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  • 1
    Language: English
    In: PLoS ONE, 01 January 2016, Vol.11(1), p.e0146378
    Description: Delayed graft function is a prevalent clinical problem in renal transplantation for which there is no objective system to predict occurrence in advance. It can result in a significant increase in the necessity for hospitalisation post-transplant and is a significant risk factor for other post-transplant complications.The importance of microRNAs (miRNAs), a specific subclass of small RNA, have been clearly demonstrated to influence many pathways in health and disease. To investigate the influence of miRNAs on renal allograft performance post-transplant, the expression of a panel of miRNAs in pre-transplant renal biopsies was measured using qPCR. Expression was then related to clinical parameters and outcomes in two independent renal transplant cohorts.Here we demonstrate, in two independent cohorts of pre-implantation human renal allograft biopsies, that a novel pre-transplant renal performance scoring system (GRPSS), can determine the occurrence of DGF with a high sensitivity (〉90%) and specificity (〉60%) for donor allografts pre-transplant, using just three senescence associated microRNAs combined with donor age and type of organ donation.These results demonstrate a relationship between pre-transplant microRNA expression levels, cellular biological ageing pathways and clinical outcomes for renal transplantation. They provide for a simple, rapid quantitative molecular pre-transplant assay to determine post-transplant allograft function and scope for future intervention. Furthermore, these results demonstrate the involvement of senescence pathways in ischaemic injury during the organ transplantation process and an indication of accelerated bio-ageing as a consequence of both warm and cold ischaemia.
    Keywords: Sciences (General)
    E-ISSN: 1932-6203
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  • 2
    Language: English
    In: BMC public health, 04 June 2013, Vol.13, pp.538
    Description: Several instruments have been developed to assess psychosocial workload. We compared two of these instruments, the Effort-Reward Imbalance (ERI) model and the Copenhagen Psychosocial Questionnaire (COPSOQ) with regard to congruent validity and internal validity. This analysis is based on a population-based sample of the baseline examination of 2,783 employees from the Gutenberg Health Study (GHS). About half of the participants completed the ERI questionnaire (n = 1,342), the other half completed the COPSOQ (n = 1,441). First, the two samples were compared and descriptive analyses were carried out calculating mean values for both instruments in general, then separately for age, gender and main occupational groups. Second, we analyzed the relationship between ERI and COPSOQ scales on the workplace situation and on the workplace outcomes: job satisfaction, general health, burnout, satisfaction with life, by applying stepwise logistic regression analysis. For the majority of occupations, high effort as reflected by the ERI corresponded with high demands as reflected by the COPSOQ. Comparably, high reward (according to ERI) yielded a good agreement with high "influence and development" (according to COPSOQ). However, we could also find differences between ERI and COPSOQ concerning the intensity of psychosocial workload in some occupations (e.g., physicians/pharmacists or warehouse managers/warehousemen/transport workers). These differences point to differing theoretical concepts of ERI and COPSOQ. When the ability of ERI and COPSOQ was examined to determine the associations with health and work outcomes, burnout could be better predicted by the COPSOQ; this might be due to the fact that COPSOQ comprises the constructs "work-privacy conflict" and "emotional demand", which are closely related to burnout. However, methodological differences between these instruments limit their direct comparability. The ERI and COPSOQ instrument yielded similar results for most occupational groups. The slightly stronger association between psychosocial workload as assessed by COPSOQ and burnout might be explained by its broader approach. The ability of the ERI and COPSOQ instrument to reflect relevant risk factors for clinically manifest disorders (e.g., coronary heart disease) will be derived from subsequent prospective analyses of the GHS with the follow-up data.
    Keywords: Models, Psychological ; Surveys and Questionnaires ; Workload -- Psychology
    E-ISSN: 1471-2458
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  • 3
    Language: English
    In: PLoS ONE, 2012, Vol.7(5), p.e37839
    Description: The regenerative potential declines upon aging. This might be due to cell-intrinsic changes in stem and progenitor cells or to influences by the microenvironment. Mesenchymal stem cells (MSC) raise high hopes in regenerative medicine. They are usually culture expanded in media with fetal calf serum (FCS) or other serum supplements such as human platelet lysate (HPL). In this study, we have analyzed the impact of HPL-donor age on culture expansion. 31 single donor derived HPLs (25 to 57 years old) were simultaneously compared for culture of MSC. Proliferation of MSC did not reveal a clear association with platelet counts of HPL donors or growth factors concentrations (PDGF-AB, TGF-β1, bFGF, or IGF-1), but it was significantly higher with HPLs from younger donors (〈35 years) as compared to older donors (〉45 years). Furthermore, HPLs from older donors increased activity of senescence-associated beta-galactosidase (SA-βgal). HPL-donor age did not affect the fibroblastoid colony-forming unit (CFU-f) frequency, immunophenotype or induction of adipogenic differentiation, whereas osteogenic differentiation was significantly lower with HPLs from older donors. Concentrations of various growth factors (PDGF-AB, TGF-β1, bFGF, IGF-1) or hormones (estradiol, parathormone, leptin, 1,25 vitamin D3) were not associated with HPL-donor age or MSC growth. Taken together, our data support the notion that aging is associated with systemic feedback mechanisms acting on stem and progenitor cells, and this is also relevant for serum supplements in cell culture: HPLs derived from younger donors facilitate enhanced expansion and more pronounced osteogenic differentiation.
    Keywords: Research Article ; Biology ; Medicine ; Biotechnology ; Physiology ; Hematology ; Developmental Biology
    E-ISSN: 1932-6203
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  • 4
    In: Annals of the New York Academy of Sciences, May 2013, Vol.12871(1), pp.45-58
    Description: In recent years, vitamin D has been received increased attention due to the resurgence of vitamin D deficiency and rickets in developed countries and the identification of extraskeletal effects of vitamin D, suggesting unexpected benefits of vitamin D in health and disease, beyond bone health. The possibility of extraskeletal effects of vitamin D was first noted with the discovery of the vitamin D receptor (VDR) in tissues and cells that are not involved in maintaining mineral homeostasis and bone health, including skin, placenta, pancreas, breast, prostate and colon cancer cells, and activated T cells. However, the biological significance of the expression of the VDR in different tissues is not fully understood, and the role of vitamin D in extraskeletal health has been a matter of debate. This report summarizes recent research on the roles for vitamin D in cancer, immunity and autoimmune diseases, cardiovascular and respiratory health, pregnancy, obesity, erythropoiesis, diabetes, muscle function, and aging.
    Keywords: Vitamin D ; Cancer ; Immunity ; Pregnancy ; Obesity ; Diabetes ; Pulmonary Disease ; Muscle ; Aging ; Cognitive Function
    ISSN: 0077-8923
    E-ISSN: 1749-6632
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  • 5
    Language: English
    In: Journal of Molecular Neuroscience, 2012, Vol.47(3), pp.495-504
    Description: To investigate the involvement of neurotrophins and nerve fibres in the pathogenesis of adenomyosis, we performed a retrospective, clinical study. Hysterectomy specimens from 40 patients with histologically proven adenomyosis and from 20 patients without adenomyosis or endometriosis were used for immunohistochemical analysis. In order to investigate neurotrophic properties in adenomyosis, the antibodies against nerve growth factor (NGF), neurotrophin 3 (NT-3), the high-affinity NGF receptor (TrkA), the low-affinity neurotrophin receptor (p75 NTR ), the neuronal marker S100 (for myelinated nerve fibres) and protein gene product 9.5 (PGP9.5; for intact nerve fibres) were used. There was no significant difference in the NGF, NT-3 and p75 NTR expression in the myometrium or endometrium between the adenomyosis and the control group. The nerve fibre density (S100, PGP9.5 and p75 NTR ) did not significantly differ between the adenomyosis and control group, the nerve fibre density of the adenomyosis group was tendentially decreased when compared with the nonporous control group. The present study suggests that endometrial and uterine neurotrophin expression and endometrial innervation are not altered in adenomyosis; however, women with adenomyosis or with adenomyosis/endometriosis tendentially had less myometrial nerve fibres than the control group.
    Keywords: Adenomyosis ; Neurotrophins ; Uterine innervation ; Endometrial nerve fibres
    ISSN: 0895-8696
    E-ISSN: 1559-1166
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  • 6
    In: Clinical Respiratory Journal, January 2018, Vol.12(1), pp.68-75
    Description: Byline: Sylvia Lehmann, Steffen Leonhardt, Chuong Ngo, Lukas Bergmann, Simone Schrading, Konrad Heimann, Norbert Wagner, Klaus Tenbrock Keywords: cystic fibrosis; EIT; gravity; infiltration; lung; overinflation Abstract Introduction Electrical Impedance Tomography (EIT) is a tomographic, radiation-free technique based on the injection of a harmless alternating current. Objective As electrical impedance strictly correlates with the variation of air content, EIT delivers highly dynamic information about global and regional ventilation. We want to demonstrate the potential of EIT individualizing ventilation by positioning. Methods Gravity-dependent EIT findings were analyzed retrospectively in a critically ill mechanically ventilated pediatric patient with cystic fibrosis and coincident lung diseases. To further evaluate gravity-dependent changes in ventilation, six adult healthy and spontaneously breathing volunteers were investigated during simultaneous detection of EIT, breathing patterns, tidal volume (VT) and breathing frequency (BF). Results EIT findings in healthy lungs in five positions showed gravity-dependent effects of ventilation with overall ventilation of predominantly the right lung (except during left-side positioning) and with the ventral lung in supine, prone and upright position. These EIT-derived observations are in line with pathophysiological mechanisms and earlier EIT studies. Unexpectedly, the patient with cystic fibrosis and lobectomy of the right upper and middle lobe one year earlier, showed improvement of global and regional ventilation in the right position despite reduced lung volume and overinflation of this side. This resulted in individualized positioning and improvement of ventilation. Conclusions Although therapeutic recommendations are available for gravitational influences of lung ventilation, they can be contradictory depending on the underlying lung disease. EIT has the potential to guide therapists in the positioning of patients according to their individual condition and disease, especially in case of multiple lung injury. Article Note: Dr. med. S. Lehmann has obtained permission from all co-authors for the submission of the manuscript. Authorship and contributorship Dr. S. Lehmann: Designed and performed study, collected and analyzed data and wrote the paper. Prof. Dr.-Ing. Dr. med. Steffen Leonhardt: Co-designed the study and reviewed the paper. Chuong Ngo: Analyzed data and reviewed the paper. Lukas Bergmann: Analyzed data and reviewed the paper. Dr. med. Simone Schrading: Performed radiologic data correlation and reviewed the paper. Dr. med. Konrad Heimann: Reviewed the paper. Prof. Dr. Norbert Wagner: Reviewed the paper. PD Dr. Klaus Tenbrock: Co-designed the study and reviewed the paper. Ethics All volunteers provided written informed consent for this study and publication of the results. Conflict of interest S. Leonhardt discloses previous financial support for unrestricted research into EIT-based perfusion imaging from DrAaAaAeAnger Medical Gmb LAaAaAeA beck, Germany; he has also previously received honoraria for lecturi and consulting. There is no conflict of interest with this specific project. All other authors confirm no conflict of interest.
    Keywords: Cystic Fibrosis ; Eit ; Gravity ; Infiltration ; Lung ; Overinflation
    ISSN: 1752-6981
    E-ISSN: 1752-699X
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  • 7
    Language: English
    In: Journal of Personality and Social Psychology, 2009, Vol.97(3), pp.549-565
    Description: Bipolar disorders and substance use disorders (SUDs) show high co-occurrence. One explanation for this co-occurrence may be common personality vulnerabilities involved in both. The authors tested whether high behavioral approach system (BAS) sensitivity and impulsiveness are shared personality vulnerabilities in bipolar spectrum disorders and substance use problems and their co-occurrence in a longitudinal study of 132 individuals on the bipolar spectrum and 153 control participants. At Time 1, participants completed the Behavioral Inhibition System/BAS Scales and the Impulsive Nonconformity Scale. Substance use problems were assessed via the Michigan Alcoholism Screening Test and the Drug Abuse Screening Test at 4-month intervals for 1 year. Participants with bipolar disorder had higher rates of lifetime SUDs and substance use problems during the follow-up, relative to control participants. In line with hypotheses, higher BAS sensitivity and impulsiveness predicted bipolar status and increased substance use problems prospectively. BAS total, BAS Fun Seeking, and impulsiveness mediated the association between bipolar spectrum status and prospective substance use problems, with impulsiveness as the most important mediator. High BAS sensitivity and impulsiveness may represent shared personality vulnerabilities for both disorders and may partially account for their co-occurrence.
    Keywords: Bipolar Spectrum ; Substance Use ; Behavioral Approach System (Bas) Sensitivity ; Impulsiveness
    ISSN: 0022-3514
    E-ISSN: 1939-1315
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  • 8
    Language: English
    In: Genome research, February 2013, Vol.23(2), pp.248-59
    Description: Pluripotent stem cells evade replicative senescence, whereas other primary cells lose their proliferation and differentiation potential after a limited number of cell divisions, and this is accompanied by specific senescence-associated DNA methylation (SA-DNAm) changes. Here, we investigate SA-DNAm changes in mesenchymal stromal cells (MSC) upon long-term culture, irradiation-induced senescence, immortalization, and reprogramming into induced pluripotent stem cells (iPSC) using high-density HumanMethylation450 BeadChips. SA-DNAm changes are highly reproducible and they are enriched in intergenic and nonpromoter regions of developmental genes. Furthermore, SA-hypomethylation in particular appears to be associated with H3K9me3, H3K27me3, and Polycomb-group 2 target genes. We demonstrate that ionizing irradiation, although associated with a senescence phenotype, does not affect SA-DNAm. Furthermore, overexpression of the catalytic subunit of the human telomerase (TERT) or conditional immortalization with a doxycycline-inducible system (TERT and SV40-TAg) result in telomere extension, but do not prevent SA-DNAm. In contrast, we demonstrate that reprogramming into iPSC prevents almost the entire set of SA-DNAm changes. Our results indicate that long-term culture is associated with an epigenetically controlled process that stalls cells in a particular functional state, whereas irradiation-induced senescence and immortalization are not causally related to this process. Absence of SA-DNAm in pluripotent cells may play a central role for their escape from cellular senescence.
    Keywords: DNA Methylation ; Cellular Senescence -- Genetics ; Pluripotent Stem Cells -- Metabolism
    ISSN: 10889051
    E-ISSN: 1549-5469
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  • 9
    Language: English
    In: International Journal of Legal Medicine, 2017, Vol.131(4), pp.1023-1037
    Description: Older traffic participants have higher risks of injury than the population up to 65 years in case of comparable road traffic accidents and further, higher mortality rates at comparable injury severities. Rib fractures as risk factors are currently discussed. However, death on scene is associated with hardly survivable injuries and might not be a matter of neither rib fractures nor age. As 60% of traffic accident fatalities are estimated to die on scene, they are not captured in hospital-based trauma registries and injury patterns remain unknown. Our database comprises 309 road traffic fatalities, autopsied at the Institute of Legal Medicine Munich in 2004 and 2005. Injuries are coded according to Abbreviated Injury Scale, AIS© 2005 update 2008 [1]. Data used for this analysis are age, sex, site of death, site of accident, traffic participation mode, measures of injury severity, and rib fractures. The injury patterns of elderly, aged 65+ years, are compared to the younger ones divided by their site of death. Elderly with death on scene more often show serious thorax injuries and pelvic fractures than the younger. Some hints point towards older fatalities showing less frequently serious abdominal injuries. In hospital, elderly fatalities show lower Injury Severity Scores (ISSs) compared to the younger. The number of rib fractures is significantly higher for the elderly but is not the reason for death. Results show that young and old fatalities have different injury patterns and reveal first hints towards the need to analyze death on scene more in-depth.
    Keywords: Traffic fatalities ; Elderly ; Rib fracture ; Injury pattern ; Prehospital mortality ; Abbreviated Injury Scale
    ISSN: 0937-9827
    E-ISSN: 1437-1596
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  • 10
    Language: English
    In: Cephalalgia, May 2018, Vol.38(6), pp.1167-1176
    Description: Background Familial hemiplegic migraine (FHM) is a rare, genetic form of migraine with aura. The severity of the aura imposes an effective prophylaxis that is currently based on standard anti-migraine drugs. To this concern, only short-term reports are currently available. Methods Eight patients from a multigenerational FHM type 1 family harbouring a T666M mutation in the CACNA1A gene were referred to our ataxia outpatient clinic. Medical history, general and neurological examination as well as therapeutic approaches were recorded regularly on a routine basis for an average period of 13 years (range 9–15 years). Brain imaging studies and EEG data were also collected. Results Our long-term follow-up revealed that ictal manifestations, which usually improve after the adolescence, may reoccur later in the adulthood. Permanent neurological signs as assessed by means of clinical evaluation as well as follow-up MRIs, EEGs and neuropsychological testing remained stable. Interval therapy with non-selective calcium antagonists reduced the burden of migraine attacks and was well tolerated in the long term.
    Keywords: Familial Hemiplegic Migraine ; Cacna1a Gene ; Long-Term Treatment ; Migraine Prophylaxis ; Calcium Antagonists ; Clinical Phenotype ; Medicine
    ISSN: 0333-1024
    E-ISSN: 1468-2982
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