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In a recent report, the cellular receptor CD55 was identified as a molecule essential for the invasion of human erythrocytes by Plasmodium falciparum, the causal agent of the most severe form of malaria. As this invasion process represents a critical step during infection with the parasite, it was hypothesized that genetic variants in the gene could affect severe malaria (SM) susceptibility. We performed high-resolution variant discovery of rare and common genetic variants in the human CD55 gene. Association testing of these variants in over 1700 SM cases and unaffected control individuals from the malaria-endemic Ashanti Region in Ghana, West Africa, were performed on the basis of single variants, combined rare variant analyses, and reconstructed haplotypes. A total of 26 genetic variants were detected in coding and regulatory regions of CD55. Five variants were previously unknown. None of the single variants, rare variants, or haplotypes showed evidence for association with SM or P. falciparum density. Here, we present the first comprehensive analysis of variation in the CD55 gene in the context of SM and show that genetic variants present in a Ghanaian study group appear not to influence susceptibility to the disease.

The contribution of interleukin- (IL-) 4 receptor-alpha- (Rα-) dependent events in the pathogenesis of tuberculosis (TB) is controversial. We have recently shown IL-13 overexpression in mice to cause recrudescent Mtb replication and centrally necrotizing granulomas strongly resembling pathology of human TB. A deletion of IL-4Rα completely abrogates TB tissue pathology in these mice. To validate our results in human TB patients, we here determined the association of distinct variants of the IL4, IL13, IL4RA, IL13RA1, and IL13RA2 genes with cavity formation in a large Ghanaian cohort of HIV-negative individuals with newly diagnosed pulmonary TB. In fact, the structural variant of the IL4RA I50V, previously shown to result in enhanced signal transduction, was significantly associated with greater cavity size, and a variant of IL13RA2 was associated with disease in females. To evaluate whether the human-like TB pathology in IL-13-overexpressing mice is specifically mediated through the IL-4Rα subunit, we analyzed IL-13 transgenic mice with a genetic ablation of the IL-4Rα. In these mice, the IL-13-mediated increased susceptibility, human-like pathology of collagen deposition around centrally necrotizing granulomas, and alternative macrophage activation were abolished. Together, our genetic association study in human TB patients further supports the assumption that IL-13/IL-4Rα-dependent mechanisms are involved in mediating tissue pathology of human TB.

Toll like receptors (TLR) are key elements of the innate immune response and involved in the recognition of pathogens. To test common and rare TLR variants involved in susceptibility or resistance to infection with Mycobacterium tuberculosis we screened the exons of the genes encoding TLR 1, 2, 4, and the adaptor molecule TIRAP in more than 4500 tuberculosis (TB) cases and controls from Ghana. The analysis yielded 109 variants with possible functional impact, including 101 non-synonymous variants, three stop-variants, and five indels. Association analyses yielded a significant result for the TLR1 variant rs3923647, conferring strong protection against TB (Odds ratio [OR] 0.21, CI confidence interval [CI] 0.05-0.6, Pnominal 1 x 10-3) when applying a recessive model of inheritance. Replication analyses with an additional 3370 Ghanaian cases and control samples, and with data from a recent TB study of 533 African-Americans confirmed the protective effect and resulted in a combined OR of 0.19, with a nominal P value of 2.2 x 10-5, and a corrected P value of 4.1 x 10-4. The SNP is located near the binding pocket of TLR1 and causes an amino acid exchange from histidine to leucine at position 305. The observed effect may, therefore, be attributable to structural changes in the recognition site of the TLR1 molecule, allowing to bind those mycobacterial ligands which preferentially may induce a protective immune response. This is supported by the analysis of BCG-stimulated peripheral blood mononuclear cells, showing increased induction of the proinflammatory cytokine IFN-γ in carriers of the mutant TLR1 rs3923647 TT genotype, compared to the IFN-γ levels of individuals with the AT and AA genotypes.

In this paper we prove that the full Keller–Segel system, a quasilinear strongly coupled reaction-crossdiffusion system of four parabolic equations, is well-posed in the sense that it always admits an unique local-in-time solution in an adequate function space, provided that the initial values are suitably regular. The proof is done via an abstract solution theorem for nonlocal quasilinear equations by Amann and is carried out for general source terms. It is fundamentally based on recent nontrivial elliptic and parabolic regularity results which hold true even on rather general nonsmooth spatial domains. For space dimensions 2 and 3, this enables us to work in a nonsmooth setting which is not available in classical parabolic systems theory. Apparently, there exists no comparable existence result for the full Keller–Segel system up to now. Due to the large class of possibly nonsmooth domains admitted, we also obtain new results for the ‘standard’ Keller–Segel system consisting of only two equations as a special case. [ABSTRACT FROM AUTHOR]

Magnetic Resonance (MR) thermometry is used for the monitoring of MR-guided microwave ablations (MWA), and for the intraoperative evaluation of ablation regions. Nevertheless, the accuracy of temperature mapping may be compromised by electromagnetic interference emanating from the microwave (MW) generator. This study evaluated different setups for improving magnetic resonance imaging (MRI) during MWA with a modified MW generator. MWA was performed in 15 gel phantoms comparing three setups: The MW generator was placed outside the MR scanner room, either connected to the MW applicator using a penetration panel with a radiofrequency (RF) filter and a 7 m coaxial cable (Setup 1), or through a waveguide using a 5 m coaxial cable (Setup 2). Setup 3 employed the MW generator within the MR scan room, connected by a 5 m coaxial cable. The coaxial cables in setups 2 and 3 were modified with custom shielding to reduce interference. The setups during ablation (active setup) were compared to a reference setup without the presence of the MW system. Thermometry and thermal dose maps (CEM43 model) were compared for the three configurations. Primary endpoints for assessment were signal-to-noise ratio (SNR), temperature precision, Sørensen-Dice-Coefficient (DSC), and RF-noise spectra. Setup 3 showed highly significant electromagnetic interference during ablation with a SNR decrease by -60.4%±13.5% (p<0.001) compared to reference imaging. For setup 1 and setup 2 no significant decrease in SNR was measured with differences of -2.9%±9.8% (p=0.6) and -1.5%±12.8% (p=0.8), respectively. SNR differences were significant between active setups 1 and 3 with -51.2%±16.1% (p<0.001) and between active setups 2 and 3 with -59.0%±15.5% (p<0.001) but not significant between active setups 1 and 2 with 19.0%±13.7% (p=0.09). Furthermore, no significant differences were seen in temperature precision or DSCs between all setups, ranging from 0.33 °C ± 0.04 °C (Setup 1) to 0.38 °C ± 0.06 °C (Setup 3) (p=0.6) and from 87.0%±1.6% (Setup 3) to 88.1%±1.6% (Setup 2) (p=0.58), respectively. Both setups (1 and 2) with the MW generator outside the MR scanner room were beneficial to reduce electromagnetic interference during MWA. Moreover, provided that a shielded cable is utilized in setups 2 and 3, all configurations displayed negligible differences in temperature precision and DSCs, indicating that the location of the MW generator does not significantly impact the accuracy of thermometry during MWA., Competing Interests: Declaration of Competing Interest Frank Wacker reports financial support was provided by Siemens Healthineers. Frank Wacker reports financial support was provided by ProMedicus. Frank Wacker reports financial support was provided by Delcath Systems Inc. Frank Wacker reports financial support was provided by Profound Medical. If there are other authors, they declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Author(s). Published by Elsevier GmbH.. All rights reserved.)

Purpose: To evaluate workflow efficiency and diagnostic quality of a free-breathing 3D stack-of-stars gradient echo (Radial GRE) sequence compared to a breath-hold 3D Cartesian gradient echo (Cartesian GRE) sequence for needle position control in MR-guided liver interventions., Materials and Methods: 12 MR-guided liver interventions were performed on a 1.5 T Siemens Aera and analyzed retrospectively. 15 series of the Radial GRE sequence were compared to 14 series of the Cartesian GRE sequence regarding the time interval between two consecutive live-scans for needle tracking (Tracking-2-Tracking-Time). The quality of both sequences was compared by the SNR within comparable slices in liver and tumor ROIs. The CNR was calculated by subtraction of the SNR values. Subjective image quality scores of three radiologists were assessed and inter-rater reliability was tested by Fleiss' kappa. Values are given as mean ± SD. P-values < 0.05 were considered as significant., Results: The median Tracking-2-Tracking-Time was significantly shorter for the Radial GRE sequence, 185 ± 42 s vs. 212 ± 142 s (p = 0.04) and the median SNR of the liver and tumor ROIs were significantly higher in the Radial GRE sequence, 249 ± 92 vs. 109 ± 67 (p = 0.03) and 165 ± 74 vs. 77 ± 43 (p = 0.02). CNR between tumor and liver ROIs showed a tendency to be higher for the Radial GRE sequence without significance, 68 ± 48 vs. 49 ± 32 (p = 0.28). Mean subjective image quality was 3.33 ± 1.08 vs. 2.62 ± 0.95 comparing Radial and Cartesian GRE with a Fleiss' kappa of 0.39 representing fair inter-rater reliability., Conclusion: A free-breathing 3D stack-of-stars gradient echo sequence can simplify the workflow and reduce intervention time, while providing superior image quality. Under local anesthesia, it increases patient comfort and reduces potential risks for needle dislocations in MR-guided liver interventions by avoiding respiratory arrests for needle position control., (© 2023. The Author(s).)

Background: Managers have a significant impact on the health and well-being of employees, particularly when the managers lead in a health-specific way and intentionally foster their employees' health. However, the data on contextual and individual factors influencing the practice of health-specific leadership is at present limited., Objective: To survey the experiences of healthcare managers with health-specific leadership skills and identify the drivers and barriers in the practice of health-specific leadership., Methods: Semi-structured interviews were conducted with 51 managers from 18 geriatric-care facilities in Germany, between November 2014 and February 2015. The interviews were analysed through qualitative content analysis., Results: In their reports, managers mentioned several drivers and barriers in the practice of health-specific leadership. These drivers and barriers were found at the leader level, the employee level, and the organizational level. The factors identified relate to the theoretical aspects of health-specific leadership: health value, health awareness, health behaviour, and role modelling., Conclusion: For successful practice of health-specific leadership, the findings suggest a more holistic approach for worksite health promotion. Managers should promote personal initiative that benefit employee health, encourage their employees to exhibit healthy behaviour themselves, address organizational resources and restrictions, and gain competencies in change management.

Background: The aim of this study was to analyze the neurological involvement and outcome in pediatric patients with hemolytic uremic syndrome (HUS) during the 2011 epidemic caused by Escherichia coli O104:H4., Methods: Clinical data and data from magnetic resonance imaging (MRI) scans and electroencephalography (EEG) during the acute phase of the disease and during follow-up at 3 and 6 months were analyzed in 50 patients. Twenty-five of these patients underwent neuropsychological testing (WISC IV) during follow-up., Results: Neurological involvement (stupor or coma, seizures, visual disturbances, paresis, myocloni) was initially observed in 14/50 (28%) patients. One patient died. EEG abnormalities were more frequent in patients with neurological involvement than in those without (12/14 vs. 13/25, respectively). Cranial MRI scans were analyzed in nine patients with neurological involvement, of whom five showed abnormal findings. At the 3- and 6-month follow-ups, EEG abnormalities were found in 14/40 (35%) and 7/36 (19%) patients, respectively, whereas 28/42 (67%) and 17/39 (44%) patients, respectively, complained about on-going reduced performance. Neuropsychological testing showed a slightly lower global intelligence quotient in patients with neurological involvement versus those without (113.4 ± 2.8 vs. 119.4 ± 1.8, respectively)., Conclusions: Neurological involvement was frequent in our cohort. Accordingly, the incidence of pathological EEG findings was high, even in patients without clinical signs of neurological involvement. Nevertheless, major neurological sequelae were rare, and neuropsychological outcome was favorable after 6 months.