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  • 1
    In: Translational Psychiatry, Springer Science and Business Media LLC, Vol. 13, No. 1 ( 2023-02-23)
    Abstract: Tourette Syndrome (TS) is a complex neurodevelopmental disorder characterized by vocal and motor tics lasting more than a year. It is highly polygenic in nature with both rare and common previously associated variants. Epidemiological studies have shown TS to be correlated with other phenotypes, but large-scale phenome wide analyses in biobank level data have not been performed to date. In this study, we used the summary statistics from the latest meta-analysis of TS to calculate the polygenic risk score (PRS) of individuals in the UK Biobank data and applied a Phenome Wide Association Study (PheWAS) approach to determine the association of disease risk with a wide range of phenotypes. A total of 57 traits were found to be significantly associated with TS polygenic risk, including multiple psychosocial factors and mental health conditions such as anxiety disorder and depression. Additional associations were observed with complex non-psychiatric disorders such as Type 2 diabetes, heart palpitations, and respiratory conditions. Cross-disorder comparisons of phenotypic associations with genetic risk for other childhood-onset disorders (e.g.: attention deficit hyperactivity disorder [ADHD], autism spectrum disorder [ASD] , and obsessive-compulsive disorder [OCD]) indicated an overlap in associations between TS and these disorders. ADHD and ASD had a similar direction of effect with TS while OCD had an opposite direction of effect for all traits except mental health factors. Sex-specific PheWAS analysis identified differences in the associations with TS genetic risk between males and females. Type 2 diabetes and heart palpitations were significantly associated with TS risk in males but not in females, whereas diseases of the respiratory system were associated with TS risk in females but not in males. This analysis provides further evidence of shared genetic and phenotypic architecture of different complex disorders.
    Type of Medium: Online Resource
    ISSN: 2158-3188
    Language: English
    Publisher: Springer Science and Business Media LLC
    Publication Date: 2023
    detail.hit.zdb_id: 2609311-X
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  • 2
    In: Pathogens, MDPI AG, Vol. 10, No. 8 ( 2021-08-19), p. 1053-
    Abstract: Cystoisospora (C.) belli is a coccidian parasite associated with acute or chronic gastroenteritis in immunocompromised patients. Dissatisfactory sensitivity of microscopy as the diagnostic standard approach has been described. Here, we comparatively evaluated two real-time PCRs targeting ribosomal RNA gene sequences of C. belli in stool in a test comparison without a reference standard applying latent class analysis. Therefore, 1000 stool samples from Ghanaian HIV (human immunodeficiency virus) patients (n = 905) as well as military returnees from the tropics (n = 95) were assessed by both assays in parallel. After the exclusion of 33 samples showing PCR inhibition, 29 and 33 positive results were recorded with the 5.8S rRNA gene/ITS-2 sequence PCR and the ITS-2 sequence PCR, respectively, resulting in an accuracy-adjusted prevalence of 3.2%. Nearly perfect agreement between both assays was indicated by Fleiss’ kappa of 0.933 with sensitivity and specificity of 92.8% and 100% as well as 100% and 99.8% for the 5.8S rRNA gene/ITS-2 sequence PCR and the ITS-2 sequence PCR, respectively. Both assays proved to be suitable for the diagnosis of C. belli in human stool samples with slightly better sensitivity of the ITS-2 sequence assay, while the 5.8S rRNA gene/ITS-2 sequence PCR may be considered for confirmatory testing.
    Type of Medium: Online Resource
    ISSN: 2076-0817
    Language: English
    Publisher: MDPI AG
    Publication Date: 2021
    detail.hit.zdb_id: 2695572-6
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  • 3
    In: Microorganisms, MDPI AG, Vol. 11, No. 5 ( 2023-05-17), p. 1313-
    Abstract: Potential etiological relevance for gastroenteric disorders including diarrhea has been assigned to Arcobacter butzleri. However, standard routine diagnostic algorithms for stool samples of patients with diarrhea are rarely adapted to the detection of this pathogen and so, A. butzleri is likely to go undetected unless it is specifically addressed, e.g., by applying pathogen-specific molecular diagnostic approaches. In the study presented here, we compared three real-time PCR assays targeting the genes hsp60, rpoB/C (both hybridization probe assays) and gyrA (fluorescence resonance energy transfer assay) of A. butzleri in a test comparison without a reference standard using a stool sample collection with a high pretest probability from the Ghanaian endemicity setting. Latent class analysis was applied with the PCR results obtained with a collection of 1495 stool samples showing no signs of PCR inhibition to assess the real-time PCR assays’ diagnostic accuracy. Calculated sensitivity and specificity were 93.0% and 96.9% for the hsp60-PCR, 100% and 98.2% for the rpoB/C-PCR, as well as 12.7% and 99.8% for the gyrA-PCR, respectively. The calculated A. butzleri prevalence within the assessed Ghanaian population was 14.7%. As indicated by test results obtained with high-titer spiked samples, cross-reactions of the hsp60-assay and rpoB/C-assay with phylogenetically related species such as A. cryaerophilus can occur but are less likely with phylogenetically more distant species like, e.g., A. lanthieri. In conclusion, the rpoB/C-assay showed the most promising performance characteristics as the only assay with sensitivity 〉 95%, albeit associated with a broad 95%-confidence interval. In addition, this assay showed still-acceptable specificity of 〉 98% in spite of the known cross-reactivity with phylogenetically closely related species such as A. cryaerophilus. If higher certainty is desired, the gyrA-assay with specificity close to 100% can be applied for confirmation testing with samples showing positive rpoB/C-PCR results. However, in case of a negative result in the gyrA-assay, this cannot reliably exclude the detection of A. butzleri in the rpoB/C-assay due to the gyrA-assay’s very low sensitivity.
    Type of Medium: Online Resource
    ISSN: 2076-2607
    Language: English
    Publisher: MDPI AG
    Publication Date: 2023
    detail.hit.zdb_id: 2720891-6
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  • 4
    In: Pathogens, MDPI AG, Vol. 11, No. 7 ( 2022-07-02), p. 760-
    Abstract: Both Schistosoma spp. (species) and Leishmania spp. are prevalent in Ghana in West Africa. However, little is known about their local occurrence in immunocompromised individuals. In the study presented here, the real-time PCR-(polymerase chain reaction-)based screening for repetitive DNA (deoxyribonucleotide acid) sequences from the genomes of Leishmania (L.) spp. and Schistosoma (S.) spp. was performed in the serum of HIV-(human immunodeficiency virus-)infected Ghanaian patients. In 1083 assessed serum samples from HIV-positive and HIV-negative Ghanian patients, Leishmania spp.-specific DNA was not detected, while the diagnostic accuracy-adjusted prevalence estimation suggested a 3.6% prevalence of the S. mansoni complex and a 0.5% prevalence of the S. haematobium complex. Associations of schistosomiasis with younger age, as well as with the male sex, could be shown but not with an HIV status. Weakly significant signals for the associations of schistosomiasis with an increased viral load, reduced CD4+ (CD = cluster of differentiation) T cell count, and a reduced CD4+/CD8+ ratio could be observed but was inconsistently lost in the case of the stratification on the species complex level. So, it is concluded that factors other than HIV status are more likely to have influenced the occurrence of Schistosoma spp. infections in the assessed Ghanaian patients. Potential associations between HIV infection-associated factors, such as the viral load and the immune status of the patients, for which weak signals were observed in this hypothesis-forming retrospective assessment, should be confirmed by prospective, sufficiently powered investigations.
    Type of Medium: Online Resource
    ISSN: 2076-0817
    Language: English
    Publisher: MDPI AG
    Publication Date: 2022
    detail.hit.zdb_id: 2695572-6
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  • 5
    In: Pathogens, MDPI AG, Vol. 12, No. 8 ( 2023-07-30), p. 999-
    Abstract: Medical complications during pregnancy have been frequently reported from Western Africa with a particular importance of infectious complications. Placental tissue can either become the target of infectious agents itself, such as, e.g., in the case of urogenital schistosomiasis, or be subjected to contamination with colonizing or infection-associated microorganisms of the cervix or the vagina during vaginal delivery. In the retrospective cross-sectional assessment presented here, the quantitative dimension of infection or colonization with selected resistant or pathogenic bacteria and parasites was regionally assessed. To do so, 274 collected placental tissues from Ivory Coastal and Ghanaian women were subjected to selective growth of resistant bacteria, as well as to molecular screening for beta-lactamase genes, Schistosoma spp. and selected bacterial causative agents of sexually transmitted infections (STI). Panton–Valentine-negative methicillin-resistant Staphylococcus aureus (MRSA) was grown from 1.8% of the tissue samples, comprising the spa types t008 and t688, as well as the newly detected ones, t12101 (n = 2) and t12102. While the culture-based recovery of resistant Enterobacterales and nonfermentative rod-shaped Gram-negative bacteria failed, molecular assessments confirmed beta-lactamase genes in 31.0% of the samples with multiple detections of up to four resistance genes per sample and blaCTX-M, blaIMP, blaGES, blaVIM, blaOXA-58-like, blaNDM, blaOXA-23-like, blaOXA-48-like and blaKPC occurring in descending order of frequency. The beta-lactamase genes blaOXA-40/24-like, blaNMC_A/IMI, blaBIC, blaSME, blaGIM and blaDIM were not detected. DNA of the urogenital schistosomiasis-associated Schistosoma haematobium complex was recorded in 18.6% of the samples, but only a single positive signal for S. mansoni with a high cycle-threshold value in real-time PCR was found. Of note, higher rates of schistosomiasis were observed in Ghana (54.9% vs. 10.3% in Ivory Coast) and Cesarean section was much more frequent in schistosomiasis patients (61.9% vs. 14.8% in women without Schistosoma spp. DNA in the placenta). Nucleic acid sequences of nonlymphogranuloma-venereum-associated Chlamydia trachomatis and of Neisseria gonorrhoeae were recorded in 1.1% and 1.9% of the samples, respectively, while molecular attempts to diagnose Treponema pallidum and Mycoplasma genitalium did not lead to positive results. Molecular detection of Schistosoma spp. or STI-associated pathogens was only exceptionally associated with multiple resistance gene detections in the same sample, suggesting epidemiological distinctness. In conclusion, the assessment confirmed considerable prevalence of urogenital schistosomiasis and resistant bacterial colonization, as well as a regionally expected abundance of STI-associated pathogens. Continuous screening offers seem advisable to minimize the risks for the pregnant women and their newborns.
    Type of Medium: Online Resource
    ISSN: 2076-0817
    Language: English
    Publisher: MDPI AG
    Publication Date: 2023
    detail.hit.zdb_id: 2695572-6
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  • 6
    In: Microorganisms, MDPI AG, Vol. 11, No. 3 ( 2023-02-28), p. 625-
    Abstract: An Indigenous agropastoralist population called the Wiwa from the Sierra Nevada de Santa Marta, in North-East Colombia, shows high rates of gastrointestinal infections. Chronic gut inflammatory processes and dysbiosis could be a reason, suggesting an influence or predisposing potential of the gut microbiome composition. The latter was analyzed by 16S rRNA gene amplicon next generation sequencing from stool samples. Results of the Wiwa population microbiomes were associated with available epidemiological and morphometric data and compared to control samples from a local urban population. Indeed, locational-, age-, and gender-specific differences in the Firmicutes/Bacteriodetes ratio, core microbiome, and overall genera-level microbiome composition were shown. Alpha- and ß-diversity separated the urban site from the Indigenous locations. Urban microbiomes were dominated by Bacteriodetes, whereas Indigenous samples revealed a four times higher abundance of Proteobacteria. Even differences among the two Indigenous villages were noted. PICRUSt analysis identified several enriched location-specific bacterial pathways. Moreover, on a general comparative scale and with a high predictive accuracy, we found Sutterella associated with the abundance of enterohemorrhagic Escherichia coli (EHEC), Faecalibacteria associated with enteropathogenic Escherichia coli (EPEC) and helminth species Hymenolepsis nana and Enterobius vermicularis. Parabacteroides, Prevotella, and Butyrivibrio are enriched in cases of salmonellosis, EPEC, and helminth infections. Presence of Dialister was associated with gastrointestinal symptoms, whereas Clostridia were exclusively found in children under the age of 5 years. Odoribacter and Parabacteroides were exclusively identified in the microbiomes of the urban population of Valledupar. In summary, dysbiotic alterations in the gut microbiome in the Indigenous population with frequent episodes of self-reported gastrointestinal infections were confirmed with epidemiological and pathogen-specific associations. Our data provide strong hints of microbiome alterations associated with the clinical conditions of the Indigenous population.
    Type of Medium: Online Resource
    ISSN: 2076-2607
    Language: English
    Publisher: MDPI AG
    Publication Date: 2023
    detail.hit.zdb_id: 2720891-6
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  • 7
    In: JAMA Oncology, American Medical Association (AMA), Vol. 8, No. 1 ( 2022-01-20), p. e215445-
    Type of Medium: Online Resource
    ISSN: 2374-2437
    Language: English
    Publisher: American Medical Association (AMA)
    Publication Date: 2022
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  • 8
    In: European Child & Adolescent Psychiatry, Springer Science and Business Media LLC, Vol. 31, No. 10 ( 2022-10), p. 1539-1548
    Type of Medium: Online Resource
    ISSN: 1018-8827 , 1435-165X
    RVK:
    Language: English
    Publisher: Springer Science and Business Media LLC
    Publication Date: 2022
    detail.hit.zdb_id: 1463026-6
    SSG: 5,2
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  • 9
    Online Resource
    Online Resource
    Ovid Technologies (Wolters Kluwer Health) ; 2023
    In:  ASAIO Journal Vol. 69, No. Supplement 2 ( 2023-06), p. 112-112
    In: ASAIO Journal, Ovid Technologies (Wolters Kluwer Health), Vol. 69, No. Supplement 2 ( 2023-06), p. 112-112
    Type of Medium: Online Resource
    ISSN: 1058-2916
    Language: English
    Publisher: Ovid Technologies (Wolters Kluwer Health)
    Publication Date: 2023
    detail.hit.zdb_id: 2083312-X
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  • 10
    In: Open Forum Infectious Diseases, Oxford University Press (OUP), Vol. 9, No. Supplement_2 ( 2022-12-15)
    Abstract: Numerous predictive clinical scores with varying discriminatory performance have been developed in the context of the current coronavirus disease 2019 (COVID-19) pandemic. To support clinical application, we test the transferability of the frequently applied 4C mortality score (4C score) to the German prospective Cross-Sectoral Platform (SUEP) of the National Pandemic Cohort Network (NAPKON) compared to the non COVID-19 specific quick sequential organ failure assessment score (qSOFA). Our project aims to externally validate these two scores, stratified for the most prevalent variants of concerns (VOCs) of severe acute respiratory syndrome coronavirus type 2 (SARS-CoV-2) in Germany. Methods A total of 685 adults with polymerase chain reaction (PCR)-detected SARS-CoV-2 infection were included from NAPKON-SUEP. Patients were recruited from 11/2020 to 03/2022 at 34 university and non-university hospitals across Germany. Missing values were complemented using multiple imputation. Predictive performance for in-hospital mortality at day of baseline visit was determined by area under the curve (AUC) with 95%-confidence interval (CI) stratified by VOCs of SARS-CoV-2 (alpha, delta, omicron) (Figure 1). Figure 1:Study flow chart with inclusion criteria and methodological workflow. Results Preliminary results suggest a high predictive performance of the 4C score for in-hospital mortality (Table 1). This applies for the overall cohort (AUC 0.813 (95%CI 0.738-0.888)) as well as the VOC-strata (alpha: AUC 0.859 (95%CI 0.748-0.970); delta: AUC 0.769 (95%CI 0.657-0.882); omicron: AUC 0.866 (95%CI 0.724-1.000)). The overall mortality rates across the defined 4C score risk groups are 0.3% (low), 3.2% (intermediate), 11.6% (high), and 49.5% (very high). The 4C score performs significantly better than the qSOFA (Chi2-test: p=0.001) and the qSOFA does not seem to be a suitable tool in this context. Table 1:Discriminatory performance of the 4C Mortality Score and the qSOFA score within the validation cohort NAPKON-SUEP stratified by the Variant of Concerns of SARS-CoV-2. Conclusion Despite its development in the early phase of the pandemic and improved treatment, external validation of the 4C score in NAPKON-SUEP indicates a high predictive performance for in-hospital mortality across all VOCs. However, since the qSOFA was not specifically designed for this predictive issue, it shows low discriminatory performance, as in other validation studies. Any interpretations regarding the omicron stratum are limited due to the sample size. Disclosures Daniel Pape, Dr., Advanz Pharma Germany: Support for attending meetings and/or travel for ECCMID 2021 Martin Hower, n/a, MSD: Advisor/Consultant|Trogarzo: Advisor/Consultant|ViiV Healthcare: Advisor/Consultant Björn-Erik O. Jensen, Dr. med., GILEAD: Advisor/Consultant|GILEAD: Lectures, Travel|GSK: Lectures, Travel Jörg J. Vehreschild, Univ.-Prof. Dr. med., Ärztekammer Nordrhein: Honoraria|Academy for Infectious Medicine, University Manchester: Honoraria|Astellas Pharma: Grant/Research Support|Astellas Pharma: Honoraria|Back Bay Strategies: Honoraria|Basilea: Grant/Research Support|Basilea: Honoraria|Deutsches Zetrum für Luft- und Raumfahrt (DLR): Grant/Research Support|German Centre for Infection Research (DZIF): Grant/Research Support|German Centre for Infection Research (DZIF): Honoraria|German Federal Ministry of Education and Research (BMBF): Grant/Research Support|German Society for Infectious Diseases (DGI): Honoraria|German Society for Internal Medicine (DGIM): Honoraria|GILEAD: Advisor/Consultant|GILEAD: Grant/Research Support|GILEAD: Honoraria|Janssen: Honoraria|Merck / MSD: Grant/Research Support|Merck / MSD: Honoraria|Molecular Health: Honoraria|Netzwerk Universitätsmedizin: Honoraria|NordForsk: Honoraria|Pfizer: Advisor/Consultant|Pfizer: Grant/Research Support|Pfizer: Honoraria|Rigshospitalet Copenhagen: Grant/Research Support|Shionogi: Advisor/Consultant|Shionogi: Honoraria|University Hospital Aachen: Honoraria|University Hospital Freiburg/ Congress and Communication: Honoraria|University of Bristol: Grant/Research Support.
    Type of Medium: Online Resource
    ISSN: 2328-8957
    Language: English
    Publisher: Oxford University Press (OUP)
    Publication Date: 2022
    detail.hit.zdb_id: 2757767-3
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