Browsing by Subject "Humans"

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  • Leppäniemi, A.; Tolonen, M.; Tarasconi, A.; Segovia-Lohse, H.; Gamberini, E.; Kirkpatrick, A.W.; Ball, C.G.; Parry, N.; Sartelli, M.; Wolbrink, D.; Van Goor, H.; Baiocchi, G.; Ansaloni, L.; Biffl, W.; Coccolini, F.; Di Saverio, S.; Kluger, Y.; Moore, E.; Catena, F. (2019)
    Although most patients with acute pancreatitis have the mild form of the disease, about 20-30% develops a severe form, often associated with single or multiple organ dysfunction requiring intensive care. Identifying the severe form early is one of the major challenges in managing severe acute pancreatitis. Infection of the pancreatic and peripancreatic necrosis occurs in about 20-40% of patients with severe acute pancreatitis, and is associated with worsening organ dysfunctions. While most patients with sterile necrosis can be managed nonoperatively, patients with infected necrosis usually require an intervention that can be percutaneous, endoscopic, or open surgical. These guidelines present evidence-based international consensus statements on the management of severe acute pancreatitis from collaboration of a panel of experts meeting during the World Congress of Emergency Surgery in June 27-30, 2018 in Bertinoro, Italy. The main topics of these guidelines fall under the following topics: Diagnosis, Antibiotic treatment, Management in the Intensive Care Unit, Surgical and operative management, and Open abdomen. © 2019 The Author(s).
  • Saari, Sini; Kemppainen, Esa; Tuomela, Tero; Oliveira, M.T.; Dufour, E.; Jacobs, H.T. (2019)
    The mitochondrial alternative oxidase, AOX, present in most eukaryotes apart from vertebrates and insects, catalyzes the direct oxidation of ubiquinol by oxygen, by-passing the terminal proton-motive steps of the respiratory chain. Its physiological role is not fully understood, but it is proposed to buffer stresses in the respiratory chain similar to those encountered in mitochondrial diseases in humans. Previously, we found that the ubiquitous expression of AOX from Ciona intestinalis in Drosophila perturbs the development of flies cultured under low-nutrient conditions (media containing only glucose and yeast). Here we tested the effects of a wide range of nutritional supplements on Drosophila development, to gain insight into the physiological mechanism underlying this developmental failure. On low-nutrient medium, larvae contained decreased amounts of triglycerides, lactate, and pyruvate, irrespective of AOX expression. Complex food supplements, including treacle (molasses), restored normal development to AOX-expressing flies, but many individual additives did not. Inhibition of AOX by treacle extract was excluded as a mechanism, since the supplement did not alter the enzymatic activity of AOX in vitro. Furthermore, antibiotics did not influence the organismal phenotype, indicating that commensal microbes were not involved. Fractionation of treacle identified a water-soluble fraction with low solubility in ethanol, rich in lactate and tricarboxylic acid cycle intermediates, which contained the critical activity. We propose that the partial activation of AOX during metamorphosis impairs the efficient use of stored metabolites, resulting in developmental failure. © 2019 The Authors. Journal of Experimental Zoology Part A: Ecological Genetics and Physiology Published by Wiley Periodicals, Inc.
  • Sagath, L.; Lehtokari, V.-L.; Välipakka, S.; Udd, B.; Wallgren-Pettersson, C.; Pelin, K.; Kiiski, K. (2018)
    Background: Our previous array, the Comparative Genomic Hybridisation design (CGH-array) for nemaline myopathy (NM), named the NM-CGH array, revealed pathogenic copy number variation (CNV) in the genes for nebulin (NEB) and tropomyosin 3 (TPM3), as well as recurrent CNVs in the segmental duplication (SD), i.e. triplicate, region of NEB (TRI, exons 82-89, 90-97, 98-105). In the light of this knowledge, we have designed and validated an extended CGH array, which includes a selection of 187 genes known to cause neuromuscular disorders (NMDs). Objective: Our aim was to develop a reliable method for CNV detection in genes related to neuromuscular disorders for routine mutation detection and analysis, as a much-needed complement to sequencing methods. Methods: We have developed a novel custom-made 4×180 k CGH array for the diagnostics of NMDs. It includes the same tiled ultra-high density coverage of the 12 known or putative NM genes as our 8×60 k NM-CGH-array but also comprises a selection of 175 additional genes associated with NMDs, including titin (TTN), at a high to very high coverage. The genes were divided into three coverage groups according to known and potential pathogenicity in neuromuscular disorders. Results: The array detected known and putative CNVs in all three gene coverage groups, including the repetitive regions of NEB and TTN. Conclusions: The targeted neuromuscular disorder 4×180 k array-CGH (NMD-CGH-array v1.0) design allows CNV detection for a broader spectrum of neuromuscular disorders at a high resolution. © 2018 - IOS Press and the authors. All rights reserved.
  • Honkanen, Tuomas; Mäntysaari, M.; Leino, Tuomo; Avela, J.; Kerttula, L.; Haapamäki, V.; Kyröläinen, Heikki (2019)
    Background: A small cross sectional area (CSA) of the paraspinal muscles may be related to low back pain among military aviators but previous studies have mainly concentrated on spinal disc degeneration. Therefore, the primary aim of the study was to investigate the changes in muscle CSA and composition of the psoas and paraspinal muscles during a 5-year follow up among Finnish Air Force (FINAF) fighter pilots. Methods: Study population consisted of 26 volunteered FINAF male fighter pilots (age: 20.6 (±0.6) at the baseline). The magnetic resonance imaging (MRI) examinations were collected at baseline and after 5 years of follow-up. CSA and composition of the paraspinal and psoas muscles were obtained at the levels of 3-4 and 4-5 lumbar spine. Maximal isometric strength tests were only performed on one occasion at baseline. Results: The follow-up comparisons indicated that the mean CSA of the paraspinal muscles increased (p <0.01) by 8% at L3-4 level and 7% at L4-5 level during the 5-year period. There was no change in muscle composition during the follow-up period. The paraspinal and psoas muscles' CSA was positively related to overall maximal isometric strength at the baseline. However, there was no association between LBP and muscle composition or CSA. Conclusions: The paraspinal muscles' CSA increased among FINAF fighter pilots during the first 5 years of service. This might be explained by physically demanding work and regular physical activity. However, no associations between muscle composition or CSA and low back pain (LBP) experienced were observed after the five-year follow-up. © 2019 The Author(s).
  • Sandström, John (Helsingin yliopisto, 2019)
    Finland har världens högsta incidens för typ 1 diabetes (T1D). Incidensen har ökat mångfalt under de senaste årtiondena i Finland och i andra utvecklade länder. Bl.a. detta och sjukdomens säsongberoende natur har riktat blickarna mot säsongberoende miljö-faktorer som utlösare av sjukdomsprocessen. Denna studies syfte var att undersöka om detta säsongberoende kan påvisas också i Finland och hur den förhåller sig till kön och ålder. Studiepopulationen bestod av 0–14 åriga finländska barn som hade diagnosticerats med T1D under åren 2002–2015. Säsonganalyser gällande diagnostidpunkten gjordes med hjälp av Poissons regressionsanalys, som säsongmodifierades. Vi observerade inci-densmönstret i förhållande till debutmånad samt säsongberoendets förhållande till kön och ålder. Diabetikerbarnen jämfördes med den teoretiska populationsenliga riskgrup-pen bestående av totalt antal levande 0–14 åringar i Finland per månad. Vår studie utvisade ett starkt säsongberoende. Säsongberoendet påverkades inte av kön men verkade bli kraftigare med stigande diagnosålder. Incidensen för pojkar var högre än hos flickor. Den årliga incidenstrenden var sjunkande fr.o.m. år 2006. Intressant var också att den yngsta åldersgruppen uppvisade den klart mest sjunkande incidenstrenden bland grupperna vilket väcker frågor om rotavirusvaccinets roll gällande incidensföränd-ringen. Rotavirusvaccinet infogades i det nationella vaccinationsprogrammet år 2009. Resultaten kan generera nya insikter angående sjukdomens patogenes och etiologi.
  • Kaipio, Johanna; Karisalmi, N.; Hiekkanen, K.; Stenhammar, H.; Lahdenne, P. (IOS PRESS, 2019)
    Studies in Health Technology and Informatics
    Patient experience (PX) is an important evaluation criterion for quality in healthcare. Compared to patient satisfaction, however less research has focused on the development of instruments to measure experiences of patients and their families. In the article, we describe the process of developing a PX questionnaire for the parents of pediatric patients in the context of children's hospital and illustrate the questionnaire items for measuring PX. The phases of the development process included retrospective interviews, description of the themes influencing PX and the metrics for measuring PX, as well as iterative development of three versions of questionnaires including data gathering and factor analysis. The final versions of the surveys suggested for implementation at the hospitals include eight PX statements for the outpatient clinic and five statements for the ward. Compared to satisfaction surveys, the developed surveys emphasize the aspects of parent's attitude towards the illness, support for families, and daily arrangements with a child patient. © 2019 American Psychological Association Inc. All rights reserved.
  • Jämsä, J.O.; Palojoki, S.H.; Lehtonen, L.; Tapper, A.-M. (2018)
    OBJECTIVES: To determine if and in what ways serious patient safety incidents differ from nonserious patient safety incidents. METHODS: Statistical analysis was performed on patient safety incident reports that were reported in 2015 in Finland's largest hospital district (Helsinki and Uusimaa, HUS). Reports were divided into two groups: nonserious incidents and serious incidents. Differences between groups were studied from several types of categorically divided information. RESULTS: Of the total number of reports (15,863), 1% were serious incidents (175). Serious and nonserious incidents differed significantly from each other. Serious incidents concerning laboratory, imaging, or medical equipment were more common. On the other hand, incidents concerning medication, infusion, and blood transfusion were less frequent. In serious incidents, the proportion of doctors reporting was greater, and contributing factors were better recognized, the most common being working of procedures. CONCLUSIONS: In the future, special attention should be given to the particular aspects of serious patient safety incidents, such as safe use of medical equipment, training, and handling of procedures. Root cause analysis is an effective way to handle serious incidents and enables the prevention of their reoccurrence. However, a systematic follow-up of the root cause analysis should be developed. © 2018 American Society for Health Care Risk Management of the American Hospital Association.
  • Hemilä Harri (2009)
    Since 1971, 21 placebo-controlled studies have been made to establish whether vitamin C at a dosage of ≥1 g/day affects the common cold. These studies have not found any consistent evidence that vitamin C supplementation reduces the incidence of the common cold in the general population. Nevertheless, in each of the 21 studies, vitamin C reduced the duration of episodes and the severity of the symptoms of the common cold by an average of 23%. However, there have been large variations in the benefits observed, and clinical significance cannot be clearly inferred from the results. Still, the consistency of the results indicates that the role of vitamin C in the treatment of the common cold should be reconsidered.
  • ALBINO Study Group; Maiwald, C.A.; Annink, K.V.; Rüdiger, M.; Benders, M.J.N.L.; Van Bel, F.; Allegaert, K.; Naulaers, G.; Bassler, D.; Klebermaß-Schrehof, K.; Vento, M.; Guimarães, H.; Stiris, T.; Cattarossi, L.; Metsäranta, M.; Vanhatalo, S.; Mazela, J.; Metsvaht, T.; Jacobs, Y. (2019)
    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,, May 22, 2017. © 2019 The Author(s).
  • Fagerstedt, K.W.; Salonen, T.; Zhao, F.; Kytölä, S.; Böhling, T.; Andersson, L.C. (2018)
    Myxoinflammatory fibroblastic sarcoma is a soft-tissue neoplasm most frequently found in the distal extremities of middle-aged adults. Most myxoinflammatory fibroblastic sarcoma are low-grade tumors with propensity for local recurrence after incomplete removal. We report a myxoinflammatory fibroblastic sarcoma which developed in the foot of a 41-year-old male and showed an exceptionally aggressive course with metastatic spread and fatal outcome within 16 months. We managed to establish a spontaneously transformed continuous cell line, called JU-PI, from a metastatic lesion. The JU-PI cells have a sub-tetraploid karyotype including the 1;10 chromosomal translocation and amplification of the proximal end of 3p; these features are considered genetic signatures of myxoinflammatory fibroblastic sarcoma. Both the primary tumor and the JU-PI cells showed nuclear expression of the TFE3 transcription factor but TFE3-activating chromosomal rearrangements were not found. To our knowledge, JU-PI is the first established myxoinflammatory fibroblastic sarcoma cell line. JU-PI cells offer a tool for investigating the molecular oncology of myxoinflammatory fibroblastic sarcoma. © 2018, © The Author(s) 2018.
  • Omoruyi, I.M.; Pohjanvirta, R. (2018)
    Mounting evidence of the effects of endocrine-disrupting chemicals (EDCs) in humans has led to assaying a vast array of food items (processed or packaged) as possible sources of human exposure to estrogens. In this study, we investigated the current situation in this respect of different food supplements and beer brands. Eleven food supplements and 24 beer brands were obtained from Helsinki, Finland. Sample preparation was carried out by established methods while estrogenic activities were assessed by a yeast bioluminescent assay, using two recombinant yeast strains (Saccharomyces cerevisiae BMAEREluc/ERα and S. cerevisiae BMA64/luc). All the food supplements as well as 81% of the beer samples tested were found to be estrogenic, with estradiol equivalent concentrations of food supplements and beer brands ranging from 7.5 to 11.5 µg/ml and from below detection limits to 43.6 ng/ml, respectively. The estrogenic activities detected in beer samples were not dependent on the beer's alcoholic content, the country of production, or the size of the production brewery. The results of our study imply that both food supplements and beers can be a significant source of human exposure to estrogens. Therefore, further studies and regular surveillance are warranted. © 2018, © 2018 Taylor & Francis Group, LLC.
  • Kuchenbaecker, K.B.; McGuffog, L.; Barrowdale, D.; Lee, Andrew; Soucy, P.; Dennis, J.; Domchek, S.M.; Robson, M.; Spurdle, A.B.; Ramus, S.J.; Mavaddat, N.; Terry, M.B.; Neuhausen, S.L.; Schmutzler, R.K.; Simard, J.; Pharoah, P.D.P.; Offit, K.; Couch, F.J.; Chenevix-Trench, G.; Easton, D.F.; Antoniou, A.C.; Healey, S.; Lush, M.; Hamann, U.; Southey, M.; John, E.M.; Chung, W.K.; Daly, M. B.; Buys, S.S.; Goldgar, D.E.; Dorfling, C.M.; van Rensburg, E.J.; Ding, Y.C.; Ejlertsen, B.; Gerdes, A.-M.; Hansen, T.V.O.; Slager, S.; Hallberg, E.; Benitez, J.; Osorio, A.; Cohen, N.; Lawler, W.; Weitzel, J.N.; Peterlongo, P.; Pensotti, V.; Dolcetti, R.; Barile, M.; Aittomäki, K.; Nevanlinna, H.; Rantala, J. (2017)
    Background: Genome-wide association studies (GWAS) have identified 94 common single-nucleotide polymorphisms (SNPs) associated with breast cancer (BC) risk and 18 associated with ovarian cancer (OC) risk. Several of these are also associated with risk of BC or OC for women who carry a pathogenic mutation in the high-risk BC and OC genes BRCA1 or BRCA2. The combined effects of these variants on BC or OC risk for BRCA1 and BRCA2 mutation carriers have not yet been assessed while their clinical management could benefit from improved personalized risk estimates. Methods: We constructed polygenic risk scores (PRS) using BC and OC susceptibility SNPs identified through population-based GWAS: for BC (overall, estrogen receptor [ER]-positive, and ER-negative) and for OC. Using data from 15 252 female BRCA1 and 8211 BRCA2 carriers, the association of each PRS with BC or OC risk was evaluated using a weighted cohort approach, with time to diagnosis as the outcome and estimation of the hazard ratios (HRs) per standard deviation increase in the PRS. Results: The PRS for ER-negative BC displayed the strongest association with BC risk in BRCA1 carriers (HR = 1.27, 95% confidence interval [CI] = 1.23 to 1.31, P = 8.2 × 10-53). InBRCA2 carriers, the strongest association with BC risk was seen for the overall BCPRS (HR = 1.22, 95% CI = 1.17 to 1.28, P = 7.2 × 10-20). The OC PRS was strongly associated with OC risk for both BRCA1 and BRCA2 carriers. These translate to differences in absolute risks (more than 10% in each case) between the top and bottom deciles of the PRS distribution; for example, the OC risk was 6% by age 80 years for BRCA2 carriers at the 10th percentile of the OC PRS compared with 19% risk for those at the 90th percentile of PRS. Conclusions: BC and OC PRS are predictive of cancer risk in BRCA1 and BRCA2 carriers. Incorporation of the PRS into risk prediction models has promise to better inform decisions on cancer risk management. © The Author 2017.
  • Paavola, Mika; Malmivaara, Antti; Taimela, Simo; Kanto, Kari; Järvinen, Teppo L. N. (2017)
    Introduction: Arthroscopic subacromial decompression (ASD) is the most commonly performed surgical intervention for shoulder pain, yet evidence on its efficacy is limited. The rationale for the surgery rests on the tenet that symptom relief is achieved through decompression of the rotator cuff tendon passage. The primary objective of this superiority trial is to compare the efficacy of ASD versus diagnostic arthroscopy (DA) in patients with shoulder impingement syndrome (SIS), where DA differs only by the lack of subacromial decompression. A third group of supervised progressive exercise therapy (ET) will allow for pragmatic assessment of the relative benefits of surgical versus non-operative treatment strategies. Methods and Analysis: Finnish Subacromial Impingement Arthroscopy Controlled Trial is an ongoing multicentre, three-group randomised controlled study. We performed two-fold concealed allocation, first by randomising patients to surgical (ASD or DA) or conservative (ET) treatment in 2:1 ratio and then those allocated to surgery further to ASD or DA in 1:1 ratio. Our two primary outcomes are pain at rest and at arm activity, assessed using visual analogue scale (VAS). We will quantify the treatment effect as the difference between the groups in the change in the VAS scales with the associated 95% CI at 24 months. Our secondary outcomes are functional assessment (Constant score and Simple shoulder test), quality of life (15D and SF-36), patient satisfaction, proportions of responders and non-responders, reoperations/treatment conversions, all at 2 years post-randomisation, as well as adverse effects and complications. We recruited a total of 210 patients from three tertiary referral centres. We will conduct the primary analysis on the intention-to-treat basis. Ethics and Dissemination: The study was approved by the Institutional Review Board of the Pirkanmaa Hospital District and duly registered at The findings of this study will be disseminated widely through peer-reviewed publications and conference presentations. © 2017 Article author(s).
  • Peltonen, Laura-Maria; Junttila, Kristiina; Salanterä, Sanna (IOS PRESS, 2018)
    Studies in Health Technology and Informatics
    Day-to-day operations management in hospital units is difficult due to continuously varying situations, several actors involved and a vast number of information systems in use. The aim of this study was to describe front-line physicians' satisfaction with existing information systems needed to support the day-to-day operations management in hospitals. A cross-sectional survey was used and data chosen with stratified random sampling were collected in nine hospitals. Data were analyzed with descriptive and inferential statistical methods. The response rate was 65 % (n = 111). The physicians reported that information systems support their decision making to some extent, but they do not improve access to information nor are they tailored for physicians. The respondents also reported that they need to use several information systems to support decision making and that they would prefer one information system to access important information. Improved information access would better support physicians' decision making and has the potential to improve the quality of decisions and speed up the decision making process.
  • Global Burden of Disease Cancer Collaboration; Fitzmaurice, C.; Doku, D.T.; Hadkhale, K.; Meretoja, T.J.; Neupane, S. (2019)
    Importance: Cancer and other noncommunicable diseases (NCDs) are now widely recognized as a threat to global development. The latest United Nations high-level meeting on NCDs reaffirmed this observation and also highlighted the slow progress in meeting the 2011 Political Declaration on the Prevention and Control of Noncommunicable Diseases and the third Sustainable Development Goal. Lack of situational analyses, priority setting, and budgeting have been identified as major obstacles in achieving these goals. All of these have in common that they require information on the local cancer epidemiology. The Global Burden of Disease (GBD) study is uniquely poised to provide these crucial data. Objective: To describe cancer burden for 29 cancer groups in 195 countries from 1990 through 2017 to provide data needed for cancer control planning. Evidence Review: We used the GBD study estimation methods to describe cancer incidence, mortality, years lived with disability, years of life lost, and disability-Adjusted life-years (DALYs). Results are presented at the national level as well as by Socio-demographic Index (SDI), a composite indicator of income, educational attainment, and total fertility rate. We also analyzed the influence of the epidemiological vs the demographic transition on cancer incidence. Findings: In 2017, there were 24.5 million incident cancer cases worldwide (16.8 million without nonmelanoma skin cancer [NMSC]) and 9.6 million cancer deaths. The majority of cancer DALYs came from years of life lost (97%), and only 3% came from years lived with disability. The odds of developing cancer were the lowest in the low SDI quintile (1 in 7) and the highest in the high SDI quintile (1 in 2) for both sexes. In 2017, the most common incident cancers in men were NMSC (4.3 million incident cases); tracheal, bronchus, and lung (TBL) cancer (1.5 million incident cases); and prostate cancer (1.3 million incident cases). The most common causes of cancer deaths and DALYs for men were TBL cancer (1.3 million deaths and 28.4 million DALYs), liver cancer (572000 deaths and 15.2 million DALYs), and stomach cancer (542000 deaths and 12.2 million DALYs). For women in 2017, the most common incident cancers were NMSC (3.3 million incident cases), breast cancer (1.9 million incident cases), and colorectal cancer (819000 incident cases). The leading causes of cancer deaths and DALYs for women were breast cancer (601000 deaths and 17.4 million DALYs), TBL cancer (596000 deaths and 12.6 million DALYs), and colorectal cancer (414000 deaths and 8.3 million DALYs). Conclusions and Relevance: The national epidemiological profiles of cancer burden in the GBD study show large heterogeneities, which are a reflection of different exposures to risk factors, economic settings, lifestyles, and access to care and screening. The GBD study can be used by policy makers and other stakeholders to develop and improve national and local cancer control in order to achieve the global targets and improve equity in cancer care. © 2019 American Medical Association. All rights reserved.
  • eQTLGen Consortium (2018)
    Understanding the difference in genetic regulation of gene expression between brain and blood is important for discovering genes for brain-related traits and disorders. Here, we estimate the correlation of genetic effects at the top-associated cis-expression or -DNA methylation (DNAm) quantitative trait loci (cis-eQTLs or cis-mQTLs) between brain and blood (r b ). Using publicly available data, we find that genetic effects at the top cis-eQTLs or mQTLs are highly correlated between independent brain and blood samples (r b = 0.70 for cis-eQTLs and r ^ b = 0.78 for cis-mQTLs). Using meta-analyzed brain cis-eQTL/mQTL data (n = 526 to 1194), we identify 61 genes and 167 DNAm sites associated with four brain-related phenotypes, most of which are a subset of the discoveries (97 genes and 295 DNAm sites) using data from blood with larger sample sizes (n = 1980 to 14,115). Our results demonstrate the gain of power in gene discovery for brain-related phenotypes using blood cis-eQTL/mQTL data with large sample sizes. © 2018 The Author(s).
  • Vink, P.; Torrell, J.M.R.; Fructuoso, A.S.; Kim, Sung-Joo; Kim, Sang-Il; Zaltzman, J.; Ortiz, F.; Plana, J.M.C.; Rodriguez, A.M.F.; Rodrigo, H.R.; Marti, M.C.; Perez, R.; Roncero, F.M.G.; Kumar, D.; Chiang, Y.-J.; Doucette, K.; Pipeleers, L.; Morales, M.L.A.; Rodriguez-Ferrero, M.L.; Secchi, Antonio; McNeil, S.A.; Campora, L.; Di Paolo, E.; El Idrissi, M.; López-Fauqued, M.; Salaun, B.; Heineman, T.C.; Oostvogels, L. (2020)
    Background. The incidence of herpes zoster is up to 9 times higher in immunosuppressed solid organ transplant recipients than in the general population. We investigated the immunogenicity and safety of an adjuvanted recombinant zoster vaccine (RZV) in renal transplant (RT) recipients ≥18 years of age receiving daily immunosuppressive therapy. Methods. In this phase 3, randomized (1:1), observer-blind, multicenter trial, RT recipients were enrolled and received 2 doses of RZV or placebo 1-2 months (M) apart 4-18M posttransplant. Anti-glycoprotein E (gE) antibody concentrations, gE-specific CD4 T-cell frequencies, and vaccine response rates were assessed at 1M post-dose 1, and 1M and 12M post-dose 2. Solicited and unsolicited adverse events (AEs) were recorded for 7 and 30 days after each dose, respectively. Solicited general symptoms and unsolicited AEs were also collected 7 days before first vaccination. Serious AEs (including biopsy-proven allograft rejections) and potential immune-mediated diseases (pIMDs) were recorded up to 12M post-dose 2. Results. Two hundred sixty-four participants (RZV: 132; placebo: 132) were enrolled between March 2014 and April 2017. gE-specific humoral and cell-mediated immune responses were higher in RZV than placebo recipients across postvaccination time points and persisted above prevaccination baseline 12M post-dose 2. Local AEs were reported more frequently by RZV than placebo recipients. Overall occurrences of renal function changes, rejections, unsolicited AEs, serious AEs, and pIMDs were similar between groups. Conclusions. RZV was immunogenic in chronically immunosuppressed RT recipients. Immunogenicity persisted through 12M postvaccination. No safety concerns arose. © The Author(s) 2019.
  • Jaiswal, Alok; Yadav, Bhagwan; Wennerberg, Krister; Aittokallio, Tero (Humana press, 2019)
    Methods in Molecular Biology
    High-throughput drug sensitivity testing provides a powerful phenotypic profiling approach to identify effective drug candidates for individual cell lines or patient-derived samples. Here, we describe an experimental-computational pipeline, named target addiction scoring (TAS), which mathematically transforms the drug response profiles into target addiction signatures, and thereby provides a ranking of potential therapeutic targets according to their functional importance in a particular cancer sample. The TAS pipeline makes use of drug polypharmacology to integrate the drug sensitivity and selectivity profiles through systems-wide interconnection networks between drugs and their targets, including both primary protein targets as well as secondary off-targets. We show how the TAS pipeline enables one to identify not only single-target addictions but also combinatorial coaddictions among targets that often underlie synergistic drug combinations. © Springer Science+Business Media, LLC, part of Springer Nature 2019.