Whole blood Fe isotopic signature in a sub-Saharan African population

The Fe isotopic composition of an individual's whole blood has recently been shown to be an interesting clinical indicator of Fe status. The present study aimed to evaluate the influence of several endemic characteristics of a representative population of the South Kivu province, an Fe-rich volcanic African region, on the whole blood Fe isotopic composition. Both diabetes mellitus and the ferroportin Q248H mutation are very common in Africa and are strongly associated with impairments in Fe metabolism. Fe isotopic analysis of whole blood samples was carried out using multi-collector inductively coupled plasma-mass spectrometry (after chromatographic isolation of the target element). Forty-two male subjects (between 48 and 59 years old) living in Bukavu (South Kivu) were enrolled in this study. Among the selected population, wild-type subjects and subjects presenting the ferroportin Q248H mutation (heterozygotes and homozygotes) were included. Within each group, diabetic and non-diabetic patients were considered. The whole blood delta Fe-56 value ranged from -3.09% to -2.41%. The delta Fe-56 value shows a significant negative correlation with the ferritin concentration. No correlation could be established between the whole blood delta Fe-56 value and the transferrin concentration, transferrin saturation or serum Fe concentration. The ferroportin Q248H mutation did not seem to have affected the whole blood Fe isotopic signature. The whole blood delta Fe-56 values were significantly higher in diabetic subjects than in non-diabetic subjects and showed a significant negative correlation with body mass index (BMI) values

Novel injectable gellan gum hydrogel composites incorporating Zn- and Sr-enriched bioactive glass microparticles:high-resolution X-Ray micro-computed tomography, antibacterial and in vitro testing

Mineralization of hydrogel biomaterials is desirable to improve their suitability as materials for bone regeneration. In this study, gellan gum (GG) hydrogels were formed by simple mixing of GG solution with bioactive glass microparticles of 45S5 composition, leading to hydrogel formation by ion release from the amorphous bioactive glass microparticles. This resulted in novel injectable, self‐gelling composites of GG hydrogels containing 20% bioactive glass. Gelation occurred within 20 minutes. Composites containing the standard 45S5 bioactive glass preparation were markedly less stiff. X‐ray μCT proved to be a highly sensitive technique capable of detecting microparticles of diameter approximately 8 μm, i.e. individual microparticles, and accurately visualizing the size distribution of bioactive glass microparticles and their aggregates, and their distribution in GG hydrogels. The widely used melt‐derived 45S5 preparation served as a standard and was compared to a calcium‐rich, sol‐gel derived preparation (A2), as well as A2 enriched with zinc (A2Zn5) and strontium (A2Sr5).A2, A2Zn and A2Sr bioactive glass particles were more homogeneously dispersed in GG hydrogels than 45S5. Composites containing all four bioactive glass preparations exhibited antibacterial activity against methicillin‐resistant Staphylococcus aureus (MRSA). Composites containing A2Zn5 and A2Sr5 bioactive glasses supported the adhesion and growth of osteoblast‐like cells and were considerably more cytocompatible than 45S5. All composites underwent mineralization with calcium‐deficient hydroxyapatite (CDHA) upon incubation in simulated body fluid (SBF). The extent of mineralization appeared to be greatest for composites containing A2Zn5 and 45S5. The results underline the importance of the choice of bioactive glass when preparing injectable, self‐gelling composites

Antimicrobial resistance among migrants in Europe: a systematic review and meta-analysis

BACKGROUND: Rates of antimicrobial resistance (AMR) are rising globally and there is concern that increased migration is contributing to the burden of antibiotic resistance in Europe. However, the effect of migration on the burden of AMR in Europe has not yet been comprehensively examined. Therefore, we did a systematic review and meta-analysis to identify and synthesise data for AMR carriage or infection in migrants to Europe to examine differences in patterns of AMR across migrant groups and in different settings. METHODS: For this systematic review and meta-analysis, we searched MEDLINE, Embase, PubMed, and Scopus with no language restrictions from Jan 1, 2000, to Jan 18, 2017, for primary data from observational studies reporting antibacterial resistance in common bacterial pathogens among migrants to 21 European Union-15 and European Economic Area countries. To be eligible for inclusion, studies had to report data on carriage or infection with laboratory-confirmed antibiotic-resistant organisms in migrant populations. We extracted data from eligible studies and assessed quality using piloted, standardised forms. We did not examine drug resistance in tuberculosis and excluded articles solely reporting on this parameter. We also excluded articles in which migrant status was determined by ethnicity, country of birth of participants' parents, or was not defined, and articles in which data were not disaggregated by migrant status. Outcomes were carriage of or infection with antibiotic-resistant organisms. We used random-effects models to calculate the pooled prevalence of each outcome. The study protocol is registered with PROSPERO, number CRD42016043681. FINDINGS: We identified 2274 articles, of which 23 observational studies reporting on antibiotic resistance in 2319 migrants were included. The pooled prevalence of any AMR carriage or AMR infection in migrants was 25·4% (95% CI 19·1-31·8; I2 =98%), including meticillin-resistant Staphylococcus aureus (7·8%, 4·8-10·7; I2 =92%) and antibiotic-resistant Gram-negative bacteria (27·2%, 17·6-36·8; I2 =94%). The pooled prevalence of any AMR carriage or infection was higher in refugees and asylum seekers (33·0%, 18·3-47·6; I2 =98%) than in other migrant groups (6·6%, 1·8-11·3; I2 =92%). The pooled prevalence of antibiotic-resistant organisms was slightly higher in high-migrant community settings (33·1%, 11·1-55·1; I2 =96%) than in migrants in hospitals (24·3%, 16·1-32·6; I2 =98%). We did not find evidence of high rates of transmission of AMR from migrant to host populations. INTERPRETATION: Migrants are exposed to conditions favouring the emergence of drug resistance during transit and in host countries in Europe. Increased antibiotic resistance among refugees and asylum seekers and in high-migrant community settings (such as refugee camps and detention facilities) highlights the need for improved living conditions, access to health care, and initiatives to facilitate detection of and appropriate high-quality treatment for antibiotic-resistant infections during transit and in host countries. Protocols for the prevention and control of infection and for antibiotic surveillance need to be integrated in all aspects of health care, which should be accessible for all migrant groups, and should target determinants of AMR before, during, and after migration. FUNDING: UK National Institute for Health Research Imperial Biomedical Research Centre, Imperial College Healthcare Charity, the Wellcome Trust, and UK National Institute for Health Research Health Protection Research Unit in Healthcare-associated Infections and Antimictobial Resistance at Imperial College London

Clonal chromosomal mosaicism and loss of chromosome Y in elderly men increase vulnerability for SARS-CoV-2

The pandemic caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2, COVID-19) had an estimated overall case fatality ratio of 1.38% (pre-vaccination), being 53% higher in males and increasing exponentially with age. Among 9578 individuals diagnosed with COVID-19 in the SCOURGE study, we found 133 cases (1.42%) with detectable clonal mosaicism for chromosome alterations (mCA) and 226 males (5.08%) with acquired loss of chromosome Y (LOY). Individuals with clonal mosaic events (mCA and/or LOY) showed a 54% increase in the risk of COVID-19 lethality. LOY is associated with transcriptomic biomarkers of immune dysfunction, pro-coagulation activity and cardiovascular risk. Interferon-induced genes involved in the initial immune response to SARS-CoV-2 are also down-regulated in LOY. Thus, mCA and LOY underlie at least part of the sex-biased severity and mortality of COVID-19 in aging patients. Given its potential therapeutic and prognostic relevance, evaluation of clonal mosaicism should be implemented as biomarker of COVID-19 severity in elderly people. Among 9578 individuals diagnosed with COVID-19 in the SCOURGE study, individuals with clonal mosaic events (clonal mosaicism for chromosome alterations and/or loss of chromosome Y) showed an increased risk of COVID-19 lethality

Surgical site infection after gastrointestinal surgery in high-income, middle-income, and low-income countries: a prospective, international, multicentre cohort study

Background: Surgical site infection (SSI) is one of the most common infections associated with health care, but its importance as a global health priority is not fully understood. We quantified the burden of SSI after gastrointestinal surgery in countries in all parts of the world. Methods: This international, prospective, multicentre cohort study included consecutive patients undergoing elective or emergency gastrointestinal resection within 2-week time periods at any health-care facility in any country. Countries with participating centres were stratified into high-income, middle-income, and low-income groups according to the UN's Human Development Index (HDI). Data variables from the GlobalSurg 1 study and other studies that have been found to affect the likelihood of SSI were entered into risk adjustment models. The primary outcome measure was the 30-day SSI incidence (defined by US Centers for Disease Control and Prevention criteria for superficial and deep incisional SSI). Relationships with explanatory variables were examined using Bayesian multilevel logistic regression models. This trial is registered with ClinicalTrials.gov, number NCT02662231. Findings: Between Jan 4, 2016, and July 31, 2016, 13 265 records were submitted for analysis. 12 539 patients from 343 hospitals in 66 countries were included. 7339 (58·5%) patient were from high-HDI countries (193 hospitals in 30 countries), 3918 (31·2%) patients were from middle-HDI countries (82 hospitals in 18 countries), and 1282 (10·2%) patients were from low-HDI countries (68 hospitals in 18 countries). In total, 1538 (12·3%) patients had SSI within 30 days of surgery. The incidence of SSI varied between countries with high (691 [9·4%] of 7339 patients), middle (549 [14·0%] of 3918 patients), and low (298 [23·2%] of 1282) HDI (p < 0·001). The highest SSI incidence in each HDI group was after dirty surgery (102 [17·8%] of 574 patients in high-HDI countries; 74 [31·4%] of 236 patients in middle-HDI countries; 72 [39·8%] of 181 patients in low-HDI countries). Following risk factor adjustment, patients in low-HDI countries were at greatest risk of SSI (adjusted odds ratio 1·60, 95% credible interval 1·05–2·37; p=0·030). 132 (21·6%) of 610 patients with an SSI and a microbiology culture result had an infection that was resistant to the prophylactic antibiotic used. Resistant infections were detected in 49 (16·6%) of 295 patients in high-HDI countries, in 37 (19·8%) of 187 patients in middle-HDI countries, and in 46 (35·9%) of 128 patients in low-HDI countries (p < 0·001). Interpretation: Countries with a low HDI carry a disproportionately greater burden of SSI than countries with a middle or high HDI and might have higher rates of antibiotic resistance. In view of WHO recommendations on SSI prevention that highlight the absence of high-quality interventional research, urgent, pragmatic, randomised trials based in LMICs are needed to assess measures aiming to reduce this preventable complication

Al determination in whole blood samples as AlF via high-resolution continuum source graphite furnace molecular absorption spectrometry : potential application to forensic diagnosis of drowning

In this work, a new methodology for direct determination of Al in whole blood samples by means of high-resolution continuum source graphite furnace molecular absorption spectrometry has been developed, based on the formation of the AlF diatomic molecule in the graphite furnace and the subsequent monitoring of its molecular absorption. The proposed methodology provides an alternative method to conventional atomic absorption, solving most of the problems related to the latter technique, particularly matrix effects, providing a straightforward alternative for blood analysis. The addition of NH(4)F center dot HF, which is required for promotion of the AlF molecule, was found to improve sample matrix removal for whole blood samples, whether they contain EDTA or heparin as anticoagulant agents. Besides minimizing residues in the graphite platform, this circumstance enabled the use of aqueous standards to build a calibration curve, avoiding the need for the cumbersome method of standard additions, while not affecting significantly detection capabilities (1.8 mu g L(-1) LOD). The method developed was also used for exploring the possibilities of Al as a chemical marker assisting forensic diagnosis of death-by-drowning. For this purpose, a set of samples (water and blood) obtained from 8 drowning suspects and two controls were analysed for their Al levels. Although additional studies with a large number of samples would be needed in order to draw definitive conclusions from a forensic point of view, a positive correlation between Al concentration in the drowning water and Al concentration in the blood of drowning suspects was found, supporting the validity of Al as a marker for drowning diagnosis

Isotope ratio mapping by means of laser ablation-single collector-ICP-mass spectrometry : Zn tracer studies in thin sections of Daphnia magna

In this paper, the possibilities of LA-single collector-ICP-mass spectrometry for obtaining isotope ratio images of thin sections of Daphnia magna specimens exposed to isotopically enriched Zn tracers were evaluated. Zn was selected considering its importance in ecotoxicological studies. All aspects of the analytical methodology deployed were carefully studied and optimized for obtaining the best isotope ratio precision and accuracy. The development of this methodological approach consisted of: (i) evaluation of the performance of two different medium mass resolution exit slits, a conventional one providing a mass resolution of m/Delta m approximate to 4000 and triangular shaped peaks, and another (wider) one, offering a lower mass resolution (m/Delta m approximate to 2000), but providing enhanced ion transmission and flat-topped peaks; (ii) the use of a wet plasma for improving plasma robustness; (iii) thorough optimization of the ablation conditions (such as laser spot size, repetition rate, scan speed and laser fluence) and data acquisition parameters (such as scan mode, the number of nuclides monitored, mass window, the number of samples per peak and dwell times); and (iv) adequate data treatment including the use of the moving average of 5 individual values. With the methodology developed, isotope ratio images with 30 micrometer spatial resolution scale were obtained for exposed and unexposed Daphnia magna individuals. The typical overall uncertainty of the measurements was approximately 5% RSD for the Zn-66/Zn-64 and Zn-68/Zn-64 ratios, which can be considered as satisfactory taking into account that the amount of Zn present per 30 mu m x 30 mu m pixel only reached a few picograms in the most favourable cases (giving rise to 10 000-20 000 counts per s for Zn-64). These results open the possibility for tracer studies with stable isotopes to be carried out using single collector instrumentation, a much more widespread analytical technique than multi-collector ICP-MS

A simple dilute-and-shoot approach for the determination of ultra-trace levels of arsenic in biological fluids via ICP-MS using CH3F/He as a reaction gas

The performance of a mixture of CH3F/He (1/9) as a reaction gas for the determination of As in biological fluids using a quadrupole ICP-MS instrument has been explored. A simple (dilute-and-shoot) interference-free method has been developed to quantify As concentrations at trace and ultra-trace levels in matrices with a high Cl content. As+ reacts with CH3F (through CH3F addition, followed by HF elimination) with high efficiency forming AsCH2+ as the primary reaction product, which can be monitored at a mass-to-charge ratio of 89, free from the Cl-based interferents (e.g., (ArCl+)-Ar-40-Cl-35 and (CaCl+)-Ca-40-Cl-35) that hamper the monitoring of As-75(+). Matrix effects are overcome by the use of Te as an internal standard and the addition of 3% v/v ethanol to all samples and calibration standard solutions. The method presented was validated by analysing a set of reference materials (blood, serum and urine) and by assessing As recovery from a set of real blood samples. With this method, the limit of detection was calculated to be 0.8 ng L-1 As, favourably comparable to the vast majority of values reported in the literature, even with those obtained using more sophisticated sector-field instrumentation