Gut bacteria promote proliferation in benign S/RG/C2 colorectal tumour cells, and promote proliferation, migration and invasion in malignant HCT116 cells.

Colorectal cancer (CRC) is a significant global health burden with a rising incidence worldwide. Distinct bacterial populations are associated with CRC development and progression, and it is thought that the relationship between CRC and associated gut bacteria changes during the progression from normal epithelium to benign adenoma and eventually malignant carcinoma and metastasis. This study compared the interaction of CRC-associated species Enterotoxigenic Bacteroides fragilis, Enterococcus faecalis and Fusobacterium nucleatum and one probiotic species, Escherichia coli Nissle 1917 with a colorectal adenoma (S/RG/C2) and a colorectal adenocarcinoma (HCT116) derived cell line. Gentamicin protection assays showed that all species displayed higher attachment to benign tumour monolayers when compared to malignant monolayers. However, invasion of 3/4 species was higher in the HCT116 cells than in the adenoma cells. All species were found to persist within tumour cell monolayers for a minimum of 48 h under standard aerobic cell culture conditions, with persistence significantly higher in HCT116 cells. Downstream assays were performed to analyse the behaviour of S/RG/C2 and HCT116 cells post-infection and revealed that all species increased the tumour cell yield of both cell lines. The migratory and invasive potential of HCT116 cells was increased after infection with F. nucleatum; however, no species significantly altered these characteristics in S/RG/C2 cells. These results add to the growing evidence for the involvement of microorganisms in CRC progression and suggest that these interactions may be dependent on tumour cell-specific characteristics.

Real-World Progression-Free Survival as an Endpoint in Lung Cancer: Replicating Atezolizumab and Docetaxel Arms of the OAK Trial Using Real-World Data.

Evaluating cancer treatments in real-world data (RWD) requires informative endpoints. This study replicated the atezolizumab and docetaxel arms of the OAK trial using RWD and compared progression-free survival (PFS) outcomes derived from abstracted physician's notes in RWD (rwPFS) against PFS outcomes derived from the clinical trial PFS (ctPFS). Atezolizumab and docetaxel arms of the phase III OAK randomized controlled trial (RCT; NCT02008227) were replicated in a US nationwide real-world database using selected OAK inclusion/exclusion criteria and propensity score-based adjustment for baseline prognostic variables. Concordance of outcomes was assessed using Kaplan-Meier medians and hazard ratios (HRs). The RWD cohorts comprised 133 patients on atezolizumab and 479 patients on docetaxel. After adjustment, prognostic variables were balanced between RCT arms and corresponding RWD cohorts. The rwPFS and ctPFS outcomes showed better concordance for docetaxel (2.99 vs. 3.52 months; HR: 0.99, 95% confidence interval (CI): 0.85-1.15) than for atezolizumab (3.71 vs. 2.76 months; HR: 0.8, 95% CI: 0.61-1.02). Excluding events labeled "pseudo-progression" from both RWD and RCT improved concordance for atezolizumab (4.24 vs. 4.14 months; HR: 0.95, 95% CI: 0.70-1.25). These findings were robust across sensitivity analyses. Replicating RCTs using RWD and comparing outcomes can help characterize RWD endpoints. Similarity of results between rwPFS and ctPFS at the cohort level may depend on drug category, highlighting the need for further studies to verify and understand when the corresponding outcomes can be compared, including within the same patient.

Non-Positive Experiences Encountered by Pupils During Participation in a Mindfulness-Informed School-Based Intervention.

Mindfulness-informed school-based mental health curricula show much promise in cultivating a positive school climate which supports the well-being and mental health of pupils and staff. However, non-positive pupil outcomes and experiences of school-based mental health interventions are often under-recognised and under-reported. This study sought to capture non-positive pupil experiences of a popular mindfulness-informed curriculum. Some pupils across all schools in the study described non-positive experiences, including having troubling thoughts and emotions, and not finding the programme effective. Contexts surrounding these experiences are explored and linked to existing literature, and subsequent recommendations for improvements are made, including the importance of having clear programme structure, definitions and aims, acknowledging and accommodating fidelity issues as best as possible, and better highlighting the potential for non-positive experiences and how they may be reduced.

Deployment of whole genome next-generation sequencing of SARS-CoV-2 in a military maritime setting.

BACKGROUND: SARS-CoV-2 can spread rapidly on maritime platforms. Several outbreaks of SARS-CoV-2 have been reported on warships at sea, where transmission is facilitated by living and working in close quarters. Core components of infection control measures such as social distancing, patient isolation and quarantine of exposed persons are extremely difficult to implement. Whole genome sequencing (WGS) of SARS-CoV-2 has facilitated epidemiological investigations of outbreaks, impacting on outbreak management in real time by identifying transmission patterns, clusters of infection and guiding control measures. We suggest such a capability could mitigate against the impact of SARS-CoV-2 in maritime settings. METHODS: We set out to establish SARS-CoV-2 WGS using miniaturised nanopore sequencing technology aboard the Royal Fleet Auxiliary ARGUS while at sea. Objectives included designing a simplified protocol requiring minimal reagents and processing steps, the use of miniaturised equipment compatible for use in limited space, and a streamlined and standalone data analysis capability to allow rapid in situ data acquisition and interpretation. RESULTS: Eleven clinical samples with blinded SARS-CoV-2 status were tested at sea. Following viral RNA extraction and ARTIC sequencing library preparation, reverse transcription and ARTIC PCR-tiling were performed. Samples were subsequently barcoded and sequenced using the Oxford Nanopore MinION Mk1B. An offline version of the MinKNOW software was used followed by CLC Genomics Workbench for downstream analysis for variant identification and phylogenetic tree construction. All samples were correctly classified, and relatedness identified. CONCLUSIONS: It is feasible to establish a small footprint sequencing capability to conduct SARS-CoV-2 WGS in a military maritime environment at sea with limited access to reach-back support. This proof-of-concept study has highlighted the potential of deploying such technology in the future to military environments, both maritime and land-based, to provide meaningful clinical data to aid outbreak investigations.

Brucella suis in three dogs: presentation, diagnosis and clinical management.

Brucella suis is an emerging, zoonotic disease predominantly affecting dogs and humans that engage in feral pig hunting in Australia and other countries. Although B. suis infection in dogs shares some clinical similarities to the host-adapted species (B. canis), B. suis remains an incompletely understood pathogen in dogs with limited published data on its pathogenesis and clinical features. This case series describes the presentations, diagnosis, and clinical management of B. suis infection in three dogs: (1) a bitch with dystocia, abortion and mastitis; (2) an entire male dog with septic arthritis and presumptive osteomyelitis; and (3) a castrated male dog with lymphadenitis. Unique features of these cases are reported including the first documented detection of B. suis from milk and isolation from lymph nodes of canine patients, as well as the follow-up of pups born to a B. suis-infected bitch. Consistent with previous reports, all three dogs showed a favourable clinical response to combination antibiotic therapy with rifampicin and doxycycline. Individually tailored drug regimens were required based on the clinical presentation and other factors, including owner expectations and compliance with therapy as well as a zoonotic risk assessment (generally considered low, except around time of whelping). The authors include their recommendations for the clinical management of dogs that are at-risk or seropositive for B. suis with or without clinical signs or laboratory-confirmed infection.

Occurrence and removal of drugs and endocrine disruptors in water supply systems in the metropolitan region of Belo Horizonte (Minas Gerais State, Brazil).

This study evaluates both the occurrence and removal of 24 compounds, including drugs and endocrine disruptors, in 8 water treatment plants (WTP) located in the metropolitan region of Belo Horizonte (Minas Gerais State, Brazil). The compounds 4-nonylphenol, 4-octylphenol, 17α-ethinylestradiol, 17ß-estradiol, acyclovir, bisphenol A, bezafibrate, caffeine, dexamethasone, diclofenac sodium, diltiazem, estrone, estriol, gemfibrozil, ibuprofen, linezolid, loratadine, losartan, metformin, naproxen, paracetamol, promethazine, propranolol and sulfamethoxazole were monitored at 3 sampling points (raw water, filtered water, treated water) over 10 or 12 collection campaigns for each WTP. The results showed that bisphenol A occurred at higher concentrations during the dry period with a maximum concentration of 3257.1 ng L-1, while the compounds 4-nonylphenol and losartan exhibited higher concentrations in the rainy period with maximum concentrations of 8577.2 ng L-1 and 705.8 ng L-1, respectively. Regarding the removal of compounds in the monitored WTPs, the clarification step demonstrated better removals for 4-nonylphenol, bisphenol-A, paracetamol, and sulfamethoxazole, whereas the disinfection step mainly removed the compounds 4-octylphenol and estrone. Margin of exposure (ME) assessment results indicated that only dexamethasone, ethinyl estradiol, diclofenac, estradiol, and estrone were classified as imminent risk or alert considering the 95th percentile concentration found in the samples of treated water.

Replication of Overall Survival, Progression-Free Survival, and Overall Response in Chemotherapy Arms of Non-Small Cell Lung Cancer Trials Using Real-World Data.

PURPOSE: The utility of real-world data (RWD) for use as external controls in drug development is informed by studies that replicate trial control arms for different endpoints. The purpose of this study was to replicate control arms from four non-small cell lung cancer (NSCLC) randomized controlled trials (RCT) to analyze overall survival (OS), progression-free survival (PFS), and overall response rate (ORR) using RWD. PATIENTS AND METHODS: This study used RWD from a nationwide de-identified database and a clinico-genomic database to replicate OS, PFS, and ORR endpoints in the chemotherapy control arms of four first-line NSCLC RCTs evaluating atezolizumab [IMpower150-wild-type (WT), IMpower130-WT, IMpower131, and IMpower132]. Additional objectives were to develop a definition of real-world PFS (rwPFS) and to evaluate the real-world response rate (rwRR) endpoint. RESULTS: Baseline demographic and clinical characteristics were balanced after application of propensity score weighting methods. For rwPFS and OS, RWD external controls were generally similar to their RCT control counterparts. Across all four trials, the hazard ratio (HR) point estimates comparing trial controls with external controls were closer to 1.0 for the PFS endpoint than for the OS endpoint. An exploratory assessment of rwRR in RWD revealed a slight but nonsignificant overestimation of RCT ORR, which was unconfounded by baseline characteristics. CONCLUSIONS: RWD can be used to reasonably replicate the OS and PFS of chemotherapy control arms of first-line NSCLC RCTs. Additional studies can provide greater insight into the utility of RWD in drug development.

Real-world data prognostic model of overall survival in patients with advanced NSCLC receiving anti-PD-1/PD-L1 immune checkpoint inhibitors as second-line monotherapy.

BACKGROUND AND AIM: The objective of this retrospective, observational, noninterventional cohort study was to investigate prognostic factors of overall survival (OS) in patients with advanced non-small cell lung cancer (aNSCLC) and to develop a novel prognostic model. METHODS: A total of 4049 patients with aNSCLC diagnosed between January 2011 and February 2020 who received atezolizumab, nivolumab, or pembrolizumab as second-line monotherapy were selected from a real-world deidentified database to build the cohort. Patients could not have received first-line treatment with clinical study drug(s) nor immune checkpoint inhibitors including anti-programmed cell death 1 (PD-1)/programmed death-ligand 1 (PD-L1), and anti-cytotoxic T-lymphocyte-associated protein 4 therapies. RESULTS: Patients had a median age of 69 years; 45% were female, 75% White, 70% had stage IV at initial diagnosis, and 70% had nonsquamous histology. A Cox proportional hazards model with lasso regularization was used to build a prognostic model for OS using 18 baseline demographic and clinical factors based on the real-world data cohort. The risk-increasing prognostic factors were abnormally low albumin and chloride levels, Eastern Cooperative Oncology Group performance status score ≥ 2, and abnormally high levels of alkaline phosphatase and white blood cells. The risk-decreasing prognostic factors were PD-L1 positivity, longer time from advanced diagnosis to start of first-line therapy, and higher systolic blood pressure. The performance of the model was validated using data from the OAK trial, and the c-index for the OAK trial validation cohort was 0.65 and 0.67 for the real-world data cohort. CONCLUSIONS: Based on baseline demographic and clinical factors from a real-world setting, this prognostic model was developed to discriminate the risk of death in patients with aNSCLC treated with checkpoint inhibitors as second-line monotherapy, and it performed well in the real-world data and clinical trial cohorts.

Occurrence and removal of drugs and endocrine disruptors in the Bolonha Water Treatment Plant in Belém/PA (Brazil).

This study aimed to investigate the occurrence of drugs and endocrine disrupters in water supplies and in water for human consumption. Twelve sampling campaigns were carried out during the rainy and dry season at four sampling points in the Bolonha Complex, in the city of Belém, northern region of Brazil: Bolonha reservoir (catchment) and Water Treatment Plant (WTP) Bolonha (filtered water chamber, treated water tank, and washing water from the filters). The determination of the compounds was performed by solid phase extraction followed by gas and liquid chromatography coupled to mass spectrometry. The results confirmed the anthropic influence that the reservoir and WTP-Bolonha have been suffering, as consequence of the discharge of domestic sewage in natura. Among 25 microcontaminants analyzed, 12 were quantified in raw water and 10 in treated water. The antiallergic Loratadine (LRT) was the contaminant that occurred most frequently in all sample points, having been poorly removed (median 12%) in the conventional treatment used. Losartana (LST), 4-octylphenol (4-OP), and Bisphenol A (BPA) also occurred very frequently in raw water with concentrations ranging from 3.7 to 194 ng L-1. Although such contaminants occurred in treated water in concentrations varying from 4.0 to 135 ng L-1, the estimated margin of exposure ranged from 55 to 3333 times which indicates low risk of human exposure to such contaminants through ingestion of treated water.

Occurrence of contaminants of emerging concern in surface waters from Paraopeba River Basin in Brazil: seasonal changes and risk assessment.

This study describes the application of gas chromatography coupled to mass spectrometry (GC-MS) to evaluate the occurrence of 12 CECs-contaminants of emerging concern (bisphenol A, diclofenac, 17ß-estradiol, estriol, estrone, 17α-ethinylestradiol, gemfibrozil, ibuprofen, naproxen, 4-nonylphenol, 4-octylphenol, and acetaminophen) in surface waters from Paraopeba River Basin, Minas Gerais State, Brazil. The analytical procedure was validated and applied to 60 surface water samples collected across four sampling campaigns along the upper and middle watershed. Methods for CECs determination involved sample filtration, and solid-phase extraction (SPE) with subsequent derivatization of the target compounds prior to their analysis by GC-MS. The LOQ varied from 3.6 to 14.4 ng/L and extraction recoveries ranged from 46.1 to 107.1% for the lowest spiked concentration level (10 ng/L). The results showed a profile of spatial distribution of compounds, as well as the influence of rainfall. Ibuprofen (1683.9 ng/L), bisphenol (1587.7 ng/L), and naproxen (938.4 ng/L) occurred in higher concentrations during the rainy season, whereas during the dry season, the concentrations of bisphenol (1057.7 ng/L), estriol (991.0 ng/L), and estrone (978.4 ng/L) were highlighted. The risk assessment of human exposure shows that for most contaminants, the concentration is well below the estimated thresholds for chronic toxicity from water intake. However, estradiol and 17α-ethinylestradiol showed concentrations in the same order of magnitude as the guide values estimated for babies.

NHS Health Checks for people with mental ill-health 2013-2017: an observational study.

AIMS: People living with serious mental ill-health experience adverse cardiovascular outcomes causing some of the greatest health inequality gaps in England, UK. We describe uptake of the NHS Health Check programme in people with mental ill-health, and rates of new diagnoses and management of cardiovascular risk factors in those who attend NHS Health Checks in comparison to those people without mental ill-health. METHODS: We used a large nationally representative database of people registered with general practitioners in England (QResearch). Between 2013 and 2017, we analysed attendance at NHS Health Checks and outcomes in the succeeding 12 months, in people with serious mental illness (SMI) including psychoses and in people prescribed long-term antidepressant medications (LTAD), with comparison to attendees who did not have these conditions. Hazard ratios (HR) were used to describe the association between outcomes and SMI and LTAD adjusting for sociodemographic variables. RESULTS: In those eligible for the NHS Health Check programme, we found a higher percentage of people with SMI attended an NHS Health Check (65 490, 19.8%) than those without SMI (524 728, 16.6%); adjusted HR 1.05 [95% confidence interval 1.02-1.08]. We also observed a higher percentage of attendance in people on LTAD (46 437, 20.1%) compared to people who were not prescribed LTAD (543 781, 16.7%); adjusted HR 1.10 (1.08-1.13). People with SMI were more likely to be identified with chronic kidney disease (CKD, HR 1.23, 1.12-1.34) and type 2 diabetes (HR 1.14, 1.03-1.25) within the 12 months following their NHS Health Check compared with those without SMI. People on LTAD were more likely to be identified with CKD (HR 1.55, 1.42-1.70) and type 2 diabetes (HR 1.45, 1.31-1.60) and also hypertension, cardiovascular disease, non-diabetic hyperglycaemia, familial hypercholesterolemia and dementia within the 12 months following their NHS Health Check. Statins were more likely to be prescribed to NHS Health Check attendees with SMI and those on LTAD than those without these conditions; HR 1.31 (1.25-1.38) and 1.91 (1.82-2.01), respectively. Antihypertensives were more likely to be prescribed to those on LTAD; HR 1.21 (1.14-1.29). CONCLUSIONS: We found evidence that people with SMI or on LTAD treatment were 5-10% more likely to access NHS Health Checks than people without these conditions. People with SMI or on LTAD treatment who attended NHS Health Checks had higher rates of diagnosis of CKD, type 2 diabetes and some other relevant co-morbidities and increased treatment with statins and also anti-hypertensive medication in people on LTAD. This is likely to contribute to equitable reduction in adverse cardiovascular events for people with mental ill-health.

In vitro and in vivo antitumoral activity of a ternary copper (II) complex.

Recently, a high number of copper derivatives has been evaluated as DNA-targeting metallodrugs, due to the lower toxicity and its potential to cleave DNA. Several strategies have been testing to develop metal compounds effective against tumour cells. In this work, the ternary copper (doxycycline)-(1,10-phenanthroline) complex [Cu(dox)(phen)]2+ was especially designed as an antitumoral drug, previously showing high cytotoxicity and DNA cleavage activity. We aimed to further investigate the in vitro cytotoxic activity in both tumoral and non-tumoral cells, in vitro genotoxic potential, and in vivo antitumor activity using BALB/C mouse injected with sarcoma S180 and Ehrlich cell lines. Our results indicated that this compound exhibits a moderate genotoxic potential, with selective growth inhibition of tumor cells, especially the murine melanoma B16F10. Its main mechanism of action seems to be through ROS generation. We have further shown a significant reduction of the implanted tumor size in the animal model, suggesting that this compound has great antitumoral potential against many tumor types. [Cu(dox)(phen)]2+ is selectively cytotoxic for melanoma B16F10 and showed high chemotherapeutic potential in vivo against implanted sarcoma S180 and Ehrlich ascites tumours.

Comparative analysis of three laboratory based serological assays for SARS-CoV-2 in an Australian cohort.

Many unanswered questions remain regarding the role of SARS-CoV-2 serological assays in this unfolding COVID-19 pandemic. These include their utility for the diagnosis of acute SARS-CoV-2 infection, past infection or exposure, correlation with immunity and the effective duration of immunity. This study examined the performance of three laboratory based serological assays, EUROIMMUN Anti-SARS-CoV-2 IgA/IgG, MAGLUMI 2000 Plus 2019-nCov IgM/IgG and EDI Novel Coronavirus (COVID-19) IgM/IgG immunoassays. We evaluated 138 samples from a reference non-infected population and 71 samples from a cohort of 37 patients with SARS-CoV-2 confirmed positive by RT-PCR. The samples were collected at various intervals of 0-45 days post symptoms onset (PSO). Specificity and sensitivity of these assays was 60.9%/71.4% (IgA) and 94.2%/63.3% (IgG) for EUROIMMUN; 98.5%/18.4% (IgM) and 97.8%/53.1% (IgG) for MAGLUMI; and 94.9%/22.5% (IgM) and 93.5%/57.1% (IgG) for EDI, respectively. When samples collected ≥14 days PSO were considered, the sensitivities were 100.0 and 100.0%; 31.0 and 82.8%; 34.5 and 57.1%, respectively. Using estimated population prevalence of 0.1, 1, and 10%, the positive predictive value of all assays remained low. The EUROIMMUN Anti-SARS-CoV-2 IgA lacked specificity for acute diagnosis and all IgM assays offered poor diagnostic utility. Seroconversion can be delayed although all patients had seroconverted at 28 days in our cohort with the EUROIMMUN Anti-SARS-CoV-2 IgG. Despite this, with specificity of only 94% this assay would not be satisfactory for seroprevalence studies in the general Australian population given this is likely to be currently <1%.

North Atlantic climate far more predictable than models imply.

Quantifying signals and uncertainties in climate models is essential for the detection, attribution, prediction and projection of climate change1-3. Although inter-model agreement is high for large-scale temperature signals, dynamical changes in atmospheric circulation are very uncertain4. This leads to low confidence in regional projections, especially for precipitation, over the coming decades5,6. The chaotic nature of the climate system7-9 may also mean that signal uncertainties are largely irreducible. However, climate projections are difficult to verify until further observations become available. Here we assess retrospective climate model predictions of the past six decades and show that decadal variations in North Atlantic winter climate are highly predictable, despite a lack of agreement between individual model simulations and the poor predictive ability of raw model outputs. Crucially, current models underestimate the predictable signal (the predictable fraction of the total variability) of the North Atlantic Oscillation (the leading mode of variability in North Atlantic atmospheric circulation) by an order of magnitude. Consequently, compared to perfect models, 100 times as many ensemble members are needed in current models to extract this signal, and its effects on the climate are underestimated relative to other factors. To address these limitations, we implement a two-stage post-processing technique. We first adjust the variance of the ensemble-mean North Atlantic Oscillation forecast to match the observed variance of the predictable signal. We then select and use only the ensemble members with a North Atlantic Oscillation sufficiently close to the variance-adjusted ensemble-mean forecast North Atlantic Oscillation. This approach greatly improves decadal predictions of winter climate for Europe and eastern North America. Predictions of Atlantic multidecadal variability are also improved, suggesting that the North Atlantic Oscillation is not driven solely by Atlantic multidecadal variability. Our results highlight the need to understand why the signal-to-noise ratio is too small in current climate models10, and the extent to which correcting this model error would reduce uncertainties in regional climate change projections on timescales beyond a decade.

Eosinophil granule major basic protein 1 deposition in eosinophilic esophagitis correlates with symptoms independent of eosinophil counts.

In patients with eosinophilic esophagitis (EoE), symptoms often do not correlate with peak eosinophil counts (PEC) determined on histopathological examination of biopsy specimens. This may be because eosinophils degranulate during active disease and lose their morphological identity as intact cells and, therefore, are not enumerated on microscopic examination. Eosinophil granule proteins that are released into tissues with degranulation, including major basic protein 1 (eMBP1), likely contribute to disease pathogenesis and, therefore, may correlate with symptoms better than PEC. We sought to determine whether symptoms in patients with EoE more closely relate to eosinophil granule protein deposition than to eosinophil enumeration, especially in patients with fewer than 15 eosinophils per high power field (HPF). Esophageal biopsy specimens from 34 patients diagnosed with EoE were obtained for histopathological examination and for evaluation of eMBP1 staining by indirect immunofluorescence. PEC by histopathology were compared to extracellular eMBP1 grades by immunostaining. PEC and eMBP1 grades also were analyzed for their relationship to symptoms and clinical course. Biopsy specimens from 19 of the 34 patients had fewer than 15 PEC on histopathological examination, and the other 15 patients had 15 or greater PEC. Positive eMBP1 immunostaining was found in all symptomatic patients. EoE symptoms were related to eMBP1 immunostaining grades (p = 0.0001), but not PEC (P = 0.14). Eosinophil granule protein deposition, specifically eMBP1, is increased in esophageal biopsy specimens from symptomatic patients with EoE and may be a marker of disease activity, including patients with EoE who have 'resolved' disease.

Oxidative treatments for atenolol removal in water: Elucidation by mass spectrometry and toxicity evaluation of degradation products.

RATIONALE: The presence of pharmaceuticals in water is a worldwide concern due to potential damage to human and environmental health. For example, compounds such as the ß-blocker atenolol (ATE), widely used for the treatment of cardiac disease, are detected in drinking water since conventional water treatment plants are not designed to remove them. Thus, the evaluation of ATE removal at different water oxidative treatment processes, identification of its degradation products and evaluation of their toxicity is necessary. METHODS: Aqueous solutions of ATE (10 mg/L) were submitted to oxidative treatments of chlorination ([NaClO] = 10 mg/L), ozonation ([O3 ] = 8 mg/L), photocatalysis ([TiO2 ] = 120 mg/L and UV-C light) and photolysis (UV-C light). The removal of ATE and formation of degradation products (DPs) were monitored by mass spectrometry. To assess acute cytotoxicity, DPs were submitted to colorimetric MTT assay using HepG2 cells. The Ecological Structure Activity Relationships (ECOSAR) software was applied to estimate the acute and chronic toxicity of identified DPs at different trophic levels. RESULTS: Photocatalysis was the treatment that demonstrated greater efficiency, removing 94% of the initial ATE. For the four tested treatments, 12 DPs were confirmed after 30 min. Moreover, some of the identified DPs were unpublished in the literature. Through high-resolution mass spectrometry (HRMS), it was possible to elucidate the structure of the DPs. Solutions of DPs were not considered to be toxic to HepG2 cells. Only the DP with a molecular formula of C13 H19 NO3 (m/z 238.1438) could be considered detrimental to daphnid and green algae. CONCLUSIONS: Low rates of organic matter removal and high rates of ATE degradation were obtained in the applied treatments after 30 min. Although the treated solutions were not toxic to HepG2 cells, one of the degradation products can be considered an environmental concern since it presents chronic toxicity to daphnid and green algae.

Ethnic variations in the risk of hypoglycaemia among people with Type 2 diabetes prescribed insulins and/or sulfonylureas: a historical cohort study using general practice-recorded data.

AIM: To identify ethnic differences in hypoglycaemic risk among people with Type 2 diabetes prescribed insulins and/or sulfonylureas in community settings. METHODS: Using routine general practice-recorded data, two cohorts of adults with Type 2 diabetes from east London were studied between January 2013 and December 2015: (1) adults prescribed insulins ± other antidiabetes medications (n=7269) and (2) adults prescribed sulfonylureas ± other antidiabetes medications excluding insulins (n=12 502). Incidence rate ratios of hypoglycaemia by ethnicity, adjusting for age, sex, socio-economic status and clustering within Clinical Commissioning Groups, were estimated using random effects Poisson regression. RESULTS: Compared with white British people prescribed insulins, those of black Caribbean ethnicity were at increased hypoglycaemic risk [adjusted incidence rate ratio 1.56 (95% CI 1.21,2.01)], while Bangladeshi people had a lower risk [adjusted incidence rate ratio 0.49 (95% CI, 0.38,0.64)]. In the sulfonylurea cohort, black Caribbean, black African and Indian people all had increased risks of hypoglycaemia compared with white British people [adjusted incidence rate ratios 1.63 (95% CI 1.15,2.29), 1.90 (95% CI 1.32,2.75) and 1.93 (95% CI 1.39,2.69), respectively]. CONCLUSION: The differences in hypoglycaemic risk among people with Type 2 diabetes prescribed insulin and/or sulfonylureas warrant further investigation of any differing biological responses and/or cultural attitudes to antidiabetes therapy among ethnic groups, and should be considered by clinicians evaluating the treatment goals of people with Type 2 diabetes using insulins or sulfonylureas.