Molecular detection of mobilized colistin resistance (mcr-1) gene in Escherichia coli isolates from Port Harcourt, Nigeria

The emergence of plasmid borne colistin resistance in recent years has been problematic as a result of the potential for rapid dissemination through bacterial populations. This mcr-1 mediated resistance has been reported from around the globe and active surveillance is essential to monitor the developing issue. This study set out to determine the occurrence of such strains in a group of 60 Escherichia coli isolates using DNA extraction and amplification techniques. Following molecular confirmation of the identities of the E. coli isolates based on the detection of E. coli specific 16sRNA gene fragments, phenotypic colistin resistance of isolates was determined and isolates were screened for the mcr-1 gene using standard procedures. Of the 35 confirmed E. coli isolates, 60% were found to be colistin resistant, with a higher level of resistance noted among the non-clinical isolates. Plasmid mediated mcr-1 resistance was however found to be present in only 8.6% of total isolates, making up 14.3% of the colistin resistant strains. This mcr-1 mediated resistance was only noted in clinical isolates however. This detection of mcr-1 mediated colistin resistance in E. coli isolates from Port Harcourt, Nigeria is worrisome as it could point at a looming epidemic of colistin resistance and hence the development of untreatable bacterial isolates. Further studies are essential to properly assess the scope and spread of this situation.Keywords: Colistin resistance, mcr-1, Escherichia coli, Nigeri

Characterizing the metabolic phenotype of intestinal villus blunting in Zambian children with severe acute malnutrition and persistent diarrhea

Background: Environmental enteric dysfunction (EED) is widespread throughout the tropics and in children is associated with stunting and other adverse health outcomes. One of the hallmarks of EED is villus damage. In children with severe acute malnutrition (SAM) the severity of enteropathy is greater and short term mortality is high, but the metabolic consequences of enteropathy are unknown. Here, we characterize the urinary metabolic alterations associated with villus health, classic enteropathy biomarkers and anthropometric measurements in severely malnourished children in Zambia. Methods/Principal findings: We analysed 20 hospitalised children with acute malnutrition aged 6 to 23 months in Zambia. Small intestinal biopsies were assessed histologically (n = 15), anthropometric and gut function measurements were collected and the metabolic phenotypes were characterized by 1H nuclear magnetic resonance (NMR) spectroscopy. Endoscopy could not be performed on community controls children. Growth parameters were inversely correlated with enteropathy biomarkers (p = 0.011) and parameters of villus health were inversely correlated with translocation and permeability biomarkers (p = 0.000 and p = 0.015). Shorter villus height was associated with reduced abundance of metabolites related to gut microbial metabolism, energy and muscle metabolism (p = 0.034). Villus blunting was also related to increased sucrose excretion (p = 0.013). Conclusions/Significance: Intestinal villus blunting is associated with several metabolic perturbations in hospitalized children with severe undernutrition. Such alterations include altered muscle metabolism, reinforcing the link between EED and growth faltering, and a disruption in the biochemical exchange between the gut microbiota and host. These findings extend our understanding on the downstream consequences of villus blunting and provide novel non-invasive biomarkers of enteropathy dysfunction. The major limitations of this study are the lack of comparative control group and gut microbiota characterization

Effects of Englerina drummondii Balle ex Polhill and Wiens leaves extract on selected female rat organs’ weights

Background: Herbal medicine are patronized by several people across the globe This herbal medicine is routinely use and are more accessible and available. This study aimed to investigate the effects of Englerina drummondii Balle ex Polhill and Wiens leaves on rat organs (thyroid gland, kidneys, ovary and fallopian tubes) weights in female rats. Methods: 20 female rats were selected randomly into 4 groups with 5 rats per group. Group 1 received 5 ml/kg of water, group 2 received extract 100 mg/kg, group 3 received extract 200 mg/kg, and group 4 received extract 400 mg/kg. Administration of extract was done for 28 days. Results: The study revealed significance decreased in the weight of the left ovary organ when extract of medium dose (200 mg/kg) and high dose (400 mg/kg) was administered, as compared to control. The result also shows decrease in the organs weight of the thyroid gland, left kidney, right and left fallopian tubes extract of low, medium and high dose were administered. The right kidney shows increase when low dose extract was given but decrease when both low and medium dose of extract was given. However, this decrease is not significance and could be due to dose or time dependent. Statistical analysis was done using statistical package for the social sciences (SPSS) version 23 and p<0.05 was significant. Conclusions: There was significance decreased in the weight of the left ovary organ when extract of medium dose (200 mg/kg) and high dose (400 mg/kg) was administered. Also, there is decrease in other organs weight when low, medium and high dose was given but not significance

Inflammation and epithelial repair predict mortality, hospital readmission, and growth recovery in complicated severe acute malnutrition.

Severe acute malnutrition (SAM) is the most high-risk form of undernutrition, particularly when children require hospitalization for complications. Complicated SAM is a multisystem disease with high inpatient and postdischarge mortality, especially in children with comorbidities such as HIV; however, the underlying pathogenesis of complicated SAM is poorly understood. Targeted multiplex biomarker analysis in children hospitalized with SAM (n = 264) was conducted on plasma samples, and inflammatory markers were assessed on stool samples taken at recruitment, discharge, and 12 to 24 and 48 weeks after discharge from three hospitals in Zimbabwe and Zambia. Compared with adequately nourished controls (n = 173), we found that at baseline, complicated SAM was characterized by systemic, endothelial, and intestinal inflammation, which was exacerbated by HIV infection. This persisted over 48 weeks despite nutritional recovery and was associated with children's outcomes. Baseline plasma concentrations of vascular endothelial growth factor, glucagon-like peptide-2, and intestinal fatty acid-binding protein were independently associated with lower mortality or hospital readmission over the following 48 weeks. Following principal components analysis of baseline biomarkers, higher scores of a component representing growth factors was associated with greater weight-for-height z score recovery and lower mortality or hospital readmission over the 48 weeks. Conversely, components representing higher gut and systemic inflammation were associated with higher mortality or hospital readmission. These findings highlight the interplay between inflammation, which damages tissues, and growth factors, which mediate endothelial and epithelial regeneration, and support further studies investigating interventions to reduce inflammation and promote epithelial repair as an approach to reducing mortality and improving nutritional recovery

Determinants and effects of sexual exploitation among female students of tertiary institutions in Rivers State

Background: Labor induction methods are continuously evolving to ensure safer and more effective outcomes for both mother and neonate. The present study aimed to assess the effectiveness and safety of combined use of misoprostol with intracervical catheter for labor induction. Methods: This single-blinded, parallel-group randomized control trial conducted at Shaheed Suhrawardy Medical College, Dhaka, Bangladesh, included 200 women with term gestation and Bishop score ≤6. Participants were divided into two groups: the intervention group (group B) received misoprostol juice and Foley’s catheter, while the control group (group A) received misoprostol in the posterior fornix. Results: In Group A, 58% had vaginal deliveries, while in Group B, 65% had vaginal deliveries. Group B experienced a longer mean length of labor in the 1st stage (13.25±1.095) compared to Group A (12.98±1.982, p=0.008). The 3rd stage was shorter for Group B (10.00±0.000) than Group A (12.02±2.469, p<0.001). The most common induction reason was labor pain with an unfavorable cervix (31 in Group A and 33 in Group B). Group B had a higher percentage of inductions at less than 12 hours and a lower percentage at more than 24 hours. Neonatal outcomes were generally better for Group B. The Cox regression hazard model showed a lower likelihood of positive outcomes in Group B (hazard ratio 0.337, 95% CI 0.243-0.469, p=0.000), indicating a statistically significant difference between the groups. Conclusions: The combined use of misoprostol with Foley’s catheter for labor induction is safe and effective, resulting in shorter labor duration and higher rates of vaginal delivery compared to misoprostol alone

Transcriptomic analysis of enteropathy in Zambian children with severe acute malnutrition.

BACKGROUND: Children with severe acute malnutrition (SAM), with or without diarrhoea, often have enteropathy, but there are few molecular data to guide development of new therapies. We set out to determine whether SAM enteropathy is characterised by specific transcriptional changes which might improve understanding or help identify new treatments. METHODS: We collected intestinal biopsies from children with SAM and persistent diarrhoea. mRNA was extracted from biopsies, sequenced, and subjected to a progressive set of complementary analytical approaches: NOIseq, Gene Set Enrichment Analysis (GSEA), and correlation analysis of phenotypic data with gene expression. FINDINGS: Transcriptomic profiles were generated for biopsy sets from 27 children of both sexes, under 2 years of age, of whom one-third were HIV-infected. NOIseq analysis, constructed from phenotypic group extremes, revealed 66 differentially expressed genes (DEGs) out of 21,386 mapped to the reference genome. These DEGs include genes for mucins and mucus integrity, antimicrobial defence, nutrient absorption, C-X-C chemokines, proteases and anti-proteases. Phenotype - expression correlation analysis identified 1221 genes related to villus height, including increased cell cycling gene expression in more severe enteropathy. Amino acid transporters and ZIP zinc transporters were specifically increased in severe enteropathy, but transcripts for xenobiotic metabolising enzymes were reduced. INTERPRETATION: Transcriptomic analysis of this rare collection of intestinal biopsies identified multiple novel elements of pathology, including specific alterations in nutrient transporters. Changes in xenobiotic metabolism in the gut may alter drug disposition. Both NOIseq and GSEA identified gene clusters similar to those differentially expressed in pediatric Crohn's disease but to a much lesser degree than those identified in coeliac disease. FUND: Bill & Melinda Gates Foundation OPP1066118. The funding agency had no role in study design, data collection, data analysis, interpretation, or writing of the report

Gene expression profiles compared in environmental and malnutrition enteropathy in Zambian children and adults

Background:: Environmental enteropathy (EE) contributes to growth failure in millions of children worldwide, but its relationship to clinical malnutrition has not been elucidated. We used RNA sequencing to compare duodenal biopsies from adults and children with EE, and from children with severe acute malnutrition (SAM), to define key features of these malnutrition-related enteropathies. Methods:: RNA was extracted and sequenced from biopsies of children with SAM in hospital (n=27), children with non-responsive stunting in the community (n=30), and adults living in the same community (n=37) using an identical sequencing and analysis pipeline. Two biopsies each were profiled and differentially expressed genes (DEGs) were computed from the comparisons of the three groups. DEG lists from these comparisons were then subjected to analysis with CompBio software to assemble a holistic view of the biological landscape and IPA software to interrogate canonical pathways. Findings:: Dysregulation was identified in goblet cell/mucin production and xenobiotic metabolism/detoxification for both cohorts of children, versus adults. Within the SAM cohort, substantially greater induction of immune response and barrier function, including NADPH oxidases was noted, concordant with broadly reduced expression of genes associated with the brush border and intestinal structure/transport/absorption. Interestingly, down regulation of genes associated with the hypothalamic-pituitary-adrenal axis was selectively observed within the cohort of children with stunting. Interpretation:: Gene expression profiles in environmental enteropathy and severe acute malnutrition have similarities, but SAM has several distinct transcriptional features. The intestinal capacity to metabolise drugs and toxins in malnourished children requires further study. Funding:: Bill & Melinda Gates Foundation (OPP1066118

Malnutrition enteropathy in Zambian and Zimbabwean children with severe acute malnutrition: A multi-arm randomized phase II trial.

Malnutrition underlies almost half of all child deaths globally. Severe Acute Malnutrition (SAM) carries unacceptable mortality, particularly if accompanied by infection or medical complications, including enteropathy. We evaluated four interventions for malnutrition enteropathy in a multi-centre phase II multi-arm trial in Zambia and Zimbabwe and completed in 2021. The purpose of this trial was to identify therapies which could be taken forward into phase III trials. Children of either sex were eligible for inclusion if aged 6-59 months and hospitalised with SAM (using WHO definitions: WLZ <-3, and/or MUAC <11.5 cm, and/or bilateral pedal oedema), with written, informed consent from the primary caregiver. We randomised 125 children hospitalised with complicated SAM to 14 days treatment with (i) bovine colostrum (n = 25), (ii) N-acetyl glucosamine (n = 24), (iii) subcutaneous teduglutide (n = 26), (iv) budesonide (n = 25) or (v) standard care only (n = 25). The primary endpoint was a composite of faecal biomarkers (myeloperoxidase, neopterin, α1-antitrypsin). Laboratory assessments, but not treatments, were blinded. Per-protocol analysis used ANCOVA, adjusted for baseline biomarker value, sex, oedema, HIV status, diarrhoea, weight-for-length Z-score, and study site, with pre-specified significance of P < 0.10. Of 143 children screened, 125 were randomised. Teduglutide reduced the primary endpoint of biomarkers of mucosal damage (effect size -0.89 (90% CI: -1.69,-0.10) P = 0.07), while colostrum (-0.58 (-1.4, 0.23) P = 0.24), N-acetyl glucosamine (-0.20 (-1.01, 0.60) P = 0.67), and budesonide (-0.50 (-1.33, 0.33) P = 0.32) had no significant effect. All interventions proved safe. This work suggests that treatment of enteropathy may be beneficial in children with complicated malnutrition. The trial was registered at ClinicalTrials.gov with the identifier NCT03716115