Consecutive Eyeball Pressure Tests Reflect Clinically Relevant Vagal Dysfunction and Recovery in a Patient With Guillain-Barré-Syndrome With Tenacious Cardiac Dysautonomia

Cardiac dysautonomia is a potentially life-threatening complication of Guillain-Barré syndrome (GBS). Proper and prompt recognition of patients at risk and subsequent intensive care unit (ICU) monitoring are mandatory to prevent fatal outcome. Eyeball pressure testing (EP) has been suggested as an easy applicable bedside test for vagal overreactivity in GBS and thus identifying patients at risk. Yet, there is only sparse follow-up data concerning the course of EP findings in GBS. We report a 25 years-old male patient with GBS who underwent consecutive EP (n = 11) during his ICU stay over a period of 11 weeks. The series of tests performed in this patient (and corresponding clinical events) show that EP data might represent an approximation of vagal dysfunction and vagal recovery in GBS. Interestingly, we observed a much longer duration of pathological EP compared to a previous report. The tenacious cardiac dysautonomia in this patient necessitated long-term application of a transvenous temporary pacemaker

Unusual multisystemic involvement and a novel BAG3 mutation revealed by NGS screening in a large cohort of myofibrillar myopathies

Myofibrillar myopathies (MFM) are a group of phenotypically and genetically heterogeneous neuromuscular disorders, which are characterized by protein aggregations in muscle fibres and can be associated with multisystemic involvement.Methods We screened a large cohort of 38 index patients with MFM for mutations in the nine thus far known causative genes using Sanger and next generation sequencing (NGS). We studied the clinical and histopathological characteristics in 38 index patients and five additional relatives (n = 43) and particularly focused on the associated multisystemic symptoms.Results We identified 14 heterozygous mutations (diagnostic yield of 37%), among them the novel p.Pro209Gln mutation in the BAG3 gene, which was associated with onset in adulthood, a mild phenotype and an axonal sensorimotor polyneuropathy, in the absence of giant axons at the nerve biopsy. We revealed several novel clinical phenotypes and unusual multisystemic presentations with previously described mutations: hearing impairment with a FLNC mutation, dysphonia with a mutation in DES and the first patient with a FLNC mutation presenting respiratory insufficiency as the initial symptom. Moreover, we described for the first time respiratory insufficiency occurring in a patient with the p.Gly154Ser mutation in CRYAB. Interestingly, we detected a polyneuropathy in 28% of the MFM patients, including a BAG3 and a MYOT case, and hearing impairment in 13%, including one patient with a FLNC mutation and two with mutations in the DES gene. In four index patients with a mutation in one of the MFM genes, typical histological findings were only identified at the ultrastructural level (29%).Conclusions We conclude that extraskeletal symptoms frequently occur in MFM, particularly cardiac and respiratory involvement, polyneuropathy and/or deafness. BAG3 mutations should be considered even in cases with a mild phenotype or an adult onset. We identified a genetic defect in one of the known genes in less than half of the MFM patients, indicating that more causative genes are still to be found. Next generation sequencing techniques should be helpful in achieving this aim

New design tools for lightweight aerospace structures

This paper presents two new design tools for lightweight aerospace structures. The first tool is the Tailored Fibre Placement (TFP) design tool TACO. It is used to optimize the fibre orientations of structures made of Carbon Fibre Reinforcement Plastics (CFRP). The optimization concept is explained and results are given for a horizontal tail plane connection beam of an aircraft. The second tool, iBuck, is a fast, semi-analytical local buckling and post-buckling tool for stiffened panels that are loaded in-plane. The panels are assumed to be representative for an aircraft fuselage and are stiffened in axial and circumferential direction. Results are presented for axially loaded panels and compared to FE-results

Lokaler Arbeitsmarkt beeinflusst die Berufschancen von Geflüchteten

Bürmann M, Tsolak D, Goebel J, Kühne S. Lokaler Arbeitsmarkt beeinflusst die Berufschancen von Geflüchteten. DIW Wochenbericht. Vol 30/31. Berlin: Deutsches Institut für Wirtschaftsforschung (DIW); 2023

Closing the cohesin ring: structure and function of its Smc3-kleisin interface

Through their association with a kleisin subunit (Scc1), cohesin’s Smc1 and Smc3 subunits are thought to form tripartite rings that mediate sister chromatid cohesion. Unlike the structure of Smc1/Smc3 and Smc1/Scc1 interfaces, that of Smc3/Scc1 is not known. Disconnection of this interface is thought to release cohesin from chromosomes in a process regulated by acetylation. We show here that the N-terminal domain of yeast Scc1 contains two a helices, forming a four-helix bundle with the coiled coil emerging from Smc3’s adenosine triphosphatase head. Mutations affecting this interaction compromise cohesin’s association with chromosomes. The interface is far from Smc3 residues, whose acetylation prevents cohesin’s dissociation from chromosomes. Cohesin complexes holding chromatids together in vivo do indeed have the configuration of hetero-trimeric rings, and sister DNAs are entrapped within these

Closing the cohesin ring: structure and function of its Smc3-kleisin interface

Through their association with a kleisin subunit (Scc1), cohesin’s Smc1 and Smc3 subunits are thought to form tripartite rings that mediate sister chromatid cohesion. Unlike the structure of Smc1/Smc3 and Smc1/Scc1 interfaces, that of Smc3/Scc1 is not known. Disconnection of this interface is thought to release cohesin from chromosomes in a process regulated by acetylation. We show here that the N-terminal domain of yeast Scc1 contains two a helices, forming a four-helix bundle with the coiled coil emerging from Smc3’s adenosine triphosphatase head. Mutations affecting this interaction compromise cohesin’s association with chromosomes. The interface is far from Smc3 residues, whose acetylation prevents cohesin’s dissociation from chromosomes. Cohesin complexes holding chromatids together in vivo do indeed have the configuration of hetero-trimeric rings, and sister DNAs are entrapped within these

Inductively powered implant for monitoring and application of telemetric metronomic photodynamic therapy

Photodynamic therapy (PDT) is a promising treatment for numerous kinds of cancer. A potential advantage of PDT compared to other cancer treatments like radiotherapy and chemotherapy is its selectivity. PDT is based on a photosensitive substance that is administered to a patient. The substance has selective uptake by cancerous tissue and when illuminated with a certain wavelength it destroys the tissue in close proximity. Metronomic PDT is a new proposed technique for treating patients with cancer. For this technique a new kind of light source is needed. The purpose of this thesis is to develop the light source needed for this technique. This light source also needs to monitor the treatment and should be controlled and powered from the outside. An optode chip has been developed which carries one or two LEDs used as light source and up to four photodiodes. The photodiodes were designed after Monte Carlo simulations to get an indication of the amount of incident light. The readout of the photodiodes consists of a transimpedance amplifier and an A/D converter. The LED is driven with pulse width modulation to adjust intensity. The communication is implemented with a Radio Frequency Identification technique. The power for the implant is provided by an inductive power link that was designed for low power dissipation in the coil. The power is buffered in a capacitor in case the coupling of the two coils is lost. It also allows the field to be switched off during measurement. The whole implant is controlled with a microcontroller, which has PWM and A/D conversion on chip. The several devices are soldered on a flexible printed circuit board. The flexible PCB was shaped in such a way that the coils for communication and power could be big enough to get a reasonable coupling and was designed for an animal model. The big part is placed on the shoulders of the rat, the optode is attached to the head of the rat. The electronic components are encapsulated with medical grade silicone. The optode chip is mounted with bond wires on the flexible circuit board and is encapsulated with a biocompatible polymer. The main function of the implant, illuminate a specific volume with a specific wavelength, was successfully implanted. The fluence rate monitoring and temperature monitoring were also successfully implemented. The monitoring of the amount of photosensitizer and oxygen was not implemented but experiments can be done with the current optode chip. The total system has been successfully tested outside the animal. The first animal test is planned in the near future. In the future the whole system needs to be developed further, the several discrete components on the implant need to be implemented on chip. A system with multiple optodes needs to be developed.Electrical Engineering, Mathematics and Computer Scienc