Time Spent on School-Related Activities at Home During the Pandemic: A Longitudinal Analysis of Social Group Inequality Among Secondary School Students.

Substantial educational inequalities have been documented in Germany for decades. In this article, we examine whether educational inequalities among children have increased or remained the same since the school closures of spring 2020 due to the COVID-19 pandemic. Our perspective is longitudinal: We compare the amount of time children in secondary schools spent on school-related activities at home before the pandemic, during school closures, and immediately after returning to in-person learning. We operationalize family socio-economic status using the highest parental educational attainment. Based on the theoretical assumption that the pandemic affected everyone equally, we formulate a hypothesis of equalization during the first period of school closures. For the period thereafter, however, we assume that parents with a low level of education had more difficulties bearing the additional burden of supervising and supporting their children's learning activities. Thus, for that period, we postulate an increase in educational inequality. To study our hypotheses, we use data from the 2019 wave of the SOEP and the SOEP-CoV study, both of which are probability samples. The SOEP-CoV study provides a unique database, as it was conducted during the lockdown of spring 2020 and in the following month. For statistical analysis, we use probit regressions at three measurement points (in 2019, in 2020 during the school closures, and in the month after closures). The comparison of these three time points makes our analysis and findings unique in the research on education during the COVID-19 pandemic, in particular with regard to Germany-wide comparisons. Our results confirm the hypothesis of equalization during the first school closures and the hypothesis of an increase in educational in the subsequent period. Our findings have direct policy implications regarding the need to further expand support systems for children.

[Parents' subjective burden of home schooling their children at times of the Corona-related lockdown in spring 2020]. / Subjektive Belastung der Eltern durch die Beschulung ihrer Kinder zu Hause zu Zeiten des Corona-bedingten Lockdowns im Frühjahr 2020.

The Corona-related school closures and the closure of childcare facilities in April and May 2020 meant an immense challenge for many parents. Suddenly, children had to be looked after and educated at home all day. In this paper, we address the question of the subjective burden that parents faced when schooling their children at home. In doing so, we pay special attention to the individual resources of the parents as well as to their family situation and their working life. In particular, we examine the subjective perception of stress of single parents. For our analyses we use data from the SOEP-CoV study, a special survey of the Socio-Economic Panel (SOEP) on the topic of Corona. Overall, we found moderate levels of stress from the demands of schooling their children at home among all parents surveyed (N = 1508, of which N = 243 were single parents). However, parents with a low level of education and single parents felt particularly burdened, especially if they were employed at the time of the school closures. Our analyses suggest that precisely these groups of parents had problems comprehensively meeting the demands of home schooling under the given circumstances.

[Celebrations with consequences: fever, dyspnea and chest pain]. / Feierlichkeiten mit Folgen: Fieber, Dyspnoe und Thoraxschmerz.

HISTORY: We report on a 35-year-old male patient who presented to the emergency department a day after celebrations. The night before, the alcoholized patient tried to spit fire with an oily fuel paste. A fever, dyspnea and chest pain were present. FINDINGS AND DIAGNOSIS: The patient is febrile, but in reduced general conditions. In laboratory chemistry shows elevated inflammatory parameters. Due to the conventional radiology findings we completed the diagnostic with a CT-scan, which shows confirmed streaky opacities, especially in the middle lobe. DIAGNOSIS: Based on the very suggestive history and diagnostic findings, a fire eater's lung was diagnosed. THERAPY AND COURSE: Under treatmen with CoAmoxicillin, oxygen, inhalation with Ipratropiumbromid/Salbutamol and symptomatic treatment, we could reach a clinical improvement and discharged within three days. CONCLUSION: Aspiration of oily fuel paste led to lipoid pneumonia. Few such cases have been described so far, but the medical history, symptoms and radiological imaging are very characteristic. Antibiotic therapy is not primarily necessary, however, depending on the clinical condition may help to prevent bacterial superinfection. The administration of systemic steroids is controversial in this situation.

Role of tattoos in football: Behavioral patterns and success-analysis of the FIFA World Cup 2018.

Epidemiologic studies suggest that individuals with tattoos are more extroverted, aggressive, and more likely to take risks than individuals with no tattoos. Whether these personality traits affect athletic performance is uncertain. We compared behavioral patterns and rates of success of football players at the International Federation of Association Football (FIFA) World Cup 2018 by tattoo status. In this cross-sectional study, 32.7% of football players had visible tattoos (241 of 736), mostly on their arms (97.1%). Footballers with tattoos played longer on average (208 versus 160 minutes; P < .001), received more cards (.38 versus .27; P < .001), and committed more fouls per player (2.64 versus 2.2; P < .001). Players with tattoos attempted more shots at goal (P = .016), but without higher goal success (P = .204). The higher number of disciplinary events (being whistled for fouls and given yellow or red cards) and longer playing time of football players with tattoos may reflect personality traits reported in nonathletic individuals with tattoos, such as dominance, extroversion, aggressiveness, and willingness to take risks.

Sexually transmitted coinfections in patients with anogenital warts - a retrospective analysis of 196 patients.

BACKGROUND AND OBJECTIVES: Anogenital warts (AGWs) are most commonly caused by low-risk human papillomavirus (HPV) types, and although they are the most frequent viral sexually transmitted infections (STIs), little is known about STI coinfections in affected patients. We therefore sought to assess STI coinfection rates in patients with AGW, specify STI coinfections and calculate the number needed to screen (NNS) for each STI. METHODS: A retrospective cross-sectional study analyzing data sets from AGW patients treated in our clinic between 2008-2016. RESULTS: 142/196 (72 %) patients had been variably screened for infections with HIV, HBV and HCV, Treponema pallidum, Neisseria gonorrhoeae, Chlamydia trachomatis, Mycoplasma genitalium and HSV. The STI coinfection rate in all tested patients was 24.6 %, yielding an NNS of 4.1 to detect any STI. Of note, the coinfection rate did not differ significantly between heterosexual men, homosexual men and women, respectively. The NNS for syphilis was 8.4, for HIV 14.0, for HCV 28.5 and for HBV 39.0. The NNS for asymptomatic patients tested for HSV, Chlamydia trachomatis and Mycoplasma genitalium were 1.4, 5.3 and 12.0, respectively. CONCLUSION: Due to the high prevalence of STI coinfections, AGW patients should be screened for other STIs.

Structural and motivational mechanisms of academic achievement: a mediation model of social-background effects on academic achievement.

This paper takes up ongoing discussions on the inequality of educational opportunities and formulates a conceptual model to link separate lines of research. Our particular focus is on combining motivational and structural approaches into a mediation model that explains differences in academic achievement. In the literature, four main mechanisms of social reproduction are discussed. Two main pathways refer to (1) parents' expectations regarding their children's academic success and (2) replicating cultural capital through intra-familial cultural practices. (3) Parents' perception of children's abilities depends on social position and is influential for expectations of success. (4) For all three pathways, we expect effects on students' motivational characteristics, which in turn influence academic achievement. We test our conceptual model by structural equation modelling using longitudinal data from primary school students in Germany. Empirical evidence is in line with the assumptions in the model. Cultural reproduction and expectations of success can be seen as the key components of the model. However, both chains of reproduction are related to each other by parents' perception of child's ability, and their effects are mediated by child's motivational characteristics.

Phase I trial of active specific immunotherapy with autologous dendritic cells pulsed with autologous irradiated tumor stem cells in hepatitis B-positive patients with hepatocellular carcinoma.

BACKGROUND AND OBJECTIVES: Hepatocellular carcinoma (HCC) is often associated with chronic hepatitis due to hepatitis-B or -C viruses. Active specific immunotherapy (ASI) with autologous dendritic cells (DC) presenting antigens from autologous tumor stem cell (TC) lines is associated with promising long-term survival in metastatic cancer, but hepatitis patients were excluded. ASI might benefit high-risk primary HCC patients following surgical resection, but first it is important to show that ASI does not exacerbate hepatitis. METHODS: Previously untreated HCC patients with a solitary lesion > 5 cm, or three lesions with at least one > 3 cm, or more than three lesions, underwent surgical resection from which autologous TC lines were established. Irradiated TC were incubated with autologous DC to create DC-TC. After one course of trans-arterial chemoembolization therapy (TACE), three weekly subcutaneous injections of DC-TC suspended in granulocyte-macrophage colony stimulating factor were administered. Patients were monitored for eight weeks. RESULTS: HCC cell lines were established within five weeks for 15/15 patients. Eight patients, all with chronic hepatitis B, were treated. There was no increase in hepatic transaminases, hepatitis B antigens, or viral DNA. CONCLUSION: Autologous DC-TC did not exacerbate HBV in these HCC patients. A phase II efficacy trial is being planned.

Analysis of a novel highly metastatic melanoma cell line identifies osteopontin as a new lymphangiogenic factor.

Tumor cell invasion and metastasis are hallmarks of malignancy. Despite recent advances in the understanding of lymphatic spread, the mechanisms by which tumors metastasize to sentinel/distant lymph nodes and beyond are poorly understood. To gain new insights into this complex process, we established highly metastatic melanoma cell lines by in vivo passaging the B16 parental cell line through the lymphatic system. In this study we characterized morphology, rate of cell proliferation, colony formation, migration, tumorigenicity, lymph flow, and capacities to induce tumor- and sentinel lymph node-lymphangiogenesis. Furthermore, microarray-based comparative analysis between parental and passaged cell lines was performed to identify specific gene expression profiles. The most differentially expressed gene was SPP (osteopontin), a secreted glycophosphoprotein which is known to be involved in cancer metastasis. Overexpression of osteopontin in B16 F1-variant was confirmed by western blot analysis and quantitative RT-PCR. Treatment of cultured lymphatic endothelial cells (LECs) with osteopontin promoted cell migration mediated by the integrin α9 pathway. Our results identify osteopontin as a novel lymphangiogenic factor.

Osteopontin is a prognostic factor for survival of acute myeloid leukemia patients.

Osteopontin (OPN) is a glycoprotein that is secreted by osteoblasts and hematopoietic cells. OPN suppresses the proliferation of hematopoietic stem cells in vitro and may regulate the hematopoietic stem cell pool. Increased serum OPN concentrations occur in chronic myeloid leukemia, multiple myeloma, and acute myeloid leukemia (AML). In the present study, we analyzed the prognostic impact of OPN in AML by investigating the expression and relevance of OPN in newly diagnosed AML patients from 2 large study groups (the German AML Cooperative Group and the Dutch-Belgian Hematology Oncology Cooperative group). IHC (n = 84), ELISAs of blood/BM sera (n = 41), and microarray data for mRNA levels (n = 261) were performed. Expression of OPN protein was increased in AML patients both in BM blasts (IHC) and in BM serum (ELISA) compared with healthy controls. Patients expressing high levels of OPN within the BM (IHC) experienced shortened overall survival (OS; P = .025). Multivariate analysis identified karyotype, blast clearance (day 16), and the level of OPN expression as independent prognostic factors for OS. This prompted us to analyze microarray data from 261 patients from a third cohort. The analysis confirmed OPN as a prognostic marker. In summary, high OPN mRNA expression indicated decreased event-free survival (P = .0002) and OS (P = .001). The prognostic role of OPN was most prominent in intermediate-risk AML. These data provide evidence that OPN expression is an independent prognostic factor in AML.

The GDI-like solubilizing factor PDEδ sustains the spatial organization and signalling of Ras family proteins.

We identify a role for the GDI-like solubilizing factor (GSF) PDEδ in modulating signalling through Ras family G proteins by sustaining their dynamic distribution in cellular membranes. We show that the GDI-like pocket of PDEδ binds and solubilizes farnesylated Ras proteins, thereby enhancing their diffusion in the cytoplasm. This mechanism allows more effective trapping of depalmitoylated Ras proteins at the Golgi and polycationic Ras proteins at the plasma membrane to counter the entropic tendency to distribute these proteins over all intracellular membranes. Thus, PDEδ activity augments K/Hras signalling by enriching Ras at the plasma membrane; conversely, PDEδ down-modulation randomizes Ras distributions to all membranes in the cell and suppresses regulated signalling through wild-type Ras and also constitutive oncogenic Ras signalling in cancer cells. Our findings link the activity of PDEδ in determining Ras protein topography to Ras-dependent signalling.

Compounds in clinical Phase III and beyond.

Targeted therapies against cancer have become more and more important. In particular, the inhibition of tumor angiogenesis and vascular targeting have been the focus of new treatment strategies. Numerous new substances were developed as angiogenesis inhibitors and evaluated in clinical trials for safety, tolerance, and efficacy. With positive study results, some of these molecules have already been approved for clinical use. For example, this is true for the vascular endothelial growth factor neutralizing antibody bevacizumab (BEV) in metastatic colorectal cancer, nonsmall cell lung cancer, renal cancer, and breast cancer. The tyrosine kinase (TK) inhibitors sorafenib and sunitinib have been approved for metastatic renal cancer as well as for hepatocellular carcinoma, and sunitinib has also been approved for gastrointestinal stroma tumors. In this chapter we try to give an overview of the substances currently investigated in Phase III studies and beyond with regard to antiangiogenesis in cancer therapy.

Hydrophobic and basic domains target proteins to lipid droplets.

In recent years, progress in the study of the lateral organization of the plasma membrane has led to the proposal that mammalian cells use two different organelles to store lipids: intracellular lipid droplets (LDs) and plasma membrane caveolae. Experimental evidence suggests that caveolin (CAV) may act as a sensitive lipid-organizing molecule that physically connects these two lipid-storing organelles. Here, we determine the sequences necessary for efficient sorting of CAV to LDs. We show that targeting is a process cooperatively mediated by two motifs. CAV's central hydrophobic domain (Hyd) anchors CAV to the endoplasmic reticulum (ER). Next, positively charged sequences (Pos-Seqs) mediate sorting of CAVs into LDs. Our findings were confirmed by identifying an equivalent, non-conserved but functionally interchangeable Pos-Seq in ALDI, a bona fide LD-resident protein. Using this information, we were able to retarget a cytosolic protein and convert it to an LD-resident protein. Further studies suggest three requirements for targeting via this mechanism: the positive charge of the Pos-Seq, physical proximity between Pos-Seq and Hyd and a precise spatial orientation between both motifs. The study uncovers remarkable similarities with the signals that target proteins to the membrane of mitochondria and peroxisomes.

Combined anti-PDGFRalpha and PDGFRbeta targeting in non-small cell lung cancer.

Activation of the platelet-derived growth factor (PDGF)-receptors is critically involved into various stromal cell functions including recruitment of stromal cells and vascular endothelial growth factor (VEGF) induction in tumor and perivascular cells. To evaluate the effects of combined PDGFRalpha and -beta inhibition in a non-small cell lung cancer model, we stably transfected A549 lung cancer cells with the PDGF-A mutant PDGF-0. PDGF-0 has been generated by substituting amino acids in the binding region of PDGF-A with the corresponding VEGF-A region, leading to a decreased receptor-binding affinity and activation. Compared with control vector transfected cells, transfection with PDGF-0 had no impact on monolayer growth and apoptosis in vitro, but significantly impaired the number of colony formation in soft agar. After subcutaneous injections, all mice developed tumors within 5 days. While control vector transfected A549 cells were characterized by constant tumor growth, PDGF-0 transfected A549 revealed a reduced tumor mass (p < 0.001) with no further growth beyond 14 days (2 months observation time) and complete regressions in 7 of 13 cases. Immunohistochemical analyses revealed that PDGF-0 transfected tumors demonstrated decreased recruitment of periendothelial cells, while the tumor invasion zone was similar to control vector transfectants. Similarly, conditioned medium from PDGF-0 transfected cells induced significantly less migration of smooth muscle cells and fibroblasts in vitro. Interestingly, in PDGF-0 transfectants, neither total vessel count nor VEGF expression were significantly altered. These studies demonstrate that combined inhibition of PDGFRalpha and -beta results in markedly decreased tumor growth in vivo because of impaired recruitment of periendothelial cells.

KIBRA modulates directional migration of podocytes.

Asymmetric delivery and distribution of macromolecules are essential for cell polarity and for cellular functions such as differentiation, division, and signaling. Injury of podocytes, which are polarized epithelial cells, changes the dynamics of the actin meshwork, resulting in foot process retraction and proteinuria. Although the spatiotemporal control of specific protein-protein interactions is crucial for the establishment of cell polarity, the mechanisms controlling polarity-dependent differentiation and division are incompletely understood. In this study, yeast two-hybrid screens were performed using a podocyte cDNA library and the polarity protein PATJ as bait. The protein KIBRA was identified as an interaction partner of PATJ and was localized to podocytes, tubular structures, and collecting ducts. The last four amino acids of KIBRA mediated binding to the eighth PDZ domain of PATJ. In addition, KIBRA directly bound to synaptopodin, an essential organizer of the podocyte cytoskeleton. Stable knockdown of KIBRA in immortalized podocytes impaired directed cell migration, suggesting that KIBRA modulates the motility of podocytes by linking polarity proteins and cytoskeleton-associated protein complexes.

Evolutionary analysis and molecular dissection of caveola biogenesis.

Caveolae are an abundant feature of mammalian cells. Integral membrane proteins called caveolins drive the formation of caveolae but the precise mechanisms underlying caveola formation, and the origin of caveolae and caveolins during evolution, are unknown. Systematic evolutionary analysis shows conservation of genes encoding caveolins in metazoans. We provide evidence for extensive and ancient, local and genomic gene duplication, and classify distinct caveolin gene families. Vertebrate caveolin-1 and caveolin-3 isoforms, as well as an invertebrate (Apis mellifera, honeybee) caveolin, all form morphologically identical caveolae in caveolin-1-null mouse cells, demonstrating that caveola formation is a conserved feature of evolutionarily distant caveolins. However, coexpression of flotillin-1 and flotillin-2 did not cause caveola biogenesis in this system. In contrast to the other tested caveolins, C. elegans caveolin is efficiently transported to the plasma membrane but does not generate caveolae, providing evidence of diversity of function in the caveolin gene family. Using C. elegans caveolin as a template to generate hybrid caveolin constructs we now define domains of caveolin required for caveolae biogenesis. These studies lead to a model for caveola formation and novel insights into the evolution of caveolin function.

A novel switch region regulates H-ras membrane orientation and signal output.

The plasma membrane nanoscale distribution of H-ras is regulated by guanine nucleotide binding. To explore the structural basis of H-ras membrane organization, we combined molecular dynamic simulations and medium-throughput FRET measurements on live cells. We extracted a set of FRET values, termed a FRET vector, to describe the lateral segregation and orientation of H-ras with respect to a large set of nanodomain markers. We show that mutation of basic residues in helix alpha4 or the hypervariable region (HVR) selectively alter the FRET vectors of GTP- or GDP-loaded H-ras, demonstrating a critical role for these residues in stabilizing GTP- or GDP-H-ras interactions with the plasma membrane. By a similar analysis, we find that the beta2-beta3 loop and helix alpha5 are involved in a novel conformational switch that operates through helix alpha4 and the HVR to reorient the H-ras G-domain with respect to the plasma membrane. Perturbation of these switch elements enhances MAPK activation by stabilizing GTP-H-ras in a more productive signalling conformation. The results illustrate how the plasma membrane spatially constrains signalling conformations by acting as a semi-neutral interaction partner.

Lipid rafts and membrane traffic.

Membrane rafts are regions of increased lipid acyl chain order that differ in their lipid and protein composition from the surrounding membrane. By providing an additional level of compartmentalization they have been proposed to serve many functions in cellular signal transduction and trafficking. We will review their potential involvement in different forms of membrane traffic, explicitly excluding signalling, and discuss select aspects of the raft hypothesis in its current form.

Structure and dynamics of the full-length lipid-modified H-Ras protein in a 1,2-dimyristoylglycero-3-phosphocholine bilayer.

Ras proteins regulate signal transduction processes that control cell growth and proliferation. Their disregulation is a common cause of human tumors. Atomic level structural and dynamical information in a membrane environment is crucial for understanding signaling specificity among Ras isoforms and for the design of selective anti-cancer agents. Here, the structure of the full-length H-Ras protein in complex with a 1,2-dimyristoylglycero-3-phosphocholine (DMPC) bilayer obtained from modeling and all-atom explicit solvent molecular dynamics simulations, as well as experimental validation of the main results, are presented. We find that, in addition to the lipid anchor, H-Ras membrane binding involves direct interaction of residues in the catalytic domain with DMPC phosphates. Two modes of binding (possibly modulated by GTP/GDP exchange) differing in the orientation and bilayer contact of the soluble domain as well as in the participation of the flexible linker in membrane binding are proposed. These results are supported by our initial in vivo experiments. The overall structures of the protein and the bilayer remain similar to those of the isolated components, with few localized structural and dynamical changes. The implications of the results to membrane lateral segregation and other aspects of Ras signaling are discussed.