging as an important mediator of skin inflammation. These abnormal immune profiles were recapitulated by pharmacological inhibition of autophagy and verified in patient keratinocytes, where they were reversed by IL-36 blockade. These findings show that keratinocytes play a key role in skin autoinflammation and identify autophagy modulation of IL-36 signaling as a therapeutic target.
  • Pirinen, Matti; Benner, Christian; Marttinen, Pekka; Jarvelin, Marjo-Riitta; Rivas, Manuel A.; Ripatti, Samuli (2017)
    Genetic research utilizes a decomposition of trait variances and covariances into genetic and environmental parts. Our software package biMM is a computationally efficient implementation of a bivariate linear mixed model for settings where hundreds of traits have been measured on partially overlapping sets of individuals.
  • Roslund, Marja; Puhakka, Riikka; Grönroos, Mira; Nurminen, Noora; Oikarinen, Sami; Gazali, Ahmad M.; Cinek, Ondrej; Kramna, Lenka; Siter, Nathan; Vari, Heli; Soininen, Laura; Parajuli, Anirudra; Rajaniemi, Juho; Kinnunen, Tuure; Laitinen, Olli H.; Hyöty, Heikki; Sinkkonen, Aki; The ADELE Research Group (2020)
    As the incidence of immune-mediated diseases has increased rapidly in developed societies, there is an unmet need for novel prophylactic practices to fight against these maladies. This study is the first human intervention trial in which urban environmental biodiversity was manipulated to examine its effects on the commensal microbiome and immunoregulation in children. We analyzed changes in the skin and gut microbiota and blood immune markers of children during a 28-day biodiversity intervention. Children in standard urban and nature-oriented daycare centers were analyzed for comparison. The intervention diversified both the environmental and skin Gammaproteobacterial communities, which, in turn, were associated with increases in plasma TGF-beta 1 levels and the proportion of regulatory T cells. The plasma IL-10:IL-17A ratio increased among intervention children during the trial. Our findings suggest that biodiversity intervention enhances immunoregulatory pathways and provide an incentive for future prophylactic approaches to reduce the risk of immune-mediated diseases in urban societies.
  • Lietzen, Raija; Virtanen, Pekka; Kivimaki, Mika; Korkeila, Jyrki; Suominen, Sakari; Sillanmaki, Lauri; Koskenvuo, Markku; Vahtera, Jussi (2017)
    Objective: This prospective, population-based cohort study of 1102 Finnish adults with asthma, examined whether exposure to stressful life events is associated with the intensity of usage of inhaled short-acting beta(2)-agonists. Methods: Survey data was collected by two postal questionnaires. Baseline characteristics were obtained in 1998 and data on 19 specific stressful events (e.g. death of a child or spouse or divorce) within the six preceding months in 2003. Exposure to life events was indicated by a sum score weighted by mean severity of the events. Participants were linked to records of filled prescriptions for inhaled short-acting beta(2)-agonists from national registers from 2000 through 2006. The rates of purchases of short-acting beta(2)-agonists before (2000 2001), during (2002 2003) and after (2004-2006) the event exposure were estimated using repeated-measures Poisson regression analyses with the generalized estimating equation. Results: Of the 1102 participants, 162 (15%) were exposed to highly stressful events, 205 (19%) to less stressful events. During the 7-year observation period, 5955 purchases of filled prescription for inhaled short-acting beta(2)-agonists were recorded. After exposure to highly stressful events, the rate of purchases of beta(2)-agonists was 1.50 times higher (95% confidence interval (CI): 1.05, 2.13) than before the stressful event occurred. Among those with low or no exposure to life events, the corresponding rate ratios were not elevated (rate ratio 0.81, 95% CI: 0.66, 0.99 and 0.95, 95% CI: 0.83, 1.09 respectively). Conclusion: An increase in beta(2)-agonist usage after severe life events suggests that stressful experiences may worsen asthma symptoms.
  • Kaartinen, Niina E.; Knekt, Paul; Kanerva, Noora Karoliina; Valsta, Liisa M.; Eriksson, Johan Gunnar; Rissanen, Harri; Jaaskelainen, Tuija; Männistö, Satu (2016)
    Background: The relationship between carbohydrate intake, dietary glycaemic index (GI) and load (GL), and obesity remains unsolved. Sugar intake and obesity represent a timely topic, but studies on sugar subcategories are scarce. We aimed to study whether total carbohydrate, sucrose, lactose, fibre, dietary GI, and GL are associated with obesity in 25-79-year-old Finns. Methods: Our pooled analysis included three cross-sectional population-based studies: the DILGOM Study (n = 4842), the Helsinki Birth Cohort Study (n =1979), and the Health 2000 Survey (n = 5521). Diet was assessed by a validated food-frequency questionnaire, and anthropometric measurements were collected by standardised protocols. Pooled odds ratios (OR) and 95% confidence intervals (CI) were calculated using logistic regression analysis. Results: In the model, which included sex, age, education, smoking, physical activity, and energy intake, the likelihood of being obese (body mass index >= 30 kg/m(2)) appeared lower in the highest quartiles of total carbohydrate (OR 0.65; 95% CI 0.57-0.74; P for trend <0.0001), sucrose (OR 0.53; 95% CI 0.47-0.61; P <0.0001), and dietary GL (OR 0.64; 95% CI 0.56-0.73; P <0.0001) compared to the lowest quartiles. In contrast, dietary GI did not associate with obesity. Fibre intake associated inversely with abdominal obesity (OR 0.80; 95% CI 0.71-0.90; P <0.001). The inverse sucrose obesity relationship appeared stronger in high fruit consumers compared to low fruit consumers (P for interaction 0.02). Conclusions: Although most of the studied carbohydrate exposures were associated with a diminished likelihood of being obese, prospective studies are needed to assess temporal relations to support causal inference.
  • Garcia-Larsen, Vanessa; Thawer, Narjis; Charles, David; Cassidy, Aedin; van Zele, Thibaut; Thilsing, Trine; Ahlström, Matti; Haahtela, Tari; Keil, Thomas; Matricardi, Paolo M.; Brozek, Grzegorz; Kowalski, Marek L.; Makowska, Joanna; Nizankowska-Mogilnicka, Ewa; Rymarczyk, Barbara; Loureiro, Carlos; Bom, Ana Todo; Bachert, Claus; Forsberg, Bertil; Janson, Christer; Toren, Kjell; Potts, James F.; Burney, Peter G. J. (2018)
    Background: Flavonoids exert anti-inflammatory properties and modulate oxidative stress in vitro, suggesting a protective effect on lung function, but epidemiological studies examining this association are scarce. Methods: A stratified random sample was drawn from the GA(2)LEN screening survey, in which 55,000 adults aged 15 to 75 answered a questionnaire on respiratory symptoms. Post-bronchodilator spirometry was obtained from 2850 subjects. Forced vital capacity (FVC), the ratio between the forced exhaled volume in 1 second (FEV1) and FVC (FEV1/FVC), FVC below lower limit of normal (FVC <LLN), and FEV1/FVC <LLN were calculated. Intake of the six main subclasses of flavonoids was estimated using the GA(2)LEN Food Frequency Questionnaire. Adjusted associations between outcomes and each subclass of flavonoids were examined with multivariate regressions. Simes' procedure was used to test for multiple comparisons. Results: A total of 2599 subjects had valid lung function and dietary data. A lower prevalence of FVC <LLN (airway restriction) was observed in those with higher total flavonoid (adjusted odds ratio (aOR), higher vs. lowest quintile intake 0.58; 95% Confidence Interval (CI) 0.36, 0.94), and pro-anthocyanidin intakes (aOR 0.47; 95% CI 0.27, 0.81). A higher FEV1/FVC was associated with higher intakes of total flavonoids and pro-anthocyanidins (adjusted correlation coefficient (a -coeff 0.33; 0.10, 0.57 and a -coeff 0.44; 95% CI 0.19, 0.69, respectively). After Simes' procedure, the statistical significance of each of these associations was attenuated but remained below 0.05, with the exception of total flavonoids and airway restriction. Conclusions: This population-based study in European adults provides cross-sectional evidence of a positive association of total flavonoid intake and pro-anthocyanidins and ventilatory function, and a negative association with spirometric restriction in European adults.
  • Andersen, Petter I.; Ianevski, Aleksandr; Lysvand, Hilde; Oksenych, Valentyn; Bjørås, Magnar; Telling, Kaidi; Lutsar, Irja; Dampis, Uga; Irie, Yasuhiko; Tenson, Tanel; Kantele, Anu; Kainov, Denis (2020)
    Viral diseases are one of the leading causes of morbidity and mortality in the world. Virus-specific vaccines and antiviral drugs are the most powerful tools to combat viral diseases. However, broad-spectrum antiviral agents (BSAAs, i.e. compounds targeting viruses belonging to two or more viral families) could provide additional protection of the general population from emerging and re-emerging viral diseases, reinforcing the arsenal of available antiviral options. Here, we review discovery and development of BSAAs and summarize the information on 120 safe-in-man agents in a freely accessible database ( Future and ongoing pre-clinical and clinical studies will increase the number of BSAAs, expand the spectrum of their indications, and identify drug combinations for treatment of emerging and re-emerging viral infections as well as co-infections. (C) 2020 The Authors. Published by Elsevier Ltd on behalf of International Society for Infectious Diseases.
  • Tani, Haruna; Mito, Takayuki; Velagapudi, Vidya; Ishikawa, Kaori; Umehara, Moe; Nakada, Kazuto; Suomalainen, Anu; Hayashi, Jun-Ichi (2019)
    In a previous study, we proposed that age-related mitochondrial respiration defects observed in elderly subjects are partially due to age-associated downregulation of nuclear-encoded genes, including serine hydroxymethyltransferase 2 (SHMT2), which is involved in mitochondrial one-carbon (1C) metabolism. This assertion is supported by evidence that the disruption of mouse Shmt2 induces mitochondrial respiration defects in mouse embryonic fibroblasts generated from Shmt2-knockout E13.5 embryos experiencing anaemia and lethality. Here, we elucidated the potential mechanisms by which the disruption of this gene induces mitochondrial respiration defects and embryonic anaemia using Shmt2-knockout E13.5 embryos. The livers but not the brains of Shmt2-knockout E13.5 embryos presented mitochondrial respiration defects and growth retardation. Metabolomic profiling revealed that Shmt2 deficiency induced foetal liver-specific downregulation of 1C-metabolic pathways that create taurine and nucleotides required for mitochondrial respiratory function and cell division, respectively, resulting in the manifestation of mitochondrial respiration defects and growth retardation. Given that foetal livers function to produce erythroblasts in mouse embryos, growth retardation in foetal livers directly induced depletion of erythroblasts. By contrast, mitochondrial respiration defects in foetal livers also induced depletion of erythroblasts as a consequence of the inhibition of erythroblast differentiation, resulting in the manifestation of anaemia in Shmt2-knockout E13.5 embryos.
  • de Groot, Pieter F.; Belzer, Clara; Aydin, Omrum; Levin, Evgeni; Levels, Johannes H.; Aalvink, Steven; Boot, Fransje; Holleman, Frits; van Raalte, Daniel H.; Scheithauer, Torsten P.; Simsek, Suat; Schaap, Frank G.; Damink, Steven W. M. Olde; Roep, Bart O.; Hoekstra, Joost B.; de Vos, Willem M.; Nieuwdorp, Max (2017)
    Objective Environmental factors driving the development of type 1 diabetes (T1D) are still largely unknown. Both animal and human studies have shown an association between altered fecal microbiota composition, impaired production of short-chain fatty acids (SCFA) and T1D onset. However, observational evidence on SCFA and fecal and oral microbiota in adults with longstanding T1D vs healthy controls (HC) is lacking. Research design and methods We included 53 T1D patients without complications or medication and 50 HC matched for age, sex and BMI. Oral and fecal microbiota, fecal and plasma SCFA levels, markers of intestinal inflammation (fecal IgA and calprotectin) and markers of low-grade systemic inflammation were measured. Results Oral microbiota were markedly different in T1D (eg abundance of Streptococci) compared to HC. Fecal analysis showed decreased butyrate producing species in T1D and less butyryl-CoA transferase genes. Also, plasma levels of acetate and propionate were lower in T1D, with similar fecal SCFA. Finally, fecal strains Christensenella and Subdoligranulum correlated with glycemic control, inflammatory parameters and SCFA. Conclusions We conclude that T1D patients harbor a different amount of intestinal SCFA (butyrate) producers and different plasma acetate and propionate levels. Future research should disentangle cause and effect and whether supplementation of SCFA-producing bacteria or SCFA alone can have disease-modifying effects in T1D.
  • Iotova, Violeta; Schalin-Jäntti, Camilla; Bruegmann, Petra; Broesamle, Manuela; Bratina, Natasa; Tillmann, Vallo; Hiort, Olaf; Pereira, Alberto M. (2021)
    Objective: The European Reference Network on Rare Endocrine Conditions (Endo-ERN), operational since 2017, consists of 71 health care providers (HCPs) in 19 EU member states. Our objective was to assess education and knowledge on rare endocrine conditions. Design and methods: A survey was developed and sent through the DIGIT-EUROSURVEY system to all Endo-ERN HCPs. Results: Response rate was 55% (n = 146), 95% physicians, 58% > 20 years of experience, 96% academics. Largest knowledge gaps were reported for the transition and neonatal ages, and for the GPs. Less than 50% of HCPs had structured educational rare diseases (RD) plans, while 86% used RD specific guidelines. HCPs would share educational materials within Endo-ERN (74%), and participate in an accreditation model (85%). E-learning portals of the endocrine scientific societies used 58 % (ESPE) and 64% (ESE). Most participants (90%) regarded Endo-ERN coordinated educational activities (annual meetings slots, webinars, etc.) as highly important and supported a common educational platform. Social media was perceived as important for educating patients (86%) but not for physicians (36%). Seventy-five % had developed patient education materials; only 31% had specific children's materials, and by-country avail ability varied from 0 to 100%. Respondents provided newly diagnosed patients with their own material in the national language (81%); referred to advocacy groups (68%), and relevant online sources (50%). Respondents believed the European Commission should fund education through Endo-ERN. Conclusion: Identified knowledge gaps in rare endocrine disorders set the basis for fast catch-up through collaboration, alignment with patients' needs, and further development of existing and newly developed educational resources.
  • Ndika, Joseph; Airaksinen, Liisa; Suojalehto, Hille; Karisola, Piia; Fyhrquist, Nanna; Puustinen, Anne; Alenius, Harri (2017)
    Background: Seasonal allergic rhinitis (SAR) caused by intermittent exposure to seasonal pollen causes itching, nasal congestion, and repeated sneezing, with profound effects on quality of life, work productivity, and school performance. Although both the genotype and environmental factors can contribute to the immunologic basis of allergic reactions, the molecular underpinnings associated with the pathogenesis of allergic rhinitis are not entirely clear. Methods: To address these questions, nasal epithelial brushings were collected from 29 patients with SAR and 31 control subjects during and after the pollen season. We then implemented an orbitrap-based, bottom-up, label-free quantitative proteomics approach, followed by multivariate analyses to identify differentially abundant (DA) proteins among the 4 sample groups. Results: We identified a total of 133 DA proteins for which the most significantly overrepresented functional category was found to be interferon 1 signaling. Two proteins, cystatin 1 and myeloblastin, the former of which protects against protease activity of allergens and the latter with a role in epithelial barrier function, were DA in patients with SAR and control subjects, irrespective of season. Moreover, interferon-inducible protein with tetratricopeptide repeats 1, cystatin 1, and interferon-inducible protein with tetratricopeptide repeats 3 were found to be differentially regulated between patients with SAR and control subjects, with inverse abundance dynamics during the transition from fall to spring. Conclusion: We identified type 1 interferon-regulated proteins as biomarkers in patients with SAR, potentially playing an important role in its pathogenesis. Moreover, when compared with patients with SAR, healthy subjects exhibit an antagonistic proteomic response across seasons, which might prove to be a therapeutic target for disease prevention.