Treatment of Cognitive Deficits and Behavioral Symptoms Following COVID-19-Associated Autoimmune Encephalitis With Intravenous Immunoglobulin: A Case Report and Review of the Literature.

Coronavirus disease 2019 (COVID-19) is associated with long-term neuropsychiatric sequelae. We describe a 60-year-old male patient's history and symptom trajectory encompassing the development of behavioral symptoms and cognitive deficits following pneumonia and subsequent autoimmune encephalitis associated with COVID-19. We also describe changes in these facets with correlative changes in his immunological parameters after both acute intravenous immunoglobulin (IVIG) therapy and chronic periodic IVIG therapy every two weeks over the course of two years. ​​​​​​We review the literature on the treatment of long COVID-19 symptoms spanning cognitive and behavioral domains. In addition, we also elucidate current literature on the role of IVIG infusions for these symptoms using our patient's presentation and improvement in symptoms as an illustrative example.

Catheter ablation of intramural outflow tract premature ventricular complexes: a multicentre study.

AIMS: Ablation of outflow tract ventricular arrhythmias may be limited by a deep intramural location of the arrhythmogenic source. This study evaluates the acute and long-term outcomes of patients undergoing ablation of intramural outflow tract premature ventricular complexes (PVCs). METHODS AND RESULTS: This multicenter series included patients with structurally normal heart or nonischemic cardiomyopathy and intramural outflow tract PVCs defined by: (a) ≥ 2 of the following criteria: (1) earliest endocardial or epicardial activation < 20ms pre-QRS; (2) Similar activation in different chambers; (3) no/transient PVC suppression with ablation at earliest endocardial/epicardial site; or (b) earliest ventricular activation recorded in a septal coronary vein. Ninety-two patients were included, with a mean PVC burden of 21.5±10.9%. Twenty-six patients had had previous ablations. All PVCs had inferior axis, with LBBB pattern in 68%. In 29 patients (32%) direct mapping of the intramural septum was performed using an insulated wire or multielectrode catheter, and in 13 of these cases the earliest activation was recorded within a septal vein. Most patients required special ablation techniques (one or more), including sequential unipolar ablation in 73%, low-ionic irrigation in 26%, bipolar ablation in 15% and ethanol ablation in 1%. Acute PVC suppression was achieved in 75% of patients. Following the procedure, the PVC burden was reduced to 5.8±8.4%. The mean follow-up was 15±14 months and 16 patients underwent a repeat ablation. CONCLUSION: Ablation of intramural PVCs is challenging; acute arrhythmia elimination is achieved in 3/4 patients, and non-conventional approaches are often necessary for success.

Noise and Critical Sound Levels During Non-Invasive Ventilation of a Preterm Infant in the Incubator.

BACKGROUND: Preterm birth and the subsequent necessary treatment in neonatal intensive care units (NICU) subjects the preterm infant to non-physiological noise exposure with potentially adverse consequences for short- and long-term development. Adjusters to improve the acoustic environment for the preterm infant need to be defined. METHODS: Sound pressure level measurements during routine procedures in a NICU were performed by »" microphones placed inside and outside the incubator. The microphones need to be suitably positioned to measure sound pressure levels that are representative for the sound field inside and outside the incubator. The sound pressure level spectra generated by respiratory support and corresponding monitor alarms were compared. RESULTS: Inside the incubator, higher sound level pressures (in dBA) were generated primarily by the use of the system components of the incubator itself than outside, whereas when the incubator was closed, it had an insulating effect on sounds generated in the NICU. Non-invasive ventilation resulted in an increase in sound pressure levels from 50 to 60 dBA in the neonate's environment, with sound pressure levels increasing particularly in the frequency range above 1 kHz. CONCLUSION: Preterm infants are exposed to high sound levels, especially in the non-physiological high-frequency range, particularly during non-invasive ventilation. The continuous sound exposure could be further reduced to some extent by an optimized design of the incubator.

Phototherapeutic Keratectomy for Salzmann's Nodular Degeneration. What Effect Does the Choice of Excimer Laser Have on Treatment Success? / Phototherapeutische Keratektomie bei Salzmannʼscher nodulärer Degeneration. Welche Auswirkung hat die Wahl des Excimerlasers auf den Erfolg der Behandlung?

PURPOSE: The aim of this study was to assess the difference in treatment success after phototherapeutic keratectomy (PTK) for Salzmann's nodular degeneration (SND) using two excimer lasers with different specifications. PATIENTS AND METHODS: 272 PTK procedures, which had been performed on 246 eyes with SND from 181 patients, were retrospectively examined in the period from 2007 to 2017. Until 2014 the excimer laser MEL70 (Carl Zeiss Meditec Vertriebsgesellschaft mbH, Oberkochen, Germany) was used for PTK following manual pannectomy, and after 2014 the excimer laser Amaris 750S (Schwind eye-tech-solutions GmbH, Kleinostheim, Germany) was used. Treatment success was assessed on basis of visual acuity, refraction, and astigmatism, as well as pachymetry and endothelial cell count, recorded at the following time points: T1 = preoperative, T2 = 6-week follow-up, T3 = 6-month follow-up. The Wilcoxon-Mann-Whitney U test and the chi-square test with a significance level of 5% were used to compare the data. RESULTS: A significantly higher improvement of 0.17 ± 0.33 logMAR could be shown for visual acuity in the Schwind group (p < 0.013) after 6 months. In the Zeiss group, visual acuity improved by only 0.11 ± 0.36 (logMAR p < 0.057). Regarding refraction, a significant reduction of the spherical equivalent (SEQ) (p < 0.001) by 3.35 ± 2.76 diopters (D) after 6 months could only be shown for the Schwind group. SEQ did not change significantly in the Zeiss group (p < 0.676). The topographic astigmatism was significantly improved after 6 months in both study groups, by 1.73 ± 1.99 D in the Schwind group (p < 0.001) and by 1.99 ± 2.21 D in the Zeiss group (p < 0.0001). Haze had to be treated in 12.7% of the cases in the Schwind group and in 16.2% of the cases in the Zeiss group. No endothelial cell damage was found in either group. CONCLUSIONS: In both study groups, the patients with SND clearly benefited from PTK. However, a significantly higher advantage for visual acuity and refraction was shown for the Schwind group compared with the Zeiss group. In contrast to the usual hyperopic effect of PTK in other diagnoses, PTK in SND showed a "myopic shift", which can be explained by the often midperipheral SND nodes and the associated asymmetric tear film pooling prior to surgery.

Factors Associated with Return to Work After Heart Transplantation: A Systematic Review of the Literature.

BACKGROUND: Heart transplantation represents one of the last treatment options for advanced heart failure. Little is known about the factors associated with return to work in patients after heart transplantation. The aim of this study was to identify those factors. METHODS: A systematic literature review was conducted in the PubMed, LILACS, SCIELO and ScienceDirect databases using the keywords "trasplante cardiaco", "calidad de vida", "reingreso laboral", "return to work", "heart transplantation" and "occupation related". Quantitative studies with patients over 18 years of age that were published between January 2007 and June 2017 were included. RESULTS: A total of 6 articles were included, none from Latin America. Heart transplantation patients had a mean age of 51 years; approximately 17% were over 65 years of age; 73-84% were males; 7-16.4% were professionals; 70-86.6% were previously employed; and 30-60% returned to work. The following factors were related to return to work: higher education (p = 0.0017), young age (p = 0.003), better scores on the physical and mental domains of the SF-36 questionnaire (p = 0.035), higher six-minute walk test results (median of 560 m), and previous employment with less than 24 months interrupted by the inability to work (p = 0.017). Return to work occurred, on average, 6 to 7.5 months after heart transplantation. CONCLUSIONS: Return to work after heart transplantation is variable, with a tendency to be low, and is lower in patients near to retirement age. Protective factors were related to the social, physical and mental environment.

Explainable machine learning determines effects on the sound absorption coefficient measured in the impedance tube.

Measurements of acoustic properties of sound absorbing materials in impedance tubes show poor reproducibility, which was demonstrated in round robin tests. The impedance tube measurements are standardized but lack precise definitions of the actual measurement setup, specimen preparation, and other factors that introduce uncertainty in practice. In this paper, machine learning models identify those factors that mostly affect the sound absorption coefficient from a large data set of more than 3000 absorption spectra measured in one impedance tube. The specimens are manufactured from one polyurethane foam, and different cutting technologies, different operators, different specimen diameters, different specimen thicknesses, and two different approaches to mount the specimens in the impedance tube are considered. Explainable machine learning techniques allow the identification and quantification of the most influential factors and, furthermore, the frequency ranges that are the most affected by the choice of these setup factors. The results indicate that besides the specimen thickness, also the operator affects the absorption coefficient by a directional and non-random relationship. Hence, it needs to be controlled carefully. The method proves to be a promising pathway for knowledge discovery from acoustic measurement data using explainability approaches for machine learning models.

Sound Transmission Loss of a Sandwich Plate with Adjustable Core Layer Thickness.

Compressible Constrained Layer Damping (CCLD) is a novel, semi-active, lightweight-compatible solution for vibration mitigation based on the well-known constrained layer damping principle. The sandwich-like CCLD set-up consists of a base structure, a constraining plate, and a compressible open-cell foam core in between, enabling the adjustment of the structure's vibration behaviour by changing the core compression using different actuation pressures. The aim of the contribution is to show to what degree, and in which frequency range the acoustic behaviour can be tuned using CCLD. Therefore, the sound transmission loss (TL), as an important vibro-acoustic index, is determined in an acoustic window test stand at different actuation pressures covering a frequency range from 0.5 to 5 kHz. The different actuation pressures applied cause a variation of the core layer thickness (from 0.9 d0 to 0.3 d0), but the resulting changes of the stiffness and damping of the overall structure have no significant influence on the TL up to approximately 1 kHz for the analysed CCLD design. Between 1 kHz and 5 kHz, however, the TL can be influenced considerably well by the actuation pressure applied, due to a damping-dominated behaviour around the critical frequency.

A novel two-promoter-one-gene system of the chorionic gonadotropin ß gene enables tissue-specific expression.

The New World monkey (NWM), Callithrix jacchus, a preferred model in medical research, displays an interesting endocrine regulation of reproduction: LH, the heterodimeric glycoprotein hormone, is functionally replaced by the chorionic gonadotropin (CG), a hormone indispensable for establishment of pregnancy in humans and normally expressed in the placenta. In the marmoset pituitary, the expression of the ß-subunit (CGB) gene is regulated similar to human LH ß-subunit, but its placental regulation is unknown. This study intended to decipher the underlying mechanism of tissue-specific expression of CGB in the marmoset placenta. We identified a new placental transcriptional start site, described a new, previously undiscovered exon, and define a novel placental core promoter in the marmoset CGB gene. This promoter contains a TATA box and binding sites for activating protein 2 and selective promoter factor 1, the latter acting synergistically by forming a regulation cassette. Differential first exon usage directed the tissue-specific expression. Methylation analyses revealed a tissue-specific pattern in the placental promoter indicating additional epigenetic regulation of gene expression. Our findings point toward a hitherto unknown evolutionary plasticity in the LH/CG hormonal system in NWM, which could be used as a model to study human CGB regulation in clinical pathologies.

Primate FSH-receptor promoter nucleotide sequence heterogeneity affects FSH-receptor transcription.

Follicle-stimulating hormone (FSH) is essential for primate reproduction and acts via the FSH-receptor (FSHR). Although the FSHR expression is highly cell-specific, knowledge of the FSHR promoter and its transcriptional regulation is very limited. We applied a comparative genomic approach of important primate lineages to characterize the FSHR core promoter region. The core promoter sequences of the human and different primate species display significant variations in species-specific promoter activities shown by relative luciferase activity (RLA), ranging from 0.7-fold in the bonobo up to 3.5-fold in the chimpanzee compared to human. Comparison of the core promoter sequences revealed only very few interspecies nucleotide mismatches. Sequence homology ranged between 88% in the marmoset to 98% in chimpanzee compared to human FSHR. Mutagenesis of a single nucleotide next to a putative E-twenty-six (ETS) binding site caused a significant increase for human and a decrease for chimpanzee in RLA. An accompanying change in the pattern of protein binding to mutated human and chimpanzee ETS binding sites was demonstrated by EMSA, confirming a hitherto unknown role for this ETS binding site in FSHR promoter activity. Although the FSHR promoter displays a great sequence homology among primates, single nucleotide changes have significant impact on FSHR promoter activity. Thus promoter studies of closely related species could yield important insights into different regulatory promoter elements caused by nucleotide substitutions.

Pulling apart catalytically active Tn5 synaptic complexes using magnetic tweezers.

The Tn5 transposase is an example of a class of proteins that move DNA sequences (transposons) via a process called transposition. DNA transposition is a widespread genetic mobility mechanism that has profoundly affected the genomes of nearly all organisms. We have used single-DNA micromanipulation experiments to study the process by which Tn5 DNA transposons are identified and processed by their transposase protein. We have determined that the energy barrier to disassemble catalytically active synaptic complexes is 16 kcal mol(-1). However, we have found that the looping organization of DNA segments by transposase is less sequence-driven than previously thought. Loops anchored at some non-transposon end sequences display a disassembly energy barrier of 14 kcal mol(-1), nearly as stable as the synapses formed at known transposon end sequences. However, these non-transposon end sequence independent complexes do not mediate DNA cleavage. Therefore, the sequence-sensitivity for DNA binding and looping by Tn5 transposase is significantly less than that required for DNA cleavage. These results have implications for the in vivo down regulation of transposition and the cis-transposition bias of transposase.

Micromanipulation studies of chromatin fibers in Xenopus egg extracts reveal ATP-dependent chromatin assembly dynamics.

We have studied assembly of chromatin using Xenopus egg extracts and single DNA molecules held at constant tension by using magnetic tweezers. In the absence of ATP, interphase extracts were able to assemble chromatin against DNA tensions of up to 3.5 piconewtons (pN). We observed force-induced disassembly and opening-closing fluctuations, indicating our experiments were in mechanochemical equilibrium. Roughly 50-nm (150-base pair) lengthening events dominated force-driven disassembly, suggesting that the assembled fibers are chiefly composed of nucleosomes. The ATP-depleted reaction was able to do mechanical work of 27 kcal/mol per 50 nm step, which provides an estimate of the free energy difference between core histone octamers on and off DNA. Addition of ATP led to highly dynamic behavior with time courses exhibiting processive runs of assembly and disassembly not observed in the ATP-depleted case. With ATP present, application of forces of 2 pN led to nearly complete fiber disassembly. Our study suggests that ATP hydrolysis plays a major role in nucleosome rearrangement and removal and that chromatin in vivo may be subject to highly dynamic assembly and disassembly processes that are modulated by DNA tension.

Tn5 transposase loops DNA in the absence of Tn5 transposon end sequences.

Transposases mediate transposition first by binding specific DNA end sequences that define a transposable element and then by organizing protein and DNA into a highly structured and stable nucleoprotein 'synaptic' complex. Synaptic complex assembly is a central checkpoint in many transposition mechanisms. The Tn5 synaptic complex contains two Tn5 transposase subunits and two Tn5 transposon end sequences, exhibits extensive protein-end sequence DNA contacts and is the node of a DNA loop. Using single-molecule and bulk biochemical approaches, we found that Tn5 transposase assembles a stable nucleoprotein complex in the absence of Tn5 transposon end sequences. Surprisingly, this end sequence-independent complex has structural similarities to the synaptic complex. This complex is the node of a DNA loop; transposase dimerization and DNA specificity mutants affect its assembly; and it likely has the same number of proteins and DNA molecules as the synaptic complex. Furthermore, our results indicate that Tn5 transposase preferentially binds and loops a subset of non-Tn5 end sequences. Assembly of end sequence-independent nucleoprotein complexes likely plays a role in the in vivo downregulation of transposition and the cis-transposition bias of many bacterial transposases.

Defining characteristics of Tn5 Transposase non-specific DNA binding.

While non-specific DNA plays a role in target localization for many recombinases, transcription factors and restriction enzymes, the importance of non-specific DNA interactions for transposases has not been investigated. Here, we discuss non-specific DNA-Tn5 Transposase (Tnp) interactions and suggest how they stabilize the Tnp and modulate Tnp localization of the 19 bp Tnp recognition end sequences (ESes). DNA protection assays indicate that full-length Tnp interacts efficiently with supercoiled DNA that does not contain ESes. These interactions significantly prolong the lifetime of Tnp, in vitro. The balance between non-specific DNA bound and free Tnp is affected by DNA topology, yet, intermolecular transfer of active Tnp occurs with both supercoiled and linear non-specific DNA. Experiments with substrates of varying lengths show that Tn5 Tnp can utilize non-specific DNA to facilitate localization of an intramolecular ES over distances less than 464 bp. Finally, synaptic complex formation is inhibited in the presence of increasing concentrations of supercoiled and linear pUC19. These experiments strongly suggest that Tn5 Tnp has a robust non-specific DNA binding activity, that non-specific DNA modulates ES sequence localization within the global DNA, most likely through a direct transfer mechanism, and that non-specific DNA binding may play a role in the cis bias manifested by Tn5 transposition.