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Abstract. The Self-Report Symptom Inventory (SRSI) intends to measure symptom overreporting. To assess the Dutch and German SRSI equivalence, both versions were split into two half-forms. Forty bilingual participants were randomly allocated to two groups that completed the first half in German and the second half in Dutch or vice versa. Each group completed the SRSI honestly and then under feigning instructions. For both conditions, the Dutch and German SRSI did not statistically significantly differ within and across the two groups. For most comparisons, the Bayes factor was ≥ 3, indicating moderate evidence favoring the equivalence of language versions and half-forms. Genuine and pseudosymptoms endorsement was significantly higher in the feigning than in the honest condition (both Zs = 5.44, rrb = 1.00). The SRSI standard cut score correctly identified honest responding and detected 80% of feigned responses. Our results align with Giger and Merten’s (2019) German and French SRSI equivalence study.

Some researchers argue that the modified Stroop task (MST) can be employed to rule out feigning. According to these authors, modified Stroop interference effects are beyond conscious control and therefore indicative of genuine psychopathology. We examined this assumption using a within-subject design. In the first session, students (N = 22) responded honestly, while in the second session they were asked to read a vignette about test anxiety and then fake this condition. During both sessions, we administered an MST consisting of neutral, anxiety-related, and test anxiety-related words. Participants also completed the Self-Report Symptom Inventory (SRSI; Merten et al., 2016) that focuses on over-reporting of pseudosymptoms. Our feigning instructions were successful in that students succeeded in generating the typical MST effect by providing longer response latencies on anxiety related (r = 0.43) and test anxiety-related (r = 0.31) words, compared with neutral words. Furthermore, students endorsed significantly more pseudosymptoms on the SRSI (r = 0.62) in the feigning session than in the honest control condition. We conclude that the MST effect is not immune to feigning tendencies, while the SRSI provides promising results that require future research.

Los resultados encontrados en la evaluación de la validez de los síntomas (SVT) deberían ser inmunes a las variables sociodemográficas. Así, los sujetos sanos y cooperadores deberían superar los tests de SVT. El ob- jetivo de este estudio es obtener datos de referencia de una serie de pruebas utilizadas en la evaluación de la validez de los síntomas, en una muestra representativa de 100 ciudadanos suizos, germano-hablantes, de entre 18 y 60 años: Medical Symptom Validity Test, Structured Inventory of Malingered Symptomatology, Amsterdam Short-Term Memory Test, Emotional Numbing Test, Reliable Digit Span y Maximum Span Forward. Los análisis de regresión múltiple reflejaron que las variables edad e inteligencia verbal afectaron a los resultados de varias de las pruebas, mientras que no fue así para las variables sexo y nivel educativo. La tasa de resultados positivos osciló entre el 1% (Emotional Numbing Test, Structured Inventory of Malin- gered Symptomatology) y el 4% (Maximum Span Forward). Una cuestión relevante que se desprende de este estudio es si dichos resultados positivos en las muestras de referencia

Hasta no hace mucho tiempo la evaluación de la validez de los síntomas en Europa, tanto en su vertiente científico-académica como en la práctica profesional, estaba muy por detrás de los avances que se producían en Norteamérica y particularmente la simulación se consideraba un tema tabú entre los profesionales de la Psicología y la Medicina. En la última década las cosas parecen haber cambiado, observándose un incremento en el interés por la evaluación del sesgo de respuesta negativo. Las tasas base de prevalencia obtenidas utilizando pruebas de rendimiento subóptimo en contextos civiles y forenses son similares a las obtenidas en Norteamérica. Los fenómenos de exageración de síntomas en autoinformes y rendimiento insuficiente en pruebas neuropsicológicas parecen ocurrir en semejante proporción de pacientes. Aunque se han producido avances notables en el establecimiento de la evaluación de la validez de los síntomas como una parte integral e indispensable de la evaluación psicológica y neuropsicológica en algunos países europeos, en otros sin embargo la situación es mucho más incipiente. De hecho, en algunos países sigue existiendo una gran resistencia a la evaluación de la validez de los síntomas proveniente de algunos profesionales de la psiquiatría y la neuropsicología.

After solid-organ transplantation, reactivation of the cytomegalovirus (CMV) is often observed in seronegative patients and associated with a high risk of disease and mortality. CMV-specific T cells can prevent CMV reactivation. In a phase 1 trial, CMV-seronegative patients with end-stage renal disease listed for kidney transplantation were subjected to CMV phosphoprotein 65 (CMVpp65) peptide vaccination and further investigated for T-cell responses. To this end, CMV-specific CD8+ T cells were characterized by bulk T-cell-receptor (TCR) repertoire sequencing and combined single-cell RNA and TCR sequencing. In patients mounting an immune response to the vaccine, a common SYE(N)E TCR motif known to bind CMVpp65 was detected. CMV-peptide-vaccination-responder patients had TCR features distinct from those of non-responders. In a non-responder patient, a monoclonal inflammatory T-cell response was detected upon CMV reactivation. The identification of vaccine-induced CMV-reactive TCRs motifs might facilitate the development of cellular therapies for patients wait-listed for kidney transplantation.

Abstract Background The goal of this study was to apply the varicella zoster virus (VZV) vaccine to patients with pediatric rheumatic diseases (PRD) at risk for severe chickenpox, without interrupting their current immunosuppression, including biological agents, using an immunological-based pre-vaccination checklist to assure safety. A pre-vaccination checklist was implemented to ensure adequate immune competence prior to immunization. Methods This prospective study included seronegative patients (VZV-IgG ≤200 mIU/ml) and patients who had previously received only a single dose of VZV vaccine. All vaccinees demonstrated clinically inactive PRD. Patients were categorized according to their actual treatment in low-intensity IS (LIIS) and high-intensity IS (HIIS) including biological therapy. The pre-vaccination checklist defined thresholds for the following basic laboratory tests: white blood cell count ≥3000/mm3, lymphocytes ≥1200/mm3, serum IgG ≥500 mg/dl, IgM ≥20 mg/dl, tetanus toxoid antibody ≥0.1 IU/ml. In case of HIIS additional specifications included a CD4+ lymphocyte count ≥200/mm3 and a positive T-cell function (via analyzable positive control of a standard tuberculosis interferon-gamma-release-assay (TB-IGRA) indicating mitogen-induced T cell proliferation). Patients who met the criteria of the pre-vaccination checklist received the first and/or second VZV vaccination. Immunologic response and side effects were monitored. Results Twenty-three patients were recruited of whom nine had already received one VZV immunization before initiating IS. All patients met the pre-vaccination checklist criteria despite ongoing IS. There was no overall difference in VZV-IgG levels when comparing the LIIS (n=9) and HIIS (n=14) groups. In total, 21 patients (91%) showed a positive vaccination response, after the first immunization the median VZV-IgG across all patients was 224 (59-1219) mIU/ml (median (range)), after booster immunization it increased to 882 (30-4685) mIU/ml. Two patients in the HIIS group failed to raise positive VZV-IgG, despite booster immunization. All nine patients receiving only the second immunization on IS reached high titers of VZV-IgG >500 mIU/ml (1117 (513-4685) mIU/ml). There were no cases of rash or other vaccine-induced varicella disease symptoms and no evidence of PRD flare. Conclusions VZV vaccination is safe and largely immunogenic in children with ongoing IS fulfilling an immunological based pre-vaccination checklist. This new approach is based on immunologic function rather than on type of medications. Trial registration number ISRCRTN trial registration number 21654693, date of registration February 12, 2018, retrospectively registered.

Presentation to the special issue on Kant's Metaphysics of Morals

Despite Kant's explicit statement that every murderer must suffer death, there are at least four situations to be found in Kant's work in which the killing of a human being should not lead to the death penalty: when too many murderers are involved; when a mother kills her illegitimate child; when one duellist kills the other; when one person pushes another off a plank in order to save his life. This paper discusses these situation and concentrates on the last situation - Kant's interpretation of the plank of Carneades – with an eye to what they learn us about Kant understanding of the law. Does Kant acknowledge a legal vacuum? In order to come to a conclusion, Kant's 'solution' of the plank is compared with those suggested by other authors, such as Cicero, Pufendorf and Lon Fuller in his famous 'speluncean explorers' case.

Human cytomegalovirus (HCMV) persistently infects 40–90% of the human population but in the face of a normal immune system, viral spread and dissemination are efficiently controlled thus preventing clinically signs and disease. HCMV-infected hosts produce a remarkably large amount of HCMV-specific CD4+ and CD8+ T cells that can even reach 20–50% of total T memory cells in the elderly. How HCMV may elicit such large and long-lasting T-cell responses in the absence of detectable viremia has not been elucidated yet. Additionally, HCMV is known to encode several gene products that potently inhibit T-cell recognition of infected cells. The best characterized are the four immune evasive US2, US3, US6, and US11 genes that by different mechanisms account for major histocompatibility complex (MHC) class I and class II degradation and intracellular retention in infected cells. By infecting M1 and M2 human macrophages (Mφ) with the wild-type HCMV strain TB40E or a mutant virus deleted of the four immune evasive genes US2, US3, US6, and US11, we demonstrated that human Mφ counteract the inhibitory potential of the US2-11 genes and remain capable to present peptides via MHC class I and class II molecules. Moreover, by sorting the infected and bystander cells, we provide evidence that both infected and bystander Mφ contribute to antigen presentation to CD4+ and CD8+ T cells. The T cells responding to TB40E-infected Mφ show markers of the T effector memory compartment, produce interferon-γ, and express the lytic granule marker CD107a on the cell surface, thus mirroring the HCMV-specific T cells present in healthy seropositive individuals. All together, our findings reveal that human Mφ escape inhibition of MHC-dependent antigen presentation by HCMV and continue to support T cell proliferation and activation after HCMV infection. Taking into account that Mφ are natural targets of HCMV infection and a site of viral reactivation from latency, our findings support the hypothesis that Mφ play crucial roles for the lifelong maintenance and expansion of HCMV-committed T cells in the human host.

We show that focused ion beam/scanning electron microscopy (FIB/SEM) tomography is an excellent method to analyze the three-dimensional structure of a fibroblast nucleus infected with human cytomegalovirus (HCMV). We found that the previously described infoldings of the inner nuclear membrane, which are unique among its kind, form an extremely complex network of membrane structures not predictable by previous two-dimensional studies. In all cases they contained further invaginations (2nd and 3rd order infoldings). Quantification revealed 5498HCMV capsids within two nuclear segments, allowing an estimate of 15,000 to 30,000 capsids in the entire nucleus five days post infection. Only 0.8% proved to be enveloped capsids which were exclusively detected in 1st order infoldings (perinuclear space). Distribution of the capsids between 1st, 2nd and 3rd order infoldings is in complete agreement with the envelopment/de-envelopment model for egress of HCMV capsids from the nucleus and we confirm that capsid budding does occur at the large infoldings. Based on our results we propose the pushing membrane model: HCMV infection induces local disruption of the nuclear lamina and synthesis of new membrane material which is pushed into the nucleoplasm, forming complex membrane infoldings in a highly abundant manner, which then may be also used by nucleocapsids for budding.

INTRODUCTION: C-reactive protein (CRP), white blood cell (WBC) and absolute neutrophil counts (ANC) are important inflammatory biomarkers in the early diagnosis of infections. However, little is known on their profile and usefulness in fever case management in children attending outpatient clinic in rural north-eastern Tanzania. METHODS: patients aged between 2 and 59 months presenting with fever at Korogwe District Hospital were enrolled. Venous blood was collected for evaluation of serum CRP, WBC and ANC. Individual patient diagnosis was based on integrated management of childhood illness (IMCI) guidelines and laboratory investigations (blood and urine cultures). RESULTS: a total of 867 patients were enrolled, out of which 691 (79.7%) had complete clinical and laboratory data available for analysis. Acute upper respiratory tract infection 284 (41.1%), acute gastroenteritis 127 (18.4%) and pneumonia 100 (14.5%) were the most frequent diagnoses. The geometric mean levels of serum CRP, WBC and ANC were 10.4 (95% CI: 9.2 - 11.8), 11.5 (95% CI: 11.1 - 11.9) and 5.5 (95% CI: 5.2 - 5.8), respectively. CRPd"20, WBCd"15 (103cells/L) and ANCd"10 103cells/L) were observed in the majority of the patients with upper respiratory tract infection, pneumonia, acute gastroenteritis and non-specific febrile illness. Only serum CRP levels were positively correlated with positive blood cultures at a calculated cut-off value of 37.3 mg/L, giving a specificity of 77.8% and sensitivity of 74.2%. CONCLUSION: CRP assessment together with IMCI guidelines may be useful in assisting the diagnosis and management of paediatric febrile infections in Tanzania.

The recombination-activating genes (RAGs) and the DNA cross-link repair 1C gene (DCLRE1C) encode the enzymes RAG1, RAG2 and Artemis. They are critical components of the V(D)J recombination machinery. V(D)J recombination is well known as a prerequisite for the development and antigen diversity of T and B cells. New findings suggested that RAG deficiency impacts the cellular fitness and function of murine NK cells. It is not known whether NK cells from severe combined immunodeficiency (SCID) patients with defective RAGs or DCLRE1C (RAGs−/DCLRE1C−-NK) are active against virus infections. Here, we evaluated the anti-HCMV activity of RAGs−/DCLRE1C−-NK cells. NK cells from six SCID patients were functional in inhibiting HCMV transmission between cells in vitro. We also investigated the expansion of HCMV-induced NK cell subset in the RAG- or DCLRE1C-deficient patients. A dynamic expansion of NKG2C+ NK cells in one RAG-2-deficient patient was observed post HCMV acute infection. Our study firstly reveals the antiviral activity of human RAGs−/ DCLRE1C−-NK cells.

Review of: B. Sharon Byrd and Joachim Hruschka, Kant’s Doctrine of Right. A Commentary (Cambridge University Press, Cambridge 2010) 336 p.

Cytomegalovirus (CMV) is a pathogen of emerging importance for patients with septic shock. In this prospective study, 25 immunocompetent CMV-seropositive patients with septic shock and an intensive care unit stay of >7 days were monitored by using quantitative pp65-antigenemia assay, shell vial culture, and virus isolation. Within 2 weeks, active CMV infection with low-level pp65-antigenemia (median 3 positive/5 × 105 leukocytes) developed in 8 (32%) patients. Infection was controlled within a few weeks (median 26 days) without use of antiviral therapy. Duration of intensive care and mechanical ventilation were significantly prolonged in patients with active CMV infection. CMV reactivation was associated with concomitant herpes simplex virus reactivation (p = 0.004). The association between active CMV infection and increased illness could open new therapeutic options for patients with septic shock. Future interventional studies are required.

BACKGROUND: We determined antibodies to the pandemic influenza A (H1N1) 2009 virus in children to assess: the incidence of (H1N1) 2009 infections in the 2009/2010 season in Germany, the proportion of subclinical infections and to compare titers in vaccinated and infected children. METHODOLOGY/PRINCIPAL FINDINGS: Eight pediatric hospitals distributed over Germany prospectively provided sera from in- or outpatients aged 1 to 17 years from April 1(st) to July 31(st) 2010. Vaccination history, recall of infections and sociodemographic factors were ascertained. Antibody titers were measured with a sensitive and specific in-house hemagglutination inhibition test (HIT) and compared to age-matched sera collected during 6 months before the onset of the pandemic in Germany. We analyzed 1420 post-pandemic and 300 pre-pandemic sera. Among unvaccinated children aged 1-4 and 5-17 years the prevalence of HI titers (≥1∶10) was 27.1% (95% CI: 23.5-31.3) and 53.5% (95% CI: 50.9-56.2) compared to 1.7% and 5.5%, respectively, for pre-pandemic sera, accounting for a serologically determined incidence of influenza A (H1N1) 2009 during the season 2009/2010 of 25,4% (95% CI : 19.3-30.5) in children aged 1-4 years and 48.0% (95% CI: 42.6-52.0) in 5-17 year old children. Of children with HI titers ≥1∶10, 25.5% (95% CI: 22.5-28.8) reported no history of any infectious disease since June 2009. Among vaccinated children, 92% (95%-CI: 87.0-96.6) of the 5-17 year old but only 47.8% (95%-CI: 33.5-66.5) of the 1-4 year old children exhibited HI titers against influenza A virus (H1N1) 2009. CONCLUSION: Serologically determined incidence of influenza A (H1N1) 2009 infections in children indicates high infection rates with older children (5-17 years) infected twice as often as younger children. In about a quarter of the children with HI titers after the season 2009/2010 subclinical infections must be assumed. Low HI titers in young children after vaccination with the AS03(B)-adjuvanted split virion vaccine need further scrutiny.

Recombinant viruses labelled with fluorescent proteins are useful tools in molecular virology with multiple applications (e.g., studies on intracellular trafficking, protein localization, or gene activity). We generated by homologous recombination three recombinant cytomegaloviruses carrying the enhanced yellow fluorescent protein (EYFP) fused with the viral proteins IE-2, ppUL32 (pp150), and ppUL83 (pp65). In growth kinetics, the three viruses behaved all like wild type, even at low multiplicity of infection (MOI). The expression of all three fusion proteins was detected, and their respective localizations were the same as for the unmodified proteins in wild-type virus-infected cells. We established the in vivo measurement of fluorescence intensity and used the recombinant viruses to measure inhibition of viral replication by neutralizing antibodies or antiviral substances. The use of these viruses in a pilot screen based on fluorescence intensity and high-content analysis identified cellular kinase inhibitors that block viral replication. In summary, these viruses with individually EYFP-tagged proteins will be useful to study antiviral substances and the dynamics of viral infection in cell culture.