Initial screening of mangrove endophytic fungi for antimicrobial compounds and heavy metal biosorption potential

Endophytic fungi provide protection to their host plant and the fungi often produce antimicrobial compounds to aid the host fighting off pathogens. These bioactive compounds were secondary metabolites which were often produced as waste- or by-products. In the present study, endophytic fungi isolated from mangrove plants and soils were characterized and their antimicrobial production and bioremediation potential of heavy metals copper (Cu) and zinc (Zn) were assessed. Twelve (12) isolated and identified endophytic fungi belonged to seven species; Penicillium, Curvularia, Diaporthe, Aspergillus, Guignardia, Neusartorya and Eupenicillium. Antimicrobial activities of these 12 fungal endophytes were tested against Gram negative bacteria; Bacillus subtilis, Staphylococcus aureus, Gram positive bacteria; Escherichia coli and fungi; Candida albicans and Aspergillus niger among others. Two isolates (related to Guignardia sp. and Neusartoya sp.) showed strong antimicrobial (and antifungal) activity whereas the rest showed no activity. Compounds were isolated from both isolates and screened using HPLC. Both isolates displayed chemically very interesting chromatograms as they possessed a high diversity of basic chemical structures and peaks over a wide range of polarities, with structures similar to Trimeric catechin and Helenalin among others. For bioremediation assessment, the results showed maximum biosorption capacity for two isolates related to Curvularia sp. and Neusartorya sp., with the former removing 25 mg Cu/g biomass and the latter removing 24 mg Zn/g biomass. Our results indicated the potential of mangrove endophytic fungi in producing bioactive compounds and also highlighted their potential for the treatment of heavy metal-contaminated wastewater

Initial screening of mangrove endophytic fungi for antimicrobial compounds and heavy metal biosorption potential

Endophytic fungi provide protection to their host plant and the fungi often produce antimicrobial compounds to aid the host fighting off pathogens. These bioactive compounds were secondary metabolites which were often produced as waste- or by-products. In the present study, endophytic fungi isolated from mangrove plants and soils were characterized and their antimicrobial production and bioremediation potential of heavy metals copper (Cu) and zinc (Zn) were assessed. Twelve (12) isolated and identified endophytic fungi belonged to seven species; Penicillium, Curvularia, Diaporthe, Aspergillus, Guignardia, Neusartorya and Eupenicillium. Antimicrobial activities of these 12 fungal endophytes were tested against Gram negative bacteria; Bacillus subtilis, Staphylococcus aureus, Gram positive bacteria; Escherichia coli and fungi; Candida albicans and Aspergillus Niger among others. Two isolates (related to Guignardia sp. and Neusartoya sp.) showed strong antimicrobial (and antifungal) activity whereas the rest showed no activity. Compounds were isolated from both isolates and screened using HPLC. Both isolates displayed chemically very interesting chromatograms as they possessed a high diversity of basic chemical structures and peaks over a wide range of polarities, with structures similar to Trimeric catechin and Helenalin among others. For bioremediation assessment, the results showed maximum biosorption capacity for two isolates related to Curvularia sp. and Neusartorya sp., with the former removing 25 mg Cu/g biomass and the latter removing 24 mg Zn/g biomass. Our results indicated the potential of mangrove endophytic fungi in producing bioactive compounds and also highlighted their potential for the treatment of heavy metal-contaminated wastewate

A novel formulation of inhaled sodium cromoglicate (PA101) in idiopathic pulmonary fibrosis and chronic cough: a randomised, double-blind, proof-of-concept, phase 2 trial

Background Cough can be a debilitating symptom of idiopathic pulmonary fibrosis (IPF) and is difficult to treat. PA101 is a novel formulation of sodium cromoglicate delivered via a high-efficiency eFlow nebuliser that achieves significantly higher drug deposition in the lung compared with the existing formulations. We aimed to test the efficacy and safety of inhaled PA101 in patients with IPF and chronic cough and, to explore the antitussive mechanism of PA101, patients with chronic idiopathic cough (CIC) were also studied. Methods This pilot, proof-of-concept study consisted of a randomised, double-blind, placebo-controlled trial in patients with IPF and chronic cough and a parallel study of similar design in patients with CIC. Participants with IPF and chronic cough recruited from seven centres in the UK and the Netherlands were randomly assigned (1:1, using a computer-generated randomisation schedule) by site staff to receive PA101 (40 mg) or matching placebo three times a day via oral inhalation for 2 weeks, followed by a 2 week washout, and then crossed over to the other arm. Study participants, investigators, study staff, and the sponsor were masked to group assignment until all participants had completed the study. The primary efficacy endpoint was change from baseline in objective daytime cough frequency (from 24 h acoustic recording, Leicester Cough Monitor). The primary efficacy analysis included all participants who received at least one dose of study drug and had at least one post-baseline efficacy measurement. Safety analysis included all those who took at least one dose of study drug. In the second cohort, participants with CIC were randomly assigned in a study across four centres with similar design and endpoints. The study was registered with ClinicalTrials.gov (NCT02412020) and the EU Clinical Trials Register (EudraCT Number 2014-004025-40) and both cohorts are closed to new participants. Findings Between Feb 13, 2015, and Feb 2, 2016, 24 participants with IPF were randomly assigned to treatment groups. 28 participants with CIC were enrolled during the same period and 27 received study treatment. In patients with IPF, PA101 reduced daytime cough frequency by 31·1% at day 14 compared with placebo; daytime cough frequency decreased from a mean 55 (SD 55) coughs per h at baseline to 39 (29) coughs per h at day 14 following treatment with PA101, versus 51 (37) coughs per h at baseline to 52 (40) cough per h following placebo treatment (ratio of least-squares [LS] means 0·67, 95% CI 0·48–0·94, p=0·0241). By contrast, no treatment benefit for PA101 was observed in the CIC cohort; mean reduction of daytime cough frequency at day 14 for PA101 adjusted for placebo was 6·2% (ratio of LS means 1·27, 0·78–2·06, p=0·31). PA101 was well tolerated in both cohorts. The incidence of adverse events was similar between PA101 and placebo treatments, most adverse events were mild in severity, and no severe adverse events or serious adverse events were reported. Interpretation This study suggests that the mechanism of cough in IPF might be disease specific. Inhaled PA101 could be a treatment option for chronic cough in patients with IPF and warrants further investigation

Large-scale phenotyping of patients with long COVID post-hospitalization reveals mechanistic subtypes of disease

One in ten severe acute respiratory syndrome coronavirus 2 infections result in prolonged symptoms termed long coronavirus disease (COVID), yet disease phenotypes and mechanisms are poorly understood1. Here we profiled 368 plasma proteins in 657 participants ≥3 months following hospitalization. Of these, 426 had at least one long COVID symptom and 233 had fully recovered. Elevated markers of myeloid inflammation and complement activation were associated with long COVID. IL-1R2, MATN2 and COLEC12 were associated with cardiorespiratory symptoms, fatigue and anxiety/depression; MATN2, CSF3 and C1QA were elevated in gastrointestinal symptoms and C1QA was elevated in cognitive impairment. Additional markers of alterations in nerve tissue repair (SPON-1 and NFASC) were elevated in those with cognitive impairment and SCG3, suggestive of brain–gut axis disturbance, was elevated in gastrointestinal symptoms. Severe acute respiratory syndrome coronavirus 2-specific immunoglobulin G (IgG) was persistently elevated in some individuals with long COVID, but virus was not detected in sputum. Analysis of inflammatory markers in nasal fluids showed no association with symptoms. Our study aimed to understand inflammatory processes that underlie long COVID and was not designed for biomarker discovery. Our findings suggest that specific inflammatory pathways related to tissue damage are implicated in subtypes of long COVID, which might be targeted in future therapeutic trials

Multiorgan MRI findings after hospitalisation with COVID-19 in the UK (C-MORE): a prospective, multicentre, observational cohort study

Introduction: The multiorgan impact of moderate to severe coronavirus infections in the post-acute phase is still poorly understood. We aimed to evaluate the excess burden of multiorgan abnormalities after hospitalisation with COVID-19, evaluate their determinants, and explore associations with patient-related outcome measures. Methods: In a prospective, UK-wide, multicentre MRI follow-up study (C-MORE), adults (aged ≥18 years) discharged from hospital following COVID-19 who were included in Tier 2 of the Post-hospitalisation COVID-19 study (PHOSP-COVID) and contemporary controls with no evidence of previous COVID-19 (SARS-CoV-2 nucleocapsid antibody negative) underwent multiorgan MRI (lungs, heart, brain, liver, and kidneys) with quantitative and qualitative assessment of images and clinical adjudication when relevant. Individuals with end-stage renal failure or contraindications to MRI were excluded. Participants also underwent detailed recording of symptoms, and physiological and biochemical tests. The primary outcome was the excess burden of multiorgan abnormalities (two or more organs) relative to controls, with further adjustments for potential confounders. The C-MORE study is ongoing and is registered with ClinicalTrials.gov, NCT04510025. Findings: Of 2710 participants in Tier 2 of PHOSP-COVID, 531 were recruited across 13 UK-wide C-MORE sites. After exclusions, 259 C-MORE patients (mean age 57 years [SD 12]; 158 [61%] male and 101 [39%] female) who were discharged from hospital with PCR-confirmed or clinically diagnosed COVID-19 between March 1, 2020, and Nov 1, 2021, and 52 non-COVID-19 controls from the community (mean age 49 years [SD 14]; 30 [58%] male and 22 [42%] female) were included in the analysis. Patients were assessed at a median of 5·0 months (IQR 4·2–6·3) after hospital discharge. Compared with non-COVID-19 controls, patients were older, living with more obesity, and had more comorbidities. Multiorgan abnormalities on MRI were more frequent in patients than in controls (157 [61%] of 259 vs 14 [27%] of 52; p<0·0001) and independently associated with COVID-19 status (odds ratio [OR] 2·9 [95% CI 1·5–5·8]; padjusted=0·0023) after adjusting for relevant confounders. Compared with controls, patients were more likely to have MRI evidence of lung abnormalities (p=0·0001; parenchymal abnormalities), brain abnormalities (p<0·0001; more white matter hyperintensities and regional brain volume reduction), and kidney abnormalities (p=0·014; lower medullary T1 and loss of corticomedullary differentiation), whereas cardiac and liver MRI abnormalities were similar between patients and controls. Patients with multiorgan abnormalities were older (difference in mean age 7 years [95% CI 4–10]; mean age of 59·8 years [SD 11·7] with multiorgan abnormalities vs mean age of 52·8 years [11·9] without multiorgan abnormalities; p<0·0001), more likely to have three or more comorbidities (OR 2·47 [1·32–4·82]; padjusted=0·0059), and more likely to have a more severe acute infection (acute CRP >5mg/L, OR 3·55 [1·23–11·88]; padjusted=0·025) than those without multiorgan abnormalities. Presence of lung MRI abnormalities was associated with a two-fold higher risk of chest tightness, and multiorgan MRI abnormalities were associated with severe and very severe persistent physical and mental health impairment (PHOSP-COVID symptom clusters) after hospitalisation. Interpretation: After hospitalisation for COVID-19, people are at risk of multiorgan abnormalities in the medium term. Our findings emphasise the need for proactive multidisciplinary care pathways, with the potential for imaging to guide surveillance frequency and therapeutic stratification

Physical, cognitive, and mental health impacts of COVID-19 after hospitalisation (PHOSP-COVID): a UK multicentre, prospective cohort study

Background The impact of COVID-19 on physical and mental health and employment after hospitalisation with acute disease is not well understood. The aim of this study was to determine the effects of COVID-19-related hospitalisation on health and employment, to identify factors associated with recovery, and to describe recovery phenotypes. Methods The Post-hospitalisation COVID-19 study (PHOSP-COVID) is a multicentre, long-term follow-up study of adults (aged ≥18 years) discharged from hospital in the UK with a clinical diagnosis of COVID-19, involving an assessment between 2 and 7 months after discharge, including detailed recording of symptoms, and physiological and biochemical testing. Multivariable logistic regression was done for the primary outcome of patient-perceived recovery, with age, sex, ethnicity, body-mass index, comorbidities, and severity of acute illness as covariates. A post-hoc cluster analysis of outcomes for breathlessness, fatigue, mental health, cognitive impairment, and physical performance was done using the clustering large applications k-medoids approach. The study is registered on the ISRCTN Registry (ISRCTN10980107). Findings We report findings for 1077 patients discharged from hospital between March 5 and Nov 30, 2020, who underwent assessment at a median of 5·9 months (IQR 4·9–6·5) after discharge. Participants had a mean age of 58 years (SD 13); 384 (36%) were female, 710 (69%) were of white ethnicity, 288 (27%) had received mechanical ventilation, and 540 (50%) had at least two comorbidities. At follow-up, only 239 (29%) of 830 participants felt fully recovered, 158 (20%) of 806 had a new disability (assessed by the Washington Group Short Set on Functioning), and 124 (19%) of 641 experienced a health-related change in occupation. Factors associated with not recovering were female sex, middle age (40–59 years), two or more comorbidities, and more severe acute illness. The magnitude of the persistent health burden was substantial but only weakly associated with the severity of acute illness. Four clusters were identified with different severities of mental and physical health impairment (n=767): very severe (131 patients, 17%), severe (159, 21%), moderate along with cognitive impairment (127, 17%), and mild (350, 46%). Of the outcomes used in the cluster analysis, all were closely related except for cognitive impairment. Three (3%) of 113 patients in the very severe cluster, nine (7%) of 129 in the severe cluster, 36 (36%) of 99 in the moderate cluster, and 114 (43%) of 267 in the mild cluster reported feeling fully recovered. Persistently elevated serum C-reactive protein was positively associated with cluster severity. Interpretation We identified factors related to not recovering after hospital admission with COVID-19 at 6 months after discharge (eg, female sex, middle age, two or more comorbidities, and more acute severe illness), and four different recovery phenotypes. The severity of physical and mental health impairments were closely related, whereas cognitive health impairments were independent. In clinical care, a proactive approach is needed across the acute severity spectrum, with interdisciplinary working, wide access to COVID-19 holistic clinical services, and the potential to stratify care. Funding UK Research and Innovation and National Institute for Health Research

Effect of Aging, Antioxidant, and Mono- and Divalent Ions at High Temperature on the Rheology of New Polyacrylamide-Based Co-Polymers

The viscosity of four new polymers was investigated for the effect of aging at high temperature, with varying degrees of salinity and hardness. The four sulfonated based polyacrylamide co-polymers were FLOCOMB C7035; AN132 VHM; SUPERPUSHER SAV55; and THERMOASSOCIATIF copolymers. All polymer samples were aged at 80 °C for varying times (from zero to at least 90 days) with and without isobutyl alcohol (IBA) as an antioxidant. To see the effect of divalent ions on the polymer solution viscosity, parallel experiments were performed in a mixture of CaCl2-NaCl of the same ionic strength as 5 wt % NaCl. The polymers without IBA showed severe viscosity reduction after aging for 90 days in both types of preparation (5 wt % NaCl or CaCl2-NaCl). In the presence of IBA, viscosity was increased when aging time was increased for 5 wt % NaCl. In CaCl2-NaCl, on the other hand, a viscosity reduction was observed as aging time was increased. This behavior was observed for all polymers except AN132 VHM

Assessment of Polyacrylamide Based Co-Polymers Enhanced by Functional Group Modifications with Regards to Salinity and Hardness

This research aims to test four new polymers for their stability under high salinity/high hardness conditions for their possible use in polymer flooding to improve oil recovery from hydrocarbon reservoirs. The four sulfonated based polyacrylamide co-polymers were FLOCOMB C7035; SUPERPUSHER SAV55; THERMOASSOCIATIF; and AN132 VHM which are basically sulfonated polyacrylamide copolymers of AM (acrylamide) with AMPS (2-Acrylamido-2-Methylpropane Sulfonate). AN132 VHM has a molecular weight of 9–11 million Daltons with 32 mol % degree of sulfonation. SUPERPUSHER SAV55 mainly has about 35 mol % sulfonation degree and a molecular weight of 9–11 million Daltons. FLOCOMB C7035, in addition, has undergone post-hydrolysis step to increase polydispersity and molecular weight above 18 million Daltons but it has a sulfonation degree much lower than 32 mol %. THERMOASSOCIATIF has a molecular weight lower than 12 million Daltons and a medium sulfonation degree of around 32 mol %, and also contains LCST (lower critical solution temperature) type block, which is responsible for its thermoassociative characteristics. This paper discusses the rheological behavior of these polymers in aqueous solutions (100–4500 ppm) with NaCl (0.1–10 wt %) measured at 25 °C. The effect of hardness was investigated by preparing a CaCl2-NaCl solution of same ionic strength as the 5 wt % of NaCl. In summary, it can be concluded that the rheological behavior of the newly modified co-polymers was in general agreement to the existing polymers, except that THERMOASSOCIATIF polymers showed unique behavior, which could possibly make them a better candidate for enhanced oil recovery (EOR) application in high salinity conditions. The other three polymers, on the other hand, are better candidates for EOR applications in reservoirs containing high divalent ions. These results are expected to be helpful in selecting and screening the polymers for an EOR application

Distribution and association of interpregnancy weight change with subsequent pregnancy outcomes in Asian women

The extent of interpregnancy weight change and its association with subsequent pregnancy outcomes among Asians remain unclear. We examined changes in maternal body mass index (BMI) between the first two deliveries and outcomes in the second delivery. Medical records of women with their first two consecutive deliveries between 2015 and 2020 at KK Women’s and Children’s Hospital, Singapore were retrieved. Gestational-age-adjusted BMI was determined by standardising to 12 weeks gestation and interpregnancy BMI change was calculated as the difference between both pregnancies. Pregnancy outcomes were analysed using modified Poisson regression models. Of 6264 included women with a median interpregnancy interval of 1.44 years, 40.7% had a stable BMI change within ± 1 kg/m2, 10.3% lost > 1 kg/m2, 34.3% gained 1–3 kg/m2 and 14.8% gained ≥ 3 kg/m2. Compared to women with stable BMI change, those with > 1 kg/m2 loss had higher risk of low birthweight (adjusted risk ratio [RR] 1.36; 95% confidence interval 1.02–1.80), while those with 1–3 kg/m2 gain had higher risks of large-for-gestational-age birth (1.16; 1.03–1.31), gestational diabetes (1.25; 1.06–1.49) and emergency Caesarean delivery (1.16; 1.03–1.31); these risks were higher in those with ≥ 3 kg/m2 gain. Our study strengthens the case for interpregnancy weight management to improve subsequent pregnancy outcomes

Distribution and association of interpregnancy weight change with subsequent pregnancy outcomes in Asian women.

Acknowledgements: The authors would like to thank KK Women’s and Children’s Hospital for the institutional support received during this study, and Ms Nathalie Ang for data cleaning.Funder: Lien Foundation Optimising Maternal and Child Health Programme FundThe extent of interpregnancy weight change and its association with subsequent pregnancy outcomes among Asians remain unclear. We examined changes in maternal body mass index (BMI) between the first two deliveries and outcomes in the second delivery. Medical records of women with their first two consecutive deliveries between 2015 and 2020 at KK Women's and Children's Hospital, Singapore were retrieved. Gestational-age-adjusted BMI was determined by standardising to 12 weeks gestation and interpregnancy BMI change was calculated as the difference between both pregnancies. Pregnancy outcomes were analysed using modified Poisson regression models. Of 6264 included women with a median interpregnancy interval of 1.44 years, 40.7% had a stable BMI change within ± 1 kg/m2, 10.3% lost > 1 kg/m2, 34.3% gained 1-3 kg/m2 and 14.8% gained ≥ 3 kg/m2. Compared to women with stable BMI change, those with > 1 kg/m2 loss had higher risk of low birthweight (adjusted risk ratio [RR] 1.36; 95% confidence interval 1.02-1.80), while those with 1-3 kg/m2 gain had higher risks of large-for-gestational-age birth (1.16; 1.03-1.31), gestational diabetes (1.25; 1.06-1.49) and emergency Caesarean delivery (1.16; 1.03-1.31); these risks were higher in those with ≥ 3 kg/m2 gain. Our study strengthens the case for interpregnancy weight management to improve subsequent pregnancy outcomes