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Genome-wide association identifies seven loci for pelvic organ prolapse in Iceland and the UK Biobank.
Get PDFTo access publisher's full text version of this article, please click on the hyperlink in Additional Links field or click on the hyperlink at the top of the page marked DownloadPelvic organ prolapse (POP) is a downward descent of one or more of the pelvic organs, resulting in a protrusion of the vaginal wall and/or uterus. We performed a genome-wide association study of POP using data from Iceland and the UK Biobank, a total of 15,010 cases with hospital-based diagnosis code and 340,734 female controls, and found eight sequence variants at seven loci associating with POP (P 5%) and one with minor allele frequency of 4.87%. Some of the variants associating with POP also associated with traits of similar pathophysiology. Of these, rs3820282, which may alter the estrogen-based regulation of WNT4, also associates with leiomyoma of uterus, gestational duration and endometriosis. Rs3791675 at EFEMP1, a gene involved in connective tissue homeostasis, also associates with hernias and carpal tunnel syndrome. Our results highlight the role of connective tissue metabolism and estrogen exposure in the etiology of POP.UCL Hospitals NIHR Biomedical Research Centr
Visualizing metabolic network dynamics through time-series metabolomic data.
Get PDFTo access publisher's full text version of this article, please click on the hyperlink in Additional Links field or click on the hyperlink at the top of the page marked DownloadBackground: New technologies have given rise to an abundance of -omics data, particularly metabolomic data. The scale of these data introduces new challenges for the interpretation and extraction of knowledge, requiring the development of innovative computational visualization methodologies. Here, we present GEM-Vis, an original method for the visualization of time-course metabolomic data within the context of metabolic network maps. We demonstrate the utility of the GEM-Vis method by examining previously published data for two cellular systems-the human platelet and erythrocyte under cold storage for use in transfusion medicine.
Results: The results comprise two animated videos that allow for new insights into the metabolic state of both cell types. In the case study of the platelet metabolome during storage, the new visualization technique elucidates a nicotinamide accumulation that mirrors that of hypoxanthine and might, therefore, reflect similar pathway usage. This visual analysis provides a possible explanation for why the salvage reactions in purine metabolism exhibit lower activity during the first few days of the storage period. The second case study displays drastic changes in specific erythrocyte metabolite pools at different times during storage at different temperatures.
Conclusions: The new visualization technique GEM-Vis introduced in this article constitutes a well-suitable approach for large-scale network exploration and advances hypothesis generation. This method can be applied to any system with data and a metabolic map to promote visualization and understand physiology at the network level. More broadly, we hope that our approach will provide the blueprints for new visualizations of other longitudinal -omics data types. The supplement includes a comprehensive user's guide and links to a series of tutorial videos that explain how to prepare model and data files, and how to use the software SBMLsimulator in combination with further tools to create similar animations as highlighted in the case studies.United States Department of Health & Human Services
National Institutes of Health (NIH) - USA
Institute for Systems Biology's Translational Research Fellowship
Landspitali University Hospital Research Fund
University of Iceland Research Fund
Novo Nordisk Foundation through the Center for Biosustainability at the Technical University of Denmark
YNF10CC1016517
German Research Foundation (DFG)
DZIF (German Center for Infection Research)
University of Tubinge
Risk of hernia formation after radical prostatectomy: a comparison between open and robot-assisted laparoscopic radical prostatectomy within the prospectively controlled LAPPRO trial.
No full textTo access publisher's full text version of this article click on the hyperlink belowPurpose: In addition to incisional hernia, inguinal hernia is a recognized complication to radical retropubic prostatectomy. To compare the risk of developing inguinal and incisional hernias after open radical prostatectomy compared to robot-assisted laparoscopic prostatectomy.
Method: Patients planned for prostatectomy were enrolled in the prospective, controlled LAPPRO trial between September 2008 and November 2011 at 14 hospitals in Sweden. Information regarding patient characteristics, operative techniques and occurrence of postoperative inguinal and incisional hernia were retrieved using six clinical record forms and four validated questionnaires.
Results: 3447 patients operated with radical prostatectomy were analyzed. Within 24 months, 262 patients developed an inguinal hernia, 189 (7.3%) after robot-assisted laparoscopic prostatectomy and 73 (8.4%) after open radical prostatectomy. The relative risk of having an inguinal hernia after robot-assisted laparoscopic prostatectomy was 18% lower compared to open radical retropubic prostatectomy, a non-significant difference. Risk factors for developing an inguinal hernia after prostatectomy were increased age, low BMI and previous hernia repair. The incidence of incisional hernia was low regardless of surgical technique. Limitations are the non-randomised setting.
Conclusions: We found no difference in incidence of inguinal hernia after open retropubic and robot-assisted laparoscopic radical prostatectomy. The low incidence of incisional hernia after both procedures did not allow for statistical analysis. Risk factors for developing an inguinal hernia after prostatectomy were increased age and BMI.University of Gothenburg
Swedish Cancer Society
Swedish Research Council
Region Vastra Gotaland
Sahlgrenska University Hospital (ALFBGB)
Mrs. Mary von Sydow Foundation
Anna and Edvin Berger Foundation
Swedish Society of Medicin
Dentistry in the High Arctic
No full textTo access publisher's full text version of this article, please click on the hyperlink in Additional Links field or click on the hyperlink at the top of the page marked DownloadAð vera tannlæknir 1316 kílómetrum frá Norðurpólnum býður upp á ýmsar áskoranir. Veðurfar, samgöngur, aldursdreifing íbúa,
mismunandi þjóðerni og menning gefur tilefni fyrir spennandi og áhugaverðan vinnudag. Náttúran, myrkrið, ljósið og ísbjarnarhættan
hefur einnig mikil áhrif á daglegt líf.Being the world´s northernmost dentist offers a variety of challenges. Arctic weather and limited means of transportation can mean
isolation and delays in medical assistance. Different nationalities and cultures, as well as age distribution of the population of the
Svalbard archipelago provide for an intense, busy, exciting and interesting workday. Astounding nature, extreme darkness and light,
and the need for polar bear protection also has a major impact on everyday life
Fitness, body composition and quality of life following cancer treatment
No full textTo access publisher's full text version of this article, please click on the hyperlink in Additional Links field or click on the hyperlink at the top of the page marked DownloadTILGANGUR
Sífellt fleiri lifa lengi eftir meðferð vegna krabbameins. Þekking á
langtímaáhrifum krabbameinsmeðferðar á þrek, holdafar og heilsutengd lífsgæði fólks, er mikilvæg fyrir þennan vaxandi samfélagshóp. Tilgangur rannsóknarinnar var tvíþættur: (a) að mæla þrek,
holdafar, heilsutengd lífsgæði og persónueinkenni fólks sem hefur
lokið við læknismeðferð vegna krabbameina undanfarin 10 ár; og
(b) að athuga hvort þrek hafi fylgni við holdafar og heilsutengd lífsgæði fólks sem hefur lokið við læknismeðferð vegna krabbameina.
EFNIVIÐUR OG AÐFERÐIR
Áttatíu þátttakendur (25-77 ára) af báðum kynjum, sem voru í
sjúkdómshléi eða álitnir læknaðir af krabbameini, svöruðu spurningalistum um heilsutengd lífsgæði (SF-36v2 og EQ-5D-3L) og
persónuleika D (DS14). Blóðþrýstingur, líkamsþyngdarstuðull (LÞS),
fituprósenta, þrek metið með 6 mínútna gönguprófi (6MWT) og
ummál mittis og mjaðma var mælt. Notað var SPSS til að fá lýsandi
tölfræði og við útreikning á fylgnistuðlum, miðað var við 95% marktektarmörk.
NIÐURSTÖÐUR
Tveir af hverjum þremur þátttakendum voru með einhverja þætti
holdafars yfir viðmiðunarmörkum. Rúmlega helmingur þátttakenda
var yfir kjörþyngd, 66,3% voru með mittisummál yfir viðmiðunarmörkum, 45,0% voru með hlutfall milli mittis og mjaðma yfir
viðmiðunarmörkum. Gengin vegalengd í 6MWT var að meðaltali
634 m +/- 83 m. Marktæk fylgni (p<0,05) mældist á milli 6MWT og
holdafars, ásamt 6MWT við flesta þætti heilsutengdra lífsgæða.
Aðeins 13,8% þátttakenda mældust með persónuleika D.
ÁLYKTANIR
Holdafar fólks sem hefur lokið við krabbameinsmeðferð er almennt
yfir viðmiðunarmörkum. Þrek hefur fylgni við heilsutengd lífsgæði
og holdafar fólks sem hefur lokið við krabbameinsmeðferð.Introduction: Five-year survival of people diagnosed with cancer
has increased in past decades. Knowledge of the long-term effects
of cancer treatment on fitness, body composition and health related
quality of life (HR-QoL) is important for cancer patients. The study
aimed to evaluate body composition, HR-QoL and personality D of
people post cancer treatment in the last 10 years; and to observe
whether fitness was correlated with body composition and HR-QoL
amongst them.
Material and methods: Eighty participants 25 - 77 y/o of both genders
in remission from cancer answered questionnaires on HR-QoL (SF-36v2
and EQ-5D-3L), personality D (DS14), general health, lifestyle and cancer
treatment. Participants had their blood pressure measured, conducted
the 6-minute walk test (6MWT) and had their body composition measured: body mass index, body fat percentage, waist and hip circumferences. SPSS was used for statistical analysis.
Results: Approximately 2/3 of the participants had body composition
over recommended values. Over half were overweight or obese. 66.3%
had waist circumference over recommended values and 45.0% had
waist/hip ratio over recommended values. 6MWT average distance was
634 m +/- 83 m. Significant correlation (p<0.05) was found between
6MWT and body composition and most categories of HR-QoL.
Increased fitness correlated with better body composition and higher
HR-QoL. Only 13.8% of participants showed personality D.
Conclusion: Cancer survivor‘s body composition is generally not at its
best. It is important that people diagnosed with cancer are informed on
the importance of healthy body composition. Fitness is an indicator for
HR-QoL and body composition of cancer survivors.
Key words: Cancer, fitness, body composition, quality of life, personality
Identification of Genetic Loci Shared Between Attention-Deficit/Hyperactivity Disorder, Intelligence, and Educational Attainment.
No full textTo access publisher's full text version of this article click on the hyperlink belowBackground: Attention-deficit/hyperactivity disorder (ADHD) is a neurodevelopmental disorder that is consistently associated with lower levels of educational attainment. A recent large genome-wide association study identified common gene variants associated with ADHD, but most of the genetic architecture remains unknown.
Methods: We analyzed independent genome-wide association study summary statistics for ADHD (19,099 cases and 34,194 controls), educational attainment (N = 842,499), and general intelligence (N = 269,867) using a conditional/conjunctional false discovery rate (FDR) statistical framework that increases power of discovery by conditioning the FDR on overlapping associations. The genetic variants identified were characterized in terms of function, expression, and biological processes.
Results: We identified 58 linkage disequilibrium-independent ADHD-associated loci (conditional FDR < 0.01), of which 30 were shared between ADHD and educational attainment or general intelligence (conjunctional FDR < 0.01) and 46 were novel risk loci for ADHD.
Conclusions: These results expand on previous genetic and epidemiological studies and support the hypothesis of a shared genetic basis between these phenotypes. Although the clinical utility of the identified loci remains to be determined, they can be used as resources to guide future studies aiming to disentangle the complex etiologies of ADHD, educational attainment, and general intelligence.
Keywords: ADHD; Cognition; Genetic overlap; Mental health; Pleiotropy; Psychiatric disorder.United States Department of Health & Human Services
National Institutes of Health (NIH) - USA
Research Council of Norway
South-East Norway Regional Health Authority
KG Jebsen Foundation
GE Healthcar
Long-term outcomes after coronary artery bypass surgery in patients with diabetes.
No full textTo access publisher's full text version of this article click on the hyperlink belowObjectives: Our aim was to investigate the outcome of patients with diabetes undergoing coronary artery bypass grafting (CABG) surgery in a whole population with main focus on long-term mortality and complications.
Methods: This was a nationwide retrospective analysis of all patients who underwent isolated primary CABG in Iceland between 2001 and 2016. Overall survival together with the composite end point of major adverse cardiac and cerebrovascular events was compared between patients with diabetes and patients without diabetes during a median follow-up of 8.5 years. Multivariable regression analyses were used to evaluate the impact of diabetes on both short- and long-term outcomes.
Results: Of a total of 2060 patients, 356 (17%) patients had diabetes. Patients with diabetes had a higher body mass index (29.9 vs 27.9 kg/m2) and more often had hypertension (83% vs 62%) and chronic kidney disease (estimated glomerular filtration rate ≤60 ml/min/1.73 m2, 21% vs 14%). Patients with diabetes had an increased risk of operative mortality [odds ratio 2.52, 95% confidence interval (CI) 1.27-4.80] when adjusted for confounders. 5-Year overall survival (85% vs 91%, P < 0.001) and 5-year freedom from major adverse cardiac and cerebrovascular events were also inferior for patients with diabetes (77% vs 82%, P < 0.001). Cox regression analysis adjusting for potential confounders showed that the diagnosis of diabetes significantly predicted all-cause mortality [hazard ratio (HR) 1.87, 95% CI 1.53-2.29] and increased risk of major adverse cardiac and cerebrovascular events (HR 1.47, 95% CI 1.23-1.75).
Conclusions: Patients with diabetes have significantly lower survival after CABG, both within 30 days and during long-term follow-up.
Keywords: Complications; Coronary artery bypass grafting; Diabetes; Long term; Major adverse cardiac and cerebrovascular events; Outcome; Survival
Differences in three-dimensional upper airway anatomy between Asian and European patients with obstructive sleep apnea.
No full textTo access publisher's full text version of this article click on the hyperlink belowStudy objectives: This study evaluated differences in upper airway, soft tissues and craniofacial structures between Asians from China and Europeans from Iceland with OSA using three-dimensional magnetic resonance imaging (MRI).
Methods: Airway sizes, soft tissue volumes, and craniofacial dimensions were compared between Icelandic (N = 108) and Chinese (N = 57) patients with oxygen desaturation index (ODI) ≥ 10 events/h matched for age, gender, and ODI. Mixed effects models adjusting for height or BMI and residual differences in age and ODI were utilized.
Results: In our matched sample, compared to Icelandic OSA patients, Chinese patients had smaller BMI (p < 0.0001) and neck circumference (p = 0.011). In covariate adjusted analyses, Chinese showed smaller retropalatal airway size (p ≤ 0.002), and smaller combined soft tissues, tongue, fat pads, and pterygoid (all p ≤ 0.0001), but male Chinese demonstrated a larger soft palate volume (p ≤ 0.001). For craniofacial dimensions, Chinese demonstrated bigger ANB angle (p ≤ 0.0196), differently shaped mandibles, including shorter corpus length (p < 0.0001) but longer ramus length (p < 0.0001), and a wider (p < 0.0001) and shallower (p ≤ 0.0001) maxilla.
Conclusions: Compared to Icelandic patients of similar age, gender and ODI, Chinese patients had smaller retropalatal airway and combined soft tissue, but bigger soft palate volume (in males), and differently shaped mandible and maxilla with more bony restrictions. Results support an ethnic difference in upper airway anatomy related to OSA, which may inform targeted therapies.
Keywords: ethnicity; obstructive sleep apnea; three-dimensional magnetic resonance imaging; upper airway structure.United States Department of Health & Human Services
National Institutes of Health (NIH) - US
The challenge of implementing Less is More medicine: A European perspective.
No full textTo access publisher's full text version of this article click on the hyperlink belowThe concept of Less is More medicine emerged in North America in 2010. It aims to serve as an invitation to recognize the potential risks of overuse of medical care that may result in harm rather than in better health, tackling the erroneous assumption that more care is always better. In response, several medical societies across the world launched quality-driven campaigns ("Choosing Wisely") and published "top-five lists" of low-value medical interventions that should be used to help make wise decisions in each clinical domain, by engaging patients in conversations about unnecessary tests, treatments and procedures. However, barriers and challenges for the implementation of Less is More medicine have been identified in several European countries, where overuse is rooted in the culture and demanded by a society that requests certainty at almost any cost. Patients' high expectations, physician's behavior, lack of monitoring and pernicious financial incentives have all indirect negative consequences for medical overuse. Multiple interventions and quality-measurement efforts are necessary to widely implement Less is More recommendations. These also consist of a top-five list of actions: (1) a novel cultural approach starting from medical graduation courses, up to (2) patient and society education, (3) physician behavior change with data feedback, (4) communication training and (5) policy maker interventions. In contrast with the prevailing maximization of care, the optimization of care promoted by Less is More medicine can be an intellectual challenge but also a real opportunity to promote sustainable medicine. This project will constitute part of the future agenda of the European Federation of Internal Medicine.
Keywords: Choosing wisely; Healthcare; Medical education; Overuse; Waste
Fine-mapping of 150 breast cancer risk regions identifies 191 likely target genes.
No full textTo access publisher's full text version of this article click on the hyperlink belowGenome-wide association studies have identified breast cancer risk variants in over 150 genomic regions, but the mechanisms underlying risk remain largely unknown. These regions were explored by combining association analysis with in silico genomic feature annotations. We defined 205 independent risk-associated signals with the set of credible causal variants in each one. In parallel, we used a Bayesian approach (PAINTOR) that combines genetic association, linkage disequilibrium and enriched genomic features to determine variants with high posterior probabilities of being causal. Potentially causal variants were significantly over-represented in active gene regulatory regions and transcription factor binding sites. We applied our INQUSIT pipeline for prioritizing genes as targets of those potentially causal variants, using gene expression (expression quantitative trait loci), chromatin interaction and functional annotations. Known cancer drivers, transcription factors and genes in the developmental, apoptosis, immune system and DNA integrity checkpoint gene ontology pathways were over-represented among the highest-confidence target genes.European Union's Horizon 2020 Research and Innovation Programme under Marie Sklodowska-Curie grant
PERSPECTIVE project (Government of Canada through Genome Canada)
Canadian Institutes of Health Research (CIHR)
PERSPECTIVE project ('Ministere de l'Economie de la Science et de l'Innovation du Quebec' (Genome Quebec)
PERSPECTIVE project (Quebec Breast Cancer Foundation)
NCI Genetic Associations and Mechanisms in Oncology (GAME-ON) initiative
United States Department of Health & Human Services
National Institutes of Health (NIH) - USA
Cancer Research UK
European Community (EC)
European Union (EU)
Canadian Institutes of Health Research (CIHR)
Ministry of Economic Development, Innovation and Export Trade of Quebec
United States Department of Health & Human Services
National Institutes of Health (NIH) - US