Search

Using wave number calibrated Fourier transform spectra, ranging from the IR to the UV regions, we determined with high accuracy the energies of the levels of the first ion of Niobium. In order to increase the accuracy of the center of gravity wave numbers of the observed spectral lines, the hyperfine structure was taken into account. For this purpose, the magnetic dipole hyperfine constants A were determined for all involved levels. All but one of the previously known levels were included in the calculation. This level (at 91 493 cm−1) is considered to be non-existent. From the experimental center of gravity wave numbers of 1121 lines we deduced the energy values of 184 levels of even parity and 164 levels of odd parity in a global fit. A comparison between our results and all previously available literature values is provided. [ABSTRACT FROM AUTHOR]

Background: In order to optimise the support of children with cochlear implants (CI), it is very important to detect slow developmental processes as early as possible. Data from the LittlEARS® Auditory Questionnaire (LEAQ) from children with early bilateral CI are evaluated and presented in relation to age and hearing age and compared with language development data recorded later., Materials and Methods: This retrospective multicentre study included data from a total of 554 children for whom at least one LEAQ was completed during the course of CI rehabilitation. Children without additional disabilities who received bilateral simultaneous or sequential CI treatment were included., Results: As expected, there are high correlations between hearing age (HA) and the overall LEAQ total score. When analysed according to chronological age (CA), development runs roughly parallel to the development of children with normal hearing, albeit at a lower level. Children implanted early up to an age of ≤ 12 months consistently achieve approximately 7-8 raw points more. Only the LEAQ results of the later test times (from the age of 18 months) correlate with some areas of the speech development test for children (SETK; areas 3-5)., Conclusion: The earliest possible detection of critical developmental processes in children with CI is extremely important. In the case of very early CI fitting, the CA should be used as a reference measure in diagnostics. The LEAQ values determined for the group of children with CI are suitable to a limited extent as generally valid reference values for children with early bilateral CI. Further studies should continue to work out the correlations between early preverbal development and later speech development., (© 2024. The Author(s), under exclusive licence to Springer Medizin Verlag GmbH, ein Teil von Springer Nature.)

Background: Very early bilateral cochlear implant (CI) provision is today's established standard for children. Therefore, the assessment of preverbal and verbal performance in very early stages of development is becoming increasingly important. Performance data from cohorts of children were evaluated and presented based on diagnostic assessment using chronological age (CA) and hearing age (HA)., Methods: The present study, as part of a retrospective multicentre study, included 4 cohorts (N = 72-233) of children with bilateral CI without additional disabilities. Their results in the German parent questionnaires Elternfragebögen zur Früherkennung von Risikokindern(ELFRA‑1 and ELFRA-2) subdivided for CA and HA were statistically analysed. The data were also analysed in terms of mono-/bilingualism and age at CI provision., Results: Overall, verbal performance in relation to CA was lower than in relation to HA. Preverbal skills were largely CA appropriate. Children with bi-/multilingual language acquisition performed significantly lower. Verbal performance in ELFRA‑2 referenced to CA was negatively correlated with age at CI provision., Conclusion: In the case of early CI provision, CA should be the preferred reference mark in preverbal and verbal assessment in order to obtain exact individual performance levels and avoid bias in results. The percentiles determined are of limited use as generally valid reference values to which the individual performance of bilaterally implanted children could be compared. Further multicentre studies should be initiated., (© 2024. The Author(s).)

The BPaLM regimen (bedaquiline, pretomanid, linezolid and moxifloxacin) recently recommended by the World Health Organization offers short, safe, and effective treatment for multidrug-resistant/rifampicin-resistant tuberculosis (TB). In a survey with national TB focal points in 18 central and western European countries to explore barriers for the implementation of BPaLM, only three reported full availability of pretomanid, a necessary component of this regimen. Implementation barriers included financing and procurement. Solutions on national and supranational level are needed to guarantee universal access.

To examine the risk associated with bus riding and identify transmission chains, we investigated a COVID-19 outbreak in Germany in 2021 that involved index case-patients among bus-riding students. We used routine surveillance data, performed laboratory analyses, interviewed case-patients, and conducted a cohort study. We identified 191 case-patients, 65 (34%) of whom were elementary schoolchildren. A phylogenetically unique strain and epidemiologic analyses provided a link between air travelers and cases among bus company staff, schoolchildren, other bus passengers, and their respective household members. The attack rate among bus-riding children at 1 school was ≈4 times higher than among children not taking a bus to that school. The outbreak exemplifies how an airborne agent may be transmitted effectively through (multiple) short (<20 minutes) public transport journeys and may rapidly affect many persons.

By translating mechanical forces into molecular signals, proprioceptive neurons provide the CNS with information on muscle length and tension, which is necessary to control posture and movement. However, the identities of the molecular players that mediate proprioceptive sensing are largely unknown. Here, we confirm the expression of the mechanosensitive ion channel ASIC2 in proprioceptive sensory neurons. By combining in vivo proprioception-related functional tests with ex vivo electrophysiological analyses of muscle spindles, we showed that mice lacking Asic2 display impairments in muscle spindle responses to stretch and motor coordination tasks. Finally, analysis of skeletons of Asic2 loss-of-function mice revealed a specific effect on spinal alignment. Overall, we identify ASIC2 as a key component in proprioceptive sensing and a regulator of spine alignment., (© 2023 The Authors. Experimental Physiology published by John Wiley & Sons Ltd on behalf of The Physiological Society.)

Objectives: Quality of life plays an important place in the psychosocial development of children with Cochlear Implants (CI). We assesd health-related quality of life (HRQoL) in children with CI and in hearing children and determined relationships between HRQoL and other developmental characteristics (social-emotional development, Theory of Mind (ToM), spoken language skills)., Methods: A longitudinal study was conducted including children with CI and hearing children. We used instruments that are widely employed and have been validated for research. At time 1 social-emotional development, ToM and spoken language skills were assessed.HRQoL was assessed using the generic KINDL questionnaire, as was social-emotional development, 2.5 years later (time 2)., Results: No significant difference was seen in HRQoL between hearing children and children with CI. We show that the age of detection, the age of hearing care, and the start of early intervention are not related to HRQoL of children with CI, but relationships with some domains of social-emotional development are evident., Conclusions: This study highlights the importance of targeted intervention not only to improve spoken language skills at preschool age, but also strengthen social-emotional and social-cognitive competences.

The Russian invasion of Ukraine in 2022 caused a large migration to other European countries, including Germany. This movement impacted the TB epidemiology, as Ukraine has a higher prevalence of TB and multidrug-resistant TB rates compared to Germany. Our descriptive analysis of TB surveillance data reveals important information to improve TB care in people displaced from Ukraine. We observed an expected increase in the number of TB patients born in Ukraine, which is, however, so far below WHO/Europe estimates.

Pompe disease is a debilitating medical condition caused by a functional deficiency of lysosomal acid alpha-glucosidase (GAA). In addition to muscle weakness, people living with Pompe disease experience motor coordination deficits including an instable gait and posture. We reasoned that an impaired muscle spindle function might contribute to these deficiencies and therefore analyzed proprioception as well as muscle spindle structure and function in 4- and 8-month-old Gaa -/- mice. Gait analyses showed a reduced inter-limb and inter-paw coordination in Gaa -/- mice. Electrophysiological analyses of single-unit muscle spindle proprioceptive afferents revealed an impaired sensitivity of the dynamic and static component of the stretch response. Finally, a progressive degeneration of the sensory neuron and of the intrafusal fibers was detectable in Gaa -/- mice. We observed an increased abundance and size of lysosomes, a fragmentation of the inner and outer connective tissue capsule and a buildup of autophagic vacuoles in muscle spindles from 8-month-old Gaa -/- mice, indicating lysosomal defects and an impaired autophagocytosis. These results demonstrate a structural and functional degeneration of muscle spindles and an altered motor coordination in Gaa -/- mice. Similar changes could contribute to the impaired motor coordination in patients living with Pompe disease., (© 2023. The Author(s).)

In the field of nanotoxicology, the detection and size characterization of nanoparticles (NPs) in biological tissues become increasingly important. To gain information on both particle size and particle distribution in histological sections, laser ablation and single particle inductively coupled plasma-mass spectrometry (LA-spICP-MS) was used in combination with a liquid calibration of dissolved metal standards via a pneumatic nebulizer. In the first step, the particle size distribution of Ag NPs embedded in matrix-matched gelatine standards introduced via LA was compared with that of Ag NPs in a suspension and nebulizer-based ICP-MS. The data show that the particles remained intact by the ablation process as confirmed by transmission electron microscopy. Moreover, the optimized method was applied to CeO 2 NPs that are highly relevant for (eco-)toxicological research but, unlike Ag NPs, are multi-shaped and have a broad particle size distribution. Upon analyzing the particle size distribution of CeO 2 NPs in cryosections of rat spleen, CeO 2 NPs were found to remain unchanged in size over 3 h, 3 d, and 3 weeks post-intratracheal instillation, with the fraction of smaller particles reaching the spleen first. Overall, LA-spICP-MS combined with a calibration based on dissolved metal standards is a powerful tool to simultaneously localize and size NPs in histological sections in the absence of particle standards.

Congenital myasthenic syndromes (CMS) are predominantly characterized by muscle weakness and fatigability and can be caused by a variety of mutations in genes required for neuromuscular junction formation and maintenance. Among them, AGRN encodes agrin, an essential synaptic protein secreted by motoneurons. We have identified severe CMS patients with uncharacterized p.R1671Q, p.R1698P and p.L1664P mutations in the LG2 domain of agrin. Overexpression in primary motoneurons cultures in vitro and in chick spinal motoneurons in vivo revealed that the mutations modified agrin trafficking, leading to its accumulation in the soma and/or in the axon. Expression of mutant agrins in cultured cells demonstrated accumulation of agrin in the endoplasmic reticulum associated with induction of unfolded protein response (UPR) and impaired secretion in the culture medium. Interestingly, evaluation of the specific activity of individual agrins on AChR cluster formation indicated that when secreted, mutant agrins retained a normal capacity to trigger the formation of AChR clusters. To confirm agrin accumulation and secretion defect, iPS cells were derived from a patient and differentiated into motoneurons. Patient iPS-derived motoneurons accumulated mutant agrin in the soma and increased XBP1 mRNA splicing, suggesting UPR activation. Moreover, co-cultures of patient iPS-derived motoneurons with myotubes confirmed the deficit in agrin secretion and revealed a reduction in motoneuron survival. Altogether, we report the first mutations in AGRN gene that specifically affect agrin secretion by motoneurons. Interestingly, the three patients carrying these mutations were initially suspected of spinal muscular atrophy (SMA). Therefore, in the presence of patients with a clinical presentation of SMA but without mutation in the SMN1 gene, it can be worth to look for mutations in AGRN., (© 2022. The Author(s).)

Objectives and Study: Gastrointestinal endoscopy is often performed when investigating abdominal complaints in children. While atrophic changes of the duodenal mucosa are usually caused by celiac disease, the prevalence and clinical significance of non-atrophic duodenal changes are less clear. We studied these issues in a large pediatric endoscopic cohort., Methods: Comprehensive data on clinical features, diagnostic findings and long-term outcomes of children who had undergone upper gastrointestinal endoscopy with systematic duodenal sampling were collected. Study variables were compared between children with non-atrophic changes and normal histology, and between those with non-atrophic changes who did and did not receive a diagnosis., Results: The study comprised 1,170 consecutive children, of whom 51 (4.4%) had non-atrophic and 315 (26.9%) atrophic duodenal changes and 804 (68.7%) normal histology. The most common non-atrophic findings were non-specific inflammation ( n = 19) and intraepithelial lymphocytosis ( n = 14). Patients with non-atrophic changes presented more often with blood in stools (23.5 vs. 11.3%; p = 0.009), anemia (43.2 vs. 36.5%; p = 0.028) and positive celiac serology (34.3 vs. 12.9%; p < 0.001) than those with a normal duodenum. Twenty-four (44%) of those with non-atrophic changes received an initial diagnosis, the most common of which were inflammatory bowel disease (IBD) ( n = 8), Helicobacter pylori infection ( n = 3) and food allergy ( n = 3). The prevalence of the diagnoses did not differ from those with a normal duodenum. Those who received a diagnosis had more often blood in stools (37.5 vs. 11.1%; p = 0.027), anemia (70.6 vs. 20.0%; p = 0.002) and negative celiac serology (50.0 vs. 7.7% ; p = 0.013) than those without diagnosis. During a follow-up of 6.1-13.3 years, five of the 12 initially undiagnosed seropositive patients developed celiac disease, and one patient also developed ulcerative colitis., Conclusion: Non-atrophic duodenal changes are relatively common and associated with anemia, blood in stools, and positive celiac disease serology. Excluding potential celiac disease, those without an initial diagnosis have a favorable long-term prognosis., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Kröger, Repo, Hiltunen, Vornanen, Huhtala, Kivelä and Kurppa.)

Background: Comprehensive pathogen genomic surveillance represents a powerful tool to complement and advance precision vaccinology. The emergence of the Alpha variant in December 2020 and the resulting efforts to track the spread of this and other severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variants of concern led to an expansion of genomic sequencing activities in Germany., Methods: At Robert Koch Institute (RKI), the German National Institute of Public Health, we established the Integrated Molecular Surveillance for SARS-CoV-2 (IMS-SC2) network to perform SARS-CoV-2 genomic surveillance at the national scale, SARS-CoV-2-positive samples from laboratories distributed across Germany regularly undergo whole-genome sequencing at RKI., Results: We report analyses of 3623 SARS-CoV-2 genomes collected between December 2020 and December 2021, of which 3282 were randomly sampled. All variants of concern were identified in the sequenced sample set, at ratios equivalent to those in the 100-fold larger German GISAID sequence dataset from the same time period. Phylogenetic analysis confirmed variant assignments. Multiple mutations of concern emerged during the observation period. To model vaccine effectiveness in vitro, we employed authentic-virus neutralization assays, confirming that both the Beta and Zeta variants are capable of immune evasion. The IMS-SC2 sequence dataset facilitated an estimate of the SARS-CoV-2 incidence based on genetic evolution rates. Together with modeled vaccine efficacies, Delta-specific incidence estimation indicated that the German vaccination campaign contributed substantially to a deceleration of the nascent German Delta wave., Conclusions: SARS-CoV-2 molecular and genomic surveillance may inform public health policies including vaccination strategies and enable a proactive approach to controlling coronavirus disease 2019 spread as the virus evolves., Competing Interests: Potential conflicts of interest. The authors report no potential conflicts of interest. All authors have submitted the ICMJE Form for Disclosure of Potential Conflicts of Interest. Conflicts that the editors consider relevant to the content of the manuscript have been disclosed., (© The Author(s) 2022. Published by Oxford University Press on behalf of the Infectious Diseases Society of America.)

Introduction/aims: The muscle relaxant methocarbamol and the antimyotonic drug mexiletine are widely used for the treatment of muscle spasms, myotonia, and pain syndromes. To determine whether these drugs affect muscle spindle function, we studied their effect on the resting discharge and on stretch-induced action potential frequencies of proprioceptive afferent neurons., Methods: Single unit action potential frequencies of proprioceptive afferents from muscle spindles in the murine extensor digitorum longus muscle of adult C57BL/6J mice were recorded under resting conditions and during ramp-and-hold stretches. Maximal tetanic force of the same muscle after direct stimulation was determined. High-resolution confocal microscopy analysis was performed to determine the distribution of Na v 1.4 channels, a potential target for both drugs., Results: Methocarbamol and mexiletine inhibited the muscle spindle resting discharge in a dose-dependent manner with IC 50 values around 300 μM and 6 μM, respectively. With increasing concentrations of both drugs, the response to stretch was also affected, with the static sensitivity first followed by the dynamic sensitivity. At high concentrations, both drugs completely blocked muscle spindle afferent output. Both drugs also reversibly reduced the specific force of the extensor digitorum longus muscle after tetanic stimulation. Finally, we present evidence for the presence and specific localization of the voltage-gated sodium channel Na v 1.4 in intrafusal fibers., Discussion: In this study we demonstrate that both muscle relaxants affect muscle spindle function, suggesting impaired proprioception as a potential side effect of both drugs. Moreover, our results provide additional evidence of a peripheral activity of methocarbamol and mexiletine., (© 2022 The Authors. Muscle & Nerve published by Wiley Periodicals LLC.)

Due to the increasing use and production of CeO 2 nanoparticles (NPs), the likelihood of exposure especially via the air rapidly grows. However, the uptake of CeO 2 NPs via the lung and the resulting distribution into various cell types of remote organs are not well understood because classical analytical methods provide limited spatial information. In this study, laser ablation-inductively coupled plasma-mass spectrometry (LA-ICP-MS) was combined with immunohistochemical (IHC) staining with lanthanide-labeled antibodies to investigate the distribution of intratracheally instilled CeO 2 NPs from the rat lung to lymph nodes, spleen, and liver after 3 h, 3 days, and 21 days. We selected regions of interest after fast imaging using LA-ICP-MS in low-resolution mode and conducted high-resolution LA-ICP-MS in combination with IHC for cellular localization. The lanthanide labeling, which was largely congruent with conventional fluorescent labeling, allowed us to calculate the association rates of Ce to specific cell types. Major portions of Ce were found to be associated with phagocytic cells in the lung, lymph nodes, spleen, and liver. In the lung, almost 94% of the Ce was co-localized with CD68-positive alveolar macrophages after 21 days. Ce was also detected in the lymph nodes outside macrophages 3 h post instillation but shifted to macrophage-associated locations. In the liver, Ce accumulations associated with Kupffer cells (CD163-positive) were found. Ce-containing populations of metallophilic and marginal zone macrophages (both CD169-positive) as well as red pulp macrophages (CD68-positive) were identified as major targets in the spleen. Overall, high-resolution LA-ICP-MS analysis in combination with IHC staining with lanthanide-labeled antibodies is a suitable tool to quantify and localize Ce associated with specific cell types and to estimate their particle burden under in vivo conditions.

German national surveillance data analysis shows that hospitalisation odds associated with Omicron lineage BA.1 or BA.2 infections are up to 80% lower than with Delta infection, primarily in ≥ 35-year-olds. Hospitalised vaccinated Omicron cases' proportions (2.3% for both lineages) seemed lower than those of the unvaccinated (4.4% for both lineages). Independent of vaccination status, the hospitalisation frequency among cases with Delta seemed nearly threefold higher (8.3%) than with Omicron (3.0% for both lineages), suggesting that Omicron inherently causes less severe disease.

In spring 2021, an increasing number of infections was observed caused by the hitherto rarely described SARS-CoV-2 variant A.27 in south-west Germany. From December 2020 to June 2021 this lineage has been detected in 31 countries. Phylogeographic analyses of A.27 sequences obtained from national and international databases reveal a global spread of this lineage through multiple introductions from its inferred origin in Western Africa. Variant A.27 is characterized by a mutational pattern in the spike gene that includes the L18F, L452R and N501Y spike amino acid substitutions found in various variants of concern but lacks the globally dominant D614G. Neutralization assays demonstrate an escape of A.27 from convalescent and vaccine-elicited antibody-mediated immunity. Moreover, the therapeutic monoclonal antibody Bamlanivimab and partially the REGN-COV2 cocktail fail to block infection by A.27. Our data emphasize the need for continued global monitoring of novel lineages because of the independent evolution of new escape mutations., (© 2022. The Author(s).)