Welche Rolle spielen Kinder in Schulen und Kindertagesstätten bei der Übertragung von SARS-CoV-2? – Eine evidenzbasierte Perspektive

Are children and adolescents relevant disease vectors when it comes to the transmission of SARS-CoV-2? Moreover, do they play a role as relevant disease vectors in a~school or kindergarten setting? These questions could not be sufficiently answered at the beginning of the pandemic. Consequently, schools and childcare facilities were closed to stop the spread of SARS-CoV\hbox-2. Over the past few months, researchers have gained a~more detailed understanding of the overall pandemic situation. The SARS-CoV\hbox-2 infection rate in children below 10~years of age in 2020 has been substantially lower than in adults. In addition, it showed that children had a~milder course of disease.Although a~majority of the analyses performed in schools and childcare facilities revealed that the virus is transmitted in these facilities, these transmissions did not, however, have a~considerable influence on the overall rate of new infections. Despite these findings, German politicians continue to advocate for the closure of childcare facilities, including schools, to fight the pandemic, whereas many specialist societies such as the German Society for Pediatric Infectious Diseases (DGPI) have emphasized that such closures should be the measure of last resort in combating the pandemic. The same message is also conveyed by a~German evidence-based S3~guideline established by an interdisciplinary expert group that had already put forward clear recommendations for high incidences in the general population at the beginning of February 2021, indicating that school closures were only required in exceptional cases.In this article, we would like to outline the situation based on the currently available data, try to predict the future, and discuss the circumstances necessary to realize normal classroom teaching without accepting the risk of an uncontrolled spread of SARS-CoV\hbox-2. ZUSAMMENFASSUNG Sind Kinder und Jugendliche relevante Vektoren für die Übertragung von SARS-CoV-2? Und welche Rolle spielt es, wenn sie eine Schule oder Kindertagesstätte besuchen? Diese Fragen konnten zu Beginn der Pandemie nur unzureichend beantwortet werden. So wurden weltweit Schulen und Kinderbetreuungseinrichtungen geschlossen, um die Verbreitung von SARS-CoV\hbox-2 einzudämmen. Inzwischen ist die Rolle von Kindern im Gesamtgeschehen der Pandemie jedoch klarer. Die Rate von SARS-CoV-2-Infektionen bei Kindern unter 10~Jahren war im Jahr 2020 deutlich niedriger als die bei Erwachsenen. Zudem zeigte sich bei Kindern ein deutlich milderer Verlauf der Erkrankung.Analysen zu Ausbrüchen an Schulen und Kinderbetreuungseinrichtungen kamen mehrheitlich zu dem Ergebnis, dass die Weitergabe des Virus in den Einrichtungen zwar stattfindet, jedoch das Infektionsgeschehen insgesamt nicht maßgeblich beeinflusst. Trotz dieser Erkenntnisse hält die deutsche Politik Schulschließungen weiterhin für einen integralen Baustein der Pandemiebekämpfung, wohingegen viele Fachgesellschaften, wie die Deutsche Gesellschaft für Pädiatrische Infektiologie e. V. (DGPI), betonen, dass es sich um das letzte Mittel in der Bekämpfung der Pandemie handeln sollte. Diese Botschaft hat auch eine evidenzbasierte und auf interdisziplinärem Expertenkonsens aufgebaute S3-Leitlinie, die bereits Anfang Februar 2021 klare Empfehlungen für Zeiten hoher Inzidenzen in der Gesamtbevölkerung ausgesprochen hat, die Schulschließungen nur noch in Ausnahmefällen für notwendig erachten.In diesem Artikel möchten wir die Datenlage mit Stand Juni 2021 zu diesem Thema darlegen, einen Blick in die Zukunft wagen und diskutieren, unter welchen Umständen ein regulärer Präsenzunterricht gelingen kann, ohne das Risiko einer unkontrollierten Ausbreitung von SARS-CoV\hbox-2 in Kauf nehmen zu müssen

Growth of a cohort of very low birth weight and preterm infants born at a single tertiary health care center in South Africa

BackgroundVery low birth weight (VLBW) and extremely low birth weight (ELBW) infants are known to be at high risk of growth failure and developmental delay later in life. The majority of those infants are born in low and middle income countries.AimGrowth monitoring in a cohort of infants born with a VLBW up to 18 months corrected age was conducted in a low resource setting tertiary hospital.MethodsIn this prospective cohort study, 173 infants with a birth weight below 1,501 g admitted within their first 24 h of life were recruited and the 115 surviving until discharged were asked to follow up at 1, 3, 6, 12 and 18 months. Weight, height and head circumferences were recorded and plotted on WHO Z-score growth charts.ResultsOf the 115 discharged infants 89 were followed up at any given follow-up point (1, 3, 6, 12 and/or 18 months). By 12 months of corrected age another 15 infants had demised (13.0%). The infants' trends in weight-for-age z-scores (WAZ) for corrected age was on average below the norm up to 12 months (average estimated z-score at 12 months = −0.44; 95% CI, −0.77 to −0.11), but had reached a normal range on average at 18 months = −0.24; 95% CI, −0.65 to 0.19) with no overall difference in WAZ scores weight between males and female' infants (p > 0.7). Similar results were seen for height at 12 months corrected age with height-for-age z-scores (HAZ) of the study subjects being within normal limits (−0.24; 95% CI, −0.63 to 0.14). The mean head circumference z-scores (HCZ) initially plotted below −1.5 standard deviations (S.D.), but after 6 months the z-scores were within normal limits (mean z-score at 7 months = −0.19; 95% CI, −0.45 to 0.06).ConclusionWeight gain, length and head circumferences in infants with VLBW discharged showed a catch-up growth within the first 6–18 months of corrected age, with head circumference recovering best. This confirms findings in other studies on a global scale, which may be reassuring for health systems such as those in South Africa with a high burden of children born with low birth weights

Relationship between Functional Connectivity and Sensory Impairment: red flag, or red herring?

Resting-state functional magnetic resonance imaging (fMRI) can be used to study the functional connectivity in the somatosensory system. However, the relationship between sensory network connectivity, sensory deficits, and structural abnormality remains poorly understood. Previously, we investigated the motor network in children with congenital hemiparesis due to middle cerebral artery strokes (MCA, n = 6) or periventricular lesions (PL, n = 8). In the present study, we validate the use of interleaved resting-state data from blocked fMRI designs to investigate the somatosensory network in these patients. The approach was validated by assessing the predicted “crossed-over” connectivity between the cerebral cortex and the cerebellum. Furthermore, the impact on the volume of gray-matter (GM) in primary (S1) and secondary (S2) somatosensory cortex on functional connectivity measures was investigated. We were able to replicate the well-known “crossed-over” pattern of functional connectivity between cerebral and cerebellar cortex. The MCA group displayed more sensory deficit and significantly reduced functional connectivity in the lesioned S2 (but not in lesioned S1) when compared with the PL group. However, when accounting for GM volume loss, this difference disappeared. This study demonstrates the applicability of analyzing resting-state connectivity in patients with brain lesions. Reductions of functional connectivity within the somatosensory network were associated with sensory deficits, but were fully explained by the underlying GM damage. This underlines the influence of cortical GM volume on functional connectivity measure

POLR3A variants with striatal involvement and extrapyramidal movement disorder

Biallelic variants in POLR3A cause 4H leukodystrophy, characterized by hypomyelination in combination with cerebellar and pyramidal signs and variable non-neurological manifestations. Basal ganglia are spared in 4H leukodystrophy, and dystonia is not prominent. Three patients with variants in POLR3A, an atypical presentation with dystonia, and MR involvement of putamen and caudate nucleus (striatum) and red nucleus have previously been reported. Genetic, clinical findings and 18 MRI scans from nine patients with homozygous or compound heterozygous POLR3A variants and predominant striatal changes were retrospectively reviewed in order to characterize the striatal variant of POLR3A-associated disease. Prominent extrapyramidal involvement was the predominant clinical sign in all patients. The three youngest children were severely affected with muscle hypotonia, impaired head control, and choreic movements. Presentation of the six older patients was milder. Two brothers diagnosed with juvenile parkinsonism were homozygous for the c.1771-6C > G variant in POLR3A; the other seven either carried c.1771-6C > G (n = 1) or c.1771-7C > G (n = 7) together with another variant (missense, synonymous, or intronic). Striatal T2-hyperintensity and atrophy together with involvement of the superior cerebellar peduncles were characteristic. Additional MRI findings were involvement of dentate nuclei, hila, or peridentate white matter (3, 6, and 4/9), inferior cerebellar peduncles (6/9), red nuclei (2/9), and abnormal myelination of pyramidal and visual tracts (6/9) but no frank hypomyelination. Clinical and MRI findings in patients with a striatal variant of POLR3A-related disease are distinct from 4H leukodystrophy and associated with one of two intronic variants, c.1771-6C > G or c.1771-7C > G, in combination with another POLR3A variant

Defining the phenotypical spectrum associated with variants in TUBB2A

Background Variants in genes belonging to the tubulin superfamily account for a heterogeneous spectrum of brain malformations referred to as tubulinopathies. Variants in TUBB2A have been reported in 10 patients with a broad spectrum of brain imaging features, ranging from a normal cortex to polymicrogyria, while one patient has been reported with progressive atrophy of the cerebellar vermis. Methods In order to further refine the phenotypical spectrum associated with TUBB2A, clinical and imaging features of 12 patients with pathogenic TUBB2A variants, recruited via the international network of the authors, were reviewed. Results We report 12 patients with eight novel and one recurrent variants spread throughout the TUBB2A gene but encoding for amino acids clustering at the protein surface. Eleven patients (91.7%) developed seizures in early life. All patients suffered from intellectual disability, and 11 patients had severe motor developmental delay, with 4 patients (36.4 %) being non-ambulatory. The cerebral cortex was normal in five individuals and showed dysgyria of variable severity in seven patients. Associated brain malformations were less frequent in TUBB2A patients compared with other tubulinopathies. None of the patients had progressive cerebellar atrophy. Conclusion The imaging phenotype associated with pathogenic variants in TUBB2A is highly variable, ranging from a normal cortex to extensive dysgyria with associated brain malformations. For recurrent variants, no clear genotype-phenotype correlations could be established, suggesting the role of additional modifiers.</p

Defining the phenotypical spectrum associated with variants in TUBB2A

Background Variants in genes belonging to the tubulin superfamily account for a heterogeneous spectrum of brain malformations referred to as tubulinopathies. Variants in TUBB2A have been reported in 10 patients with a broad spectrum of brain imaging features, ranging from a normal cortex to polymicrogyria, while one patient has been reported with progressive atrophy of the cerebellar vermis. Methods In order to further refine the phenotypical spectrum associated with TUBB2A, clinical and imaging features of 12 patients with pathogenic TUBB2A variants, recruited via the international network of the authors, were reviewed. Results We report 12 patients with eight novel and one recurrent variants spread throughout the TUBB2A gene but encoding for amino acids clustering at the protein surface. Eleven patients (91.7%) developed seizures in early life. All patients suffered from intellectual disability, and 11 patients had severe motor developmental delay, with 4 patients (36.4 %) being non-ambulatory. The cerebral cortex was normal in five individuals and showed dysgyria of variable severity in seven patients. Associated brain malformations were less frequent in TUBB2A patients compared with other tubulinopathies. None of the patients had progressive cerebellar atrophy. Conclusion The imaging phenotype associated with pathogenic variants in TUBB2A is highly variable, ranging from a normal cortex to extensive dysgyria with associated brain malformations. For recurrent variants, no clear genotype-phenotype correlations could be established, suggesting the role of additional modifiers.</p

FAHN/SPG35 : a narrow phenotypic spectrum across disease classifications

The endoplasmic reticulum enzyme fatty acid 2-hydroxylase (FA2H) plays a major role in the formation of 2-hydroxy glycosphingolipids, main components of myelin. FA2H deficiency in mice leads to severe central demyelination and axon loss. In humans it has been associated with phenotypes from the neurodegeneration with brain iron accumulation (fatty acid hydroxylase-associated neurodegeneration, FAHN), hereditary spastic paraplegia (HSP type SPG35) and leukodystrophy (leukodystrophy with spasticity and dystonia) spectrum. We performed an in-depth clinical and retrospective neurophysiological and imaging study in a cohort of 19 cases with biallelic FA2H mutations. FAHN/SPG35 manifests with early childhood onset predominantly lower limb spastic tetraparesis and truncal instability, dysarthria, dysphagia, cerebellar ataxia, and cognitive deficits, often accompanied by exotropia and movement disorders. The disease is rapidly progressive with loss of ambulation after a median of 7 years after disease onset and demonstrates little interindividual variability. The hair of FAHN/SPG35 patients shows a bristle-like appearance; scanning electron microscopy of patient hair shafts reveals deformities (longitudinal grooves) as well as plaque-like adhesions to the hair, likely caused by an abnormal sebum composition also described in a mouse model of FA2H deficiency. Characteristic imaging features of FAHN/SPG35 can be summarized by the WHAT' acronym: white matter changes, hypointensity of the globus pallidus, ponto-cerebellar atrophy, and thin corpus callosum. At least three of four imaging features are present in 85% of FA2H mutation carriers. Here, we report the first systematic, large cohort study in FAHN/SPG35 and determine the phenotypic spectrum, define the disease course and identify clinical and imaging biomarkers

The three-prong method: a novel assessment of residual stress in laser powder bed fusion

<p><b>Boxplots of quantitative parameters</b> included <b>a)</b> ratio of N-acetylaspartate and N-acetylaspartylglutamate (NAA) to creatine and phosphocreatine (Cr) both for chemical shift imaging (CSI) and single voxel (SV) measurements, <b>b)</b> ratio of choline containing compounds (Cho) to Cr both for CSI and SV, <b>c)</b> myelin water fraction (MWF), <b>d)</b> magnetization transfer ratio (MTR), <b>e)</b> quantitative susceptibility mapping (QSM), and <b>f)</b> R2*. Parameters were measured in frontal white matter (WM) and two parameters within the cortico-spinal tract (CST): at the level of the posterior limb of internal capsule (PLIC) and at the level of the centrum semiovale (CS), see also <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0167274#pone.0167274.g001" target="_blank">Fig 1</a>.</p