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Aim: The primary aim of this study was to analyze frequency and characteristics of combined facial and peripheral trauma with consecutive hospitalization and treatment.
Materials and methods: The study included all patients with concomitant orthopedic-traumatolgical (OT) and craniomaxillofacial (CMF) injuries admitted to our level I trauma center in 2018. The data were collected by analysis of the institution’s database and radiological reviews and included age, sex, injury type, weekday and time of presentation. All patients were examined and treated by a team of surgeons specialized in OT and CMF directly after presentation.
Results: A total number of 1040 combined OT and CMF patients were identified. Mean age was 33.0 ± 26.2 years. 67.3% (n = 700) were male patients. Primary presentation happened most frequently on Sundays (n = 199) and between 7 and 8 pm (n = 74). 193 OT fractures were documented, where cervical spine injuries were most frequent (n = 30). 365 facial and skull fractures were recorded. 10.8% of the 204 patients with fractures of the viscerocranium presented with at least one fracture of the extremity, 7.8% (16/204) with cervical spine fractures, 33.3% (68/204) with signs of closed brain trauma and 9.8% (20/204) with intracranial hemorrhage.
Discussion: The study shows a high frequency of combined facial with OT-injuries and brain damage in a predominantly young and male cohort. Attendance by interdisciplinary teams of both CMF and OT surgeons specialized in cervical spine trauma surgery is highly advisable for adequate treatment.
Conclusion: Diagnostics and treatment should be performed by a highly specialized OT and CMF team, with a consulting neurosurgeon in a level-1 trauma center to avoid missed diagnoses and keep mortality low.
Inflammation is a highly regulated biological response of the immune system that is triggered by assaulting pathogens or endogenous alarmins. It is now well established that some soluble extracellular matrix constituents, such as small leucine-rich proteoglycans (SLRPs), can act as danger signals and trigger aseptic inflammation by interacting with innate immune receptors. SLRP inflammatory signaling cascade goes far beyond its canonical function. By choosing specific innate immune receptors, coreceptors, and adaptor molecules, SLRPs promote a switch between pro- and anti-inflammatory signaling, thereby determining disease resolution or chronification. Moreover, by orchestrating signaling through various receptors, SLRPs fine-tune inflammation and, despite their structural homology, regulate inflammatory processes in a molecule-specific manner. Hence, the overarching theme of this review is to highlight the molecular and functional specificity of biglycan-, decorin-, lumican-, and fibromodulin-mediated signaling in inflammatory and autoimmune diseases.
Children with reading and/or spelling disorders have increased rates of behavioral and emotional problems and combinations of these. Some studies also find increased rates of attention-deficit/hyperactivity disorder (ADHD), conduct disorder, anxiety disorder, and depression. However, the comorbidities of, e.g., arithmetic disorders with ADHD, anxiety disorder, and depression have been addressed only rarely. The current study explored the probability of children with specific learning disorders (SLD) in reading, spelling, and/or arithmetic to also have anxiety disorder, depression, ADHD, and/or conduct disorder. The sample consisted of 3,014 German children from grades 3 and 4 (mean age 9;9 years) who completed tests assessing reading, spelling as well as arithmetic achievement and intelligence via a web-based application. Psychopathology was assessed using questionnaires filled in by the parents. In children with a SLD we found high rates of anxiety disorder (21%), depression (28%), ADHD (28%), and conduct disorder (22%). Children with SLD in multiple learning domains had a higher risk for psychopathology and had a broader spectrum of psychopathology than children with an isolated SLD. The results highlight the importance of screening for and diagnosing psychiatric comorbidities in children with SLD.
Objective: Phenotypic (Sensititre Myco, pDST) and genotypic drug susceptibility testing (GenoType NTM DR, gDST) in M. avium complex (MAC) have become available as standardized assays, but comparable data is needed. This study aimed to investigate the phenotypic and genotypic drug susceptibility patterns in MAC clinical isolates.
Methods: Overall, 98 isolates from 85 patients were included. pDST and gDST were performed on all isolates and results compared regarding specificity and sensitivity using pDST as a reference method. The impact of drug instability on pDST results was studied using a biological assay over 14 days. In addition, the evolution of antimicrobial resistance was investigated in sequential isolates of 13 patients.
Results: Macrolide resistance was rare, 1.2% (95% CI 0.7–7.3) of isolates in the base cohort. No aminoglycoside resistances were found, but 14.1% of the studied isolates (95% CI 7.8–23.8) showed intermediate susceptibility. The GenoType NTM DR identified two out of four macrolide-resistant isolates. Antibiotic stability was demonstrated to be poor in rifampicin, rifabutin, and doxycycylin.
Conclusions: pDST results in NTM for unstable antibiotics must be interpreted with care. A combination of pDST and gDST will be useful for the guidance of antimicrobial therapy in MAC-disease.
In resource-limited or point-of-care settings, rapid diagnostic tests (RDTs), that aim to simultaneously detect HIV antibodies and p24 capsid (p24CA) antigen with high sensitivity, can pose important alternatives to screen for early infections. We evaluated the performance of the antibody and antigen components of the old and novel version of the Determine™ HIV-1/2 Ag/Ab Combo RDTs in parallel to quantifications in a fourth-generation antigen/antibody immunoassay (4G-EIA), p24CA antigen immunoassay (p24CA-EIA), immunoblots, and nucleic acid quantification. We included plasma samples of acute, treatment-naïve HIV-1 infections (Fiebig stages I–VI, subtypes A1, B, C, F, CRF02_AG, CRF02_AE, URF) or chronic HIV-1 and HIV-2 infections. The tests’ antigen component was evaluated also for a panel of subtype B HIV-1 transmitted/founder (T/F) viruses, HIV-2 strains and HIV-2 primary isolates. Furthermore, we assessed the analytical sensitivity of the RDTs to detect p24CA using a highly purified HIV-1NL4-3 p24CA standard. We found that 77% of plasma samples from acutely infected, immunoblot-negative HIV-1 patients in Fiebig stages II–III were identified by the new RDT, while only 25% scored positive in the old RDT. Both RDTs reacted to all samples from chronically HIV-1-infected and acutely HIV-1-infected patients with positive immunoblots. All specimens from chronically infected HIV-2 patients scored positive in the new RDT. Of note, the sensitivity of the RDTs to detect recombinant p24CA from a subtype B virus ranged between 50 and 200 pg/mL, mirrored also by the detection of HIV-1 T/F viruses only at antigen concentrations tenfold higher than suggested by the manufacturer. The RTD failed to recognize any of the HIV-2 viruses tested. Our results indicate that the new version of the Determine™ HIV-1/2 Ag/Ab Combo displays an increased sensitivity to detect HIV-1 p24CA-positive, immunoblot-negative plasma samples compared to the precursor version. The sensitivity of 4G-EIA and p24CA-EIA to detect the major structural HIV antigen, and thus to diagnose acute infections prior to seroconversion, is still superior.
Background: Essential Tremor (ET) is a progressive neurological disorder characterized by postural and kinetic tremor most commonly affecting the hands and arms. Medically intractable ET can be treated by deep brain stimulation (DBS) of the ventral intermediate nucleus of thalamus (VIM). We investigated whether the location of the effective contact (most tremor suppression with at least side effects) in VIM-DBS for ET changes over time, indicating a distinct mechanism of loss of efficacy that goes beyond progression of tremor severity, or a mere reduction of DBS efficacy.
Methods: We performed programming sessions in 10 patients who underwent bilateral vim-DBS surgery between 2009 and 2017 at our department. In addition to the intraoperative (T1) and first clinical programming session (T2) a third programming session (T3) was performed to assess the effect- and side effect threshold (minimum voltage at which a tremor suppression or side effects occurred). Additionally, we compared the choice of the effective contact between T1 and T2 which might be affected by a surgical induced “brain shift.”
Discussion: Over a time span of about 4 years VIM-DBS in ET showed continuous efficacy in tremor suppression during stim-ON compared to stim-OFF. Compared to immediate postoperative programming sessions in ET-patients with DBS, long-term evaluationshowednorelevantchangeinthechoiceofcontactwithrespecttosideeffects andefficacy.InthemajorityofthecasestheactivecontactatT2didnotcorrespondtothe most effective intraoperative stimulation site T1, which might be explained by a brain-shift due to cerebral spinal fluid loss after neurosurgical procedure.
Background: The feedback given to students plays an important role in their efficiency related to learning practical skills. In the present study, diverse feedback modalities have been investigated. Our hypothesis is that individualized and unsupervised video feedback can produce a similar learning experience as performing practical skills in an oral and maxillofacial surgery setting with conventional direct expert feedback (control group).
Methods: This prospective, randomized, controlled, and blinded study compared direct expert feedback (DEF), individualized video feedback (IVF) and unsupervised video feedback (UVF). The participants were fourth-year dental students from University Goethe in Frankfurt. The students were assigned to one of the three feedback methods (n = 20 per group) using simple randomization. All participants watched an instruction video for an interdental (‘Ernst’) ligature and periphery venous catheterization. Next, the students were video recorded performing the tasks by themselves (pre-test). Following this, every student received feedback using one of the above-mentioned feedback modalities. The participants then performed the same task again while being video recorded (post-test) to measure the acquired competence. Six weeks later, the students participated in an objective structured clinical examination (OSCE) to evaluate their long-term knowledge retention. All examiners were blinded regarding the students’ instructional approach and their affiliation in terms of the learning group.
Results: For the interdental ligature, we found significant improvements in performance in each feedback modality group between the pre-test and post-test (p < 0.001). UVF had the strongest effect on performance time. The comparison between each group in the post-test showed no significant differences between the three groups.
Conclusion: This study showed that IVF and UVF can be considered an alternative or adjunct to conventional methods (i.e. DEF) when learning procedural skills in oral and maxillofacial surgery. However, DEF showed to be the most effective method of feedback and therefore preferable in teaching.
Objectives: To analyze the performance of radiological assessment categories and quantitative computational analysis of apparent diffusion coefficient (ADC) maps using variant machine learning algorithms to differentiate clinically significant versus insignificant prostate cancer (PCa). Methods: Retrospectively, 73 patients were included in the study. The patients (mean age, 66.3 ± 7.6 years) were examined with multiparametric MRI (mpMRI) prior to radical prostatectomy (n = 33) or targeted biopsy (n = 40). The index lesion was annotated in MRI ADC and the equivalent histologic slides according to the highest Gleason Grade Group (GrG). Volumes of interest (VOIs) were determined for each lesion and normal-appearing peripheral zone. VOIs were processed by radiomic analysis. For the classification of lesions according to their clinical significance (GrG ≥ 3), principal component (PC) analysis, univariate analysis (UA) with consecutive support vector machines, neural networks, and random forest analysis were performed. Results: PC analysis discriminated between benign and malignant prostate tissue. PC evaluation yielded no stratification of PCa lesions according to their clinical significance, but UA revealed differences in clinical assessment categories and radiomic features. We trained three classification models with fifteen feature subsets. We identified a subset of shape features which improved the diagnostic accuracy of the clinical assessment categories (maximum increase in diagnostic accuracy ΔAUC = + 0.05, p < 0.001) while also identifying combinations of features and models which reduced overall accuracy. Conclusions: The impact of radiomic features to differentiate PCa lesions according to their clinical significance remains controversial. It depends on feature selection and the employed machine learning algorithms. It can result in improvement or reduction of diagnostic performance.
Background: Previous studies have demonstrated that CF (Cystic Fibrosis) prognosis is dependent of three major parameters: FEV1 (Forced Expiratory Pressure in one second), BMI (Body Mass Index) and need of intravenous antibiotic therapy. The CF centres of Frankfurt, Germany, and Moscow, Russia, care for cystic fibrosis patients. We decided to investigate and compare both centers from 1990 to 2015. No comparable study has been published so far.
Method: German patient data was collected from the national cystic fibrosis database “Muko.web”. Missing values were extracted from the Hospital Information System. Russian patient data were taken directly from the medical records in Moscow. In a descriptive statistical analysis with Bias and R Studio the values were compared.
Result: A total of 428 patients from Moscow (217 male, 211 female; 348 (81,3%) were P. aeruginosa positive) and 159 patients from Frankfurt (92 male, 67 female; 137 (86,2%) with P. aeruginosa positive) were compared with regard to P. aeruginosa positivity, BMI, FEV1 and need of intravenous antibiotic therapy. CF patients in Moscow stratified by age groups had lower BMI than CF patients in Frankfurt (age 16-18: p=0,003; age 19-22: p=0,004; age 23-29: p<0,001; age 30-35: p<0,001; age 36-66: p=0,024). In a matching pairs analysis including 100 patients from Frankfurt and 100 patients from Moscow for the year 2015 FEV1 was significantly lower in Moscow patients (p<0,001).
Conclusion: BMI, FEV1 and need of intravenous therapy have significant impact on survival and on quality of life of CF patients. A lower BMI and a lower FEV1 result in a worse survival and determine the prognosis. This study showed a significant difference in prognostic parameters between Frankfurt and Moscow in the crosssectional analysis for the year 2015. A further study should evaluate this difference to show whether this difference will be found over a longer period of time.
Aim: To evaluate the level of agreement between the periodontal risk assessment (PRA) and the periodontal risk calculator (PRC).
Materials and methods: Periodontal risk was retrospectively assessed among 50 patients using PRA and PRC. Both methods were modified. PRA by assessing probing pocket depths and bleeding on probing at four (PRA4) and six (PRA6) sites per tooth, PRC by permanently marking or unmarking the dichotomously selectable factors “irregular recall,” “oral hygiene in need of improvement” and “completed scaling and root planing” for PRC. Agreement between PRA and PRCred (summarized risk categories) was determined using weighted kappa.
Results: Fifty patients enrolled in periodontal maintenance (48% female, age: 63.8 ± 11.2 years) participated. PRA4 and PRA6 matched in 32 (64%) patients (κ‐coefficient = 0.48, p < .001). There was 100% agreement between both PRC versions. There was minimal agreement of PRA6 and PRCred (66%, 28% one different category, 6% two different categories; κ‐coefficient = 0.34; p = .001). PRA4 and PRCred did not match (60% agreement, 34% one different category, 6% two different categories; κ‐coefficient = 0.23; p = .13). For the SPT diagnosis of severe periodontitis, PRA6 and PRCred agreed weakly (κ‐coefficient = 0.44; p = .004).
Conclusion: PRA and PRC showed a minimal agreement. Specific disease severity may result in improved agreement.
Introduction: There is still an ongoing debate whether a transrectal ultrasound (TRUS) approach for prostate biopsies is associated with higher (infectious) complications rates compared to transperineal biopsies. This is especially of great interests in settings with elevated frequencies of multidrug resistant organisms (MDRO).
Materials and Methods: Between 01/2018 and 05/2019 230 patients underwent a TRUS-guided prostate biopsy at the department of Urology at University Hospital Frankfurt. Patients were followed up within the clinical routine that was not conducted earlier than 6 weeks after the biopsy. Among 230 biopsies, 180 patients took part in the follow-up. No patients were excluded. Patients were analyzed retrospectively regarding complications, infections and underlying infectious agents or needed interventions.
Results: Of all patients with follow up, 84 patients underwent a systematic biopsy (SB) and 96 a targeted biopsy (TB) after MRI of the prostate with additional SB. 74.8% of the patients were biopsy-naïve. The most frequent objective complications (classified by Clavien-Dindo) lasting longer than one day after biopsy were hematuria (17.9%, n = 32), hematospermia (13.9%, n = 25), rectal bleeding (2.8%, n = 5), and pain (2.2%, n = 4). Besides a known high MDRO prevalence in the Rhine-Main region, only one patient (0.6%) developed fever after biopsy. One patient each (0.6%) consulted a physician due to urinary retention, rectal bleeding or gross hematuria. There were no significant differences in complications seen between SB and SB + TB patients. The rate of patients who consulted a physician was significantly higher for patients with one or more prior biopsies compared to biopsy-naïve patients.
Conclusion: Complications after transrectal prostate biopsies are rare and often self-limiting. Infections were seen in <1% of all patients, regardless of an elevated local prevalence of MDROs. Severe complications (Clavien-Dindo ≥ IIIa) were only seen in 3 (1.7%) of the patients. Repeated biopsy is associated with higher complication rates in general.
Comprehensive analysis of tumour sub-volumes for radiomic risk modelling in locally advanced HNSCC
(2020)
Simple Summary: Radiomic risk models are usually based on imaging features, which are extracted from the entire gross tumour volume (GTV entire ). This approach does not explicitly consider the complex biological structure of the tumours. Therefore, in this retrospective study, we investigated the prognostic value of radiomic analyses based on different tumour sub-volumes using computed tomography imaging of patients with locally advanced head and neck squamous cell carcinoma who were treated with primary radio-chemotherapy. The GTV entire was cropped by different margins to define the rim and corresponding core sub-volumes of the tumour. Furthermore, the best performing tumour rim sub-volume was extended into surrounding tissue with different margins. As a result, the models based on the 5 mm tumour rim and on the 3 mm extended rim sub-volume showed an improved performance compared to models based on the corresponding tumour core. This indicates that the consideration of tumour sub-volumes may help to improve radiomic risk models.
Abstract: Imaging features for radiomic analyses are commonly calculated from the entire gross tumour volume (GTVentire). However, tumours are biologically complex and the consideration of different tumour regions in radiomic models may lead to an improved outcome prediction. Therefore, we investigated the prognostic value of radiomic analyses based on different tumour sub-volumes using computed tomography imaging of patients with locally advanced head and neck squamous cell carcinoma. The GTVentire was cropped by different margins to define the rim and the corresponding core sub-volumes of the tumour. Subsequently, the best performing tumour rim sub-volume was extended into surrounding tissue with different margins. Radiomic risk models were developed and validated using a retrospective cohort consisting of 291 patients in one of the six Partner Sites of the German Cancer Consortium Radiation Oncology Group treated between 2005 and 2013. The validation concordance index (C-index) averaged over all applied learning algorithms and feature selection methods using the GTVentire achieved a moderate prognostic performance for loco-regional tumour control (C-index: 0.61 ± 0.04 (mean ± std)). The models based on the 5 mm tumour rim and on the 3 mm extended rim sub-volume showed higher median performances (C-index: 0.65 ± 0.02 and 0.64 ± 0.05, respectively), while models based on the corresponding tumour core volumes performed less (C-index: 0.59 ± 0.01). The difference in C-index between the 5 mm tumour rim and the corresponding core volume showed a statistical trend (p = 0.10). After additional prospective validation, the consideration of tumour sub-volumes may be a promising way to improve prognostic radiomic risk models.
Introduction: Reliable and cost-effective diagnostics for hepatitis E virus (HEV) infection are necessary. The aim of our study was to investigate which diagnostic test is most accurate to detect HEV infection in immunocompetent and immunosuppressed patients in a real world setting. Patients and Methods: We performed a retrospective analysis of 1165 patients tested for HEV antibodies and HEV PCR at the same time point. Clinical, laboratory and virological data were taken from patient charts. HEV IgA was measured in a subgroup of 185 patients. Results: HEV RNA was detectable in 61 patients (5.2%); most of them (n = 49, 80.3%/n = 43, 70.5%) were HEV IgM+ and IgG+; however, 12 patients (19.6%) were HEV RNA positive/HEV IgM negative and 17 patients (27.8%) were HEV RNA positive/HEV IgG negative. Ten HEV RNA positive patients (16.4%) had neither HEV IgG nor IgM antibodies. Importantly, all of them were immunosuppressed. HEV IgA testing was less sensitive than HEV IgM for HEV diagnosis. Conclusions: HEV infection can be overlooked in patients without HEV specific antibodies. Performing PCR is necessary to diagnose or exclude HEV infection in immunocompromised hosts. In immunocompetent patients, a screening based on HEV antibodies (IgG/IgM) is sufficient.
The retinoid X receptor (RXR) is a ligand-sensing transcription factor acting mainly as a universal heterodimer partner for other nuclear receptors. Despite presenting as a potential therapeutic target for cancer and neurodegeneration, adverse effects typically observed for RXR agonists, likely due to the lack of isoform selectivity, limit chemotherapeutic application of currently available RXR ligands. The three human RXR isoforms exhibit different expression patterns; however, they share high sequence similarity, presenting a major obstacle toward the development of subtype-selective ligands. Here, we report the discovery of the saturated fatty acid, palmitic acid, as an RXR ligand and disclose a uniform set of crystal structures of all three RXR isoforms in an active conformation induced by palmitic acid. A structural comparison revealed subtle differences among the RXR subtypes. We also observed an ability of palmitic acid as well as myristic acid and stearic acid to induce recruitment of steroid receptor co-activator 1 to the RXR ligand-binding domain with low micromolar potencies. With the high, millimolar endogenous concentrations of these highly abundant lipids, our results suggest their potential involvement in RXR signaling.
Genome-wide CRISPR screens are becoming more widespread and allow the simultaneous interrogation of thousands of genomic regions. Although recent progress has been made in the analysis of CRISPR screens, it is still an open problem how to interpret CRISPR mutations in non-coding regions of the genome. Most of the tools concentrate on the interpretation of mutations introduced in gene coding regions. We introduce a computational pipeline that uses epigenomic information about regulatory elements for the interpretation of CRISPR mutations in non-coding regions. We illustrate our approach on the analysis of a genome-wide CRISPR screen in hTERT-RPE-1 cells and reveal novel regulatory elements that mediate chemoresistance against doxorubicin in these cells. We infer links to established and to novel chemoresistance genes. Our approach is general and can be applied on any cell type and with different CRISPR enzymes.
Alzheimer’s disease (AD) is the most prevalent neurodegenerative disease causing dementia and poses significant health risks to middle-aged and elderly people. Brain magnetic resonance imaging (MRI) is the most widely used diagnostic method for AD. However, it is challenging to collect sufficient brain imaging data with high-quality annotations. Weakly supervised learning (WSL) is a machine learning technique aimed at learning effective feature representation from limited or low-quality annotations. In this paper, we propose a WSL-based deep learning (DL) framework (ADGNET) consisting of a backbone network with an attention mechanism and a task network for simultaneous image classification and image reconstruction to identify and classify AD using limited annotations. The ADGNET achieves excellent performance based on six evaluation metrics (Kappa, sensitivity, specificity, precision, accuracy, F1-score) on two brain MRI datasets (2D MRI and 3D MRI data) using fine-tuning with only 20% of the labels from both datasets. The ADGNET has an F1-score of 99.61% and sensitivity is 99.69%, outperforming two state-of-the-art models (ResNext WSL and SimCLR). The proposed method represents a potential WSL-based computer-aided diagnosis method for AD in clinical practice.
Interest in time-resolved connectivity in fMRI has grown rapidly in recent years. The most widely used technique for studying connectivity changes over time utilizes a sliding windows approach. There has been some debate about the utility of shorter versus longer windows, the use of fixed versus adaptive windows, as well as whether observed resting state dynamics during wakefulness may be predominantly due to changes in sleep state and subject head motion. In this work we use an independent component analysis (ICA)-based pipeline applied to concurrent EEG/fMRI data collected during wakefulness and various sleep stages and show: 1) connectivity states obtained from clustering sliding windowed correlations of resting state functional network time courses well classify the sleep states obtained from EEG data, 2) using shorter sliding windows instead of longer non-overlapping windows improves the ability to capture transition dynamics even at windows as short as 30 s, 3) motion appears to be mostly associated with one of the states rather than spread across all of them 4) a fixed tapered sliding window approach outperforms an adaptive dynamic conditional correlation approach, and 5) consistent with prior EEG/fMRI work, we identify evidence of multiple states within the wakeful condition which are able to be classified with high accuracy. Classification of wakeful only states suggest the presence of time-varying changes in connectivity in fMRI data beyond sleep state or motion. Results also inform about advantageous technical choices, and the identification of different clusters within wakefulness that are separable suggest further studies in this direction.
Degeneration of neurons, such as the inner ear spiral ganglion neurons (SGN), may be decelerated or even stopped by neurotrophic factor treatment, such as brain-derived neurotrophic factor (BDNF), as well as electrical stimulation (ES). In a clinical setting, drug treatment of the SGN could start directly during implantation of a cochlear implant, whereas electrical stimulation begins days to weeks later. The present study was conducted to determine the effects of consecutive BDNF and ES treatments on SGN density and electrical responsiveness. An electrode drug delivery device was implanted in guinea pigs 3 weeks after deafening and five experimental groups were established: two groups received intracochlear infusion of artificial perilymph (AP) or BDNF; two groups were treated with AP respectively BDNF in addition to ES (AP + ES, BDNF + ES); and one group received BDNF from the day of implantation until day 34 followed by ES (BDNF ⇨ ES). Electrically evoked auditory brainstem responses were recorded. After one month of treatment, the tissue was harvested and the SGN density was assessed. The results show that consecutive treatment with BDNF and ES was as successful as the simultaneous combined treatment in terms of enhanced SGN density compared to the untreated contralateral side but not in regard to the numbers of protected cells.
Consensus on definition and severity grading of lymphatic complications after kidney transplantation
(2020)
Background: The incidence of lymphatic complications after kidney transplantation varies considerably in the literature. This is partly because a universally accepted definition has not been established. This study aimed to propose an acceptable definition and severity grading system for lymphatic complications based on their management strategy.
Methods: Relevant literature published in MEDLINE and Web of Science was searched systematically. A consensus for definition and a severity grading was then sought between 20 high-volume transplant centres.
Results: Lymphorrhoea/lymphocele was defined in 32 of 87 included studies. Sixty-three articles explained how lymphatic complications were managed, but none graded their severity. The proposed definition of lymphorrhoea was leakage of more than 50 ml fluid (not urine, blood or pus) per day from the drain, or the drain site after removal of the drain, for more than 1 week after kidney transplantation. The proposed definition of lymphocele was a fluid collection of any size near to the transplanted kidney, after urinoma, haematoma and abscess have been excluded. Grade A lymphatic complications have a minor and/or non-invasive impact on the clinical management of the patient; grade B complications require non-surgical intervention; and grade C complications require invasive surgical intervention.
Conclusion: A clear definition and severity grading for lymphatic complications after kidney transplantation was agreed. The proposed definitions should allow better comparisons between studies.
Considering the microbiome in stress-related and neurodevelopmental trajectories to schizophrenia
(2020)
Early life adversity and prenatal stress are consistently associated with an increased risk for schizophrenia, although the exact pathogenic mechanisms linking the exposures with the disease remain elusive. Our previous view of the HPA stress axis as an elegant but simple negative feedback loop, orchestrating adaptation to stressors among the hypothalamus, pituitary, and adrenal glands, needs to be updated. Research in the last two decades shows that important bidirectional signaling between the HPA axis and intestinal mucosa modulates brain function and neurochemistry, including effects on glucocorticoid hormones and brain-derived neurotrophic factor (BDNF). The intestinal microbiome in earliest life, which is seeded by the vaginal microbiome during delivery, programs the development of the HPA axis in a critical developmental window, determining stress sensitivity and HPA function as well as immune system development. The crosstalk between the HPA and the Microbiome Gut Brain Axis (MGBA) is particularly high in the hippocampus, the most consistently disrupted neural region in persons with schizophrenia. Animal models suggest that the MGBA remains influential on behavior and physiology across developmental stages, including the perinatal window, early childhood, adolescence, and young adulthood. Understanding the role of the microbiome on critical risk related stressors may enhance or transform of understanding of the origins of schizophrenia and offer new approaches to increase resilience against stress effects for preventing and treating schizophrenia.
Chronic coronary artery disease remains an unconquered clinical problem, affecting an increasing number of people worldwide. Despite the improved understanding of the disease development, the implementation of the many advances in diagnosis and therapy is lacking. Many clinicians continue to rely on patient's symptoms and diagnostic methods, which do not enable optimal clinical decisions. For example, echocardiography and invasive coronary catheterisation remain the mainstay investigations for stable angina patients in many places, despite the evidence on their limitations and availability of better diagnostic options. Cardiac MRI is a powerful diagnostic method, supporting robust measurements of crucial markers of cardiac structure and function, myocardial perfusion and scar, as well as providing detailed insight into myocardial tissue. Accurate and informative diagnostic readouts can help with guiding therapy, monitoring disease progress and tailoring the response to treatment. In this article, the authors outline the evidence supporting the state-of-art applications based on cardiovascular magnetic resonance, allowing the clinician optimal use of this insightful diagnostic method in everyday clinical practice.
Context information supports serial dependence of multiple visual objects across memory episodes
(2020)
Serial dependence is thought to promote perceptual stability by compensating for small changes of an object’s appearance across memory episodes. So far, it has been studied in situations that comprised only a single object. The question of how we selectively create temporal stability of several objects remains unsolved. In a memory task, objects can be differentiated by their to-be-memorized feature (content) as well as accompanying discriminative features (context). We test whether congruent context features, in addition to content similarity, support serial dependence. In four experiments, we observe a stronger serial dependence between objects that share the same context features across trials. Apparently, the binding of content and context features is not erased but rather carried over to the subsequent memory episode. As this reflects temporal dependencies in natural settings, our findings reveal a mechanism that integrates corresponding content and context features to support stable representations of individualized objects over time.
Effective connectivity (EC) is able to explore causal effects between brain areas and can depict mechanisms that underlie repair and adaptation in chronic brain diseases. Thus, the application of EC techniques in multiple sclerosis (MS) has the potential to determine directionality of neuronal interactions and may provide an imaging biomarker for disease progression. Here, serial longitudinal structural and resting-state fMRI was performed at 12-week intervals over one year in twelve MS patients. Twelve healthy subjects served as controls (HC). Two approaches for EC quantification were used: Causal Bayesian Network (CBN) and Time-resolved Partial Directed Coherence (TPDC). The EC strength was correlated with the Expanded Disability Status Scale (EDSS) and Fatigue Scale for Motor and Cognitive functions (FSMC). Our findings demonstrated a longitudinal increase in EC between specific brain regions, detected in both the CBN and TPDC analysis in MS patients. In particular, EC from the deep grey matter, frontal, prefrontal and temporal regions showed a continuous increase over the study period. No longitudinal changes in EC were attested in HC during the study. Furthermore, we observed an association between clinical performance and EC strength. In particular, the EC increase in fronto-cerebellar connections showed an inverse correlation with the EDSS and FSMC. Our data depict continuous functional reorganization between specific brain regions indicated by increasing EC over time in MS, which is not detectable in HC. In particular, fronto-cerebellar connections, which were closely related to clinical performance, may provide a marker of brain plasticity and functional reserve in MS.
Cerebral lesions may cause degeneration and neuroplastic reorganization in both the ipsi- and the contralesional hemisphere, presumably creating an imbalance of primarily inhibitory interhemispheric influences produced via transcallosal pathways. The two hemispheres are thought to mutually hamper neuroplastic reorganization of the other hemisphere. The results of preceding degeneration and neuroplastic reorganization of white matter may be reflected by Diffusion Tensor Imaging-derived diffusivity parameters such as fractional anisotropy (FA). In this study, we applied Diffusion Tensor Imaging (DTI) to contrast the white matter status of the contralesional hemisphere of young lesioned brains with and without contralateral influences by comparing patients after hemispherotomy to those who had not undergone neurosurgery. DTI was applied to 43 healthy controls (26 females, mean age ± SD: 25.07 ± 11.33 years) and two groups of in total 51 epilepsy patients with comparable juvenile brain lesions (32 females, mean age ± SD: 25.69 ± 12.77 years) either after hemispherotomy (30 of 51 patients) or without neurosurgery (21 of 51 patients), respectively. FA values were compared between these groups using the unbiased tract-based spatial statistics approach. A voxel-wise ANCOVA controlling for age at scan yielded significant group differences in FA. A post hoc t-test between hemispherotomy patients and healthy controls revealed widespread supra-threshold voxels in the contralesional hemisphere of hemispherotomy patients indicating comparatively higher FA values (p < 0.05, FWE-corrected). The non-surgery group, in contrast, showed extensive supra-threshold voxels indicating lower FA values in the contralesional hemisphere as compared to healthy controls (p < 0.05, FWE-corrected). Whereas lower FA values are suggestive of pronounced contralesional degeneration in the non-surgery group, higher FA values in the hemispherotomy group may be interpreted as a result of preceding plastic remodeling. We conclude that, whether juvenile brain lesions are associated with contralesional degeneration or reorganization partly depends on the ipsilesional hemisphere. Contralesional reorganization as observed in hemispherotomy patients was most likely enabled by the complete neurosurgical deafferentation of the ipsilesional hemisphere and, thereby, the disinhibition of the neuroplastic potential of the contralesional hemisphere. The main argument of this study is that hemispherotomy may be seen as a major plastic stimulus and as a prerequisite for contralesional neuroplastic remodeling in patients with juvenile brain lesions.
People with Parkinson’s disease (PD) experience a gradual loss of functional abilities that affects all facets of their daily life. There is a lack of longitudinal studies on coping styles in relation to the disease progression among people with PD. The aim of this study was to explore how coping styles in PD evolve over a 3-year period. Data from the longitudinal project “Home and Health in People Ageing with PD” was utilized (N = 158), including baseline and 3-year follow-up assessments. Coping was captured by ratings of 13 different coping styles. A factor analysis was conducted to analyse patterns of coping styles. Stability and change were analysed for each of the 13 styles with respect to the course of the disease. The factor analysis revealed four coping patterns: pessimistic, optimistic, persistent and support-seeking. The stability of each coping style over time ranged from 75.3% to 90.5%. Those who experienced a worsening of the disease were most inclined to change their coping style (p = 0.006). The results suggest that even when facing severe challenges due to PD in daily life, coping styles remain relatively stable over time. However, a worsening in PD severity appeared to trigger a certain re-evaluation of coping styles.
Background: The currently prevailing global threat of COVID-19 caused the publication numbers on coronaviruses to explode. The awareness of the scientific and public community is enormous. But what about the sense of all these undertakings and what can be learned about the future for a better understanding? These questions were answered with established bibliometric analyses of the time until the avalanche of publications unfolded.
Methods: Chronological, geographical aspects of publication output on coronavirus were also evaluated under the influence of epidemiological and socio-economic parameters.
Results: The trend in publication and citation numbers shows the strong influence of the past pandemics SARS and MERS with an untypical decline afterward. Research is becoming increasingly multidisciplinary over time. The USA and China, as the countries with the highest number of publications, are being displaced by other countries in the consideration of socio-economic and epidemiological aspects, which shows the effect of regional interest in corona research. A significant correlation was found between the number of SARS cases per country and related publications, while no correlation was found for MERS cases and articles.
Conclusions: The results underline the need for sustainable and forward-looking approaches that should not end with the containment of COVID-19.
Erratum for: Cyclic AMP induces transactivation of the receptors for epidermal growth factor and nerve growth factor, thereby modulating activation of MAP kinase, Akt, and neurite outgrowth in PC12 cells.Journal of biological chemistry, 2002 Nov 15;277(46):43623-30. doi: 10.1074/jbc.M203926200. Epub 2002 Sep 5.
Cortical changes in epilepsy patients with focal cortical dysplasia: new insights with T2 mapping
(2020)
Background: In epilepsy patients with focal cortical dysplasia (FCD) as the epileptogenic focus, global cortical signal changes are generally not visible on conventional MRI. However, epileptic seizures or antiepileptic medication might affect normal-appearing cerebral cortex and lead to subtle damage. Purpose: To investigate cortical properties outside FCD regions with T2-relaxometry. Study Type: Prospective study. Subjects: Sixteen patients with epilepsy and FCD and 16 age-/sex-matched healthy controls. Field Strength/Sequence: 3T, fast spin-echo T2-mapping, fluid-attenuated inversion recovery (FLAIR), and synthetic T1-weighted magnetization-prepared rapid acquisition of gradient-echoes (MP-RAGE) datasets derived from T1-maps. Assessment: Reconstruction of the white matter and cortical surfaces based on MP-RAGE structural images was performed to extract cortical T2 values, excluding lesion areas. Three independent raters confirmed that morphological cortical/juxtacortical changes in the conventional FLAIR datasets outside the FCD areas were definitely absent for all patients. Averaged global cortical T2 values were compared between groups. Furthermore, group comparisons of regional cortical T2 values were performed using a surface-based approach. Tests for correlations with clinical parameters were carried out. Statistical Tests: General linear model analysis, permutation simulations, paired and unpaired t-tests, and Pearson correlations. Results: Cortical T2 values were increased outside FCD regions in patients (83.4 ± 2.1 msec, control group 81.4 ± 2.1 msec, P = 0.01). T2 increases were widespread, affecting mainly frontal, but also parietal and temporal regions of both hemispheres. Significant correlations were not observed (P ≥ 0.55) between cortical T2 values in the patient group and the number of seizures in the last 3 months or the number of anticonvulsive drugs in the medical history. Data Conclusion: Widespread increases in cortical T2 in FCD-associated epilepsy patients were found, suggesting that structural epilepsy in patients with FCD is not only a symptom of a focal cerebral lesion, but also leads to global cortical damage not visible on conventional MRI. Evidence Level: 21. Technical efficacy Stage: 3 J. MAGN. RESON. IMAGING 2020;52:1783–1789.
Mental imagery provides an essential simulation tool for remembering the past and planning the future, with its strength affecting both cognition and mental health. Research suggests that neural activity spanning prefrontal, parietal, temporal, and visual areas supports the generation of mental images. Exactly how this network controls the strength of visual imagery remains unknown. Here, brain imaging and transcranial magnetic phosphene data show that lower resting activity and excitability levels in early visual cortex (V1-V3) predict stronger sensory imagery. Further, electrically decreasing visual cortex excitability using tDCS increases imagery strength, demonstrating a causative role of visual cortex excitability in controlling visual imagery. Together, these data suggest a neurophysiological mechanism of cortical excitability involved in controlling the strength of mental images.
Synchronization has been implicated in neuronal communication, but causal evidence remains indirect. We used optogenetics to generate depolarizing currents in pyramidal neurons of cat visual cortex, emulating excitatory synaptic inputs under precise temporal control, while measuring spike output. Cortex transformed constant excitation into strong gamma-band synchronization, revealing the well-known cortical resonance. Increasing excitation with ramps increased the strength and frequency of synchronization. Slow, symmetric excitation profiles revealed hysteresis of power and frequency. Crucially, white-noise input sequences enabled causal analysis of network transmission, establishing that cortical resonance selectively transmits coherent input components. Models composed of recurrently coupled excitatory and inhibitory units uncovered a crucial role of feedback inhibition and suggest that hysteresis can arise through spike-frequency adaptation. The presented approach provides a powerful means to investigate the resonance properties of local circuits and probe how these properties transform input and shape transmission.
Background Coronavirus disease 2019 (COVID-19) represents a significant challenge to health care systems around the world. A well-functioning primary care system is crucial in epidemic situations as it plays an important role in the development of a system-wide response.
Methods 2,187 Austrian and German GPs answered an internet suvey on preparedness, testing, staff protection, perception of risk, self-confidence, a decrease in the number of patient contacts, and efforts to control the spread of the virus in the practice during the early phase of the COVID-pandemic (3rd to 30th April).
Results The completion rate of the questionnaire was high (90.9%). GPs gave low ratings to their preparedness for a pandemic, testing of suspected cases and efforts to protect staff. The provision of information to GPs and the perception of risk were rated as moderate. On the other hand, the participants rated their self-confidence, a decrease in patient contacts and their efforts to control the spread of the disease highly.
Conclusion Primary care is an important resource for dealing with a pandemic like COVID-19. The workforce is confident and willing to take an active role, but needs to be provided with the appropriate surrounding conditions. This will require that certain conditions are met.
Registration Trial registration at the German Clinical Trials Register: DRKS00021231
Covid stories from East Africa and beyond : lived experiences and forward-looking reflections
(2020)
The coronavirus has rattled humanity, tested resolve and determination, and redefined normalcy. This compelling collection of 29 short stories and essays brings together the lived experiences of covid19 through a diversity of voices from across the African continent. The stories highlight challenges, new opportunities, and ultimately the deep resilience of Africans and their communities. Bringing into conversation the perspectives of laypeople, academics, professionals, domestic workers, youth, and children, the volume is a window into the myriad ways in which people have confronted, adapted to, and sought to tackle the coronavirus and its trail of problems. The experiences of the most vulnerable are specifically explored, and systemic changes and preliminary shifts towards a new global order are addressed. Laughter as a coping mechanism is a thread throughout.
SARS-CoV-2 is the causative agent of COVID-19. Severe COVID-19 disease has been associated with disseminated intravascular coagulation and thrombosis, but the mechanisms underlying COVID-19-related coagulopathy remain unknown. The risk of severe COVID-19 disease is higher in males than in females and increases with age. To identify gene products that may contribute to COVID-19-related coagulopathy, we analyzed the expression of genes associated with the Gene Ontology (GO) term “blood coagulation” in the Genotype-Tissue Expression (GTEx) database and identified four procoagulants, whose expression is higher in males and increases with age (ADAMTS13, F11, HGFAC, KLKB1), and two anticoagulants, whose expression is higher in females and decreases with age (C1QTNF1, SERPINA5). However, the expression of none of these genes was regulated in a proteomics dataset of SARS-CoV-2-infected cells and none of the proteins have been identified as a binding partner of SARS-CoV-2 proteins. Hence, they may rather generally predispose individuals to thrombosis without directly contributing to COVID-19-related coagulopathy. In contrast, the expression of the procoagulant transferrin (not associated to the GO term “blood coagulation”) was higher in males, increased with age, and was upregulated upon SARS-CoV-2 infection. Hence, transferrin warrants further examination in ongoing clinic-pathological investigations.
SARS-CoV-2 is the causative agent of COVID-19. Severe COVID-19 disease has been associated with disseminated intravascular coagulation and thrombosis, but the mechanisms underlying COVID-19-related coagulopathy remain unknown. Since the risk of severe COVID-19 disease is higher in males than in females and increases with age, we combined proteomics data from SARS-CoV-2-infected cells with human gene expression data from the Genotype-Tissue Expression (GTEx) database to identify gene products involved in coagulation that change with age, differ in their levels between females and males, and are regulated in response to SARS-CoV-2 infection. This resulted in the identification of transferrin as a candidate coagulation promoter, whose levels increases with age and are higher in males than in females and that is increased upon SARS-CoV-2 infection. A systematic investigation of gene products associated with the GO term “blood coagulation” did not reveal further high confidence candidates, which are likely to contribute to COVID-19-related coagulopathy. In conclusion, the role of transferrin should be considered in the course of COVID-19 disease and further examined in ongoing clinic-pathological investigations.
The novel coronavirus infection (COVID-19) is caused by the new coronavirus SARS-CoV-2 and is characterized by an exaggerated inflammatory response that can lead to severe manifestations such as adult respiratory syndrome, sepsis, coagulopathy, and death in a proportion of patients. Among other factors and direct viral effects, the increase in the vasoconstrictor angiotensin II, the decrease in the vasodilator angiotensin, and the sepsis-induced release of cytokines can trigger a coagulopathy in COVID-19. A coagulopathy has been reported in up to 50% of patients with severe COVID-19 manifestations. An increase in d-dimer is the most significant change in coagulation parameters in severe COVID-19 patients, and progressively increasing values can be used as a prognostic parameter indicating a worse outcome. Limited data suggest a high incidence of deep vein thrombosis and pulmonary embolism in up to 40% of patients, despite the use of a standard dose of low-molecular-weight heparin (LMWH) in most cases. In addition, pulmonary microvascular thrombosis has been reported and may play a role in progressive lung failure. Prophylactic LMWH has been recommended by the International Society on Thrombosis and Haemostasis (ISTH) and the American Society of Hematology (ASH), but the best effective dosage is uncertain. Adapted to the individual risk of thrombosis and the d-dimer value, higher doses can be considered, especially since bleeding events in COVID-19 are rare. Besides the anticoagulant effect of LMWH, nonanticoagulant properties such as the reduction in interleukin 6 release have been shown to improve the complex picture of coagulopathy in patients with COVID-19.
Attention-Deficit/Hyperactivity Disorder (ADHD) and obesity are frequently comorbid, genetically correlated, and share brain substrates. The biological mechanisms driving this association are unclear, but candidate systems, like dopaminergic neurotransmission and circadian rhythm, have been suggested. Our aim was to identify the biological mechanisms underpinning the genetic link between ADHD and obesity measures and investigate associations of overlapping genes with brain volumes. We tested the association of dopaminergic and circadian rhythm gene sets with ADHD, body mass index (BMI), and obesity (using GWAS data of N = 53,293, N = 681,275, and N = 98,697, respectively). We then conducted genome-wide ADHD–BMI and ADHD–obesity gene-based meta-analyses, followed by pathway enrichment analyses. Finally, we tested the association of ADHD–BMI overlapping genes with brain volumes (primary GWAS data N = 10,720–10,928; replication data N = 9428). The dopaminergic gene set was associated with both ADHD (P = 5.81 × 10−3) and BMI (P = 1.63 × 10−5); the circadian rhythm was associated with BMI (P = 1.28 × 10−3). The genome-wide approach also implicated the dopaminergic system, as the Dopamine-DARPP32 Feedback in cAMP Signaling pathway was enriched in both ADHD–BMI and ADHD–obesity results. The ADHD–BMI overlapping genes were associated with putamen volume (P = 7.7 × 10−3; replication data P = 3.9 × 10−2)—a brain region with volumetric reductions in ADHD and BMI and linked to inhibitory control. Our findings suggest that dopaminergic neurotransmission, partially through DARPP-32-dependent signaling and involving the putamen, is a key player underlying the genetic overlap between ADHD and obesity measures. Uncovering shared etiological factors underlying the frequently observed ADHD–obesity comorbidity may have important implications in terms of prevention and/or efficient treatment of these conditions.
Extracellular signal-regulated kinase 3 (ERK3), known also as mitogen-activated protein kinase 6 (MAPK6), is an atypical member of MAPK kinase family, which has been poorly studied. Little is known regarding its function in biological processes, yet this atypical kinase has been suggested to play important roles in the migration and invasiveness of certain cancers. The lack of tools, such as a selective inhibitor, hampers the study of ERK3 biology. Here, we report the crystal structure of the kinase domain of this atypical MAPK kinase, providing molecular insights into its distinct ATP binding pocket compared to the classical MAPK ERK2, explaining differences in their inhibitor binding properties. Medium-scale small molecule screening identified a number of inhibitors, several of which unexpectedly exhibited remarkably high inhibitory potencies. The crystal structure of CLK1 in complex with CAF052, one of the most potent inhibitors identified for ERK3, revealed typical type-I binding mode of the inhibitor, which by structural comparison could likely be maintained in ERK3. Together with the presented structural insights, these diverse chemical scaffolds displaying both reversible and irreversible modes of action, will serve as a starting point for the development of selective inhibitors for ERK3, which will be beneficial for elucidating the important functions of this understudied kinase.
Culturally adapted cognitive behavioral therapy (CA-CBT) is a well-evaluated, transdiagnostic group intervention for refugees that uses psychoeducation, meditation, and stretching exercises. In the current study, we added problem-solving training to CA-CBT and evaluated this treatment (i.e., CA-CBT+) in a randomized controlled pilot trial with a sample of Farsi-speaking refugees. Participants (N = 24) were male refugees diagnosed with DSM-5 PTSD, major depressive disorder, and anxiety disorders who were randomly assigned to either a treatment or waitlist control (WLC) condition. Treatment components were adapted both to the specific cultural background and the current social problems of asylum seekers. Assessments were performed pretreatment, 12-weeks posttreatment, and 1-year follow-up. The primary treatment outcome was the General Health Questionnaire (GHQ-28); secondary outcome measures included the Posttraumatic Stress Disorder Checklist, Patient Health Questionnaire, Somatic Symptom Scale, World Health Organization Quality of Life, and Emotion Regulation Scale. Eleven of 12 participants were randomized to CA-CBT+ completed treatment. Based on intent-to-treat data, large between-group effect sizes were seen at posttreatment in the GHQ-28, d = 3.0, and for most secondary outcome measures. Improvements for individuals in the treatment group decreased at 1-year follow-up, but effect sizes demonstrated continued large improvements on all measures as compared to pretreatment levels. In summary, CA-CBT+ led to large improvements in general psychopathological distress and quality of life, which were maintained in the long term. In addition, the dropout rate was very low, with delivery in group format. Thus, problem-solving training appears to be a promising addition to CA-CBT.
Minimal residual disease (MRD) is the strongest predictor of relapse in B-cell precursor acute lymphoblastic leukemia (BCP-ALL). In BLAST study (NCT01207388), adults with BCP-ALL in remission with MRD after chemotherapy received blinatumomab, a CD19 BiTE® immuno-oncotherapy, 15 µg/m2/day for up to four 6-week cycles (4 weeks continuous infusion, 2 weeks off). Survival was evaluated for 110 patients, including 74 who received HSCT in continuous complete remission. With a median follow-up of 59·8 months, median survival (months) was 36·5 (95% CI: 22.0–not reached [NR]). Median survival was NR (29.5–NR) for complete MRD responders (n = 84) and 14.4 (3.8–32.3) for MRD non-responders (n = 23; p = 0.002); after blinatumomab and HSCT, median survival was NR (25.7–NR) (n = 61) and 16.5 (1.1–NR) (n = 10; p = 0.065), respectively. This final analysis suggests complete MRD response during blinatumomab treatment is curative. Post-hoc analysis of study data suggests while post blinatumomab HSCT may be beneficial in appropriate patients, long-term survival without HSCT is also possible.
Although the therapeutic armamentarium for bladder cancer has considerably widened in the last few years, severe side effects and the development of resistance hamper long-term treatment success. Thus, patients turn to natural plant products as alternative or complementary therapeutic options. One of these is curcumin, the principal component of Curcuma longa that has shown chemopreventive effects in experimental cancer models. Clinical and preclinical studies point to its role as a chemosensitizer, and it has been shown to protect organs from toxicity induced by chemotherapy. These properties indicate that curcumin could hold promise as a candidate for additive cancer treatment. This review evaluates the relevance of curcumin as an integral part of therapy for bladder cancer.
Improving long-term patient and graft survival after liver transplantation (LT) remains a major challenge. Compared to the early phase after LT, long-term morbidity and mortality of the recipients not only depends on complications immediately related to the graft function, infections, or rejection, but also on medical factors such as de novo malignancies, metabolic disorders (e.g., new-onset diabetes, osteoporosis), psychiatric conditions (e.g., anxiety, depression), renal failure, and cardiovascular diseases. While a comprehensive post-transplant care at the LT center and the connected regional networks may improve outcome, there is currently no generally accepted standard to the post-transplant management of LT recipients in Germany. We therefore described the structure and standards of post-LT care by conducting a survey at 12 German LT centers including transplant hepatologists and surgeons. Aftercare structures and form of cost reimbursement considerably varied between LT centers across Germany. Further discussions and studies are required to define optimal structure and content of post-LT care systems, aiming at improving the long-term outcomes of LT recipients.
Aortic stenosis is the most common valvular disease worldwide. With transcatheter aortic valve replacement (TAVR) being increasingly expanded to lower-risk populations, several challenging issues remain to be solved. The present review aims at discussing modern approaches to such issues as well as the current status of TAVR. TAVR has undergone several developments in the recent years: an increased use of transfemoral access, the development of prostheses in order to adapt to challenging anatomies, improved delivery systems with repositioning features, and outer skirts aiming at reducing paravalvular leak. The indication of TAVR is increasingly being expanded to patients with lower surgical risk. The main clinical trials supporting such expansion are reviewed and the latest data on low-risk patients are discussed. A number of challenges need still to be addressed and are also reviewed in this paper: the need for updated international guidelines including the latest evidence; a reduction of main complications such as permanent pacemaker implantation, paravalvular leak, and stroke (and its potential prevention by using anti-embolic protection devices); the appropriate role of TAVR in patients with concomitant cardiac ischemic disease; and durability of bio-prosthetic implanted valves. Finally, the future perspectives for TAVR use and next device developments are discussed.
Diabetes is associated with platelet hyper-reactivity and enhanced risk of thrombosis development. Here we compared protein expression in platelets from healthy donors and diabetic patients to identify differentially expressed proteins and their possible function in platelet activation. Mass spectrometry analyses identified cyclin Y (CCNY) in platelets and its reduced expression in platelets from diabetic patients, a phenomenon that could be attributed to the increased activity of calpains. To determine the role of CCNY in platelets, mice globally lacking the protein were studied. CCNY-/- mice demonstrated lower numbers of circulating platelets but platelet responsiveness to thrombin and a thromboxane A2 analogue were comparable with that of wild-type mice, as was agonist-induced α and dense granule secretion. CCNY-deficient platelets demonstrated enhanced adhesion to fibronectin and collagen as well as an attenuated spreading and clot retraction, indicating an alteration in “outside in” integrin signalling. This phenotype was accompanied by a significant reduction in the agonist-induced tyrosine phosphorylation of β3 integrin. Taken together we have shown that CCNY is present in anucleated platelets where it is involved in the regulation of integrin-mediated outside in signalling associated with thrombin stimulation.
Six dentin adhesives were tested in vitro regarding their cytotoxicity on human fibroblasts. The adhesives Hybrid Bond, One-up Bond F Plus, AdheSE, Clearfil SE Bond, Optibond Solo Plus and Syntac were eluted with culture medium as single or sequentially applied adhesive part for 24 h. 75 Petri dishes were produced per group. They were evaluated triangulated, comprising the quantitative evaluation (105 ones) to determine “viable”, “dead” and “debris” cells with the use of a cell-counter and the reactivity index was also identified based on the qualitative assessment (420 ones). One-up Bond F Plus, AdheSE and Clearfil SE Bond showed a statistical difference of viable cells to the cell control. For One-up Bond F Plus, statistically, differences compared to hybrid bond and Syntac were also found. All the adhesives except One-up Bond F Plus showed significant differences between single and sequentially applied adhesive part regarding the quantitative evaluation. The test material showed a moderate grade of cytotoxicity. As a result, a statistically significant difference of the cytotoxicity between the self-etch and etch-and-rinse adhesives cannot be demonstrated regarding the qualitative evaluation and the reactivity index, but the differences between sequentially applied and single applied components can be proved.
Background: High doses of capsaicin are recommended for the treatment of neuropathic pain. However, low doses evoke mechanical hypersensitivity. Activation of the capsaicin chemosensor transient receptor potential vanilloid 1 (TRPV1) induces neurogenic inflammation. In addition to the release of pro-inflammatory mediators, reactive oxygen species are produced. These highly reactive molecules generate oxidised phospholipids and 4-hydroxynonenal (4-HNE) which then directly activate TRP ankyrin 1 (TRPA1). The apolipoprotein A-I mimetic peptide D-4F neutralises oxidised phospholipids. Here, we asked whether D-4F ameliorates neurogenic hypersensitivity in rodents by targeting reactive oxygen species and 4-HNE in the capsaicin-evoked pain model.
Results: Co-application of D-4F ameliorated capsaicin-induced mechanical hypersensitivity and allodynia as well as persistent heat hypersensitivity measured by Randell–Selitto, von Frey and Hargreaves test, respectively. In addition, mechanical hypersensitivity was blocked after co-injection of D-4F with the reactive oxygen species analogue H2O2 or 4-HNE. In vitro studies on dorsal root ganglion neurons and stably transfected cell lines revealed a TRPA1-dependent inhibition of the calcium influx when agonists were pre-incubated with D-4F. The capsaicin-induced calcium influx in TRPV1-expressing cell lines and dorsal root ganglion neurons sustained in the presence of D-4F.
Conclusions: D-4F is a promising compound to ameliorate TRPA1-dependent hypersensitivity during neurogenic inflammation.
Das PCOS ist die häufigste Endokrinopathie fertiler Frauen, die mit Infertilität und Metabolischem Syndrom ernst zu nehmende und belastende Konsequenzen haben kann. Vor dem Hintergrund einer bis heute teilweise unklaren Ätiopathogenese hat das PCOS umfassende Auswirkungen auf den Metabolismus und die Reproduktion. Aufgrund der phänotypischen Variabilität ist die Festlegung einheitlicher diagnostischer Kriterien ständiges Thema in der PCOS-Forschung. Die Rotterdam-Kriterien gelten aktuell als angemessenste Definition. Die Einführung einer aktuali- sierten Nomenklatur zur Optimierung der Diagnosefindung wird diskutiert. Die Therapie beläuft sich bisher auf symptomatische Ansätze.
Ziel dieser Arbeit war es, erstmals eine Analyse der weltweiten Forschung zum PCOS mittels szientometrischer Parameter durchzuführen. Die Erfassung der Daten aus dem WoS belief sich auf die Jahre 1900 – 2015 und ergab 6.262 Artikel zum Thema PCOS.
Die meisten Publikationen kamen aus den USA an erster, Großbritannien an zweiter und Italien an dritter Stelle. Diese drei Länder erhielten in gleicher Platzierung die meisten Zitierungen und erreichten die höchsten modifizierten h-Indizes. Bei Betrachtung der Zr standen jedoch die Niederlande aufgrund der dort veröffentlichten Rotterdam-Kriterien an erster Stelle. Im Verhältnis zur Einwohnerzahl publizierte Griechenland die meisten Artikel, gefolgt von Finnland und Slowenien. Bei Erstellung eines Quotienten aus Artikelanzahl und BIP lag Serbien vor Griechenland und Slowenien. Bezüglich der Artikel pro BIP p.c. fiel China auf den ersten Rang, danach die Türkei und die USA.
Bei den Fachzeitschriften rangierte das Journal of Clinical Endocrinology & Metabolism bezüglich des IF, der Zr und der Anzahl der Zitierungen an erster Stelle. Fertility & Sterility publizierte über die Zeit die meisten Artikel zum Thema PCOS und erlangte die zweithöchste Zahl an Zitierungen.
Die chronologische Analyse zeigt eine Abnahme der Zuteilung von Artikeln zum Fachgebiet Obstetrics & Gynecology und eine Zunahme von Reproductive Biology, während Endocrinology & Metabolism einen gleichbleibenden Anteil hat. Der Anteil kleinerer Fächer wie Research & Experimental, Nutrition & Dietetics und Pharmacy nimmt über die letzten zehn Jahre zu.
Bezüglich der Anzahl an Institutionen liegen die Türkei und Großbritannien auf Platz zwei und drei hinter den USA. Die produktivsten Forschungseinrichtungen sind die University of London, die Pennsylvania State University und die University of Athens. In der italienischen Forschungsgemeinde finden sich die meisten interinstitutionellen Kooperationen.
Die meisten Artikel, auch in Erst- und Koautorenschaft, hat R.S.Legro publiziert. S. Franks führt die Liste der Seniorautoren an. A. Dunaif erreicht bei Zitierungen, Zitationsrate und modifiziertem h-Index herausragende Werte. Wie schon bei den Institutionen liegen italienische Autoren bei der Kooperationsanalyse vorne. Unter den zehn produktionsstärksten Institutions- kooperationen finden sich mit einer griechischen und einer US-amerikanischen Liaison nur zwei nicht italienischen Ursprungs. Zum Zitierverhalten ist zu sagen, dass fast 50 % der Zitierungen Selbstzitierungen sind.
Generell dominieren Männer noch die Welt der Wissenschaft. Dies ist, in Bezug auf die PCOS-Forschung, zu jedem Zeitpunkt so gewesen und spiegelt sich bis heute in den Analysen wider. Seit 2008 ist allerdings eine Annäherung der Werte zu beobachten.
Es kristallisiert sich die Notwendigkeit einer klaren Definition und aktualisierter Nomenklatur des PCOS heraus, um die leicht stagnierende Forschung des komplexen Krankheitsbildes, dessen Ätiopathogenese nicht zur Gänze erklärt ist, anzustoßen. Überraschenderweise treten Nationen wie die Türkei, Griechenland und der Iran bei den Analysen hervor und reichen mit Produktivität und Resonanz an Staaten wie die USA und Großbritannien heran, übertreffen sie mitunter. Dies ist möglicherweise nationalen Besonderheiten, wie erhöhter Prävalenz des Syndroms bzw. erhöhtem sozialen Druck durch das Kardinalsymptom der Infertilität in diesen Ländern, geschuldet. Eine Dominanz an weiblichen Forscherinnen zeigt sich überdies im Iran und ist sonst in nur wenigen Ländern, darunter die USA, zu finden. Männliche Vorherrschaft ist also weniger an bestimmte Regionen, als vielmehr an nationale Strukturen gebunden.
Datenschutz versus Katastrophenschutz : Standortdaten als Mittel zur Bekämpfung der Corona-Pandemie
(2020)
Einige Länder setzen Standortdaten jetzt schon gezielt ein, um die weitere Ausbreitung von Covid-19 einzudämmen. Ein Gesetzentwurf von Bundesgesundheitsminister Jens Spahn, der weitreichende Befugnisse vorsah, um mithilfe von Standortdaten Kontaktpersonen von Infizierten über deren Handys zu orten, stieß auf teilweise heftige Kritik. Der Gesetzentwurf wurde daraufhin zurückgezogen, ohne dass nähere Einzelheiten an die Öffentlichkeit gelangt sind. Ein genauer Blick zeigt jedoch, dass eine Verarbeitung von Standortgesundheitsdaten nicht nur tatsächlich nützlich sein kann, sondern auch rechtlich möglich ist.