Medizin
Refine
Year of publication
- 2017 (347) (remove)
Document Type
- Article (319)
- Part of Periodical (11)
- Doctoral Thesis (9)
- Book (3)
- Contribution to a Periodical (3)
- Preprint (1)
- Report (1)
Language
- English (311)
- German (32)
- Multiple languages (3)
- Spanish (1)
Has Fulltext
- yes (347)
Is part of the Bibliography
- no (347)
Keywords
- glioblastoma (8)
- Inflammation (4)
- Neuroscience (4)
- multiple sclerosis (4)
- Apoptosis (3)
- Denosumab (3)
- Kinematic analysis (3)
- Mechanisms of disease (3)
- Mitochondria (3)
- Molecular biology (3)
Institute
Mapping cortical brain asymmetry in 17,141 healthy individuals worldwide via the ENIGMA Consortium
(2017)
Kurt Goldstein zählt zu den herausragenden deutschen Neurologen des 20. Jahrhunderts. Bekannt wurde er u. a. durch einen eigenständigen Ansatz der ganzheitlichen Neurologie. Besondere Aufmerksamkeit schenkte er dabei den Kompensationsreaktionen des Gehirns und des ganzen Menschen. In der vorliegenden Studie wird erstmals der Lebensgang dieses jüdischen Arztes in den Jahren 1933 bis 1940 genauer betrachtet.
Ursprünglich sollte das vorliegende Buch nur eine Studie über die von der Kanzlei des Führers bzw. ihrem Umfeld nach Kriegsbeginn initiierten Entwürfe zu einem NS-„Euthanasie“-Gesetz werden. Dabei sollte vor allem der wichtige, allerdings mit zahlreichen Fehlern behaftete Beitrag von Roth/Aly(1984) revidiert werden. Da diese Fehler auch den Beginn der Debatte über die „Euthanasie“ im NS-Staat und den Beginn der Planung und Durchführung der „NS-Euthanasie“ (1939/1940) betrafen, musste weiter ausgeholt werden. Die Gesetzentwürfe aus der Zeit nach Kriegsbeginn machen unzweifelhaft deutlich, dass die am Krankenmord Beteiligten wussten, dass der auf den 1.9.1939 datierte „Euthanasie“-Erlass Hitlers in legaler Hinsicht nicht „ausreichte“.
Objectives: Chronic thromboembolic pulmonary hypertension (CTEPH) is a rare, distinct pulmonary vascular disease, and therefore, there is a lack of data regarding its clinical presentation, diagnosis, and management at a national basis. We aimed to describe the demographics and management of patients with CTEPH in Northern Greece. Methods: We conducted a retrospective, observational study by a joint collaboration between two pulmonary hypertension expert centers in Greece, and the study included patients diagnosed with CTEPH. The patient population was divided into two groups depending on their operability. Results: Overall, 27 consecutive patients were included (59% female, mean age 59.3±15.1 years). Dyspnea and fatigue were the most common presenting symptoms. History of pulmonary embolism was present in 82%. Of patients, 18 (67%) were assessed as operable, of whom 10 (55%) finally underwent pulmonary endarterectomy (PEA). There were no differences in symptoms, WHO functional class, 6-min walking test distance, and hemodynamics between the operable and nonoperable groups. At the end of follow-up, all non-operable and operable patients who did not receive surgical treatment were treated with at least one pulmonary hypertension-specific drug. Conclusion: This is the first report that presents data of patients diagnosed with CTEPH in Greece. The percentage of patients who underwent surgical treatment is lower but approaches the reported rates in large registries. Considering that PEA is a relatively safe and potentially curative surgical procedure, we emphasize the need for establishing a designated PEA center in Greece. Keywords: Chronic thromboembolic pulmonary hypertension, pulmonary endarterectomy, registry, riociguat.
Various strategies have been employed to speed tissue regeneration using bioactive molecules. Interestingly, platelet concentrates derived from a patient’s own blood have been utilized as a regenerative strategy in recent years. In the present study, a novel liquid platelet formulation prepared without the use of anti-coagulants (injectable-platelet-rich fibrin, i-PRF) was compared to standard platelet-rich plasma (PRP) with gingival fibroblasts cultured on smooth and roughened titanium implant surfaces. Standard PRP and i-PRF (centrifuged at 700 rpm (60× g) for 3 min) were compared by assays for fibroblast biocompatibility, migration, adhesion, proliferation, as well as expression of platelet-derived growth factor (PDGF), transforming growth factor-β (TGF-β), collagen1 (COL1) and fibronectin (FN). The results demonstrate that i-PRF induced significantly higher cell migration, as well as higher messenger RNA (mRNA) levels of PDGF, TGF-β, collagen1 and fibronectin when compared to PRP. Furthermore, collagen1 synthesis was highest in the i-PRF group. These findings demonstrate that liquid platelet concentrates can be formulated without the use of anticoagulants and present much translational potential for future research. Future animal and clinical trials are now necessary to further investigate the potential of utilizing i-PRF for soft tissue regenerative protocols in combination with various biomaterials.
Razina pročišćenosti alogenoga koštanog bloka = Variant purification of an allogeneic bone block
(2017)
Svrha: Ovaj kratak tekst izvještava o histološkoj analizi sastava komercijalno raspoloživih alogenih koštanih blokova Maxgraft®. Materijali i metode: Na temelju objavljenih histoloških metoda prazni uzorci alogenih koštanih blokova Maxgraft® dekalcificirani su, dehidrirani i uloženi u parafin prije histološkog i histokemijskog bojenja. Nakon toga na prerezima su se procjenjivala obilježja materijala, poput strukture koštanoga matriksa i druge komponente, uključujući kolagen ili stanice/stanične ostatke. Rezultati: Uočeno je da ovi koštani blokovi imaju trabekularnu strukturu s lamelarnom podorganizacijom. Dodatno su nađeni i stanični ostatci unutar lakuna osteocita i na vanjskim površinama trabekula zajedno s ostatcima intertrabekularnog masnog i vezivnog tkiva, te kolagene strukture, vezivno-tkivne stanice i stanični ostatci. Zaključak: U skladu s dosadašnjim istraživanjima, podatci iz ovoga teksta pokazuju da neke od certificiranih tehnika pročišćavanja ne omogućuju proizvodnju alogenog materijala bez organskih stanica i tkivnih komponenata.
Objective: This study examines the interrelations of parenting practices, emotional climate, and household chaos in families with children with and without ADHD. In particular, indirect pathways from children’s ADHD symptomatology to inadequate parenting and negative emotional climate via household chaos were investigated. Method: Parenting, emotional climate, and household chaos were assessed using questionnaires and a speech sample of parents of 31 children with and 53 without ADHD, aged 7 to 13 years. Results: Group differences were found for certain parenting dimensions, the parent–child relationship, critical comments, and household chaos. While we found significant indirect effects between children’s ADHD and certain parenting dimensions through household chaos, no effects were found for any aspect of emotional climate. Conclusion: Children’s ADHD symptoms translate into inadequate parenting through household chaos, which underlines the need for interventions to improve household organization skills in parents of children with ADHD.
Intestinal carriage of multidrug-resistant bacteria among healthcare professionals in Germany
(2017)
Healthcare professionals (HCP) might be at increased risk of acquisition of multidrug-resistant bacteria (MDRB), i.e., methillicin-resistant Staphylococcus aureus (MRSA), vancomycin-resistant enterococci (VRE), and multidrug-resistant gram-negative bacteria (MDRGN) and could be an unidentified source of MDRB transmission.
The aim of this study was to determine the prevalence as well as risk factors of MDRB colonization among HCP.
HCP (n=107) taking part in an antibiotic stewardship program, were voluntarily recruited to perform a rectal swab and to fill in a questionnaire to identify risk factors of MDRB carriage, i.e. being physician, gender, travel abroad within the previous 12 months, vegetarianism, regular consumption of raw meat, contact to domestic animals, household members with contact to livestock, work or fellowship abroad, as well as medical treatment abroad and antibiotic therapy within the previous 12 months.
Selective solid media were used to determine the colonization rate with MRSA, VRE and MDRGN. MDRGN were further characterized by molecular analysis of underlying β-lactamases.
None of the participants had an intestinal colonization with MRSA or VRE. 3.7% of the participants were colonized with extended-spectrum beta-lactamase (ESBL)-producing Enterobacteriaceae, predominantly blaCTX-M type. Neither additional flouroquinolone resistance nor carbapenem resistance was detected in any of these isolates. No risk factors were identified to have a significant impact of MDRB carriage among HCP.
A colonization rate of 3.7% with ESBL-producing Enterobacteriaceae is of interest, but comparing it to previously published data with similar colonization rates in the healthy population in the same geographic area, it is probably less an occupational risk.
Objective: Extracorporeal life support (ECLS) is a life-saving procedure used in the treatment of severe cardiogenic shock. Within this retrospective single centre study, we examined our experience in this critically ill patient cohort to assess outcomes and clinical parameters by comparison of ECLS with or without selective left ventricular decompression.
Methods: Between 2004 and 2014 we evaluated 48 adult patients with INTERMACS level 1 heart failure (age 49.7 ± 19.5 years), who received either central ECLS with (n = 20, 41.7%) or ECLS without (n = 28, 58.3%, including 10 peripheral ECLS) integrated left ventricular vent in our retrospective single centre trial.
Results: Follow up was 100% with a mean of 0.83 ± 1.85 years. Bridge to ventricular assist device was feasible in 29.2% (n = 14), bridge to transplant in 10.4% (n = 5) and bridge to recovery in 8.3% (n = 4). Overall 30-day survival was 37.5%, 6-month survival 27.1% and 1-year survival 25.0%. ECLS support with left ventricular decompression showed favourable 30-day survival compared to ECLS without left ventricular decompression (p = 0.034). Thirty-day as well as long-term survival did not differ between the subgroups (central ECLS with vent, ECLS without vent and peripheral ECLS without vent). Multivariate logistic regression adjusted for age and gender revealed ECLS without vent as independent factor influencing 30-day survival.
Conclusion: ECLS is an established therapy for patients in severe cardiogenic shock. Independent of the ECLS approach, 30-day mortality is still high but with superior 30-day survival for patients with ECLS and left ventricular venting. Moreover, by unloading the ventricle, left ventricular decompression may provide an important time window for recovery or further treatment, such as bridge to bridge or bridge to transplant.
Exposure to community violence through witnessing or being directly victimized has been associated with conduct problems in a range of studies. However, the relationship between community violence exposure (CVE) and conduct problems has never been studied separately in healthy individuals and individuals with conduct disorder (CD). Therefore, it is not clear whether the association between CVE and conduct problems is due to confounding factors, because those with high conduct problems also tend to live in more violent neighborhoods, i.e., an ecological fallacy. Hence, the aim of the present study was: (1) to investigate whether the association between recent CVE and current conduct problems holds true for healthy controls as well as adolescents with a diagnosis of CD; (2) to examine whether the association is stable in both groups when including effects of aggression subtypes (proactive/reactive aggression), age, gender, site and socioeconomic status (SES); and (3) to test whether proactive or reactive aggression mediate the link between CVE and conduct problems. Data from 1178 children and adolescents (62% female; 44% CD) aged between 9 years and 18 years from seven European countries were analyzed. Conduct problems were assessed using the Kiddie-Schedule of Affective Disorders and Schizophrenia diagnostic interview. Information about CVE and aggression subtypes was obtained using self-report questionnaires (Social and Health Assessment and Reactive-Proactive aggression Questionnaire (RPQ), respectively). The association between witnessing community violence and conduct problems was significant in both groups (adolescents with CD and healthy controls). The association was also stable after examining the mediating effects of aggression subtypes while including moderating effects of age, gender and SES and controlling for effects of site in both groups. There were no clear differences between the groups in the strength of the association between witnessing violence and conduct problems. However, we found evidence for a ceiling effect, i.e., individuals with very high levels of conduct problems could not show a further increase if exposed to CVE and vice versa. Results indicate that there was no evidence for an ecological fallacy being the primary cause of the association, i.e., CVE must be considered a valid risk factor in the etiology of CD.
Callous-unemotional traits are characterized by a lack of empathy, a disregard for others' feelings and shallow or deficient affect, such as a lack of remorse or guilt. Neuroanatomical correlates of callous-unemotional traits have been demonstrated in clinical samples (i.e., adolescents with disruptive behavior disorders). However, it is unknown whether callous-unemotional traits are associated with neuroanatomical correlates within normative populations without clinical levels of aggression or antisocial behavior. Here we investigated the relationship between callous-unemotional traits and gray matter volume using voxel-based morphometry in a large sample of typically-developing boys and girls (N = 189). Whole-brain multiple regression analyses controlling for site, total intracranial volume, and age were conducted in the whole sample and in boys and girls individually. Results revealed that sex and callous-unemotional traits interacted to predict gray matter volume when considering the whole sample. This interaction was driven by a significant positive correlation between callous-unemotional traits and bilateral anterior insula volume in boys, but not girls. Insula gray matter volume explained 19% of the variance in callous-unemotional traits for boys. Our results demonstrate that callous-unemotional traits are related to variations in brain structure beyond psychiatric samples. This association was observed for boys only, underlining the importance of considering sex as a factor in future research designs. Future longitudinal studies should determine whether these findings hold over childhood and adolescence, and whether the neuroanatomical correlates of callous-unemotional traits are predictive of future psychiatric vulnerability.
Autophagy in cancer therapy
(2017)
Autophagy represents a catabolic program involved in the degradation of cellular components via lysosomes. It serves to mitigate cellular stress and to provide metabolic precursors especially upon starvation. Thereby, autophagy can support the survival of cancer cells. In addition, there is now convincing evidence showing that under certain conditions autophagy can also foster cell death. This dual function of autophagy is also relevant upon anticancer treatment, as many chemotherapeutic agents engage autophagy. A better understanding of the molecular mechanisms that are critical for mediating autophagic cell death in cancer cells will be instrumental to selectively interfere with this cellular program in order to increase the cancer cell’s response to cytotoxic drugs. This review illustrates how anticancer drug-induced autophagy is involved in mediating cell death.
Background: Computed tomography of the head (HCT) is a widely used diagnostic tool, especially for emergency and trauma patients. However, the diagnostic yield and outcomes of HCT for patients on medical intensive care units (MICUs) are largely unknown.
Methods: We retrospectively evaluated all head CTs from patients admitted to a single-center MICU during a 5-year period for CT indications, diagnostic yield, and therapeutic consequences. Uni- and multivariate analyses for the evaluation of risk factors for positive head CT were conducted.
Results: Six hundred ninety (18.8%) of all patients during a 5-year period underwent HCT; 78.7% had negative CT results, while 21.3% of all patients had at least 1 new pathological finding. The main indication for acquiring CT scan of the head was an altered mental state (AMS) in 23.5%, followed by a new focal neurology in 20.7% and an inadequate wake up after stopping sedation in 14.9% of all patients. The most common new finding was intracerebral bleeding in 6.4%. In 6.7%, the CT scan itself led to a change of therapy of any kind. Admission after resuscitation or a new focal neurology were independent predictors of a positive CT. Psychic alteration and AMS were both independent predictors of a higher chance of a negative head CT. Positive HCT during MICU is an independent predictor of lower survival.
Conclusions: New onset of focal neurologic deficit seems to be a good predictor for a positive CT, while AMS and psychic alterations seem to be very poor predictors. A positive head CT is an independent predictor of death for MICU patients.
Oxygenation-sensitive spin relaxation time T2′ and relaxation rate R2′ (1/T2′) are presumed to be markers of the cerebral oxygen extraction fraction (OEF) in acute ischemic stroke. In this study, we investigate the relationship of T2′/R2′ with dynamic susceptibility contrast-based relative cerebral blood flow (rCBF) in acute ischemic stroke to assess their plausibility as surrogate markers of the ischemic penumbra. Twenty-one consecutive patients with internal carotid artery and/or middle cerebral artery occlusion were studied at 3.0 T. A physiological model of the cerebral vasculature (VM) was used to process PWI raw data in addition to a conventional deconvolution technique. T2′, R2′, and rCBF values were extracted from the ischemic core and hypoperfused areas. Within hypoperfused tissue, no correlation was found between deconvolved rCBF and T2′ (r = −0.05, p = 0.788), or R2′ (r = 0.039, p = 0.836). In contrast, we found a strong positive correlation with T2′ (r = 0.444, p = 0.006) and negative correlation with R2′ (r = −0.494, p = 0.0025) for rCBFVM, indicating increasing OEF with decreasing CBF and that rCBF based on the vascular model may be more closely related to metabolic disturbances. Further research to refine and validate these techniques may enable their use as MRI-based surrogate markers of the ischemic penumbra for selecting stroke patients for interventional treatment strategies.
Peripheral blood leukocytosis has been implicated in promoting tumor progression leading to worse survival, but the mechanisms behind this phenomenon remain unexplored. Here, we examined the prognostic role of pretreatment white blood cell (WBC) count and clinicopathologic parameters in the context of CD8+ tumor-infiltrating lymphocytes (TIL) and myeloperoxidase+ tumor-associated neutrophils (TANs) in patients with anal squamous cell carcinoma (ASCC) treated with definitive chemoradiotherapy (CRT). After a median follow-up of 26 months, leukocytosis correlated with advanced T-stage (p < 0.001) and N-stage (p < 0.001), and predicted for worse distant-metastasis-free survival (p = 0.006), disease-free-survival (DFS, p = 0.029), and overall survival (p = 0.013). Importantly, leukocytosis was associated with a lower intraepithelial CD8+ TIL density (p = 0.014), whereas low CD8+ TIL expression in the intraepithelial compartment was associated with worse DFS (p = 0.028). Additionally, high TAN expression in the peritumoral compartment was associated with a significantly lower density of CD8+ TIL (p = 0.039), albeit, TAN expression lacked prognostic value. In conclusion, leukocytosis constitutes an important prognostic marker in ASCC patients treated with CRT. In conjunction with intratumoral TIL and TAN, these data provide for the first time important insight on the correlation of peripheral blood leukocytosis with the intratumoral immune contexture and could be relevant for future patient stratification using immunotherapies in ASCC.
Forgetting is a common phenomenon in everyday life. Although it often has negative connotations, forgetting is an important adaptive mechanism to avoid loading the memory storage with irrelevant information. A very important aspect of forgetting is its interaction with emotion. Affective events are often granted special and priority treatment over neutral ones with regards to memory storage. As a consequence, emotional information is more resistant to extinction than neutral information. It has been suggested that intentional forgetting serves as a mechanism to cope with unwanted or disruptive emotional memories and the main goal of this study was to assess forgetting of emotional auditory material using the item-method directed forgetting (DF) paradigm using a forgetting strategy based on mindfulness as a means to enhance DF. Contrary to our prediction, the mindfulness-based strategy not only did not improve DF but reduced it for neutral material. These results suggest that an interaction between processes such as response inhibition and attention is required for intentional forgetting to succeed.
In the colon, a sophisticated balance between immune reaction and tolerance is absolutely required. Dysfunction may lead to pathologic phenotypes ranging from chronic inflammatory processes to cancer development. Two prominent modulators of colon inflammation are represented by the closely related cytokines interleukin (IL)-12 and IL-23, which initiate adaptive Th1 and Th17 immune responses, respectively. In this study, we investigated the impact of the NADPH oxidase protein p47phox, which negatively regulates IL-12 in dendritic cells, on colon cancer development in a colitis-associated colon cancer model. Initially, we found that IL-12−/− mice developed less severe colitis but are highly susceptible to colon cancer. By contrast, p47phox−/− mice showed lower tumor scores and fewer high grade tumors than wild-type (WT) littermates. Treatment with toll-like receptor 9 ligand CpG2216 significantly enhanced colitis in p47phox−/− mice, whereas tumor growth was simultaneously reduced. In tumor tissue of p47phox−/− mice, the IL-23/IL-17 axis was crucially hampered. IL-23p19 protein expression in tumor tissue correlated with tumor stage. Reconstitution of WT mice with IL-23p19−/− bone marrow protected these mice from colon cancer, whereas transplantation of WT hematopoiesis into IL-23p19−/− mice increased the susceptibility to tumor growth. Our study strengthens the divergent role of IL-12 and IL-23 in colon cancer development. With the characterization of p47phox as a novel modulator of both cytokines our investigation introduces a promising new target for antitumor strategies.