Long-Term Antibody Response to SARS-CoV-2 in Children.

Almost 2 years into the pandemic and with vaccination of children significantly lagging behind adults, long-term pediatric humoral immune responses to SARS-CoV-2 are understudied. The C19.CHILD Hamburg (COVID-19 Child Health Investigation of Latent Disease) Study is a prospective cohort study designed to identify and follow up children and their household contacts infected in the early 2020 first wave of SARS-CoV-2. We screened 6113 children < 18 years by nasopharyngeal swab-PCR in a low-incidence setting after general lockdown, from May 11 to June 30, 2020. A total of 4657 participants underwent antibody testing. Positive tests were followed up by repeated PCR and serological testing of all household contacts over 6 months. In total, the study identified 67 seropositive children (1.44%); the median time after infection at first presentation was 83 days post-symptom onset (PSO). Follow-up of household contacts showed less than 100% seroprevalence in most families, with higher seroprevalence in families with adult index cases compared to pediatric index cases (OR 1.79, P = 0.047). Most importantly, children showed sustained seroconversion up to 9 months PSO, and serum antibody concentrations persistently surpassed adult levels (ratio serum IgG spike children vs. adults 90 days PSO 1.75, P < 0.001; 180 days 1.38, P = 0.01; 270 days 1.54, P = 0.001). In a low-incidence setting, SARS-CoV-2 infection and humoral immune response present distinct patterns in children including higher antibody levels, and lower seroprevalence in families with pediatric index cases. Children show long-term SARS-CoV-2 antibody responses. These findings are relevant to novel variants with increased disease burden in children, as well as for the planning of age-appropriate vaccination strategies.

Pessimistic health and optimistic wealth distributions perceptions in Germany and the UK: evidence from an online-survey.

BACKGROUND: Inequalities in health and wealth distributions are becoming pressing societal problems in many countries. How these inequalities are perceived and to what degree perceptions are aligned with actual distributions, is important for trust in public health services, social and economic policies, and policymakers. This study aims to assess perceived and desired levels of inequality in health and wealth in Germany and the UK. METHODS: The online-survey was filled out by 769 volunteers (322 from Germany, 447 from the UK), recruited from an existing commercial panel (Prolific Academic) or via Facebook advertisements in 2019. Perceived and ideal national health and wealth distributions were assessed and compared to actual health indicators (i.e. days absent from work, number of visits to general practitioners (GPs) and self-rated health), and actual wealth distributions with t-tests. RESULTS: A pronounced gap emerged between the estimated, ideal and actual inequality. Both samples strikingly underestimated the proportion of (very) good health in the national distribution by a factor of ~ 2.3 (participants estimated that 34% of the German and 36% of the UK population respectively are very healthy or healthy, while the actual proportion in the population was 75% in Germany and 84% in the UK, P < 0.001 for all). Moreover, actual health distributions were much closer to the desired than the perceived health distributions (78% of German and 72% of UK participants ideally being very healthy or healthy). A reversed pattern of results emerged for wealth in both samples, with wealth inequality being strikingly worse than desired and inequality being underestimated by a factor ~ 1.7 (P < 0.001 for all). Results were consistent across demographic groups. CONCLUSIONS: Respondents in both Germany and the UK have profoundly negative misperceptions regarding the distribution of health, which contrasts with starkly positive misperceptions regarding the distribution of wealth, indicating that the public is healthier but poorer than they think. More importantly, from a public health perspective, a high level of consensus emerged, with both healthy and wealthy participants misperceiving health and wealth distributions.

Dynamic Risk Perceptions in Times of Avian and Seasonal Influenza Epidemics: A Repeated Cross-Sectional Design.

Infectious diseases pose a serious threat to humans. Therefore, it is crucial to understand how accurately people perceive these risks. However, accuracy can be operationalized differently depending on the standard of comparison. The present study investigated accuracy in risk perceptions for three infectious diseases (avian influenza, seasonal influenza, common cold) using three different standards for accuracy: Social comparison (self vs. others' risk perceptions), general problem level (risk perceptions for diseases with varying threat levels), and dynamic problem level (risk perceptions during epidemics/seasons vs. nonepidemic/off-season times). Four online surveys were conducted using a repeated cross-sectional design. Two surveys were conducted during epidemics/seasons of avian influenza, seasonal influenza, and common cold in 2006 (n = 387) and 2016 (n = 370) and two surveys during nonepidemic/off-season times for the three diseases in 2009 (n = 792) during a swine flu outbreak and in 2018 (n = 422) during no outbreak of zoonotic influenza. While on average participants felt less at risk than others, indicating an optimistic bias, risk perceptions matched the magnitude of risk associated with the three infectious diseases. Importantly, a significant three-way interaction indicated dynamic accuracy in risk perceptions: Participants felt more at risk for seasonal influenza and common cold during influenza and cold seasons, compared with off-season times. However, these dynamic increases were more pronounced in the perceived risk for others than for oneself (optimistic bias). The results emphasize the importance of using multiple approaches to assess accuracy of risk perception as they provided different information on how accurately people gauge their risk when facing infectious diseases.

Tetrahydroquinolinyl phosphinamidates and phosphonamidates enhancing tolerance towards drought stress in crops via interaction with ABA receptor proteins.

New phosphorous-containing lead structures against drought stress in crops interacting with RCAR/(PYR/PYL) receptor proteins were identified starting from in-depth SAR studies of related sulfonamide lead structures and protein docking studies. A converging 6-step synthesis via phosphinic chlorides and phosphono chloridates as key intermediates afforded envisaged tetrahydroquinolinyl phosphinamidates and phosphonamidates. Whilst tetrahydroquinolinyl phosphonamidates 13a,b exhibited low to moderate target affinities, the corresponding tetrahydroquinolinyl phosphinamidates 12a,b revealed confirmed strong affinities for RCAR/ (PYR/PYL) receptor proteins in Arabidopsis thaliana on the same level as essential plant hormone abscisic acid (ABA) combined with promising efficacy against drought stress in vivo (broad-acre crops wheat and canola).

Identifying new lead structures to enhance tolerance towards drought stress via high-throughput screening giving crops a quantum of solace.

Novel synthetic lead structures interacting with RCAR/(PYR/PYL) receptor proteins were identified based on the results of a high-throughput screening campaign of a large compound library followed by focused SAR studies of the three most promising hit clusters. Whilst indolinylmethyl sulfonamides 8y,z and phenylsulfonyl ethylenediamines 9y,z showed strong affinities for RCAR/ (PYR/PYL) receptor proteins in wheat, thiotriazolyl acetamides 7f,s exhibited promising efficacy against drought stress in vivo (wheat, corn and canola) combined with confirmed target interaction in wheat and arabidopsis thaliana. Remarkably, binding affinities of several representatives of 8 and 9 were on the same level or even better than the essential plant hormone abscisic acid (ABA).

Relevance of the Thought-Shape Fusion Trait Questionnaire for healthy women and women presenting symptoms of eating disorders and mixed mental disorders.

Thought-shape fusion (TSF) describes the experience of marked concerns about body weight/shape, feelings of fatness, the perception of weight gain, and the impression of moral wrongdoing after thinking about eating fattening/forbidden foods. This study sets out to evaluate the short version of the TSF trait questionnaire (TSF). The sample consists of 315 healthy control women, 244 women with clinical and subthreshold eating disorders, and 113 women with mixed mental disorders (mixed). The factor structure of the TSF questionnaire was examined using exploratory and subsequent confirmatory factor analyses. The questionnaire distinguishes between a Concept scale and a Clinical Impact scale. However, a lack of measurement invariances refers to significant differences between groups in terms of factor loadings, thresholds, and residuals, which questions cross-group validity. Results indicate that the concept is understood differently in the 3 groups and refers to the suitability of the questionnaire primarily for individuals presenting with symptoms of eating disorders.

Bias in Observed Assessments in Medical Education: A Scoping Review.

PURPOSE: Observed assessments are integral to medical education but may be biased against structurally marginalized communities. Current understanding of assessment bias is limited because studies have focused on single specialties, levels of training, or social identity characteristics (SIDCs). This scoping review maps studies investigating bias in observed assessments in medical education arising from trainees' observable SIDCs at different medical training levels, with consideration of medical specialties, assessment environments, and assessment tools. METHOD: MEDLINE, Embase, ERIC, PsycINFO, Scopus, Web of Science Core Collection, and Cochrane Library were searched for articles published between January 1, 2008, and March 15, 2023, on assessment bias related to 6 observable SIDCs: gender (binary), gender nonconformance, race and ethnicity, religious expression, visible disability, and age. Two authors reviewed the articles, with conflicts resolved by consensus or a third reviewer. Results were interpreted through group review and informed by consultation with experts and stakeholders. RESULTS: Sixty-six of 2,920 articles (2.3%) were included. These studies most frequently investigated graduate medical education (44 [66.7%]), used quantitative methods (52 [78.8%]), and explored gender bias (63 [95.5%]). No studies investigated gender nonconformance, religious expression, or visible disability. One evaluated intersectionality, with SIDCs described inconsistently. General surgery (16 [24.2%]) and internal medicine (12 [18.2%]) were the most studied specialties. Simulated environments (37 [56.0%]) were studied more frequently than clinical environments (29 [43.9%]). Bias favoring men was found more in assessments of intraoperative autonomy (5 of 9 [55.6%]), whereas clinical examination bias often favored women (15 of 19 [78.9%]). When race and ethnicity bias was identified, it consistently favored White students. CONCLUSIONS: This review mapped studies of gender, race, and ethnicity bias in the medical education assessment literature, finding limited studies on other SIDCs and intersectionality. These findings will guide future research by highlighting the importance of consistent terminology, unexplored SIDCs, and intersectionality.

Lack of reassurance after unexpected positive health risk feedback - an analysis of temporal dynamics.

INTRODUCTION: How do people receive unexpected positive health risk information? While common motivational accounts predict acceptance, consistency accounts such as the cue-adaptive reasoning account (CARA) predict a 'lack of reassurance'. OBJECTIVES: We therefore tested (1) whether people prefer striving for positivity or retaining a sense of self-consistency ('lack of reassurance'), and (2) if there are systematic differences in short- and long-term reception, which would indicate temporal dynamics in processing. METHODS: As part of a longitudinal cohort study, participants of a community health screening (N = 1,055) received their actual cholesterol readings. Feedback reception was assessed immediately, at one month and six months. RESULTS: Processing trajectories for unexpected positive feedback showed a significant 'lack of reassurance' effect over time compared with expected positive feedback, while unexpected negative feedback was less threatening than expected negative feedback. CONCLUSIONS: The perseverance of this 'lack of reassurance' over time indicates that striving for consistency in self-views is a robust phenomenon, even if it means forfeiting a better view of one's own health.

An Increase in Vigorous but Not Moderate Physical Activity Makes People Feel They Have Changed Their Behavior.

Objective: While behavioral recommendations regarding physical activity commonly focus on reaching demanding goals by proposing "thresholds," little attention has been paid to the question of how much of a behavioral change is needed to make people feel that they have changed. The present research investigated this relation between actual and felt behavior change. Design: Using data from two longitudinal community samples, Study 1 and Study 2 comprised 614 (63% women) and 398 participants (61% women) with a mean age of 40.9 years (SD = 13.6) and 42.5 years (SD = 13.4), respectively. Using a stage-approach, participants were classified into four groups by asking them at the respective second measurement to indicate whether they had become more physically active since their last participation 6 months ago ("Changers"), they had tried but did not succeed in becoming more physically active ("Attempters"), they were already physically active on a regular basis ("Regular Actives"), or they had not tried to become more physically active ("Non-Attempters"). Physical activity was measured using the International Physical Activity Questionnaire (IPAQ), and fitness level was assessed as physical working capacity (PWC) via bicycle ergometry. Mixed ANOVAs including Time and Perceived Change as within and between factors were conducted, followed up by simple effect analyses. Results: Participants stating to have become more active in the past 6 months (Changers) showed a significant increase in vigorous physical activity but not in moderate physical activity, with an average of 6.8 (Study 1) and 10.6 (Study 2) metabolic equivalent value-hours (MET-hours) per week in vigorous activity. Corroborating these findings, objective fitness also significantly increased in the group of Changers. No systematic change in moderate or vigorous physical activity was observed for the three other "non-changer" groups (Regular actives, Attempters, Non-Attempters). Conclusion: The intensity of physical activity is the crucial variable for people's perception of change in physical activity. Moderate physical activity seems not to be perceived as an effective means for behavior change. It thus might fail to unfold sufficient motivational impact, despite its known positive effects on health.

Rheumatoid arthritis synovial membrane contains a 62,000-molecular-weight protein that shares an antigenic epitope with the Epstein-Barr virus-encoded associated nuclear antigen.

A monoclonal antibody, selected for reactivity with the Epstein-Barr virus (EBV)-encoded antigen EBNA-1, exhibited strong reactivity with the synovial lining cells in joint biopsies from 10 of 12 patients with rheumatoid arthritis (RA) and adherent cells eluted from these tissues. No staining of RA synovial membrane frozen tissue sections or eluted synovial-lining cells was obtained with monoclonal antibodies directed against other EBV-encoded antigens (anti-p160, anti-gp200/350) or with monoclonal antibodies directed against antigens encoded by cytomegalovirus, herpes simplex viruses, or human T cell leukemia virus type I. Among 12 osteoarthritis and normal synovial biopsies only rare reactive cells were noted. Characterization of the antigen(s) in RA synovium by the Western immunoblotting technique revealed a 62,000-molecular-weight (mol-wt) protein, in contrast to the 70,000-85,000-mol-wt EBNA-1 antigen found in EBV-transformed cells. The structural basis for the cross-reactivity of the RA synovial membrane 62,000-mol-wt protein and the EBNA-1 antigen appears to reside in the glycine-alanine rich region of these molecules. A rabbit antibody directed against a synthetic peptide (IR3-VI-2) derived from the glycine-alanine-rich region of EBNA-1 reacted with the 70,000-85,000-mol-wt EBNA-1 antigen in EBV-infected cells and with the 62,000-mol-wt molecule in RA synovial membrane extracts. Since strong antibody responses to EBNA-1 are known to exist in RA patients, these results suggest that immune responses to a cross-reactive antigen may play a role in the pathogenesis of RA.

Cognitive Distortions Associated with Imagination of the Thin Ideal: Validation of the Thought-Shape Fusion Body Questionnaire (TSF-B).

Thought-shape fusion (TSF) describes the experience of body-related cognitive distortions associated with eating disorder (ED) pathology. In the laboratory TSF has been activated by thoughts about fattening/forbidden foods and thin ideals. This study aims at validating a questionnaire to assess the trait susceptibility to TSF (i.e., body-related cognitive distortions) associated with the imagination of thin ideals, and developing an adapted version of the original TSF trait questionnaire, the Thought-Shape Fusion Body Questionnaire (TSF-B). Healthy control women (HC, n = 317) and women diagnosed with subthreshold and clinical EDs (n = 243) completed an online-questionnaire. The factor structure of the TSF-B questionnaire was examined using exploratory (EFA) and subsequent confirmatory factor analysis (CFA). EFA pointed to a two-factor solution, confirmed by CFA. Subscale 1 was named Imagination of thin ideals, containing five items referring to the imagination of female thin ideals. Subscale 2 was named Striving for own thin ideal, with seven items about pursuing/abandoning attempts to reach one's own thin ideal. The total scale and both subscales showed good convergent validity, excellent reliability, and good ability to discriminate between individuals with subthreshold/clinical EDs and HCs. Results indicate that cognitive distortions are also related to the imagination of thin ideals, and are associated with ED pathology. With two subscales, the TSF-B trait questionnaire appropriately measures this construct. Future studies should clarify whether TSF-B is predictive for the development and course of EDs. Assessing cognitive distortions with the TSF-B questionnaire could improve understanding of EDs and stimulate the development of cognitively oriented interventions. CLINICAL TRIAL REGISTRATION NUMBER: DRKS-ID: DRKS00005709.

Detection of antigens associated with Epstein-Barr virus replication in extracts from biopsy specimens of nasopharyngeal carcinomas.

By using monoclonal antibodies to different Epstein-Barr virus (EBV) polypeptides in combination with immunoblotting, we detected antigens associated with EBV replication in extracts from nasopharyngeal carcinoma (NPC) biopsy specimens. Major polypeptides associated with both the diffuse and the restricted components of the early antigen (EA) complex were found in extracts from nine of nine NPC biopsy specimens. Cells from an additional NPC biopsy specimen, passaged repeatedly in nude mice, were found to be positive for the major EA (restricted) polypeptide. This approach revealed that extracts from three of 14 biopsy specimens form other benign and malignant diseases also expressed these viral polypeptides. Therefore, for the first time, these results conclusively demonstrate the presence of EA polypeptides in extracts from NPC biopsy specimens. This finding provides at least a partial explanation for the reported prognostic value of antibodies to this antigen in patients with this disease.

Expression of Epstein-Barr virus proteins in primary CNS lymphoma in AIDS patients.

We examined the expression of the Epstein-Barr virus (EBV)-induced proteins (LMP [latent membrane protein], EBNA-2, and CD23) and a lytic protein, viral capsid antigen (VCA), in five acquired immune deficiency syndrome (AIDS)-related primary CNS lymphomas (PCNSLs). We compared that expression with the expression of the same proteins in PCNSL from six immunocompetent patients and severe combined immune deficiency (SCID) mouse brains injected with EBV-infected lymphoblastoid cell lines (LCLs). Brain biopsy tissue from an AIDS patient with progressive multifocal leukoencephalopathy (PML) and a normal brain was also studied. Three of the AIDS PCNSLs expressed both human immunoglobulin kappa and lambda light chains and two expressed lambda light chain only. All non-AIDS-related PCNSLs expressed a single light-chain isotype. All five AIDS-related PCNSLs expressed LMP-1 (> 40%), EBNA-2 (> 60%), and VCA (1 to 5%) of tumor cells. These proteins were similarly expressed in the SCID/human chimeras. None of the PCNSLs from immunocompetent subjects, the normal brain, or the brain of the patient with PML expressed these proteins. PCNSL in AIDS patients bears greater similarity to EBV-infected LCLs than to PCNSL from immunocompetent patients.

Antibodies against Epstein-Barr nuclear antigen (EBNA) in multiple sclerosis CSF, and two pentapeptide sequence identities between EBNA and myelin basic protein.

The Epstein-Barr virus (EBV) causes infectious mononucleosis and is linked to several disparate malignancies. Prior studies on patients with multiple sclerosis (MS) showed that 100% are EBV-seropositive and that their blood contains higher antibody titers than those of controls to both transformation and lytic cycle antigens. We performed three different assays for antibodies in CSF to three major EBV antigens from patients with MS and controls. Among 93 patients with MS, 79 (85%) had CSF that reacted with a 70 kD protein, shown to be the nuclear antigen, EBNA-1, whereas only 11 (13%) of 81 EBV-seropositive controls reacted, p less than 0.001. The CSF of all 14 MS patients, unreactive on immunoblots, contained oligoclonal bands on agarose electrophoresis. Together, the two techniques exhibit 100% sensitivity in the confirmatory diagnosis of MS. We also performed amino acid searches of the Protein Identification Resource sequence database for protein homologies to EBNA. Two pentapeptide identities were found between EBNA-1 and myelin basic protein: QKRPS and PRHRD. None of more than 32,000 other proteins in the database contained both pentapeptides. In healthy EBV-seropositive persons, the EBV-specific, MHC-restricted T lymphocytes keep the EBV-containing B lymphocytes locked in the transformed state. However, in the host genetically susceptible to MS, the same population of lymphocytes might recognize and interact with either of the two identified pentapeptides, inadvertently damaging MBP.

A sensitive enzyme-linked immunosorbent assay (ELISA) against the major EBV-associated antigens. I. Correlation between ELISA and immunofluorescence titers using purified antigens.

An enzyme-linked immunosorbent assay (ELISA) was developed for the major Epstein-Barr virus (EBV) associated antigens. The ELISA assay was based on purified protein components of virus-capsid antigen (VCA), early antigen (EA), membrane antigen (MA) and the nuclear antigen (EBNA). These antigens, except EBNA, were purified on immunoaffinity columns containing monoclonal antibodies, while EBNA was purified by biochemical methods. Screening of 69 human sera including 26 sera from individuals with infectious mononucleosis against these antigens in ELISA showed a good correlation with immunofluorescence titers against the major groups of EBV associated antigens. The results indicated that the ELISA technique using purified EBV proteins could be useful for detecting and monitoring antibody responses to different EBV proteins in patients with EBV-associated diseases.

Enzyme-linked immunosorbent assay for the detection of Epstein-Barr virus-induced antigens and antibodies.

Two Epstein-Barr virus (EBV)-specific ELISA tests were developed. One, based on the use of crude extracts from virus producer cells highly induced in the presence of Ara C (providing EA + VCA- cells) or in the absence of the drug (providing EA + VCA + cells) is suitable for the detection of antibodies directed against antigen complexes associated with the lytic virus cycle; i.e., EA, VCA and presumably also MA. The second, performed with purified EBNA, can be used for the detection of antibodies to the transformation-associated nuclear antigen. The tests are expected to find application in the dissection of antibody responses of patients to various antigenic subcomponents, the monitoring of EBV-coded antigens during biochemical purification, and the screening of spent media from hybridoma cultures for EBV-specific antibodies.

Evidence for antigenic distinctness of the Epstein--Barr virus-determined nuclear antigen and the Herpesvirus papio-determined nuclear antigen.

Previous serological evidence indicated that Epstein--Barr virus-determined nuclear antigen (EBNA) has cross reactive components with the herpesvirus papio-determined nuclear antigen (HUPNA) and, in addition, it has distinct components of its own, not present in HUPNA. In the present study, this hypothesis was studied by absorption experiments. Absorption of anti-EBNA positive human sera with EBNA abolished both anti-EBNA and anti-HUPNA reactivity. Absorption with HUPNA removed all anti-HUPNA reactivity but did not reduce anti-EBNA to any detectable degree, thus confirming the hypothesis.

Effect of retinoic acid (RA) on the Epstein-Barr virus (EBV)-inducing effect of sodium butyrate.

Sodium butyrate is a powerful inducer of the Epstein-Barr virus (EBV) cycle in the P3HR-1 cell line. Retinoic acid (RA) was found to reduce the butyrate induction of early antigen (EA) and viral capsid antigen (VCA) by 26-41%. This is similar to the previously reported effect of RA on IUDR and TPA induction, with certain quantitative differences between the systems.

Detection of the EBV-determined nuclear antigen (EBNA) in Burkitt's lymphoma and nasopharyngeal carcinoma biopsies by the acid fixed nuclear binding (AFNB) technique.

Epstein-Barr virus (EBV) carrying biopsies of Burkitt lymphoma (BL) and nasopharyngeal carcinoma (NPC) were used to examine the question whether the EBV-associated nuclear antigen (EBNA) can be demonstrated by the acid fixed nuclear binding (AFNB) technique, developed previously for the demonstration of EBNA in cultured cell lines [11]. Extracts of 5 BL and 5 NPC biopsies gave a brilliant, EBNA specific fluorescence after binding to acid fixed chicken red cells. Similar extracts of 3 other African tumors that are not known to carry the EBV-genome were negative, in spite of the fact that they were derived from EBV-seropositive patients with relatively high anti-EBV (VCA) antibody titers. Crude extraction and DNA-cellulose purification gave equally active extracts, provided that incubation was carried out at 4 degrees C. These results show that the acid fixed nuclear binding technique can be applied to biopsy material. This may be helpful in searching for EBNA carrying cells in heterogeneous normal and tumor tissues in vivo where the direct in situ ACIF staining for EBNA is known to meet great difficulties.

Activation of Epstein-Barr virus in latently infected cell lines.

Several methods that can switch between latency and replication of Epstein-Barr virus (EBV) have been developed. These methods made it possible to identify and characterize the majority of virus proteins associated with the virus replication and to develop new assays for diagnosis. A possible activator protein encoded from the BamHI Z fragment of EBV genome, which can disrupt latency in EBV-genome positive cell lines, has also been identified. The developments in activation of the virus lytic cycle will be reviewed in this paper.