Longitudinal metabolic and gut bacterial profiling of pregnant women with previous bariatric surgery

Due to the global increase in obesity rates and success of bariatric surgery in weight reduction, an increasing number of women now present pregnant with a previous bariatric procedure. This study investigates the extent of bariatric-associated metabolic and gut microbial alterations during pregnancy and their impact on fetal development. Design A parallel metabonomic (1H NMR spectroscopy) and gut bacterial (16S rRNA gene amplicon sequencing) profiling approach was used to determine maternal longitudinal phenotypes associated with malabsorptive/mixed (n=25) or restrictive (n=16) procedures, compared to women with similar early pregnancy body mass index but without bariatric surgery (n=70). Metabolic profiles of offspring at birth were also analysed. Results Previous malabsorptive, but not restrictive, procedures induced significant changes in maternal metabolic pathways involving branched-chain and aromatic amino acids with decreased circulation of leucine, isoleucine and isobutyrate, increased excretion of microbial-associated metabolites of protein putrefaction (phenylacetlyglutamine, p-cresol sulfate, indoxyl sulfate and p-hydroxyphenylacetate), and a shift in the gut microbiota. Urinary concentration of phenylacetylglutamine was significantly elevated in malabsorptive patients relative to controls (P=0.001) and was also elevated in urine of neonates born from these mothers (P=0.021). Furthermore, the maternal metabolic changes induced by malabsorptive surgery were associated with reduced maternal insulin resistance and fetal/birth weight. Conclusion Metabolism is altered in pregnant women with a previous malabsorptive bariatric surgery. These alterations may be beneficial for maternal outcomes, but the effect of elevated levels of phenolic and indolic compounds on fetal and infant health should be investigated further

Exploring experiences and impact of the COVID-19 pandemic on young racially minoritised people in the United Kingdom: A Qualitative Study

Within high-income-countries, the COVID-19 pandemic has disproportionately impacted people from racially minoritised backgrounds. There has been significant research interrogating the disparate impact of the virus, and recently, interest in the long-term implications of the global crisis on young people’s mental health and wellbeing. However, less work explores the experiences of young people from racialised backgrounds as they navigate the pandemic, and the specific consequences this has for their mental health. Forty young people (age 16-25) from black, mixed and other minority backgrounds and living in London, participated in consecutive focus group discussions over a two-month period, to explore the impact of the pandemic on their lives and emotional wellbeing. Thematic analysis identified seven categories describing the impact of the pandemic, indicating: deepening of existing socioeconomic and emotional challenges; efforts to navigate racism and difference within the response; and survival strategies drawing on communal and individual resources. Young people also articulated visions for a future public health response which addressed gaps in current strategies. Findings point to the need to contextualise public health responses to the pandemic in line with the lived experiences of racialised young people. We specifically note the importance of long-term culturally and socio-politically relevant support interventions. Implications for policy and practice are discusse

Isolation of Angola-like Marburg virus from Egyptian rousette bats from West Africa.

Marburg virus (MARV) causes sporadic outbreaks of severe Marburg virus disease (MVD). Most MVD outbreaks originated in East Africa and field studies in East Africa, South Africa, Zambia, and Gabon identified the Egyptian rousette bat (ERB; Rousettus aegyptiacus) as a natural reservoir. However, the largest recorded MVD outbreak with the highest case-fatality ratio happened in 2005 in Angola, where direct spillover from bats was not  shown. Here, collaborative studies by the Centers for Disease Control and Prevention, Njala University, University of California, Davis USAID-PREDICT, and the University of Makeni identify MARV circulating in ERBs in Sierra Leone. PCR, antibody and virus isolation data from 1755 bats of 42 species shows active MARV infection in approximately 2.5% of ERBs. Phylogenetic analysis identifies MARVs that are similar to the Angola strain. These results provide evidence of MARV circulation in West Africa and demonstrate the value of pathogen surveillance to identify previously undetected threats

Alignment of retention time obtained from multicapillary column gas chromatography used for VOC analysis with ion mobility spectrometry

Multicapillary column (MCC) ion mobility spectrometers (IMS) are increasingly in demand for medical diagnosis, biological applications and process control. In a MCC-IMS, volatile compounds are differentiated by specific retention time and ion mobility when rapid preseparation techniques are applied, e.g. for the analysis of complex and humid samples. Therefore, high accuracy in the determination of both parameters is required for reliable identification of the signals. The retention time in the MCC is the subject of the present investigation because, for such columns, small deviations in temperature and flow velocity may cause significant changes in retention time. Therefore, a universal correction procedure would be a helpful tool to increase the accuracy of the data obtained from a gas-chromatographic preseparation. Although the effect of the carrier gas flow velocity and temperature on retention time is not linear, it could be demonstrated that a linear alignment can compensate for the changes in retention time due to common minor deviations of both the carrier gas flow velocity and the column temperature around the MCC-IMS standard operation conditions. Therefore, an effective linear alignment procedure for the correction of those deviations has been developed from the analyses of defined gas mixtures under various experimental conditions. This procedure was then applied to data sets generated from real breath analyses obtained in clinical studies using different instruments at different measuring sites for validation. The variation in the retention time of known signals, especially for compounds with higher retention times, was significantly improved. The alignment of the retention time—an indispensable procedure to achieve a more precise identification of analytes—using the proposed method reduces the random error caused by small accidental deviations in column temperature and flow velocity significantly

Quantitative Outcomes of a One Health Approach to Investigate the First Outbreak of African Swine Fever in the Republic of Sierra Leone

African swine fever (ASF) outbreaks have been reported in Sub-Saharan countries, including West Africa states, but has never been notified in the Republic of Sierra Leone. This is the first report describing field epidemiological and laboratory investigations into the outbreak of fatal pig disease in western rural and urban districts, Freetown. A preliminary finding indicated that pigs exhibited clinical and necropsy signs suggestive of ASF. Serological (ELISA) and molecular (qRT-PCR) methods used to confirm and investigate the outbreak yielded three positive results for the ASF antibody and all negative for Swine flu; thus, confirming ASF as the etiology agent

Correlation of IDH1 Mutation with Clinicopathologic Factors and Prognosis in Primary Glioblastoma: A Report of 118 Patients from China

It has been reported that IDH1 (IDH1R132) mutation was a frequent genomic alteration in grade II and grade III glial tumors but rare in primary glioblastoma (pGBM). To elucidate the frequency of IDH1 mutation and its clinical significance in Chinese patients with pGBM, one hundred eighteen pGBMs were assessed by pyro-sequencing for IDH1 mutation status, and the results were correlated with clinical characteristics and molecular pathological factors. IDH1 mutations were detected in 19/118 pGBM cases (16.1%). Younger age, methylated MGMT promoter, high expression of mutant P53 protein, low expression of Ki-67 or EGFR protein were significantly correlated with IDH1 mutation status. Most notably, we identified pGBM cases with IDH1 mutation were mainly involved in the frontal lobe when compared with those with wild-type IDH1. In addition, Kaplan-Meier survival analysis revealed a highly significant association between IDH1 mutation and a better clinical outcome (p = 0.026 for progression-free survival; p = 0.029 for overall survival). However, in our further multivariable regression analysis, the independent prognostic effect of IDH1 mutation is limited when considering age, preoperative KPS score, extent of resection, TMZ chemotherapy, and Ki-67 protein expression levels, which might narrow its prognostic power in Chinese population in the future

Induction of APOBEC3 Exacerbates DNA Replication Stress and Chromosomal Instability in Early Breast and Lung Cancer Evolution

APOBEC3 enzymes are cytosine deaminases implicated in cancer. Precisely when APOBEC3 expression is induced during cancer development remains to be defined. Here we show that specific APOBEC3 genes are upregulated in breast DCIS, and in pre-invasive lung cancer lesions coincident with cellular proliferation. We observe evidence of APOBEC3-mediated subclonal mutagenesis propagated from TRACERx pre-invasive to invasive NSCLC lesions. We find that APOBEC3B exacerbates DNA replication stress and chromosomal instability through incomplete replication of genomic DNA, manifested by accumulation of mitotic ultrafine bridges and 53BP1 nuclear bodies in the G1 phase of the cell cycle. Analysis of TRACERx NSCLC clinical samples and mouse lung cancer models, revealed APOBEC3B expression driving replication stress and chromosome missegregation. We propose that APOBEC3 is functionally implicated in the onset of chromosomal instability and somatic mutational heterogeneity in pre-invasive disease, providing fuel for selection early in cancer evolution

Identification of a Putative Crf Splice Variant and Generation of Recombinant Antibodies for the Specific Detection of Aspergillus fumigatus

BACKGROUND: Aspergillus fumigatus is a common airborne fungal pathogen for humans. It frequently causes an invasive aspergillosis (IA) in immunocompromised patients with poor prognosis. Potent antifungal drugs are very expensive and cause serious adverse effects. Their correct application requires an early and specific diagnosis of IA, which is still not properly achievable. This work aims to a specific detection of A. fumigatus by immunofluorescence and the generation of recombinant antibodies for the detection of A. fumigatus by ELISA. RESULTS: The A. fumigatus antigen Crf2 was isolated from a human patient with proven IA. It is a novel variant of a group of surface proteins (Crf1, Asp f9, Asp f16) which belong to the glycosylhydrolase family. Single chain fragment variables (scFvs) were obtained by phage display from a human naive antibody gene library and an immune antibody gene library generated from a macaque immunized with recombinant Crf2. Two different selection strategies were performed and shown to influence the selection of scFvs recognizing the Crf2 antigen in its native conformation. Using these antibodies, Crf2 was localized in growing hyphae of A. fumigatus but not in spores. In addition, the antibodies allowed differentiation between A. fumigatus and related Aspergillus species or Candida albicans by immunofluorescence microscopy. The scFv antibody clones were further characterized for their affinity, the nature of their epitope, their serum stability and their detection limit of Crf2 in human serum. CONCLUSION: Crf2 and the corresponding recombinant antibodies offer a novel approach for the early diagnostics of IA caused by A. fumigatus