Institute of Clinical Research

Odense, Denmark

Institute of Clinical Research

Odense, Denmark
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Lemche A.V.,Institute of Clinical Research | Chaban O.S.,Bogomolets National Medical University | Lemche E.,Institute of Psychiatry
Journal of Endocrinological Investigation | Year: 2017

Purpose: Triglycerides are considered an emerging risk factor for cardiovascular mortality. Recent evidence relating depression and metabolic syndrome (MetS) implicated triglyceride levels. We thus investigated interrelations of self-reported depression severity (Zung) and MetS-related biological measures with CVD risk estimates in MetS patients. Methods: N = 101 patients fulfilling International Diabetes Federation criteria for MetS from a nationwide sampled treatment cohort for MetS with familial T2DM risk or manifest T2DM in a Ukrainian governmental health care system were participants. Both laboratory and non-laboratory measures were included. Recent European cardiological SCORE system CVD risk estimates were used as outcome variables. Results: Following correlation matrix, we entered all variables into principal component analysis (PCA; 76.7% explained variance), followed by hierarchical regression and structural equation modeling (SEM). The PCA suggested a one-factor solution, where the latent variable showed highest loadings of SCORE risk estimates, triglycerides, depression severity, and pulse pressure. A comprehensive SEM was adjusted with 92.7% explained variance: overall CVD risk related to depression, pulse pressure, triglycerides, and fasting glucose. Conclusion: The findings in this MetS sample suggest that triglycerides and depression severity are the key variables among MetS biomarkers in cross-sectionally associating with the fatal and total SCORE risk estimates in MetS. © 2016, The Author(s).

Lemche E.,King's College London | Chaban O.S.,Bogomolets National Medical University | Lemche A.V.,Institute of Clinical Research
Frontiers in Neuroscience | Year: 2016

Impact of environmental stress upon pathophysiology of the metabolic syndrome (MetS) has been substantiated by epidemiological, psychophysiological, and endocrinological studies. This review discusses recent advances in the understanding of causative roles of nutritional factors, sympathomedullo-adrenal (SMA) and hypothalamic-pituitary adrenocortical (HPA) axes, and adipose tissue chronic low-grade inflammation processes in MetS. Disturbances in the neuroendocrine systems for leptin, melanocortin, and neuropeptide Y (NPY)/agouti-related protein systems have been found resulting directly in MetS-like conditions. The review identifies candidate risk genes from factors shown critical for the functioning of each of these neuroendocrine signaling cascades. In its meta-analytic part, recent studies in epigenetic modification (histone methylation, acetylation, phosphorylation, ubiquitination) and posttranscriptional gene regulation by microRNAs are evaluated. Several studies suggest modification mechanisms of early life stress (ELS) and diet-induced obesity (DIO) programming in the hypothalamic regions with populations of POMC-expressing neurons. Epigenetic modifications were found in cortisol (here HSD11B1 expression), melanocortin, leptin, NPY, and adiponectin genes. With respect to adiposity genes, epigenetic modifications were documented for fat mass gene cluster APOA1/C3/A4/A5, and the lipolysis gene LIPE. With regard to inflammatory, immune and subcellular metabolism, PPARG, NKBF1, TNFA, TCF7C2, and those genes expressing cytochrome P450 family enzymes involved in steroidogenesis and in hepatic lipoproteins were documented for epigenetic modifications. © 2016 Lemche, Chaban and Lemche.

Struglia F.,University of L'Aquila | Gianfelice D.,University of L'Aquila | Pacifico R.,University of L'Aquila | Riccardi I.,University of L'Aquila | And 2 more authors.
Neuroscience Letters | Year: 2011

Abnormal decision-making (DM) performance has been reported in several neurobehavioral disorders such as schizophrenia, addiction, and obsessive compulsive disorders. The exploration of DM correlates in terms of symptom formation may add more knowledge about the meanings of DM performance in schizophrenia. We examined the Iowa Gambling Task (IGT) and its relationship with clinical symptoms, evaluated by Positive and Negative Symptom Scale (PANSS), in 40 schizophrenic patients and 20 controls. Schizophrenic patients did worse on IGT performance with a significant difference between the two groups in Net Score. PANSS positive symptoms were negatively correlated with Net Score and advantageous choices and directly with disadvantageous choices. Results suggest that persons with schizophrenia display a pattern of compromised DM related to positive symptoms. © 2011 Elsevier Ireland Ltd.

Monnier L.,Institute of Clinical Research | Colette C.,Institute of Clinical Research | Owens D.,University of Swansea
Diabetes and Metabolism | Year: 2013

During the past 10. years, several new basal insulin analogs have been developed. There has been for 3. years controversy on the potential increased risk for cancer with insulin glargine, which ceased with the publication of the ORIGIN trial in 2012. In insulin-treated persons with type 2 diabetes, it is usual to recommend that plasma insulin concentrations remain within a 50-200. pmol/L range in order to avoid overinsulinization, a potential causative factor for increased mitogenicity. Such concentrations are achieved when daily doses of insulin glargine or NPH insulin approximate 0.4 units/kg. However, the total plasma insulin concentrations are much greater in persons treated with insulin detemir and especially insulin degludec. These insulins derive their protracted action from the insertion of a long chain fatty acid moiety to the insulin molecule thereby increasing albumin binding. As a consequence, in persons with type 2 diabetes, stable total plasma concentrations as high as either 1600 or 6000. pmol/L are observed for insulin detemir or degludec, respectively. At present, the free to bound ratio of plasma insulin concentrations remains unknown for these two compounds. A first requirement is to understand how these insulins are eliminated or degraded and secondly to quantify the respective contributions of the free and bound fractions. Therefore, prior to early phase 2 or 3 randomized clinical trials, a better comprehension of the metabolism of all the new insulins would be invaluable. © 2013 Elsevier Masson SAS.

Hammer K.,University of the Faroe Islands | Hall E.O.C.,University of Aarhus | Mogensen O.,Institute of Clinical Research
Cancer Nursing | Year: 2013

BACKGROUND:: In mysterious ways, hope makes life meaningful even in chaotic and uncontrolled situations. When a woman is newly diagnosed with gynecologic cancer, hope is ineffable and needs exploring. Drawings help express ineffable phenomena. OBJECTIVE:: The aim of the study was to explore how women newly diagnosed with gynecologic cancer express the meaning of hope in drawings. METHOD:: Participants were 15 women who on the same day had received the diagnosis of gynecologic cancer. They were between 24 and 87 years (median, 52 years) with a variety of gynecologic cancer diagnoses. Data from 15 drawings and postdrawing interviews with the women were analyzed using visual and hermeneutic phenomenology. RESULTS:: Three themes emerged: hope as a spirit to move on, hope as energy through nature, and hope as a communion with families. CONCLUSION:: Hope as pictured in drawings often appears through metaphors and incorporates internal, external, and relational aspects. With other words, inner willpower, experiences in open nature, and closeness to loved ones contribute to hope when newly diagnosed with gynecologic cancer. IMPLICATION FOR PRACTICE:: The use of drawings in clinical situations might give cancer nurses new perceptions of hope and other phenomena. Patients might feel threat and despair when diagnosed with cancer; they need gentle truth about reality, and they long for being together with loved ones. Nurses are in a unique position to enable hope in this situation through listening and active engagement. Drawing might be a tool in understanding the hope. Drawings picture where words come short. Copyright © 2013 Wolters Kluwer Health | Lippincott Williams & Wilkins.

Siersbaek M.S.,University of Southern Denmark | Siersbaek M.S.,Institute of Clinical Research | Loft A.,University of Southern Denmark | Aagaard M.M.,University of Southern Denmark | And 5 more authors.
Molecular and Cellular Biology | Year: 2012

Peroxisome proliferator-activated receptor γ (PPARγ) is a master regulator of adipocyte differentiation and function. We and others have previously mapped PPARγ binding at a genome-wide level in murine and human adipocyte cell lines and in primary human adipocytes. However, little is known about how binding patterns of PPARγ differ between brown and white adipocytes and among different types of white adipocytes. Here we have employed chromatin immunoprecipitation combined with deep sequencing to map and compare PPARγ binding in in vitro differentiated primary mouse adipocytes isolated from epididymal, inguinal, and brown adipose tissues. While these PPARγ binding profiles are overall similar, there are clear depot-selective binding sites. Most PPARγ binding sites previously mapped in 3T3-L1 adipocytes can also be detected in primary adipocytes, but there are a large number of PPARγ binding sites that are specific to the primary cells, and these tend to be located in closed chromatin regions in 3T3-L1 adipocytes. The depot-selective binding of PPARγ is associated with highly depot-specific gene expression. This indicates that PPARγ plays a role in the induction of genes characteristic of different adipocyte lineages and that preadipocytes from different depots are differentially preprogrammed to permit PPARγ lineage-specific recruitment even when differentiated in vitro. © 2012, American Society for Microbiology.

Shackles C.,State University of New York at Stony Brook | Rundback J.H.,Interventional Institute | Herman K.,Interventional Institute | David Y.,Institute of Clinical Research | Barkarma R.,Institute of Clinical Research
Catheterization and Cardiovascular Interventions | Year: 2015

Objectives To assess the clinical outcomes of VIABAHN® stent grafts deployed across the knee to those deployed above the knee. Background The placement of stent-grafts across the knee joint and extending into the distal popliteal artery has been avoided due to a perceived higher risk of stent fractures, restenosis, and thrombosis due to the unique hemodynamic forces in this region. Methods A retrospective evaluation was conducted of 114 patients in 127 limbs. Patients were divided into two groups based on the location of the distal end of the deployed VIABAHN® stent: above knee (AK) (n = 89) in which the VIABAHN® implant ended at or above the femoral condyles and below the knee (BK) (n = 38) with extension of the graft into the below knee popliteal segment. Study end points were loss of primary, assisted, and secondary patency. Results One year primary, assisted, and secondary patency rates in the AK versus BK group were 67.7% vs. 47.2% (P = 0.0092), 77.1% vs. 53.7% (P = 0.0022), and 86.3% vs. 59.8% (P = 0.0035), respectively. Univariate analysis demonstrated an increased relative risk of a primary [RR = 2.07 (P = 0.001)], assisted [RR = 2.34 (P = 0.002)], or secondary events [RR = 2.98 (P = 0.002)] in patients when the stent was placed below the femoral condyles. Major amputations occurred in 10% of AK and 34% of BK patients (P = 0.002). Conclusions VIABAHN® stent grafts have a significantly lower clinical patency and higher rates of amputation when they extend across the knee joint. © 2014 Wiley Periodicals, Inc.

Shetty K.,Johns Hopkins University | Chen J.,University of Houston | Shin J.-H.,University of Houston | Jogunoori W.,Institute of Clinical Research | Mishra L.,University of Houston
Current Hepatitis Reports | Year: 2015

Non-alcoholic fatty liver disease (NAFLD) is being recognized as an increasingly important contributor to the burden of hepatocellular carcinoma (HCC) worldwide. It is  often accompanied by obesity and diabetes mellitus and isbelieved to be the hepatic representation of the metabolic syndrome. HCC development in NAFLD is multifactorial and complex. It is dependent on not only the well-describedmechanisms noted in chronic liver injury but also on the molecular derangements associated with obesity and dysmetabolism. These include adipocyte remodeling, adipokine secretion, lipotoxicity, and insulin resistance. Recent advances focus on the importance of the gut-liver axis in accelerating the process of oncogenesis in NAFLD. The Farnesoid X receptor (FXR) has been demonstrated to have important metabolic effects, and its pharmacological activation by obeticholic acid has been recently reported to produce histological improvement in non-alcoholic steatohepatitis (NASH). It is hoped that delineating the mechanisms o f hepatic fibrosis and oncogenesis in NASH will lead to enhanced strategies for cancer prevention, surveillance, and therapy in this population. © Springer Science+Business Media New York 2015.

Viberg B.,Odemse | Viberg B.,Institute of Clinical Research | Ryg J.,University of Southern Denmark | Ryg J.,Institute of Clinical Research | And 6 more authors.
Acta Orthopaedica | Year: 2014

Background and purpose - Internal fixation (IF) in femoral neck fractures has high reoperation rates and some predictors of failure are known, such as age, quality of reduction, and implant positioning. Finding new predictors of failure is an ongoing process, and in this study we evaluated the importance of low bone mineral density (BMD). Patients and methods - 140 consecutive patients (105 females, median age 80) treated with IF had a dual-energy X-ray absorptiometry (DXA) scan of the hip performed median 80 days after treatment. The patients' radiographs were evaluated for fracture displacement, implant positioning, and quality of reduction. From a questionnaire completed during admission, 2 variables for comorbidity and walking disability were chosen. Primary outcome was low hip BMD (amount of mineral matter per square centimeter of hip bone) compared to hip failure (resection, arthroplasty, or new hip fracture). A stratified Cox regression model on fracture displacement was applied and adjusted for age, sex, quality of reduction, implant positioning, comorbidity, and walking disability. Results - 49 patients had a T-score below -2.5 (standard deviation from the young normal reference mean) and 70 patients had a failure. The failure rate after 2 years was 22% (95% CI: 12-39) for the undisplaced fractures and 66% (CI: 56-76) for the displaced fractures. Cox regression showed no association between low hip BMD and failure. For the covariates, only implant positioning showed an association with failure. Interpretation - We found no statistically significant association between low hip BMD and fixation failure in femoral neck fracture patients treated with IF.

Tomassini A.,University of L'Aquila | Struglia F.,University of L'Aquila | Spaziani D.,University of L'Aquila | Pacifico R.,University of L'Aquila | And 3 more authors.
American Journal on Addictions | Year: 2012

The aim of the study was to assess the relationship among decision-making (DM) ability (as measured by the Iowa Gambling Task [IGT]), impulsivity, and temperament and character traits in a long-term abstinent alcohol-dependent sample. Twenty-six abstinent alcohol-dependent subjects, referred to a Drug Addiction Unit of the National Health Service of L'Aquila, were evaluated using the IGT, the Barratt Impulsiveness Scale, version 11 (BIS-11), and the Temperament and Character Inventory 125-item (TCI-125) version. Twenty-four control subjects were recruited and assessed with IGT only. The clinical and control samples were significantly different in their IGT performance, the former sample making disadvantageous choices leading to lower scores. Significant negative correlations between IGT total score and BIS Non-Planning Impulsivity and a trend toward significance with TCINovelty Seeking dimension were reported. Our data confirm the results of other studies suggesting DM impairment related to impulsive dimension as an important feature in subjects with alcohol dependence: the finding suggests a role of DM impairment in increasing proneness to a chronic relapsing course. Copyright © American Academy of Addiction Psychiatry.

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