A Helminth-Derived Chitinase Structurally Similar to Mammalian Chitinase Displays Immunomodulatory Properties in Inflammatory Lung Disease.

Immunomodulation of airway hyperreactivity by excretory-secretory (ES) products of the first larval stage (L1) of the gastrointestinal nematode Trichuris suis is reported by us and others. Here, we aimed to identify the proteins accounting for the modulatory effects of the T. suis L1 ES proteins and studied six selected T. suis L1 proteins for their immunomodulatory efficacy in a murine OVA-induced allergic airway disease model. In particular, an enzymatically active T. suis chitinase mediated amelioration of clinical signs of airway hyperreactivity, primarily associated with suppression of eosinophil recruitment into the lung, the associated chemokines, and increased numbers of RELMα + interstitial lung macrophages. While there is no indication of T. suis chitinase directly interfering with dendritic cell activation or antigen presentation to CD4 T cells, treatment of allergic mice with the worm chitinase influenced the hosts' own chitinase activity in the inflamed lung. The three-dimensional structure of the T. suis chitinase as determined by high-resolution X-ray crystallography revealed high similarities to mouse acidic mammalian chitinase (AMCase) but a unique ability of T. suis chitinase to form dimers. Our data indicate that the structural similarities between the parasite and host chitinase contribute to the disease-ameliorating effect of the helminth-derived chitinase on allergic lung inflammation.

[Development and implementation of an operational concept in a university eye hospital in the SARS-CoV-2 pandemic]. / Entwicklung und Implementierung eines Betriebskonzeptes in einer Universitätsaugenklinik im Rahmen der SARS-CoV-2-Pandemie.

The SARS-CoV­2 pandemic poses major challenges for the entire medical care system. Especially in maximum care clinical facilities, a higher exposure to potentially infectious patients or positively tested COVID-19 patients is to be expected. A hospital facility concept was developed in the Department of Ophthalmology, Goethe University, Frankfurt am Main, Germany with the aim of achieving maximum patient safety with maximum employee protection. The current infection control hygiene recommendations of the Robert Koch Institute (RKI), the leading specialist association, were taken into consideration along with the existing hospital hygiene plan of the University Hospital Frankfurt am Main. Incorporated into the developmental process were the Institute for Medical Microbiology and Hospital Hygiene, the occupational medical service department and the board of the University Hospital Frankfurt am Main. The operational concept with individualized measures ensures that (i) the care of outpatients; (ii) the performance of outpatient operations; (iii) and the care of admitted patients and patients undergoing surgery are also guaranteed during the COVID-19 pandemic. All measures have been documented in writing in the clinic's internal quality manual and are thus accessible to all employees. The concept is regularly checked for functionality, so-called stress tests and hygiene inspections are carried out and improvements are made as necessary.

Fear-potentiated startle processing in humans: Parallel fMRI and orbicularis EMG assessment during cue conditioning and extinction.

Studying neural networks and behavioral indices such as potentiated startle responses during fear conditioning has a long tradition in both animal and human research. However, most of the studies in humans do not link startle potentiation and neural activity during fear acquisition and extinction. Therefore, we examined startle blink responses measured with electromyography (EMG) and brain activity measured with functional MRI simultaneously during differential conditioning. Furthermore, we combined these behavioral fear indices with brain network activity by analyzing the brain activity evoked by the startle probe stimulus presented during conditioned visual threat and safety cues as well as in the absence of visual stimulation. In line with previous research, we found a fear-induced potentiation of the startle blink responses when elicited during a conditioned threat stimulus and a rapid decline of amygdala activity after an initial differentiation of threat and safety cues in early acquisition trials. Increased activation during processing of threat cues was also found in the anterior insula, the anterior cingulate cortex (ACC), and the periaqueductal gray (PAG). More importantly, our results depict an increase of brain activity to probes presented during threatening in comparison to safety cues indicating an involvement of the anterior insula, the ACC, the thalamus, and the PAG in fear-potentiated startle processing during early extinction trials. Our study underlines that parallel assessment of fear-potentiated startle in fMRI paradigms can provide a helpful method to investigate common and distinct processing pathways in humans and animals and, thus, contributes to translational research.

Genetic influences on the acquisition and inhibition of fear.

As a variant of the Pavlovian fear conditioning paradigm the conditional discrimination design allows for a detailed investigation of fear acquisition and fear inhibition. Measuring fear-potentiated startle responses, we investigated the influence of two genetic polymorphisms (5-HTTLPR and COMT Val(158)Met) on fear acquisition and fear inhibition which are considered to be critical mechanisms for the etiology and maintenance of anxiety disorders. 5-HTTLPR s-allele carriers showed a more stable potentiation of the startle response during fear acquisition. Homozygous COMT Met-allele carriers, which had demonstrated delayed extinction in previous investigations, show deficient fear inhibition in presence of a learned safety signal. Thus, our results provide further evidence that 5-HTTLPR and COMT Val(158)Met genotypes influence the vulnerability for the development of anxiety disorders via different mechanisms.

Clinical functional MRI of the language domain in children with epilepsy.

Functional MRI (fMRI) for the assessment of language functions is increasingly used in the diagnostic workup of patients with epilepsy. Termed "clinical fMRI," such an approach is also feasible in children who may display specific patterns of language reorganization. This study was aimed at assessing language reorganization in pediatric epilepsy patients, using fMRI. We studied 26 pediatric epilepsy patients (median age, 13.05 years; range, 5.6-18.7 years) and 23 healthy control children (median age, 9.37 years; range, 6.2-15.4 years), using two child-friendly fMRI tasks and adapted data-processing streams. Overall, 81 functional series could be analyzed. Reorganization seemed to occur primarily in homotopic regions in the contralateral hemisphere, but lateralization in the frontal as well as in the temporal lobes was significantly different between patients and controls. The likelihood to find atypical language organization was significantly higher in patients. Additionally, we found significantly stronger activation in the healthy controls in a primarily passive task, suggesting a systematic confounding influence of antiepileptic medication. The presence of a focal cortical dysplasia was significantly associated with atypical language lateralization. We conclude that important confounds need to be considered and that the pattern of language reorganization may be distinct from the patterns seen in later-onset epilepsy.

Why one task is not enough: functional MRI for atypical language organization in two children.

Functional MRI is increasingly used to determine the hemispheric dominance for language. This is especially relevant in children who may not be able to comply with the high demands of a Wada test. We here report on two children in which the full extent of language reorganization was only determined when two fMRI tasks were analyzed; in the first case, the results from the second task corroborated the shifted hemispheric dominance seen in the first task. In the second case, the second task showed an opposite hemispheric dominance, suggesting a hemispheric dissociation of language functions. These cases underline the necessity to use more than one fMRI task for the determination of hemispheric dominance, whenever possible. This is particularly relevant in children as unusual patterns of reorganization may be more likely.