Datamama, bringing pregnancy research into the future: design, development, and evaluation of a citizen science pregnancy mobile application

Background: Pregnancy mobile applications (apps) have grown in popularity over the past decade, with some being used to promote study recruitment or health behaviors. However, no app serves as an all-in-one solution for collecting general data for research purposes and providing women with useful and desirable features. Aim: To create and develop a Swiss pregnancy mobile app as an innovative means to collect research data and provide users with reliable information. Methods: Determining the key features of the app involved a review of the literature and assessment of popular apps in the Swiss AppStore. A team of engineers developed the app, which includes a pregnancy timeline, questionnaires for data collection, medical and psychological articles and a checklist with appointment reminders. The content was written and reviewed by healthcare providers considered experts in the topics adressed. The questionnaires are distributed based on the user’s gestational age, by a chatbot. The project was authorized by the ethics commission in the canton of Vaud. An online survey of ten questions, advertised on Datamama’s home screen, was conducted to assess the users’ use of the app (27.11- 19.12.2022). Results: A review of 84 articles and 25 popular apps showed the need for a comprehensive pregnancy app. The development of Datamama took 2 years and included the creation of 70 medical and psychological articles and 29 questionnaires covering 300 unique variables. Six months after the launch, there were 800 users with a 73% average participation rate in the questionnaires. Sixty-five women completed the survey, with 70.8% using the app once to multiple times per week. The primary reason for using the app was to help research by answering the questionnaires, followed by access to reliable medical information. The reason most frequently ranked first for using the app was to help research by answering the questionnaires (42/65, 67% of women rated it first), followed by access to reliable medical information (34/65, 54% women rated it second). Women rated the information as clear, understandable, and interesting with a trust rating in data handling at 98.5%. The average grade for recommending the app was 8/10, with suggestions for increasing the amount of medical content and tailoring it based on gestational age. Conclusion: Datamama is the first pregnancy app to address the needs of both patients and researchers. Initial feedback from users was positive, highlighting future challenges for success. Future work will consist in improving the app, validating the data and use it to answer specific pregnancy-related research questions

LPS-binding protein and IL-6 Mark paradoxical tuberculosis immune reconstitution inflammatory syndrome in HIV patients

Background: Tuberculosis-associated immune reconstitution inflammatory syndrome (TB-IRIS) remains a poorly understood complication in HIV-TB co-infected patients initiating antiretroviral therapy (ART). The role of the innate immune system in TB-IRIS is becoming increasingly apparent, however the potential involvement in TB-IRIS of a leaky gut and proteins that interfere with TLR stimulation by binding PAMPs has not been investigated before. Here we aimed to investigate the innate nature of the cytokine response in TB-IRIS and to identify novel potential biomarkers. Methods: From a large prospective cohort of HIV-TB co-infected patients receiving TB treatment, we compared 40 patients who developed TB-IRIS during the first month of ART with 40 patients matched for age, sex and baseline CD4 count who did not. We analyzed plasma levels of lipopolysaccharide (LPS)-binding protein (LBP), LPS, sCD14, endotoxin-core antibody, intestinal fatty acid-binding protein (I-FABP) and 18 pro-and anti-inflammatory cytokines before and during ART. Results: We observed lower baseline levels of IL-6 (p = 0.041), GCSF (p = 0.036) and LBP (p = 0.016) in TB-IRIS patients. At IRIS event, we detected higher levels of LBP, IL-1RA, IL-4, IL-6, IL-7, IL-8, G-CSF (p ≤ 0.032) and lower I-FABP levels (p = 0.013) compared to HIV-TB co-infected controls. Only IL-6 showed an independent effect in multivariate models containing significant cytokines from pre-ART (p = 0.039) and during TB-IRIS (p = 0.034). Conclusion: We report pre-ART IL-6 and LBP levels as well as IL-6, LBP and I-FABP levels during IRIS-event as potential biomarkers in TB-IRIS. Our results show no evidence of the possible contribution of a leaky gut to TB-IRIS and indicate that IL-6 holds a distinct role in the disturbed innate cytokine profile before and during TB-IRIS. Future clinical studies should investigate the importance and clinical relevance of these markers for the diagnosis and treatment of TB-IRIS. Copyright: © 2013 Goovaerts et al.SCOPUS: ar.jSCOPUS: ar.jinfo:eu-repo/semantics/publishe

Lack of elevated pre-ART elastase-ANCA levels in patients developing TB-IRIS

Background Tuberculosis-associated immune reconstitution inflammatory syndrome (TB-IRIS) in HIV-TB co-infected patients receiving antiretroviral therapy (ART) has been linked to neutrophil activation. Anti-neutrophil cytoplasmic antibodies (ANCAs) are also associated with neutrophil activation. Since ANCAs are reportedly skewed in TB and HIV infections, we investigated plasma levels of 7 ANCAs in TB-IRIS patients. Methods We retrospectively compared 17 HIV-TB patients who developed TB-IRIS with controls of similar CD4 count, age and gender who did not (HIV+TB+ n = 17), HIV-infected patients without TB (HIV+TB-, n = 17) and 10 HIV-negative (HIV-TB-) controls. Frozen plasma was collected before ART, at 3 and 9 months of ART, and examined by ELISA for levels of 7 ANCAs directed against; Proteinase 3 (PR3), Myeloperoxidase (MPO), Permeability-increasing protein (BPI), Elastase, Cathepsin, Lysozyme, and Lactoferrin. Results Compared to HIV+TB+ controls, pre-ART anti-elastase levels were lower in TB-IRIS patients (p = 0.026) and HIV-TB- controls (p = 0.044), whereas other ANCAs did not show significant differences between groups at any time point. A significant decrease over time could be observed in TB-IRIS patients during ART for anti -PR3 (p = 0.027), -lysozyme (p = 0.011), and -lactoferrin (p = 0.019). Conversely, HIV+TB+ controls showed a significant decrease over time for anti -MPO (p = 0.002), -lyzosyme (p = 0.002) and -elastase (p < 0.001). Conclusion The lack of elevated anti-elastase levels in TB-IRIS patients as opposed to HIV+TB+ controls correspond to previous findings of lowered immune capacity in patients that will develop TB-IRIS. This may suggest a specific role for anti-elastase, elastase or even matrix-metalloproteinases in TB-IRIS. The precise dynamics of neutrophil activation in HIV-TB merits further investigation and could provide more insight in the early mechanisms leading up to TB-IRIS.SCOPUS: ar.jinfo:eu-repo/semantics/publishe

Novel promoters and coding first exons in DLG2 linked to developmental disorders and intellectual disability

International audienceTissue-specific integrative omics has the potential to reveal new genic elements important for developmental disorders.METHODS:Two pediatric patients with global developmental delay and intellectual disability phenotype underwent array-CGH genetic testing, both showing a partial deletion of the DLG2 gene. From independent human and murine omics datasets, we combined copy number variations, histone modifications, developmental tissue-specific regulation, and protein data to explore the molecular mechanism at play.RESULTS:Integrating genomics, transcriptomics, and epigenomics data, we describe two novel DLG2 promoters and coding first exons expressed in human fetal brain. Their murine conservation and protein-level evidence allowed us to produce new DLG2 gene models for human and mouse. These new genic elements are deleted in 90% of 29 patients (public and in-house) showing partial deletion of the DLG2 gene. The patients' clinical characteristics expand the neurodevelopmental phenotypic spectrum linked to DLG2 gene disruption to cognitive and behavioral categories.CONCLUSIONS:While protein-coding genes are regarded as well known, our work shows that integration of multiple omics datasets can unveil novel coding elements. From a clinical perspective, our work demonstrates that two new DLG2 promoters and exons are crucial for the neurodevelopmental phenotypes associated with this gene. In addition, our work brings evidence for the lack of cross-annotation in human versus mouse reference genomes and nucleotide versus protein databases

A randomized trial of tigecycline versus ampicillin-sulbactam or amoxicillin-clavulanate for the treatment of complicated skin and skin structure infections

Background: Complicated skin and skin structure infections (cSSSIs) frequently result in hospitalization with significant morbidity and mortality.Methods: In this phase 3b/4 parallel, randomized, open-label, comparative study, 531 subjects with cSSSI received tigecycline (100 mg initial dose, then 50 mg intravenously every 12 hrs) or ampicillin-sulbactam 1.5-3 g IV every 6 hrs or amoxicillin-clavulanate 1.2 g IV every 6-8 hrs. Vancomycin could be added at the discretion of the investigator to the comparator arm if methicillin-resistant Staphylococcus aureus (MRSA) was confirmed or suspected within 72 hrs of enrollment. The primary endpoint was clinical response in the clinically evaluable (CE) population at the test-of-cure (TOC) visit. Microbiologic response and safety were also assessed. The modified intent-to-treat (mITT) population comprised 531 subjects (tigecycline, n = 268; comparator, n = 263) and 405 were clinically evaluable (tigecycline, n = 209; comparator, n = 196).Results: In the CE population, 162/209 (77.5%) tigecycline-treated subjects and 152/196 (77.6%) comparator-treated subjects were clinically cured (difference 0.0; 95% confidence interval [CI]: -8.7, 8.6). The eradication rates at the subject level for the microbiologically evaluable (ME) population were 79.2% in the tigecycline treatment group and 76.8% in the comparator treatment group (difference 2.4; 95% CI: -9.6, 14.4) at the TOC assessment. Nausea, vomiting, and diarrhea rates were higher in the tigecycline group.Conclusions: Tigecycline was generally safe and effective in the treatment of cSSSIs.Trial registration: ClinicalTrials.gov NCT00368537. © 2012 Matthews et al.; licensee BioMed Central Ltd