COVID-19 Associated Contact Restrictions in Germany: Marked Decline in Children's Outpatient Visits for Infectious Diseases without Increasing Visits for Mental Health Disorders.

Children have a low risk for severe COVID-19 infections, but indirect consequences of the pandemic may affect their health. We evaluated nationwide data on children's outpatient visits before and during the first wave of the COVID-19 pandemic in Germany. Data from the National Association of Statutory Health Insurance Physicians for all children with statutory health insurance and at least one physician's office visit between January 2019 and June 2020 were evaluated for total visits and selected diagnoses for the 2nd quarter of 2019 (8.29 million children, controls) and the 2nd quarter of 2020 (8.5 million, pandemic). Outpatient visits per child fell by 18% during the first wave of the pandemic. Outpatient visits associated with diagnosed infections fell markedly by 51%, particularly for children up to age 5 years for gastroenteritis (73%), otitis media (71%), and streptococcal angina (78%). Outpatient visits for diagnosed chronic physical disorders (diabetes, celiac disease, and hay fever) and mental and behavioral disorders showed little change. Reduced contact between children appears to markedly reduce infection transmission. Infection risks in educational settings should be attenuated after the pandemic through targeted education and counseling and appropriate relationship prevention measures to improve quality of life and opportunities for children and to reduce stress and lost work time for parents.

Parental well-being in times of Covid-19 in Germany.

We examine the effects of Covid-19 and related restrictions on individuals with dependent children in Germany. We specifically focus on the role of day care center and school closures, which may be regarded as a "disruptive exogenous shock" to family life. We make use of a novel representative survey of parental well-being collected in May and June 2020 in Germany, when schools and day care centers were closed but while other measures had been relaxed and new infections were low. In our descriptive analysis, we compare well-being during this period with a pre-crisis period for different groups. In a difference-in-differences design, we compare the change for individuals with children to the change for individuals without children, accounting for unrelated trends as well as potential survey mode and context effects. We find that the crisis lowered the relative well-being of individuals with children, especially for individuals with young children, for women, and for persons with lower secondary schooling qualifications. Our results suggest that public policy measures taken to contain Covid-19 can have large effects on family well-being, with implications for child development and parental labor market outcomes.

Obesity and skill attainment in early childhood.

This paper investigates the association between obesity and skill attainment in early childhood (aged 2-3 years). Data from the German Socio-Economic Panel Study are used to estimate models of developmental functioning in four critical areas (verbal skills, activities of daily living, motor skills, and social skills) as a function of various measures of weight (including body mass index and obesity) controlling for a rich set of child, parent, and family characteristics. The findings indicate that, among boys, obesity is associated with reduced verbal skills, social skills, motor skills, and activities of daily living. Among girls, obesity is associated with reduced verbal skills. Further investigations show that the correlations exist even for those preschool children who spend no time in day care, which implies that the correlations cannot be due solely to discrimination by teachers, classmates, or day care providers.

Relations Among Maternal Life Satisfaction, Shared Activities, and Child Well-Being.

Maternal well-being is assumed to be associated with well-being of individual family members, optimal parenting practices, and positive developmental outcomes for children. The objective of this study was to examine the interplay between maternal well-being, parent-child activities, and the well-being of 5- to 7-year-old children. In a sample of N = 291 mother-child dyads, maternal life satisfaction, the frequency of shared parent-child activities, as well as children's self-regulation, prosocial behavior, and receptive vocabulary were assessed using several methods. Data were collected in a special study of the Socio-Economic Panel Study (SOEP), a representative longitudinal survey of private households in Germany. Using structural equation modeling, significant positive direct and indirect relations between maternal life satisfaction, frequency of shared parent-child activities, children's self-regulation, prosocial behavior, and receptive vocabulary were found. The more satisfied the mother was, the more she shared activities with her child and the more the child acted prosocially. Furthermore, the higher the frequency of shared parent-child activities, the higher the child scored in all three analyzed indicators of children's well-being: self-regulation, prosocial behavior, and receptive vocabulary. The current study supports the assumption of maternal well-being as the basis of positive parenting practices and child well-being.

COX2 expression, angiogenesis, proliferation and survival in Barrett's cancer.

OBJECTIVES: To examine COX2 expression and its relation to angiogenesis, Ki67 and Bcl2 expression in Barrett's cancer. METHODS: Specimens from 48 R0-resected Barrett's adenocarcinoma were immunostained for cyclooxygenase 2 (COX2), CD 31 and alpha-sm actin to discriminate between mature and immature vessels, Mib-1 and Bcl2. COX2 staining, angiogenesis, Ki67 expression and Bcl2 expression were also measured. RESULTS: COX2 expression was increased in 25 of 48 cases. There was no significant correlation between COX2 expression and age, sex and tumor differentiation. A significant association was found between lymph node positive cases and elevated COX2 expression (p=0.008). The percentage of Ki67 positive cancer cells was 43.8% (range 15.4-67.5%) in the low COX2 group and 57.8% (range 12.0-84.6%) in the high COX2 group. The difference was statistically significant (p=0.046). The median neovascularisation coefficient in the low COX2 group was 11.68 (range 8.22-43.64) and 25.47 (range 8-38.3) in the high COX2 group. The difference was statistically significant (p=0.012). A significant difference in survival was observed between patients in the COX2 low category when compared with the COX2 high category (log-rank test p=0.013). CONCLUSIONS: Elevated COX2 expression is associated with lymph-node metastases and reduced survival in Barrett's cancer. This appears to be related to the induction of angiogenesis and proliferation.

Effect of p-nitrophenyl diazonium fluoroborate on cholinergic mechanisms.

Electrophysiological experiments were done to investigate the effect o p-nitrophenyl diazonium fluoroborate (p-NPD) on motor endplates of the frog's m. cutaneus pectoris. The compound has no direct depolarizing effect on the postsynaptic membrane and stabilizes it irreversibly when added to the bath. Longtime iontophoretical applications of p-NPD produce a biphasic effect: initially a potentiation of the depolarizations due to acetylcholine (ACh) (both iontophoretically applied and presynaptically liberated), and subsequently an inhibition of the response to ACh. When the acetylcholinesterase (AChE) is inactivated previously, only the inhibiting effect of the compound is demonstrable. The association constant of p-NPD to purified AChE and to membrane fragments of electroplax was determined by biochemical methods. The compound's affinity to the AChE was found to be about 20 times greater than to the acetylcholine receptor (AChR). Iontophoretical application of p-NPD to cholinergic neurons in the hippocampal cortex of the cat also produced the characteristic biphasic effect on ACh-induced activity of these investigated neurons. The results suggest that the biphasic effect depends on the capacity of p-NPD to combine with both the AChE and the AChR. The AChE is first inhibited with low concentrations thereby potentiating the ACh response. At higher concentrations the AChR's are progressively inhibited too, thereby diminishing the excitability of the postsynaptic membrane up to a complete block.

A meta-model of chemotherapy planning in the multi-hospital/multi-trial-center-environment of pediatric oncology.

OBJECTIVE: Chemotherapy planning in pediatric oncology is complex and time-consuming. The correctness of the calculation according to state-of-the-art research is crucial for curing the child. Computer-assistance can be of great value. The objective of our research was to work out a meta-model of chemotherapy planning based on the Unified Modeling Language (UML). The meta-model is used for the development of an application system which serves as a knowledge-acquisition tool for chemotherapy protocols in pediatric oncology as well as for providing protocol-based care. METHODS: We applied evolutionary prototyping, software reengineering techniques and grounded theory, a qualitative method in social research. We repeated the following steps several times over the years: Based on a requirements analysis (i) a meta-model was developed or adapted, respectively (ii). The meta-model served as a basis for implementing evolutionary prototypes (iii). Further requirements were identified (i) from clinical use of the systems. RESULTS: We developed a comprehensive UML-based meta-model for chemotherapy planning in pediatric oncology (chemoMM). We implemented it and introduced evolutionary prototypes (CATIPO and DOSPO) in several medical centers. Systematic validation of the prototypes enabled us to derive a final meta-model which covers the requirements that have turned out to be necessary in clinical routine. CONCLUSIONS: We have developed an application system that fits well into clinical routine of pediatric oncology in Germany. Validation results have shown that the implementation of the meta-model chemoMM can adequately support the knowledge acquisition process for protocol-based care.

The intergenerational transmission of health in early childhood--evidence from the German Socio-Economic Panel study.

Children's physical health problems have clear and lasting impacts on a variety of later life outcomes, as a growing body of research has shown. Furthermore, problems such as obesity, motor impairment, and chronic diseases entail high social costs, particularly when childhood health problems carry over into adulthood. This study examines intergenerational relationships between parent and child health based on data from the German Socio-Economic Panel (SOEP), in particular the recently introduced Mother and Child Questionnaires. Using various health measures, including anthropometric measures, information on health disorders, and "self-rated" health measures, we find significant relationships between parental and child health during the first three years of life. Overall, our results suggest that when controlling for parental income, education, and family composition, parents with poor health are more likely to have children with poor health. However, there are significant differences between health measures and age groups. For some health measures, our results suggest an increasing health gradient by age.

Pollution exposure and child health: evidence for infants and toddlers in Germany.

This paper examines the impact of outdoor pollution and parental smoking on children's health from birth until the age of three years in Germany. We use representative data from the German Socio-Economic Panel (SOEP), combined with five air pollution levels. These data were provided by the Federal Environment Agency and cover the years 2002-2007. Our work makes two important contributions. First, we use European data to replicate and extend an important US study by following the effects of pollution exposure and parental smoking on child health during the first four years of life. Second, we have health measures not only for infants but for toddlers as well. For infants, as well as for two- to three-year-olds, we are able to account for time-invariant and unobserved neighborhood and maternal characteristics. Our results suggest a significantly negative impact of some pollutants on infant health. High exposure to CO prior to birth causes, on average, a 289g lower birth weight. With respect to toddler health, we find that disorders and in particular those as bronchitis and respiratory illnesses are affected particularly by O3 levels.

A temperature-dependent switch from chaperone to protease in a widely conserved heat shock protein.

Misfolding or unfolding of polypeptides can occur as a consequence of environmental stress and spontaneous mutation. The abundance of general chaperones and proteases suggests that cells distinguish between proteins that can be refolded and "hopeless" cases fated to enter the proteolytic pathway. The mechanisms controlling this key metabolic decision are not well understood. We show here that the widely conserved heat shock protein DegP (HtrA) has both general molecular chaperone and proteolytic activities. The chaperone function dominates at low temperatures, while the proteolytic activity is present at elevated temperatures. These results show that a single cellular factor can switch between two key pathways, controlling protein stability and turnover. Implications of this finding for intracellular protein metabolism are discussed.

Rapid diagnosis of acute mumps infection by a direct immunoglobulin M antibody capture enzyme immunoassay with labeled antigen.

A new immunoglobulin M (IgM) antibody capture enzyme immunoassay with peroxidase-labeled mumps antigen (dMACEIA) is described, and its suitability for practical diagnosis of acute mumps infection is evaluated. All 54 patients with proven mumps infection that were tested showed mumps-specific IgM antibodies. On the other hand, no specific IgM antibodies were present in 16 cases of suspected mumps that could not be confirmed by classical complement fixation serology, and IgM mumps virus antibodies could be detected neither in the sera of 100 healthy individuals nor in those of 16 patients positive for rheumatoid factor. In all, 22 children with acute respiratory illness caused by parainfluenza virus and 44 patients with infections due to other viruses showed no IgM response in mumps dMACEIA. The particular characteristic in which complement fixation antibodies against mumps nucleocapsids appear before and disappear earlier than antibodies to the enveloped mumps virus could not be demonstrated in the dMACEIA. In an extensive epidemic of mumps virus infection, the dMACEIA gave a clear diagnosis of mumps infection in 200 out of 371 suspected cases. By day 2 of the illness, 71% of the patients had detectable IgM, and by day 3, all of them had detectable IgM. In 99% of the cases, dMACEIA gave a positive result in the first available serum specimens, most of which were negative for complement fixation antibodies. A positive but only moderate correlation was thus observed between the two serological procedures. IgM antibodies persisted for at least 6 weeks. The dMACEIA, performed in 3 h, offers a reliable, simple, and rapid alternative to routine methods for detection of acute mumps infection.

Barefoot and in a German kitchen: federal parental leave and benefit policy and the return to work after childbirth in Germany.

"Since 1979 German federal maternity leave and benefit policy has given women incentives to stay at home and take care of their newborn and youngest children. In 1986 this leave and benefit policy was changed in several ways, turning it into a powerful instrument for delaying mothers' return to work after childbirth.... We estimate post childbirth return to work hazards for women during the federally protected leave protection period and immediately upon completion of this leave period. During the leave mothers are less likely to return to work the longer is the time left in the leave protection period; however, this result cannot be attributed generally to high levels of maternity benefits. When the leave protection period ends, mothers with strong labor force attachment who are still on leave return to their jobs."

Use of desmopressin and erythropoietin in an anaemic Jehovah's Witness patient with severely impaired coagulation capacity undergoing stentless aortic valve replacement.

Cardiac surgery in Jehovah's Witness patients remains a challenge in the presence of concomitant congenital or acquired coagulation disorders and anaemia. We report a case of a 66-year-old female Jehovah's Witness suffering from severe calcified aortic valve stenosis requiring aortic valve replacement. The anaemic patient suffered from concomitant platelet dysfunction and deficiency of factors V and VII due to gammopathy of immunoglobulin G. The patient was preoperatively treated with recombinant erythropoietin in combination with folic acid and iron, which resulted in an increase of the haematocrit from 0.335 to 0.416 after 22 days of treatment. Haemostasis was improved by high dose aprotinin and additional desmopressin, which could be demonstrated to be effective by a preoperative test. The patients intra- and postoperative course was uneventful, her total chest tube loss was 130 ml, and she was able to be discharged without the need of any blood transfusions. The beneficial properties of erythropoietin and desmopressin in Jehovah's Witness patients are discussed.

Biochemical characterization and mass spectrometric disulfide bond mapping of periplasmic alpha-amylase MalS of Escherichia coli.

Periplasmic alpha-amylase of Escherichia coli, the malS gene product, hydrolyzes linear maltodextrins. The purified enzyme exhibited a Km of 49 microM and a Vmax of 0.36 micromol of p-nitrophenylhexaoside hydrolyzed per min per mg of protein. Amylase activity was optimal at pH 8 and was dependent on divalent cations such as Ca2+. MalS exhibited altered migration on SDS-polyacrylamide gel electrophoresis under nonreducing conditions. Analytical ultracentrifugation and electrospray mass spectrometry indicated that MalS is monomeric. The four cysteine residues are involved in intramolecular disulfide bonds. To map disulfide bonds, MalS was proteolytically digested. The resulting peptides were separated by reverse phase-high performance liquid chromatography, and matrix-assisted laser desorption/ionization mass spectrometry analysis indicated the presence of two disulfide bonds, i.e. Cys40-58 and Cys104-520. The disulfide bond at Cys40-58 is located in an N-terminal extension of about 160 amino acids which has no homology to other amylases but to the proposed peptide binding domain of GroEL, the Hsp60 of E. coli. The N-terminal extension is linked to the C-terminal amylase domain via disulfide bond Cys104-520. Reduction of disulfide bonds by dithiothreitol treatment led to aggregation suggesting that the N terminus of MalS may represent an internal chaperone domain.

Targeting of signal sequenceless proteins for export in Escherichia coli with altered protein translocase.

Most extracytoplasmic proteins are synthesized with an N-terminal signal sequence that targets them to the export apparatus. Escherichia coli prlA mutants (altered in the secY gene) are able to export cell envelope proteins lacking any signal sequence. In order to understand how such proteins are targeted for export, we isolated mutations in a signal sequenceless version of alkaline phosphatase that block its export in a prlA mutant. The mutations introduce basic amino acyl residues near the N-terminus of alkaline phosphatase. These changes do not disrupt an N-terminal export signal in this protein since the first 25 amino acids can be removed without affecting its export competence. These findings suggest that signal sequenceless alkaline phosphatase does not contain a discrete domain that targets it for export and may be targeted simply because it remains unfolded in the cytoplasm. We propose that basic amino acids near the N-terminus of a signal sequenceless protein affect its insertion into the translocation apparatus after it has been targeted for export. These findings allow the formulation of a model for the entry of proteins into the membrane-embedded export machinery.

Determinants of translocation and folding of TreF, a trehalase of Escherichia coli.

One isoform of trehalase, TreF, is present in the cytoplasm and a second, TreA, in the periplasm. To study the questions of why one enzyme is exported efficiently and the other is not and whether these proteins can fold in their nonnative cellular compartment, we fused the signal sequence of periplasmic TreA to cytoplasmic TreF. Even though this TreF construct was exported efficiently to the periplasm, it was not active. It was insoluble and degraded by the periplasmic serine protease DegP. To determine why TreF was misfolded in the periplasm, we isolated and characterized Tre(+) revertants of periplasmic TreF. To further characterize periplasmic TreF, we used a genetic selection to isolate functional TreA-TreF hybrids, which were analyzed with respect to solubility and function. These data suggested that a domain located between residues 255 and 350 of TreF is sufficient to cause folding problems in the periplasm. In contrast to TreF, periplasmic TreA could fold into the active conformation in its nonnative cellular compartment, the cytoplasm, after removal of its signal sequence.

Safety and feasibility of a cardiac support device.

The Cardiac Support Device (CSD), a preformed-knitted polyester device surgically placed over the cardiac ventricles, prevents left ventricular (LV) remodeling and improves LV ejection fraction (EF) in dogs with heart failure (HF). This study was designed to examine the safety of the CSD in patients with advanced HF. As of December 31, 1999, the CSD was implanted into 22 patients with myocardial disease. Ten patients had concomitant mitral valve repair, two patients had valve replacement (one patient aortic and one patient mitral), one patient had LV assist device (LVAD) placement, and eight patients received only the CSD. The CSD was placed while on bypass with the heart beating, attached to the epicardium groove, and tailored anteriorly to snugly fit the ventricles. There were no intraoperative deaths or complications. Two patients died early from non-CSD-related causes 4 and 23 days postoperatively; one late death occurred. Of the remaining 19 patients, none had any CSD-related adverse events during an average 3.5 +/- 0.4 month follow-up. All patients had completed 3-month follow-up. No patients had evidence of constrictive and/or restrictive physiology. Mitral valve regurgitation (MVR) improved in all patients. [table: see text] Initial findings indicate that the CSD is safe and improves heart failure symptoms and LV function. Additional studies and longer follow-up are needed to confirm these results.

Stable and long-lasting immune response in horses after DNA vaccination against equine arteritis virus.

Equine arteritis virus (EAV) is the causative agent of the equine viral arteritis. It is a small RNA virus with a linear, non-segmented plus RNA genome. EAV is a member of the Arteriviridae family that includes porcine reproductive and respiratory syndrome virus (PRSSV), simian haemorrhagic fever virus (SHFV) and lactate dehydrogenase virus (LDV). The viral transmission is via respiratory and reproductive routes. Clinical signs in horses vary, and severe infection can lead to abortions in pregnant mares or neonatal foal death. The aim of this study was to investigate the development of the immune response in horses after immunization with a DNA vaccine harbouring and expressing EAV Open Reading Frames (ORF) 2, 5, and 7, in combination with equine interleukin 2 (eqIL2). Three boosters followed the basic immunization in two-week intervals. Each immunization was a combination of gene gun and intramuscular injection. All horses developed a high titer of neutralizing antibodies after basic immunization within 2 weeks. Remarkably, this immune response was found to be independent of the age of animals. The youngest horse was six-years old, and the oldest twenty-two years old. A remarkable difference in the immune response between the young and old were not observed. The duration of immunity was investigated during a period of one year. After 12 months, neutralizing antibodies were still detectable in all the vaccinated horses.