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Changes in gene expression in carps' brains over time following acute stressors has not been studied in detail so far. Consequently, a stress trial with juvenile common carp was conducted to investigate transcriptomic differences in four brain parts in response to acute negative stressors and feed reward, focusing on appetite-related genes, serotonergic and dopaminergic pathways, and other involved systems, at 30, 60, and 90 min after treatments. The treatments showed pronounced effects on the gene expression patterns across brain parts compared to control fish. Notably, npy expression increased in the telencephalon following negative stressors and feed reward, suggesting a stress-coping mechanism by promoting food intake. Unlike zebrafish, cart expression in carp showed varying responses, indicating species-specific regulation of appetite and stress. Serotonergic and dopaminergic pathways were also affected, with alterations in the respective receptors' expression, confirming their roles in stress and reward processing. Additionally, this study highlights the involvement of the opioid- and gamma-aminobutyric acid systems in stress and feeding regulation across brain parts. Furthermore, principal component analyses revealed that neurotransmitter levels in the different brain parts contribute to the explained variance. These findings deepen our understanding of how different fish species react to acute stress and rewards.

Enterovirus D68 (EV-D68) infections are associated with severe respiratory disease and acute flaccid myelitis (AFM). The European Non-Polio Enterovirus Network (ENPEN) aimed to investigate the epidemiological and genetic characteristics of EV-D68 infections and its clinical impact during the fall-winter season of 2021-2022. From 19 European countries, 58 institutes reported 10 481 (6.8%) EV-positive samples of which 1004 (9.6%) were identified as EV-D68 (including 852 respiratory samples). Clinical data were reported for 969 cases; 78.9% of infections were reported in children (0-5 years); and 37.9% of cases were hospitalized. Acute respiratory distress was commonly noted (93.1%) followed by fever (49.4%). Neurological problems were observed in 6.4% of cases including 6 diagnosed with AFM. Phylodynamic/Nextstrain and phylogenetic analyses based on 694 sequences showed the emergence of 2 novel B3-derived lineages, with no regional clustering. In conclusion, we describe a large-scale European EV-D68 upsurge with severe clinical impact and the emergence of B3-derived lineages., Competing Interests: Potential conflicts of interest. All authors: No reported conflicts of interest. All authors have submitted the ICMJE Form for Disclosure of Potential Conflicts of Interest. Conflicts that the editors consider relevant to the content of the manuscript have been disclosed., (© The Author(s) 2024. Published by Oxford University Press on behalf of Infectious Diseases Society of America.)

Acute myelogenous leukemia (AML), a heterogeneous disease of the blood and bone marrow, is characterized by the inability of myeloblasts to differentiate into mature cell types. Dihydroorotate dehydrogenase (DHODH) is an enzyme well-known in the pyrimidine biosynthesis pathway and preclinical findings demonstrated that DHODH is a metabolic vulnerability in AML as inhibitors can induce differentiation across multiple AML subtypes. As a result of virtual screening and structure-based drug design approaches, a novel series of isoquinolinone DHODH inhibitors was identified. Further lead optimization afforded JNJ-74856665 as an orally bioavailable, potent, and selective DHODH inhibitor with favorable physicochemical properties selected for clinical development in patients with AML and myelodysplastic syndromes (MDS).

Following an interseasonal rise in mainly pediatric respiratory syncytial virus (RSV) cases in Germany in 2021, an exceptionally high number of adult cases was observed in the subsequent respiratory season of 2022/2023. The aim of this study was to compare the clinical presentation of RSV infections in the pre- and post-SARS-CoV-2 pandemic periods. Additionally, the local epidemiology of the RSV fusion protein was analyzed at a molecular genetic and amino acid level. RSV detections in adults peaked in calendar week 1 of 2023, 8 weeks earlier than the earliest peak observed in the three pre-pandemic seasons. Although the median age of the adult patients was not different (66.5 vs. 65 years), subtle differences between both periods regarding comorbidities and the clinical presentation of RSV cases were noted. High rates of comorbidities prevailed; however, significantly lower numbers of patients with a history of lung transplantation ( p = 0.009), chronic kidney disease ( p = 0.013), and immunosuppression ( p = 0.038) were observed in the 2022/2023 season. In contrast, significantly more lower respiratory tract infections ( p < 0.001), in particular in the form of pneumonia ( p = 0.015) and exacerbations of obstructive lung diseases ( p = 0.008), were detected. An ICU admission was noted for 23.7% of all patients throughout the study period. Sequence analysis of the fusion protein gene revealed a close phylogenetic relatedness, regardless of the season of origin. However, especially for RSV-B, an accumulation of amino acid point substitutions was noted, including in antigenic site Ø. The SARS-CoV-2 pandemic had a tremendous impact on the seasonality of RSV, and the introduction of new vaccination and immunization strategies against RSV warrants further epidemiologic studies of this important pathogen.

The changing expressions of certain genes as a consequence of exposure to stressors has not been studied in detail in the fish brain. Therefore, a stress trial with zebrafish was conducted, aiming at identifying relevant gene regulation pathways in different regions of the brain. As acute stressors within this trial, feed rewarding, feed restriction, and air exposure have been used. The gene expression data from the experimental fish brains have been analyzed by means of principal component analyses (PCAs), whereby the individual genes have been compiled according to the regulation pathways in the brain. The results did not indicate a mutual response across the treatment and gender groups. To evaluate whether a similar sample structure belonging to a large sample size would have allowed the classification of the gene expression patterns according to the treatments, the data have been bootstrapped and used for building random forest models. These revealed a high accuracy of the classifications, but different genes in the female and male zebrafish were found to have contributed to the classification algorithms the most. These analyses showed that less than eight genes are, in most cases, sufficient for an accurate classification. Moreover, mainly genes belonging to the stress axis, to the isotocin regulation pathways, or to the serotonergic pathways had the strongest influence on the outcome of the classification models., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Pietsch, Konrad, Wernicke von Siebenthal and Pawlak.)

Background: Viral meningitis/encephalitis (ME) is a rare but potentially harmful disease. The prompt identification of the respective virus is important to guide not only treatment but also potential public health countermeasures. However, in about 40% of cases, no virus is identified despite an extensive diagnostic workup. The aim of the present study was to analyze demographic, seasonal, and routine cerebrospinal fluid (CSF) parameters in cases of viral ME and assess their utility for the prediction of the causative virus., Methods: Demographic data, season, and routine CSF parameters (total leucocytes, CSF cell differentiation, age-adjusted CSF/serum albumin ratio, and total immunoglobulin ratios) were retrospectively assessed in cases of viral ME., Results: In total, 156 cases of acute viral ME (74 female, median age 40.0 years) were treated at a tertiary-care hospital in Germany. Specific viral infections were detected in 93 (59.6%) cases. Of these, 14 (9.0%) cases were caused by herpes simplex virus (HSV), 36 (23.1%) by varicella-zoster virus (VZV), 27 (17.3%) by enteroviruses, 9 (5.8%) by West Nile virus (WNV), and 7 (4.5%) by other specific viruses. Additionally, 64 (41.0%) cases of ME of unknown viral etiology were diagnosed. Cases of WNV ME were older, predominantly male, showed a severe disruption of the blood-CSF-barrier, a high proportion of neutrophils in CSF, and an intrathecal total immunoglobulin M synthesis in the first CSF sample. In a multinominal logistic regression analysis, the accuracy of these CSF parameters together with age and seasonality was best for the prediction of WNV (87.5%), followed by unknown viral etiology (66.7%), VZV (61.8%), and enteroviruses (51.9%)., Conclusions: Cases with WNV ME showed a specific pattern of routine CSF parameters and demographic data that allowed for their identification with good accuracy. These findings might help to guide the diagnostic workup in cases with viral ME, in particular allowing the timely identification of cases with ME due to WNV.

Errors in laboratory diagnostics of viral infections primarily occur during the preanalytical phase, which is especially observed in sample collection. Hitherto, no efforts have been made to optimize oropharyngeal smears. An accurate method to analyze the necessary conditions for a valid oropharyngeal smear test is required, especially to avoid false negative results, which can lead to promotion of the spread of viruses such as SARS-CoV-2. In this study, a maximum-force failure analysis was performed on a swab, and the highest tolerable force was then measured on 20 healthy volunteers to obtain the dimensions of the possible force to be applied on a swab. Subsequently, a device which can validate and reproducibly indicate this force during swab collection was developed. The study demonstrated that swabs generally fail at a maximum force of 5 N. Furthermore, an average force of 2.4±1.0 N was observed for the 20 volunteers. Lastly, this study described the development of a device which presents the selected force with a mean accuracy of 0.05 N (Force applied by Device 1: 0.46±0.05 N, Device 2: 1.55±0.11 N, Device 3: 2.57±0.18 N) and provides feedback via haptic and acoustic clicks as well as with a visual indicator. In the future, the swab will be analyzed for the presence of viral pathogens to determine its diagnostic performance corresponding to the force (German Clinical Trials Register Number 00024455)., Competing Interests: The authors declare that they have no competing interests., (Copyright © 2024 Melcher et al.)

Background: Pregnant women are also susceptible to SARS-CoV-2. Although an infection of the placenta may be rare, pregnancy may occasionally be affected by intrauterine failure. The knowledge of placental morphology on sudden intrauterine demise is still limited., Methods: Fetal and placental tissue of two cases of sudden intrauterine death in the second trimester were analysed morphologically and by immunohistochemistry. One case was evaluated by RT-PCR., Results: Both mothers were tested positive for the Alpha variant of SARS-CoV-2 but were oligosymptomatic for COVID-19. Unexpected sudden intrauterine death (SIUD) occurred at 15 + 2 and 27 + 3 weeks of gestation. One fetus demonstrated an intrauterine growth restriction. No malformations nor inflammatory changes were observed in either fetus on autopsy. In contrast to the placentas, the fetal tissue was negative for SARS-CoV-2 on immunohistochemical and RT-PCR analyses. Macroscopically, the placentas showed an increased consistency with a white, reticular cutting surface covering about 95% of the whole placenta. Only very focal histiocytic chronic intervillositis was noted histologically. Massive perivillous fibrin deposits with extensive necroses of the villous trophoblast were present in more than 90% of the placental tissue. Immunohistochemical staining was strong and diffusely positive for SARS-CoV-2 in the villous trophoblast and rarely within the villous stromal cells. Placental SARS-CoV-2 infection was confirmed by RT-PCR., Conclusion: Sudden intrauterine death may occur in mothers who are oligosymptomatic for COVID-19. Acute placental failure is responsible for SIUD, demonstrated by massive perivillous fibrin deposits and extensive necroses of the villous trophoblast with SARS-CoV-2-positivity based on immunohistochemical staining and RT-PCR. Detailed histopathological examination of placental and fetal tissue is mandatory to verify SARS-CoV-2 and to evaluate the pathogenesis and functionality of this disease., (© 2022. The Author(s).)

Understanding SARS-CoV-2 breakthrough infections in vaccinated healthcare workers is of key importance in mitigating the effects of the COVID-19 pandemic in healthcare facilities. An observational prospective cohort study was conducted in vaccinated employees with acute SARS-CoV-2 infection between October 2021 and February 2022. Serological and molecular testing was performed to determine SARS-CoV-2 viral load, lineage, antibody levels, and neutralizing antibody titers. A total of 571 (9.7%) employees experienced SARS-CoV-2 breakthrough infections during the enrolment period, of which 81 were included. The majority ( n = 79, 97.5%) were symptomatic and most ( n = 75, 92.6%) showed Ct values < 30 in RT-PCR assays. Twenty-four (30%) remained PCR-positive for > 15 days. Neutralizing antibody titers were strongest for the wildtype, intermediate for Delta, and lowest for Omicron variants. Omicron infections occurred at higher anti-RBD-IgG serum levels ( p = 0.00001) and showed a trend for higher viral loads ( p = 0.14, median Ct difference 4.3, 95% CI [-2.5-10.5]). For both variants, viral loads were significantly higher in participants with lower anti-RBD-IgG serum levels ( p = 0.02). In conclusion, while the clinical course of infection with both the Omicron and Delta variants was predominantly mild to moderate in our study population, waning immune response over time and prolonged viral shedding were observed.

Following the extensive non-pharmaceutical interventions (NPIs) and behavioral changes in the wake of the SARS-CoV-2 pandemic, an interseasonal rise in respiratory syncytial virus (RSV) cases was observed in Germany in 2021. The aim of this study was to characterize the local molecular epidemiology of RSV infections in comparison to the three pre-pandemic seasons. Additionally, clinical data were retrieved from patient charts to determine the clinical significance of RSV infections. RSV detections peaked in calendar week 40 of 2021, 18 weeks earlier than the usual peak observed in the three pre-pandemic seasons. Sequence analysis revealed a close phylogenetic relatedness regardless of the season of origin. A significantly higher amount of pediatric cases (88.9% of all cases, p < 0.001) was observed for season 2021/2022. For the pediatric cases, significant differences were observed for an increased number of siblings in the household ( p = 0.004), a lower rate of fever ( p = 0.007), and a reduced amount of co-infections ( p = 0.001). Although the mean age of the adult patients was significantly younger (47.1 vs. 64.7, p < 0.001), high rates of comorbidities, lower respiratory tract infections and intensive care unit admissions prevailed. The NPIs in the wake of the SARS-CoV-2 pandemic had a tremendous impact on the epidemiologic characteristics and seasonality of RSV and warrant further epidemiologic studies of this important pathogen.

Our understanding of the timing of stress responses and specific roles of different regulatory pathways that drive stress responses is incomplete. In particular, the regulation of appetite genes as a consequence of exposure to different stressors has not been studied in sufficient detail in fish. Therefore, a stress trial was conducted with koi carp, aiming at identifying typical effects of stress on regulation of appetite genes. The stressors tank manipulation, air exposure and feed rewarding were chosen. The responses to these stressors were evaluated 10, 30 and 60 min after the stressors were applied. Orexigenic and anorexigenic genes were investigated in four different brain regions (telencephalon, hypothalamus, optic tectum and rhombencephalon). The results show that, apart from the typical appetite regulation in the hypothalamus, the different brain regions also display pronounced responses of appetite genes to the different stressors. In addition, several genes in the serotonergic, dopaminergic and gaba-related pathways were investigated. These genes revealed that rearing in pairs of two and opening of the tank lid affected anorexigenic genes, such as cart and cck, which were not changed by air exposure or feed rewarding. Moreover, distress and eustress led to limited, but distinguishable gene expression pattern changes in the investigated brain regions., (© 2023 The Authors.)

Background: The currently used SARS-CoV-2 mRNA vaccines have proven to induce a strong and protective immune response. However, functional relevance of vaccine-generated antibodies and their temporal progression are still poorly understood. Thus, the central aim of this study is to gain a better understanding of systemic and mucosal humoral immune response after mRNA vaccination with BNT162b2., Methods: We compared antibody production against the S1 subunit and the RBD of the SARS-CoV-2 spike protein in sera of BNT162b2 vaccinees, heterologous ChAdOx1-S/BNT162b2 vaccinees and COVID-19 patients. We monitored the neutralizing humoral response against SARS-CoV-2 wildtype strain and three VOCs over a period of up to eight months after second and after a subsequent third vaccination., Results: In comparison to COVID-19 patients, vaccinees showed higher or similar amounts of S1- and RBD-binding antibodies but similar or lower virus neutralizing titers. Antibodies peaked two weeks after the second dose, followed by a decrease three and eight months later. Neutralizing antibodies (nAbs) poorly correlated with S1-IgG levels but strongly with RBD-IgGAM titers. After second vaccination we observed a reduced vaccine-induced neutralizing capacity against VOCs, especially against the Omicron variant. Compared to the nAb levels after the second vaccination, the neutralizing capacity against wildtype strain and VOCs was significantly enhanced after third vaccination. In saliva samples, relevant levels of RBD antibodies were detected in convalescent samples but not in vaccinees., Conclusions: Our data demonstrate that BNT162b2 vaccinated individuals generate relevant nAbs titers, which begin to decrease within three months after immunization and show lower neutralizing potential against VOCs as compared to the wildtype strain. Large proportion of vaccine-induced S1-IgG might be non-neutralizing whereas RBD-IgGAM appears to be a good surrogate marker to estimate nAb levels. A third vaccination increases the nAb response. Furthermore, the systemic vaccine does not seem to elicit readily detectable mucosal immunity., Competing Interests: The authors have declared that no competing interests exist.

Acute myelogenous leukemia (AML), a disease of the blood and bone marrow, is characterized by the inability of myeloblasts to differentiate into mature cell types. Dihydroorotate dehydrogenase (DHODH) is an enzyme well-known in the pyrimidine biosynthesis pathway; however, small molecule DHODH inhibitors were recently shown to induce differentiation in multiple AML subtypes. Using virtual screening and structure-based drug design approaches, a new series of N-heterocyclic 3-pyridyl carboxamide DHODH inhibitors were discovered. Two lead compounds, 19 and 29 , have potent biochemical and cellular DHODH activity, favorable physicochemical properties, and efficacy in a preclinical model of AML.

Objectives: Successful vaccination is key to overcoming the COVID-19 pandemic. Immunosuppressive medication is known to potentially compromise vaccination responses, and expansion of our knowledge on vaccination efficacy in patients with autoimmune inflammatory rheumatic diseases (AIIRD) is therefore of utmost importance., Methods: We conducted a single-centre observational study and evaluated the efficacy of approved COVID-19 vaccines in 303 adult AIIRD patients. Serum levels of IgG antibodies against the S1 subunit of SARS-CoV-2 spike proteins (anti-S IgG) were measured at least two weeks after vaccination. In a subgroup of patients without humoral response, T-cell responses were determined using an interferon-γ gamma release assay., Results: Overall seropositivity rate was 78.5% and was significantly lower in patients under immunosuppressive therapy (75.7 vs 93.2%, P = 0.009). No difference regarding the vaccination type was observed. Glucocorticoids, mycophenolate-mofetil, TNF inhibitors, tocilizumab, abatacept and rituximab were all associated with non-response after proper vaccination. The risk was highest under RTX therapy (OR 0.004, 95% CI 0.001, 0.023, P < 0.0001). A strong negative correlation was observed between time since vaccination with an mRNA vaccine and anti-S antibody levels (r=-0.6149, P < 0.0001). In patients without humoral response, a T-cell response was found in 50%., Conclusions: COVID-19 vaccination in patients with AIIRD is effective using any approved vaccine. Humoral response might be impaired depending on the individual immunosuppressive medication. The risk of non-response is highest under rituximab therapy. Anti-S IgG antibody levels wane over time after mRNA vaccination. Importantly, 50% of humoral non-responders showed a T-cellular response, suggesting T-cell-mediated protection to a certain extent., (© The Author(s) 2022. Published by Oxford University Press on behalf of the British Society for Rheumatology. All rights reserved. For permissions, please email: journals.permissions@oup.com.)

Despite available vaccines, antibodies and antiviral agents, the severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) pandemic still continues to cause severe disease and death. Current treatment options are limited, and emerging new mutations are a challenge. Thus, novel treatments and measures for prevention of viral infections are urgently required. Photodynamic inactivation (PDI) is a potential treatment for infections by a broad variety of critical pathogens, including viruses. We explored the infectiousness of clinical SARS-CoV-2 isolates in Vero cell cultures after PDI-treatment, using the photosensitizer Tetrahydroporphyrin-tetratosylate (THPTS) and near-infrared light. Replication of viral RNA (qPCR), viral cytopathic effects (microscopy) and mitochondrial activity were assessed. PDI of virus suspension with 1 µM THPTS before infection resulted in a reduction of detectable viral RNA by 3 log levels at day 3 and 6 after infection to similar levels as in previously heat-inactivated virions (<99.9%; p < 0.05). Mitochondrial activity, which was significantly reduced by viral infection, was markedly increased by PDI to levels similar to uninfected cell cultures. When applying THPTS-based PDI after infection, a single treatment had a virus load-reducing effect only at a higher concentration (3 µM) and reduced cell viability in terms of PDI-induced toxicity. Repeated PDI with 0.3 µM THPTS every 4 h for 3 d after infection reduced the viral load by more than 99.9% (p < 0.05), while cell viability was maintained. Our data demonstrate that THPTS-based antiviral PDI might constitute a promising approach for inactivation of SARS-CoV-2. Further testing will demonstrate if THPTS is also suitable to reduce the viral load in vivo.

Monitoring the occurrence of adverse events in the scientific literature is a mandatory process in drug marketing surveillance. This is a very time-consuming and complex task to fulfill the compliance and, most importantly, to ensure patient safety. Therefore, a machine learning (ML) algorithm has been trained to support this manual intellectual review process, by automatically providing a classification of the literature articles into two types. An algorithm has been designed to automatically classify "relevant articles" which are reporting any kind of drug safety relevant information, and those which are not reporting an adverse drug reaction as "not relevant." The review process is consisted of many rules and aspects which needed to be taken into consideration. Therefore, for the training of the algorithm, thousands of documents from previous screenings have been used. After several iterations of adjustments and fine tuning, the ML approach is definitively a great achievement in pre-sorting the articles into "relevant" and "non-relevant" and supporting the intellectual review process., (© 2022 The Authors. Clinical and Translational Science published by Wiley Periodicals LLC on behalf of American Society for Clinical Pharmacology and Therapeutics.)

Vaccination is considered one of the most important achievements of modern medicine and has saved millions of lives. As a result, the age-old fear of severe or fatal infectious diseases has largely been forgotten in society; however, the pandemic triggered by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) shows how quickly this fear can return. Also, many people have reservations about medical measures, especially if they are directed against vague dangers. Paradoxically, the success of vaccinations jeopardizes the acceptance. To counteract this development, this article provides information on basic vaccination principles, legal frameworks and components of vaccines. It explains the most important categories, goals, core elements of vaccination programs and the most important recommendations of the Standing Committee on Vaccination at the Robert Koch Institute (STIKO). It explains the current state of knowledge with respect to required resources, assessment of vaccine reactions, complication management and possible vaccine damage., (© 2021. Springer Medizin Verlag GmbH, ein Teil von Springer Nature.)

We report a rapid increase in enterovirus D68 (EV-D68) infections, with 139 cases reported from eight European countries between 31 July and 14 October 2021. This upsurge is in line with the seasonality of EV-D68 and was presumably stimulated by the widespread reopening after COVID-19 lockdown. Most cases were identified in September, but more are to be expected in the coming months. Reinforcement of clinical awareness, diagnostic capacities and surveillance of EV-D68 is urgently needed in Europe.

Globally and in all age groups, noroviruses are a main cause of gastroenteritis. To assess their local epidemiology and genetic diversity, stool samples of 7509 inpatients with gastrointestinal complaints from all age groups were analyzed. After detection of norovirus genogroup I and II RNA by real-time RT-PCR, viral capsids were genotyped by partial nucleic acid sequencing. In the case of GII.2 strains, polymerase genotypes were also assessed. Between October 2013 and September 2017, presence of norovirus RNA was shown in 611 samples (8.1%), of which 610 (99.8%) were typed successfully. Norovirus positivity rate was higher in patients aged below five years (14.8%) than in older patients (5.7%). Among the 611 norovirus positive samples, GII.4 (56.6%) strains prevailed, followed by GII.6 (11.3%), GII.3 (11.0%) and GII.2 (9.5%). The most common genogroup I (GGI) genotype was GI.3 (3.6%). In addition, rare genotypes such as GII.13, GII.14 and GII.26 were detected. Interestingly, GII.3 infections were most common in children under the age of five years. Assessment of polymerase genotypes in GII.2 viruses showed a shift from P2 to P16, with higher diversity in P2 sequences. The varying distribution of norovirus genotypes depending on season, age and setting of infection highlights the importance of frequent genotyping as a basis for vaccine development and needful adjustments.

There is increasing evidence of cardiac involvement post-SARS-CoV-2 infections in symptomatic as well as in oligo- and asymptomatic athletes. This study aimed to characterize the possible early effects of SARS-CoV-2 infections on myocardial morphology and cardiopulmonary function in athletes. Eight male elite handball players (27 ± 3.5 y) with past SARS-CoV-2 infection were compared with four uninfected teammates (22 ± 2.6 y). Infected athletes were examined 19 ± 7 days after the first positive PCR test. Echocardiographic assessment of the global longitudinal strain under resting conditions was not significantly changed (- 17.7% vs. - 18.1%). However, magnetic resonance imaging showed minor signs of acute inflammation/oedema in all infected athletes (T2-mapping: + 4.1 ms, p = 0.034) without reaching the Lake-Louis criteria. Spiroergometric analysis showed a significant reduction in VO2max (- 292 ml/min, - 7.0%), oxygen pulse (- 2.4 ml/beat, - 10.4%), and respiratory minute volume (VE) (- 18.9 l/min, - 13.8%) in athletes with a history of SARS-CoV2 infection (p < 0.05, respectively). The parameters were unchanged in the uninfected teammates. SARS-CoV2 infection caused impairment of cardiopulmonary performance during physical effort in elite athletes. It seems reasonable to screen athletes after SARS-CoV2 infection with spiroergometry to identify performance limitations and to guide the return to competition., (© 2021. The Author(s).)

Sensitivity and specificity of serological assays are key parameters for the accurate estimation of SARS-CoV-2 sero-prevalence. The aim of this study was to compare 8 readily available IgG antibody tests using a panel of well-defined serum samples of prepandemic and pandemic origin. A cross-reaction panel included samples of patients with recent infection with either of the endemic Coronaviruses 229E, NL63, HKU1, or OC43. Additionally, samples with high antibody levels against influenza virus, adenovirus, and during acute EBV infection were included. Previous infection with endemic coronaviruses caused a significant amount of cross-reactivity in two of the assays. In contrast, the confidence intervals for the assays of Abbott, DiaSorin, Euroimmun and Roche encompassed the value of 98% for samples with a previous endemic HCoV infection. For all assays, sensitivities were between 91.3% and 98.8%. Assay performance was independent of the usage of either nucleocapsid or spike proteins., Competing Interests: Conflict of interest All authors have no conflict of interest to declare., (Copyright © 2021 Elsevier Inc. All rights reserved.)

Since the beginning of the SARS-CoV-2 pandemic, swabs or other samples have increasingly been taken from the upper aero-digestive tract, since high viral loads exist here, especially in the early stages of the disease. As diagnostic options, swabs from the anterior nose, from the nasopharynx, from the oropharynx or the extraction of throat rinse water or saliva are possible. The laboratory methods available are antigen tests that can be read in a few minutes or more lengthy RT-PCR methods in a lab. Swabs are carried out by physicians, medical staff, laypeople and in the self-test, in each case according to prior instructions. Many of these factors therefore have an influence on the informative value and the sensitivity of the entire diagnostic process. The PCR laboratory method is more sensitive than the antigen method; the swabs from the nasopharynx are considered the most valid smear site; correct execution of a test can be achieved even with non-professional individuals with good instructions. Complications with such swabs are reported very rarely, given the assumed number of procedures performed. Short-term nosebleeds after traumatic smears can be assumed without publications about it being found. Broken parts of swabs had to be removed by an ENT doctor. There are only very few reports on injuries to the skullbase with CSF-leaks, including 2 times with anomalies such as meningoceles. The choice of a suitable diagnostic medium depends on many parameters such as availability, the timing of the result, a smear test by knowledgeable staff or a self-test, and a number of other practical considerations., Competing Interests: Die Autorinnen/Autoren geben an, dass kein Interessenkonflikt besteht., (Thieme. All rights reserved.)

The first part of this study evaluates the occurrence of mycotoxin patterns in feedstuffs and fish feeds. Results were extrapolated from a large data pool derived from wheat ( n = 857), corn ( n = 725), soybean meal ( n = 139) and fish feed ( n = 44) samples in European countries and based on sample analyses by liquid chromatography/tandem mass spectrometry (LC-MS/MS) in the period between 2012-2019. Deoxynivalenol (DON) was readily present in corn (in 47% of the samples) > wheat (41%) > soybean meal (11%), and in aquafeeds (48%). Co-occurrence of mycotoxins was frequently observed in feedstuffs and aquafeed samples. For example, in corn, multi-mycotoxin occurrence was investigated by Spearman's correlations and odd ratios, and both showed co-occurrence of DON with its acetylated forms (3-AcDON, 15-AcDON) as well as with zearalenone (ZEN). The second part of this study summarizes the existing knowledge on the effects of DON on farmed fish species and evaluates the risk of DON exposure in fish, based on data from in vivo studies. A meta-analytical approach aimed to estimate to which extent DON affects feed intake and growth performance in fish. Corn was identified as the ingredient with the highest risk of contamination with DON and its acetylated forms, which often cannot be detected by commonly used rapid detection methods in feed mills. Periodical state-of-the-art mycotoxin analyses are essential to detect the full spectrum of mycotoxins in fish feeds aimed to prevent detrimental effects on farmed fish and subsequent economic losses for fish farmers. Because levels below the stated regulatory limits can reduce feed intake and growth performance, our results show that the risk of DON contamination is underestimated in the aquaculture industry.

Soaking hay before feeding has been documented to reduce airborn respirable particles and water-soluble carbohydrate (WSC) content which may have positive benefits for horses suffering from Equine Asthma (EA) or Equine Metabolic Syndrome (EMS). Prolonged soaking also leaches minerals, but to-date no measurement of the loss of small intestine digestible crude protein has been documented. One aim of this study was to investigate various soaking durations on nutrient contents of hay, WSC, macronutrients, and trace elements levels. Another objective was to determine the prececal digestible crude protein (pcd CP) and amino acid (pcd AA) fraction contents and prececal digestibility (pcD). Four different batches of meadow hay were soaked in water (20° C during preparation) for 0 minutes, 15 minutes, 30 minutes, 60 minutes, and 12 hours and drained for 20 minutes. A 15 minutes soaking duration significantly reduced the levels of nearly all investigated nutrients (e.g. for fructans, and WSC, macronutrients and trace elements). However, the crude fiber, acid detergent fiber (ADF), and acid detergent lignin content increased. Metabolizable energy (ME) contents decreased by 5-15 %, pcd CP and pcd AA fell by 35 %, and the pcD declined by up to 49 %. In contrast, the pcD was 56 % before soaking. Longer soaking durations did not enhance the wash-out effect. Horse owners should be aware that soaking hay, regardless of reason, may negatively alter the nutritional value. The wide range of wash-out effects may pose risks in calculating the correct dry matter portion to prevent weight loss and maintain ME, pcd CP and pcd AA requirements, especially for horses with EMS and EA., (Copyright © 2021. Published by Elsevier Inc.)

Enteroviruses are associated with various diseases accompanied by rare but severe complications. In recent years, outbreaks of enterovirus D68 and enterovirus A71 associated with severe respiratory infections and neurological complications have been reported worldwide. Since information on molecular epidemiology in respiratory samples is still limited, the genetic diversity of enteroviruses was retrospectively analysed over a 4-year period (2013-2016) in respiratory samples from paediatric patients. Partial viral major capsid protein gene (VP1) sequences were determined for genotyping. Enteroviruses were detected in 255 (6.1%) of 4187 specimens. Phylogenetic analyses of 233 (91.4%) strains revealed 25 different genotypes distributed to Enterovirus A (39.1%), Enterovirus B (34.3%), and Enterovirus D (26.6%). The most frequently detected genotypes were enterovirus D68 (26.6%), coxsackievirus A6 (15.9%), and enterovirus A71 (7.3%). Enterovirus D68 detections were associated with lower respiratory tract infections and increased oxygen demand. Meningitis/encephalitis and other neurological symptoms were related to enterovirus A71, while coxsackievirus A6 was associated with upper respiratory diseases. Prematurity turned out as a potential risk factor for increased oxygen demand during enterovirus infections. The detailed analysis of epidemiological and clinical data contributes to the non-polio enterovirus surveillance in Europe and showed high and rapidly changing genetic diversity of circulating enteroviruses, including different enterovirus D68 variants.

Noroviruses are a leading cause of acute gastroenteritis (AGE) among adults and children worldwide. NoroSurv is a global network for norovirus strain surveillance among children <5 years of age with AGE. Participants in 16 countries across 6 continents used standardized protocols for dual typing (genotype and polymerase type) and uploaded 1,325 dual-typed sequences to the NoroSurv web portal during 2016-2020. More than 50% of submitted sequences were GII.4 Sydney[P16] or GII.4 Sydney[P31] strains. Other common strains included GII.2[P16], GII.3[P12], GII.6[P7], and GI.3[P3] viruses. In total, 22 genotypes and 36 dual types, including GII.3 and GII.20 viruses with rarely reported polymerase types, were detected, reflecting high strain diversity. Surveillance data captured in NoroSurv enables the monitoring of trends in norovirus strains associated childhood AGE throughout the world on a near real-time basis.

In this study, a stress trial was conducted with common carp, one of the most important species in aquaculture worldwide, to identify relevant gene regulation pathways in different areas of the brain. Acute distress due to exposure to air significantly activated the expression of the immediate early gene c-fos in the telencephalon. In addition, evidence for regulation of the two corticotropin-releasing factor ( crf ) genes in relation to their binding protein (corticotropin-releasing hormone-binding protein, crh-bp ) is presented in this preliminary study. Inferences on the effects of due to exposure to air were obtained by using point estimation, which allows the prediction of a single value. This constitutes the best description to date of the previously generally unknown effects of stress in different brain regions in carp. Furthermore, principal component analyses were performed to reveal possible regulation patterns in the different regions of the fish brain. In conclusion, these preliminary studies on gene regulation in the carp brain that has been influenced by exposure to a stressor reveal that a number of genes may be successfully used as markers for exposure to unfavourable conditions.

In March 2020, the SARS-CoV-2 virus outbreak was declared as a world pandemic by the World Health Organization (WHO). The only measures for controlling the outbreak are testing and isolation of infected cases. Molecular real-time polymerase chain reaction (PCR) assays are very sensitive but require highly equipped laboratories and well-trained personnel. In this study, a rapid point-of-need detection method was developed to detect the RNA-dependent RNA polymerase (RdRP), envelope protein (E), and nucleocapsid protein (N) genes of SARS-CoV-2 based on the reverse transcription recombinase polymerase amplification (RT-RPA) assay. RdRP, E, and N RT-RPA assays required approximately 15 min to amplify 2, 15, and 15 RNA molecules of molecular standard/reaction, respectively. RdRP and E RT-RPA assays detected SARS-CoV-1 and 2 genomic RNA, whereas the N RT-RPA assay identified only SARS-CoV-2 RNA. All established assays did not cross-react with nucleic acids of other respiratory pathogens. The RT-RPA assay's clinical sensitivity and specificity in comparison to real-time RT-PCR ( n = 36) were 94 and 100% for RdRP; 65 and 77% for E; and 83 and 94% for the N RT-RPA assay. The assays were deployed to the field, where the RdRP RT-RPA assays confirmed to produce the most accurate results in three different laboratories in Africa ( n = 89). The RPA assays were run in a mobile suitcase laboratory to facilitate the deployment at point of need. The assays can contribute to speed up the control measures as well as assist in the detection of COVID-19 cases in low-resource settings.

Background: The corona pandemic is currently the greatest challenge for health systems of all countries worldwide. The timely detection of the disease and the immediate separation and isolation of suspected cases make a significant contribution to breaking the chain of infection., Methods: Based on the first 35 patients admitted to the hospital with COVID-19, we evaluated the various symptoms with which patients presented., Results: The majority of patients have respiratory symptoms (e.g., cough and reduced peripheral oxygen saturation) and fever. In individual patients, however, there may only be other symptoms, e.g., gastrointestinal, neurological, or nonspecific symptoms., (© Springer Medizin Verlag GmbH, ein Teil von Springer Nature 2020.)

Enteroviruses (EVs) and human parechoviruses (HPeVs) infections are associated with various forms of disease, including gastroenteritis. As information on the molecular epidemiology of these viruses is limited in Ethiopia, the genetic diversity of EV and HPeV was investigated in the Northwestern part of the country. Of the total 450 stool samples obtained from infants and young children with diarrhea, 157 (34.9%) were positive for EV and 49 (10.9%) for HPeV RNA when tested by real-time reverse transcription polymerase chain reaction. Genotyping was performed by sequencing of the EV VP1 gene and the HPeV VP3/VP1 gene, respectively. Genotyping of EV was successful in 118 samples. Thereof, 82 (69.5%) belonged to non-polio EVs as a broad range of genotypes within species C, B, and A. Sabin polioviruses were found in 36 cases. HPeV sequences were also heterogeneous with a relative dominance of genotype 3. In conclusion, diverse EV and HPeV genotypes were found cocirculating in Northwest Ethiopia. The findings highlight the importance of continuous surveillance of these viruses in Ethiopia., (© 2020 Wiley Periodicals, Inc.)

Adherent-invasive Escherichia coli have been suggested to play a pivotal role within the pathophysiology of inflammatory bowel disease (IBD). Autoantibodies against distinct splicing variants of glycoprotein 2 (GP2), an intestinal receptor of the bacterial adhesin FimH, frequently occur in IBD patients. Hence, we aimed to functionally characterize GP2-directed autoantibodies as a putative part of IBD's pathophysiology. Ex vivo, GP2-splicing variant 4 (GP2#4) but not variant 2 was expressed on intestinal M or L cells with elevated expression patterns in IBD patients. The GP2#4 expression was induced in vitro by tumor necrosis factor (TNF)-α. The IBD-associated GP2 autoantibodies inhibited FimH binding to GP2#4 and were decreased in anti-TNFα-treated Crohn's disease patients with ileocolonic disease manifestation. In vivo, mice immunized against GP2 before infection with adherent-invasive bacteria displayed exacerbated intestinal inflammation. In summary, autoimmunity against intestinal expressed GP2#4 results in enhanced attachment of flagellated bacteria to the intestinal epithelium and thereby may drive IBD's pathophysiology., (© 2020 Crohn’s & Colitis Foundation. Published by Oxford University Press. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Following a distinct summer heat wave, nine autochthonous cases of West Nile fever and West Nile neuroinvasive disease, including one fatality, were observed in Leipzig, Germany, in August and September 2020. Phylogenetic analysis demonstrated close relationships in viruses from humans, animals and mosquitos in eastern Germany, obtained during the preceding 2 years. The described large cluster of autochthonous West Nile virus infections in Germany indicates endemic seasonal circulation of lineage 2 viruses in the area.

The rearing of less established fish species in recirculating aquaculture systems (RASs) is increasing, but may require adaptations of the rearing facilities if health impairments occur. We observed several health issues in burbot Lota lota reared for up to 2 yr in a RAS and used microbiological, histological and molecular-biological methods to identify the causative agents. Minor skin trauma led to the development of ulcers. In addition, several fillets of burbot showed pronounced granulomatous inflammation and calcification with signs of muscle fiber degeneration which resembled a condition called 'sandy flesh disease' in North American walleye. Several infectious agents were able to be excluded as a cause for the disease. Carnobacterium maltaromaticum was isolated in high numbers in some of the affected muscle tissue. However, the role of this bacterium or other causative agents or husbandry conditions remains to be elucidated.

Severe pulmonary impairment can occur after traumatic brain injury or stroke. The resulting brain-lung interactions represent key points for the treatment and the subsequent outcome of the patient. Established treatment approaches, such as permissive hypercapnia and prone positioning, present the intensive care physician with divergent treatment goals in these patients with partially increased intracranial pressure. This case report series shows the instrument-based and noninstrument-based options for the treatment of acute respiratory distress syndrome (ARDS) in the simultaneous presence of intracranial pathologies. This includes equipment based therapies using extracorporeal CO 2 elimination, special positioning maneuvers in specially designed hospital beds and positional maneuvers, such as prone positioning. With enhanced neuromonitoring it is possible to optimally adapt treatment measures focused on the lungs early and before secondary damage to the brain.

Periods of unfavorable storing conditions can lead to changes in the quality of fish feeds, as well as the development of relevant mycotoxins. In the present study, a commercial fish feed was stored under defined conditions for four weeks. The main findings indicate that even storing fish feeds under unsuitable conditions for a short duration leads to a deterioration in quality. Mycotoxin and fungal contamination were subsequently analyzed. These investigations confirmed that different storage conditions can influence the presence of fungi and mycotoxins on fish feed. Notably, ochratoxin A (OTA) was found in samples after warm (25 °C) and humid (>60% relative humidity) treatment. This confirms the importance of this compound as a typical contaminant of fish feed and reveals how fast this mycotoxin can be formed in fish feed during storage., Competing Interests: The authors declare that there are no conflicts of interest regarding the publication of this paper.

Mycotoxins are difficult to monitor continuously, and a tool to assess the risk would help to judge if there is a particular risk due to the inclusion of certain feed ingredients. For this, the toxin contents of 97 commercial fish feeds have been estimated, and the most prominent toxins in fish feed are calculated to be deoxynivalenol, zearalenone, fumonisins and enniatins. These pose a risk to fish well-being, as can be calculated by the Bayesian models for determining the critical concentrations 5% (CC5) for the different toxins. Besides fishmeal, wheat, soybean products and corn are regularly used as fish feed ingredients. The calculated scenarios show that fish are at high risk of toxin contamination if feed ingredients of low quality are chosen for feed production. Due to this, specific maximum allowable levels for several mycotoxins in fish feeds should be established.

Human adenovirus (HAdV) and human astrovirus (HAstV) are common causes of gastroenteritis. Data on the prevalence and diversity of enteric viruses are important for control and preventive measures. However, epidemiological information regarding HAdV and HAstV infections in Ethiopia are limited. Fecal specimens were collected from 450 outpatient diarrheic infants and young children in Gondar and Bahir Dar from November 2015 to April 2016. Socio-demographic information was recorded. All fecal specimens were screened for the presence of HAdV and classical HAstV using PCR. Genotyping was performed by sequencing and phylogenetic analysis. Human HAdV and HAstV were detected in 144 (32%) and 16 (3.6%) of the children, respectively. Overall, 182 different adenovirus genotypes were detected, including mixed infections. Species F adenoviruses (HAdV-40, HAdV-41) were less common than other adenoviruses (HAdV-1, -2, -3, -5,-12, -16, -31, species D types) with a frequency of 32 versus 150, respectively. The HAstV genotypes were classified as HAstV-8 (n = 10), HAstV-1 (n = 3), HAstV-2 (n = 3), and HAstV-3 (n = 1). HAstV was detected only in Gondar. Thirty-eight coinfections HAdV and one HAstV coinfections were detected. There was no significant difference in the detection rate of HAdV and HAstV between boys and girls. The detection rates also did not differ between children from rural and urban areas. Children under 6 months of age, were less often infected with both viruses. These findings suggest that HAdV and HAstV are common in children with diarrhea in Ethiopia.

Background: The impact of annual influenza epidemics and prevailing strains varies worldwide and regional. The majority of vaccines used contained two influenza A strains and only one influenza B strain (trivalent vaccine)., Aim: The aim of the study was to compare laboratory confirmed influenza B cases during three consecutive years with respect to vaccination history, clinical symptoms and molecular virology., Methods: Partial HA gene sequences were analyzed for lineage determination and complete HA sequence in cases with reported vaccination and in fatal cases. Clinical data were retrieved from patient charts., Findings: During the 2015/16 season, 75 influenza B cases were retrieved; 11 in 2016/17, and 274 in 2017/18. The frequency of Yamagata-lineage strains increased from 7.6% to 100%. No difference was detected in the relative frequency of co-morbidities in season 2017/18. 37.7% of the adult patients and 4.5% of pediatric patients were vaccinated against influenza., Interpretation: Phylogenetically, Yamagata strains clustered similarly in 2017/2018 when compared to the previous two influenza seasons. While the relative frequency of influenza B cases differed, the clinical symptoms remained similar., Conclusion: World Health Organization recommendations for the use of tetravalent vaccines that contain two influenza B strains (Yamagata and Victoria) in addition to the two influenza A strains (H1N1 and H3N2) should be implemented in national vaccination guidelines., Funding: This research was partially supported by the Association of Sponsors and Friends of Leipzig University., (Copyright © 2019 Elsevier Ltd. All rights reserved.)

Sapovirus enteric disease affects people of all ages across the globe, in both sporadic cases and outbreak settings. Sapovirus is seldom assessed in Germany and its epidemiology in the country is essentially unknown. Thus, sapovirus occurrence and genetic diversity were studied by real-time reverse transcription polymerase chain reaction (RT-PCR) and partial sequencing of major viral structural protein (VP1) gene in two different sets of stool samples: 1) a selection of 342 diarrheal stools collected from inpatient children during 2008-2009, and 2) 5555 stool samples collected during 2010-2018 from inpatients of all age groups with gastrointestinal complaints. Results showed year-round circulation of sapoviruses, with peaks during cooler months. In total, 30 samples (8.8%) of the first and 112 samples of the second set of samples (2.0%) were sapovirus positive. Capsid gene sequencing was successful in 134/142 samples (94.4%) and showed circulation of all known human pathogenic genogroups. Genotype GI.1 predominated (31.8%), followed by GII.1 (16.7%), GII.3 (14.5%), GI.2 (13.8%) and GV.1 (12.3%). Additionally, minor circulation of GI.3, GI.6, GII.2, GII.4, GII.6 and GIV.1 was shown. Consequently, sapovirus diagnostics need broadly reactive RT-PCR protocols and should particularly be considered in infants and young children. Further studies from other sampling sites are essential to extend our knowledge on sapovirus epidemiology in Germany., Competing Interests: The authors declare no conflict of interest.

Background: Sapovirus is a common cause of self-limiting diarrhea. In immunocompromised individuals chronic infections occur, but are incompletely investigated., Objectives: To investigate viral evolution in immunocompromised hosts during chronic sapovirus infection., Study Design: From January 2010 to September 2018 stool samples of 5333 in-patients were analyzed for the presence of sapovirus RNA by real-time RT-PCR. In follow-up samples of chronic diarrhea cases nucleic acid sequencing of sapovirus genomes was performed. Amino acid mutations were identified by alignments and compared to data from GenBank. Sapovirus genotypes were assessed by phylogenetic analysis of viral capsid gene (VP1)., Results: Sapovirus RNA was present in 146 stool samples of 95 patients (1.8%), most frequently in young children and infants. In patients older than 14 years, sapoviruses were exclusively detected in immunocompromised patients. Chronic diarrhea occurred in almost one third of the sapovirus positive immunocompromised individuals (n = 5) and was established by different sapovirus genotypes (GI.2, GII.1, GII.3). The maximum observed duration of sapovirus shedding was 119 days. Accumulation of amino acid mutations during chronic infection was most often detected within VP1 P2 protruding subdomain. Reduction of immunosuppression was associated with decrease of viral load and clearance of sapovirus in stool., Conclusions: Clinicians should consider immunocompromised individuals at risk to develop chronic diarrhea due to persistence of SaV infection. The identified VP1 mutations contribute to an understanding of sapovirus-host interactions. For further conclusions regarding virus immune escape and altered viral fitness structural data on sapovirus capsid and virus/receptor complex are necessary., (Copyright © 2019 Elsevier B.V. All rights reserved.)

Human parechoviruses (HPeV) are ubiquitous and mainly occur in early infancy. They are known to cause various clinical manifestations including acute gastroenteritis. To gain insight into the diversity of circulating HPeV genotypes, stool samples from patients (n = 539) with clinical signs of infectious gastroenteritis which showed negative results for other common viral and bacterial enteric pathogens were obtained during three years, 2008 to 2010. Real-time RT-PCR showed HPeV RNA in 34 (6.3%) of the samples. The HPeV detection rate was highest (8.8%) in samples derived from infants and young children under the age of two years. Genotyping was based on VP3/VP1 junction nucleic acid sequences and revealed predominant HPeV-1B (n = 16) and HPeV-3 (n = 12) strains. Those prevailed minor HPeV-6 (n = 3) as well as HPeV-2, -4 and -5 (n = 1, each) strains. To ascertain the assigned HPeV-2 genotype of uncommon strain LPZ04-2008, analysis of complete coding sequences was performed. In complete VP1 analysis strain LPZ04-2008 showed 81.2% nucleic acid identity with HPeV-2 reference strain Williamson. In phylogenetic analysis VP1 of strain LPZ04-2008 clustered with a recent HPeV-2 strain from the UK. Regarding clinical manifestations, severe disease occurred HPeV-1B, -3 and - 6 infections. In conclusion, this paper a high genetic diversity of HPeV in stool samples, including rare strains. The investigation adds data on the whole coding sequences of the rare HPeV-2 strain. Genotyping results confirm previously reported association of more severe illness with HPeV-3 and HPeV-1B strains., (Copyright © 2019. Published by Elsevier B.V.)

This is the first report of West Nile virus (WNV) infection imported by a traveller returning from a neighbouring country to Germany (Austria). Physicians should be aware of the expansion of WNV endemic areas in Europe., (© 2018 Blackwell Verlag GmbH.)

Childhood morbidity and mortality of diarrhoeal diseases are high, particularly in low-income countries and noroviruses and sapoviruses are among the most frequent causes worldwide. Their epidemiology and diversity remain not well studied in many African countries. To assess the positivity rate and the diversity of sapoviruses and noroviruses in Northwest Ethiopia, during November 2015 and April 2016, a total of 450 faecal samples were collected from outpatient children aged &lt;5 years who presented with diarrhoea. Samples were screened for noroviruses and sapoviruses by real-time RT-PCR. Partial VP1 genes were sequenced, genotyped and phylogenetically analysed. Norovirus and sapovirus stool positivity rate was 13.3% and 10.0%, respectively. Noroviruses included GII.4 (35%), GII.6 (20%), GII.17 (13.3%), GII.10 (10%), GII.2 (6.7%), GII.16 (5%), GII.7 (3.3%), GII.9, GII.13, GII.20 and GI.3 (1.7% each) strains. For sapoviruses, GI.1, GII.1 (20.0% each), GII.6 (13.3%), GI.2 (8.9%), GII.2 (11.1%), GV.1 (8.9%), GIV.1 (6.7%), GI.3 and GII.4 (2.2% each) genotypes were detected. This study demonstrates a high genetic diversity of noroviruses and sapoviruses in Northwest Ethiopia. The positivity rate in stool samples from young children with diarrhoea was high for both caliciviruses. Continued monitoring is recommended to identify trends in genetic diversity and seasonal variations.

Objectives: Rotavirus infections are common causes of infant hospitalization. The present study examined the effectiveness of anti-rotavirus vaccination in preventing rotavirus-related hospitalizations in Germany, following its state and nationwide introductions in 2008 and 2013, respectively., Methods: During 15 consecutive seasons 9557 stool samples of hospitalized children of 5 years and younger with acute gastroenteritis were screened for rotavirus A. Rotavirus G and P genotypes were assessed after vaccine introduction. Vaccine effectiveness was determined by comparison of rotavirus incidence in pre-vaccine and post-vaccine cohorts. The herd effect was calculated as the difference between the observed reduction of rotavirus-related hospitalizations and the expected direct vaccine effect., Results: The number of rotavirus-related hospitalizations declined after vaccine introduction. Approximately 26% (503/1955) of prevented cases could be attributed to the herd effect. Human rotaviruses of genotypes G3P[8], G1P[8], G9P[8], G4P[8], G2P[4] and G12P[8] were most frequent. Uncommon genotypes remained rare. The direct, indirect, total and overall vaccine effectiveness was 86% (95% confidence interval (CI) 83.2-89.1%), 48% (95% CI 42.8-52.6%), 93% (95% CI 91.3-94.3%) and 69% (95% CI 66.5-72.0%), respectively. There was no significant difference in vaccine-type or in genotype-specific vaccine effectiveness., Conclusions: Anti-rotavirus vaccination efficiently reduced rotavirus-related hospitalizations in Germany in the past decade. The vaccines analysed in this article provide a broadly heterologous and long-lasting protection. The herd effect substantially contributed to the observed drop in the number of incidences of severe rotavirus infections. Presumably, constant high vaccine coverage will lead to a continued upward trend in the overall vaccine efficiency., (Copyright © 2018 European Society of Clinical Microbiology and Infectious Diseases. Published by Elsevier Ltd. All rights reserved.)

Background: Noroviruses are a leading cause of acute gastroenteritis in all age groups. They generally cause a rapidly self-limiting illness. However, chronic norovirus diarrheal disease occurs in immunocompromised individuals, and is accompanied by persistent shedding of infectious norovirus in stool., Objectives: The study aims to characterize a novel GII.P26-GII.26 norovirus strain. Furthermore, it analyses viral mutations arising during chronic infection of an immunocompromised host., Study Design: Over the course of more than three years, stool samples were obtained from an immunocompromised patient and screened for the presence of norovirus RNA by real-time PCR and norovirus antigen by immunoassay. Viral population kinetics was analyzed by conventional and high-throughput-sequencing., Results: Real-time PCR yielded high amounts of norovirus RNA in the stool, but antigen immunoassays failed to detect the virus. The near complete norovirus genome was assigned as novel GII.P26-GII.26 genotype. Conventional as well as high-throughput sequencing pointed to a heterogeneous viral population with low rates of non-synonymous substitutions. Within-host evolution was enhanced in non-structural protein p22 and the N-terminal arm of the capsid protein VP1 but reduced in the viral polymerase RdRp. Intermittent non-synonymous substitutions in the protruding domain of the VP1 reverted fully over time., Conclusions: Confirmation of novel GII.P26-GII.26 norovirus genotypes provides insight into norovirus genetic diversity. The study further illustrates norovirus infection as an important differential diagnosis of recurrent persistent diarrhea in immunocompromised patients. The provided data on within-host evolution contribute to the insight of the mechanisms of viral persistence and pathogenesis in chronic norovirus infections., (Copyright © 2018 Elsevier B.V. All rights reserved.)

Background: Rotaviruses mortality among infants and young children is high in Sub-Saharan Africa. Recently, Ethiopia introduced the monovalent rotavirus vaccine in its national immunization program to decrease the burden of rotavirus disease and mortality. Rotavirus surveillance in Ethiopia is based largely on data provided by sentinel hospitals in its capital Addis Ababa., Objective: To assess rotavirus abundancy and diversity in outpatient infants and children outside of Addis Ababa in the early post-introduction period., Method: Fecal samples were obtained from children aged less than five years presenting with diarrhea at outpatient health institutions in two cities in Northwest Ethiopia, Gondar and Bahir Dar, from November 2015 to April 2016. Basic demographic data were assessed. Real-time RT-PCR was used to detect rotavirus A RNA. Based on sequences of VP4 and VP7 gene segments phylogenetic analysis was performed., Results: Rotavirus wildtype positivity was 25% (113/450). Rotavirus infection was less common in infants below 6 months than in children of all other age-groups. Rotavirus genotype distributions were distinct between Bahir Dar and Gondar. In total, wildtype G3P[8], G2P[4], G9P[8], G12P[8], and G3P[6] rotaviruses were detected in 68 (60.2%), 21 (18.6%), 13 (11.5%), 9 (8.0%), and 2 (1.8%) of the positive samples, respectively. Wildtype G1P[8] strains were absent. The phylogenetic analysis revealed close relatedness of current rotaviruses with Ethiopian strains of the pre-vaccination period., Conclusion: In the early period after the introduction of vaccination, rotaviruses in Northwestern Ethiopia were frequent in children of 6-59 months and diverse. High phylogenetic relatedness with strains of the pre-vaccine era, indicate absence of early vaccine-induced strain replacement. Future surveillance studies should be carried out throughout the country to gain comprehensive data on rotavirus strain diversity and to monitor the effect of the ongoing vaccine program on the disease burden and eventual rotavirus strain replacement., (Copyright © 2018. Published by Elsevier B.V.)

Ethoxyquin (EQ) is an antioxidant that has, to date, been commonly used in feed production. Reports on the detrimental effects of this substance on vertebrates are growing, but effects in aquatic systems have rarely been described. Therefore, the present study was conducted using serial concentrations of EQ ranging from 0.03 to 16.5 mg l-1 to determine effects on 3 types of aquatic organisms. In zebrafish, 5 mg l-1 EQ caused mortality (25%) and a further 62.5% of the embryos showed yolk sac edema as well as deformed bodies or missing eyes. Furthermore, all the investigated EQ concentrations decreased the heart rate of the embryos. The lowest observed effect level was 0.31 mg l-1. In addition to zebrafish, the study also used water fleas Daphnia magna and green algae (Scenedesmus obliquus and Chlorella vulgaris). These treatments revealed that daphnids are also sensitive to EQ, exhibiting detrimental effects with a half-maximal effective concentration (EC50) of 2.65 mg l-1 after 48 h of exposure. The algae appeared to be at least 2 times less sensitive to EQ than fish embryos or daphnids. The results were used to calculate the risk for aquatic life resulting in a maximum tolerable level of 1 µg l-1 for fish embryos and daphnids, with a safety factor of 300. According to current knowledge, this does not exceed environmental concentrations of this substance. However, this study raises further concern about the (until recently) legal maximum tolerable EQ levels in fish feeding and the rather slow pace at which authorization to use EQ as a feed additive for diverse animals in Europe is being suspended.

Global warming, acidification, and oxygen stress at the Paleocene-Eocene Thermal Maximum (PETM) are associated with severe extinction in the deep sea and major biogeographic and ecologic changes in planktonic and terrestrial ecosystems, yet impacts on shallow marine macrofaunas are obscured by the incompleteness of shelf sections. We analyze mollusk assemblages bracketing (but not including) the PETM and find few notable lasting impacts on diversity, turnover, functional ecology, body size, or life history of important clades. Infaunal and chemosymbiotic taxa become more common, and body size and abundance drop in one clade, consistent with hypoxia-driven selection, but within-clade changes are not generalizable across taxa. While an unrecorded transient response is still possible, the long-term evolutionary impact is minimal. Adaptation to already-warm conditions and slow release of CO 2 relative to the time scale of ocean mixing likely buffered the impact of PETM climate change on shelf faunas.