RepoMed (Medizinische Hochschule Hannover)
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Alterations of Striato-Thalamic Metabolism in Normal Aging Human Brain-An MR Metabolic Imaging Study.
No full textAging effects on striato-thalamic metabolism in healthy human brains were studied in vivo using short-TE whole brain 1H-MR spectroscopic imaging (wbMRSI) on eighty healthy subjects aged evenly between 20 to 70 years at 3T. Relative concentrations of N-acetyl-aspartate (NAA), choline, total creatine (tCr), myo-inositol (mI), glutamate, and glutamine in bilateral caudate nucleus, putamen, pallidum, and thalamus were determined using signal normalization relative to brain tissue water. Linear regression analysis was used to analyze the age-dependence of the metabolite concentrations. The metabolite concentrations revealed spatial inhomogeneity across brain regions and metabolites. With age, NAA decreased significantly in bilateral caudate nucleus and putamen, left pallidum, and left thalamus, tCr decreased in left putamen and bilateral pallidum, mI increased in bilateral caudate nucleus and right thalamus, and spectral linewidth increased in left putamen and right thalamus. In conclusion, normal aging of striato-thalamic metabolism in healthy human is associated with regional specific decreases of NAA and tCr and increases of mI, which may reflect the individual role of each brain structure within brain functionality
Low Diagnostic Value of Synovial Aspiration Culture Prior to Reimplantation in Periprosthetic Joint Infection.
No full textBackground/aim We aimed to determine the diagnostic value of the synovial aspiration culture prior to reimplantation in two- (or more) stage exchange of periprosthetic joint infection. Patients and methods This was a retrospective study, spanning over ten years including all synovial cultures of patients with two- (or more) stage exchange due to periprosthetic joint infection. Results A total of 183 patients were included, mean age was 66.6 years (range=12.8-93.4 years). Overall sensitivity of synovial aspiration cultures before reimplantation was 56.6%, specificity 84.6%, negative predictive value (NPV) 63.8%, positive predictive value (PPV) 80.2%, area under the curve (AUC) 70.6%. Sensitivity of the knee in comparison to the hip culture was significantly higher, as well as the NPV and the AUC (p=0.038). In case of complete removal of prosthesis, the sensitivity and AUC were significantly reduced, whereas the specificity was comparable with prosthesis in situ, partial removal or complete removal. Conclusion Due to the low sensitivity, obtaining several synovial cultures in the prosthesis-free interval to exclude persistence of infection, does not seem reasonable
Measurements of the local evoked potential from the cochlear nucleus in patients with an auditory brainstem implant and its implication to auditory perception and audio processor programming
No full textThe measurement of the electrically evoked compound action potential (ECAP) in cochlear implant (CI) patients is widely used to provide evidence of a functioning electrode-nerve interface, to confirm proper location of the electrode array and to program the sound processor. In patients with an auditory brainstem implant (ABI), a likewise versatile measurement would be desirable. The ECAP measurement paradigm "Alternating Polarity" was utilized to record responses via the implanted ABI electrode array placed on the cochlear nucleus. Emphasizing on the different location of stimulation and recording, these responses are called local evoked potentials (LEP). LEP measurements were conducted during the clinical routine in 16 ABI patients (12 children and 4 adults), corresponding to 191 electrode contacts. A retrospective analysis of these data revealed, that LEP responses were observed in 64.9% of all measured electrode contacts. LEP responses predicted auditory perception with a sensitivity of 90.5%. False-positive rate was 33.7%. Objective LEP thresholds were highly significantly (p < 0.001) correlated both to behavioral thresholds (Pearson's r = 0.697) and behavioral most comfortable levels (r = 0.840). Therefore, LEP measurements have the potential to support fitting in ABI patients
Spider Silk-Augmented Scaffolds and Adipose-Derived Stromal Cells Loaded with Uniaxial Cyclic Strain: first Investigations of a Novel Approach for Tendon-Like Constructs
No full textAbstract Tendon injuries still pose a challenge to reconstructive surgeons. Tendon tissue is a bradytrophic tissue and has a poor tendency to heal. Autologous tendon grafts are, therefore, still the gold standard in restorative operations but are associated with significant donor side morbidity. The experimental approach of the present study focused on the use of the biomaterial spider silk as a biocompatible and very stable carrier matrix in combination with a collagen type I hydrogel and adipose-derived stromal cells. The constructs were differentiated by axial strain to tendon-like tissue using a custom-made bioreactor. Macroscopically, tendon-like tissue could be detected which histologically showed high cell vitality even in long-term cultivation. In addition, cell morphology comparable to tenocytes could be detected in the bioreactor-stimulated tendon-like constructs compared to the controls. Immunohistochemically, tendon tissue-specific markers could be detected. Therefore, the developed tendon-like construct represents a promising approach towards patient specific tendon reconstruction, but further studies are needed. Full article (This article belongs to the Section Applied Biosciences and Bioengineering
Functional and Molecular Properties of DYT-SGCE Myoclonus-Dystonia Patient-Derived Striatal Medium Spiny Neurons.
No full textMyoclonus-dystonia (DYT-SGCE, formerly DYT11) is characterized by alcohol-sensitive, myoclonic-like appearance of fast dystonic movements. It is caused by mutations in the SGCE gene encoding ε-sarcoglycan leading to a dysfunction of this transmembrane protein, alterations in the cerebello-thalamic pathway and impaired striatal plasticity. To elucidate underlying pathogenic mechanisms, we investigated induced pluripotent stem cell (iPSC)-derived striatal medium spiny neurons (MSNs) from two myoclonus-dystonia patients carrying a heterozygous mutation in the SGCE gene (c.298T>G and c.304C>T with protein changes W100G and R102X) in comparison to two matched healthy control lines. Calcium imaging showed significantly elevated basal intracellular Ca2+ content and lower frequency of spontaneous Ca2+ signals in SGCE MSNs. Blocking of voltage-gated Ca2+ channels by verapamil was less efficient in suppressing KCl-induced Ca2+ peaks of SGCE MSNs. Ca2+ amplitudes upon glycine and acetylcholine applications were increased in SGCE MSNs, but not after GABA or glutamate applications. Expression of voltage-gated Ca2+ channels and most ionotropic receptor subunits was not altered. SGCE MSNs showed significantly reduced GABAergic synaptic density. Whole-cell patch-clamp recordings displayed elevated amplitudes of miniature postsynaptic currents and action potentials in SGCE MSNs. Our data contribute to a better understanding of the pathophysiology and the development of novel therapeutic strategies for myoclonus-dystonia
Correlation of Electrically Evoked Compound Action Potential Amplitude Growth Function Slope and Anamnestic Parameters in Cochlear Implant Patients-Identification of Predictors for the Neuronal Health Status.
No full textCochlear implants (CI) are the treatment of choice in profoundly deaf patients. Measuring the electrically evoked compound action potential (ECAP) has become an important tool for verifying the function of the spiral ganglion neurons (SGN), which are the target cells of the CI stimulation. ECAP measurement is only possible after electrode insertion. No information about the neuronal health status is available before cochlear implantation. We investigated possible correlations between the ECAP amplitude growth function (AGF) slope and anamnestic parameters to identify possible predictors for SGN health status and therefore for CI outcome. The study included patients being implanted with various electrode array lengths. Correlation analysis was performed for the mean AGF slope of the whole array, for separate electrodes as well as for grouped electrodes of the apical, medial, and basal region, with duration of deafness, age at implantation, residual hearing (grouped for electrode length), and etiology. The mean ECAP AGF slopes decreased from apical to basal. They were not correlated to the length of the electrode array or any etiology. For the mean of the full array or when grouped for the apical, middle, and basal part, the ECAP AGF slope was negatively correlated to the duration of hearing loss and the age at implantation. Since a significant negative correlation of the ECAP AGF slope and age at cochlear implantation and duration of deafness was observed, this study supports the statement that early implantation of a CI is recommended for sensorineural hearing loss. Additional factors such as the cochlear coverage and insertion angle influence the ECAP AGF slope and performance of the patient and should be included in future multifactorial analysis to study predictive parameters for the CI outcome
Protocol for a scoping review to identify and map in-service education and training materials for midwifery care in sub-Saharan Africa from 2000 to 2020.
No full textIntroduction Maternal and neonatal mortality are disproportionally high in low-and middle-income countries. In 2017 the global maternal mortality ratio was estimated to be 211 per 100 000 live births. An estimated 66% of these deaths occurred in sub-Saharan Africa. Training programmes that aim to prepare providers of midwifery care vary considerably across sub-Saharan Africa in terms of length, content and quality. To overcome the shortfalls of pre-service training and support the provision of quality care, in-service training packages for providers of midwifery care have been developed and implemented in many countries in sub-Saharan Africa. We aim to identify what in-service education and training materials have been used for providers of midwifery care between 2000 and 2020 and map their content to the International Confederation of Midwives' Essential Competencies for Midwifery Practice (ICM Competencies), and the Lancet Midwifery Series Quality Maternal and Newborn Care (QMNC) framework. Methods and analysis A search will be conducted for the years 2000-2020 in Cumulative Index of Nursing and Allied Health Literature, PubMed/MEDLINE, Social Sciences Citation Index, African Index Medicus and Google Scholar. A manual search of reference lists from identified studies and a hand search of literature from international partner organisations will be performed. Information retrieved will include study context, providers trained, focus of training and design of training. Original content of identified education and training materials will be obtained and mapped to the ICM Competencies and the Lancet Series QMNC. Ethics and dissemination A scoping review is a secondary analysis of published literature and does not require ethical approval. This scoping review will give an overview of the education and training materials used for in-service training for providers of midwifery care in sub-Saharan Africa. Mapping the content of these education and training materials to the ICM Competencies and The Lancet Series QMNC will allow us to assess their appropriateness. Findings from the review will be reflected to stakeholders involved in the design and implementation of such materials. Additionally, findings will be published in a peer-reviewed journal, and used to inform the design and content of an in-service training package for providers of midwifery care as part of the Action Leveraging Evidence to Reduce perinatal morTality and morbidity (ALERT) study, (https://alert.ki.se/) a multi-country study in Benin, Malawi, Tanzania and Uganda. Trial registration number PACTR202006793783148; Post-results
Pattern-mixture model in network meta-analysis of binary missing outcome data: one-stage or two-stage approach?
Get PDFBackground Trials with binary outcomes can be synthesised using within-trial exact likelihood or approximate normal likelihood in one-stage or two-stage approaches, respectively. The performance of the one-stage and the two-stage approaches has been documented extensively in the literature. However, little is known about how these approaches behave in the presence of missing outcome data (MOD), which are ubiquitous in clinical trials. In this work, we compare the one-stage versus two-stage approach via a pattern-mixture model in the network meta-analysis using Bayesian methods to handle MOD appropriately. Methods We used 29 published networks to empirically compare the two approaches concerning the relative treatment effects of several competing interventions and the between-trial variance (τ2), while considering the extent and level of balance of MOD in the included trials. We additionally conducted a simulation study to compare the competing approaches regarding the bias and width of the 95% credible interval of the (summary) log odds ratios (OR) and τ2 in the presence of moderate and large MOD. Results The empirical study did not reveal any systematic bias between the compared approaches regarding the log OR, but showed systematically larger uncertainty around the log OR under the one-stage approach for networks with at least one small trial or low event risk and moderate MOD. For these networks, the simulation study revealed that the bias in log OR for comparisons with the reference intervention in the network was relatively higher in the two-stage approach. Contrariwise, the bias in log OR for the remaining comparisons was relatively higher in the one-stage approach. Overall, bias increased for large MOD. For these networks, the empirical results revealed slightly higher τ2 estimates under the one-stage approach irrespective of the extent of MOD. The one-stage approach also led to less precise log OR and τ2 when compared with the two-stage approach for large MOD. Conclusions Due to considerable bias in the log ORs overall, especially for large MOD, none of the competing approaches was superior. Until a more competent model is developed, the researchers may prefer the one-stage approach to handle MOD, while acknowledging its limitations
Cognitive Performance of Patients with Adult 5q-Spinal Muscular Atrophy and with Amyotrophic Lateral Sclerosis.
Get PDFMotor neuron diseases, such as spinal muscular atrophy (SMA) and amyotrophic lateral sclerosis (ALS), share several clinical similarities while differing substantially in etiology, disease onset and progression. Cognitive dysfunction, a clinically relevant non-motor feature in a substantial proportion of ALS patients, has been less frequently investigated in SMA. In this prospective multicenter cross-sectional study, cognitive function was assessed by the Edinburgh Cognitive (and Behavioural) ALS Screen (ECAS) and a German vocabulary test (Wortschatztest, WST) in 34 adult patients with SMA types 2-4 and in 34 patients with ALS. Demographic and clinical parameters were assessed to identify factors that potentially influence cognitive function. While SMA and ALS patients were comparable in the vocabulary test, on average, SMA patients performed better than ALS patients in the cognitive domains of memory, language and executive function. Better cognitive abilities in SMA patients seemed to be related to the early onset, rather than the extent or the duration, of their physical handicap. Future studies should focus on disease-specific cognitive functions in SMA
A Revised Framework to Evaluate the Consistency Assumption Globally in a Network of Interventions.
No full textBackground The unrelated mean effects (UME) model has been proposed for evaluating the consistency assumption globally in the network of interventions. However, the UME model does not accommodate multiarm trials properly and omits comparisons between nonbaseline interventions in the multiarm trials not investigated in 2-arm trials. Methods We proposed a refinement of the UME model that tackles the limitations mentioned above. We also accompanied the scatterplots on the posterior mean deviance contributions of the trial arms under the network meta-analysis (NMA) and UME models with Bland-Altman plots to detect outlying trials contributing to poor model fit. We applied the refined and original UME models to 2 networks with multiarm trials. Results The original UME model omitted more than 20% of the observed comparisons in both networks. The thorough inspection of the individual data points' deviance contribution using complementary plots in conjunction with the measures of model fit and the estimated between-trial variance indicated that the refined and original UME models revealed possible inconsistency in both examples. Conclusions The refined UME model allows proper accommodation of the multiarm trials and visualization of all observed evidence in complex networks of interventions. Furthermore, considering several complementary plots to investigate deviance helps draw informed conclusions on the possibility of global inconsistency in the network. Highlights We have refined the unrelated mean effects (UME) model to incorporate multiarm trials properly and to estimate all observed comparisons in complex networks of interventions.Forest plots with posterior summaries of all observed comparisons under the network meta-analysis and refined UME model can uncover the consequences of potential inconsistency in the network.Using complementary plots to investigate the individual data points' deviance contribution in conjunction with model fit measures and estimated heterogeneity aid in detecting possible inconsistency