A prospective study of travellers' diarrhoea : analysis of pathogen findings by destination in various (sub)tropical regions

Objectives: Eighty million travellers visiting (sub)tropical regions contract travellers' diarrhoea (TD) each year, yet prospective data comparing the prevalence of TD pathogens in various geographical regions are scarce. Our recent study using modern molecular methods found enteropathogenic (EPEC) and enteroaggregative (EAEC) Escherichia coli to be the most frequent pathogens, followed by enterotoxigenic E. coli (ETEC) and Campylobacter. We revisited our data to compare the findings by geographical region. Methods: A total of 459 prospectively recruited travellers provided stool samples and completed questionnaires before and after visiting destinations in various geographical regions. A multiplex quantitative real-time PCR assay was used to analyse Salmonella, Yersinia, Campylobacter jejuni/Campylobacter coli, Shigella, Vibrio cholerae, EPEC, EAEC, ETEC, enterohaemorrhagic E. coli and enteroinvasive E. coli. Results: TD was contracted by 69% (316/459) of the subjects; EPEC and EAEC outnumbered ETEC and Campylobacter in all regions. Multiple pathogens were detected in 42% (133/316) of the samples. The proportions of all pathogens varied by region. The greatest differences were seen for Campylobacter: while relatively frequent in South Asia (n = 11; 20% of the 55 with TD during travel) and Southeast Asia (15/84, 15%), it was less common in East and West Africa (5/71, 7% and 1/57, 2%) and absent in South America and the Caribbean (0/40). Conclusions: EPEC and EAEC outnumbered ETEC and Campylobacter everywhere, yet the proportions of pathogen findings varied by region, with ETEC and Campylobacter rates showing the greatest differences. The high frequency of multibacterial findings in many regions indicates a need for further investigation of the clinical role of each pathogen. (C) 2017 The Authors. Published by Elsevier Ltd on behalf of European Society of Clinical Microbiology and Infectious Diseases.Peer reviewe

Serum matrix metalloproteinase 8 and tissue inhibitor of metalloproteinase 1 : Potential markers for malignant transformation of recurrent respiratory papillomatosis and for prognosis of laryngeal cancer

Background Biomarkers that could predict malignant transformation of recurrent respiratory papillomatosis (RRP) would be useful in patient follow-up. We investigated whether serum matrix metalloproteinase 8 (MMP-8) and tissue inhibitor of metalloproteinase 1 (TIMP-1) could predict malignant transformation of RRP and whether they associate with survival in laryngeal squamous cell carcinoma (LSCC) without preexisting RRP. Methods We analyzed serum MMP-8 (S-MMP-8) and serum TIMP-1 (s-TIMP-1) in 114 patients: 55 were treated for RRP and 59 for LSCC without preexisting RRP. Five patients with RRP developed LSCC during follow-up. Results Elevated S-MMP-8 level in RRP was associated with malignant transformation (P = .01). Compared to patients with RRP, S-MMP-8 in patients with LSCC was significantly higher (P <.001). Increased S-TIMP-1 level in LSCC was associated with poor overall survival (P = .02) and recurrence-free survival (P = .05). Conclusion In RRP, high S-MMP-8 may predict malignant transformation. In LSCC, elevated S-TIMP-1 is connected to poor survival.Peer reviewe

Size distributions, sources and source areas of water-soluble organic carbon in urban background air

International audienceThis paper represents the results of one year long measurement period of the size distributions of water-soluble organic carbon (WSOC), inorganic ions and gravimetric mass of particulate matter. Measurements were done at an urban background station (SMEAR III) by using a micro-orifice uniform deposit impactor (MOUDI). The site is located in northern European boreal region in Helsinki, Finland. The WSOC size distribution measurements were completed with the chemical analysis of inorganic ions, organic carbon (OC) and monosaccharide anhydrides from the filter samples. During the measurements gravimetric mass in the MOUDI collections varied between 3.4 and 55.0 ?g m?3 and the WSOC concentration was between 0.3 and 7.4 ?g m?3. On average, water-soluble particulate organic matter (WSPOM, WSOC multiplied by 1.6) comprised 25±7.7% and 7.5±3.4% of aerosol PM1 mass and the PM1?10 mass, respectively. Inorganic ions contributed 33±12% and 28±19% of the analyzed PM1 and PM1?10 aerosol mass. Five different aerosol categories corresponding to different sources or source areas were identified (long-range transport aerosols, biomass burning aerosols from wild land fires and from small-scale wood combustion, aerosols originating from marine areas and from the clean arctic areas). Clear differences in WSOC concentrations and size distributions originating from different sources or source areas were observed, although there are also many other factors which might affect the results. E.g. the local conditions and sources of volatile organic compounds (VOCs) and aerosols as well as various transformation processes are likely to have an impact on the measured aerosol composition. Using the source categories, it was identified that especially the oxidation products of biogenic VOCs in summer had a clear effect on WSOC concentrations

Increased Oxidative Burden Associated with Traffic Component of Ambient Particulate Matter at Roadside and Urban Background Schools Sites in London

As the incidence of respiratory and allergic symptoms has been reported to be increased in children attending schools in close proximity to busy roads, it was hypothesised that PM from roadside schools would display enhanced oxidative potential (OP). Two consecutive one-week air quality monitoring campaigns were conducted at seven school sampling sites, reflecting roadside and urban background in London. Chemical characteristics of size fractionated particulate matter (PM) samples were related to the capacity to drive biological oxidation reactions in a synthetic respiratory tract lining fluid. Contrary to hypothesised contrasts in particulate OP between school site types, no robust size-fractionated differences in OP were identified due high temporal variability in concentrations of PM components over the one-week sampling campaigns. For OP assessed both by ascorbate (OPAA m−3) and glutathione (OPGSH m−3) depletion, the highest OP per cubic metre of air was in the largest size fraction, PM1.9–10.2. However, when expressed per unit mass of particles OPAA µg−1 showed no significant dependence upon particle size, while OPGSH µg−1 had a tendency to increase with increasing particle size, paralleling increased concentrations of Fe, Ba and Cu. The two OP metrics were not significantly correlated with one another, suggesting that the glutathione and ascorbate depletion assays respond to different components of the particles. Ascorbate depletion per unit mass did not show the same dependence as for GSH and it is possible that other trace metals (Zn, Ni, V) or organic components which are enriched in the finer particle fractions, or the greater surface area of smaller particles, counter-balance the redox activity of Fe, Ba and Cu in the coarse particles. Further work with longer-term sampling and a larger suite of analytes is advised in order to better elucidate the determinants of oxidative potential, and to fuller explore the contrasts between site types.\ud \u

Aerosol Characteristics at a High Altitude Location in Central Himalayas: Optical Properties and Radiative Forcing

Collocated measurements of the mass concentrations of aerosol black carbon (BC) and composite aerosols near the surface were carried out along with spectral aerosol optical depths (AODs) from a high altitude station, Manora Peak in Central Himalayas, during a comprehensive aerosol field campaign in December 2004. Despite being a pristine location in the Shivalik Ranges of Central Himalayas, and having a monthly mean AOD (at 500 nm) of 0.059 $\pm$ 0.033 (typical to this site), total suspended particulate (TSP) concentration was in the range 15 - 40 micro g m^(-3) (mean value 27.1 $\pm$ 8.3 micro g m^(-3)). Interestingly, aerosol BC had a mean concentration of 1.36 $\pm$ 0.99 micro g m^(-3), contributed to ~5.0 $\pm$ 1.3 % to the composite aerosol mass. This large abundance of BC is found to have linkages to the human activities in the adjoining valley and to the boundary layer dynamics. Consequently, the inferred single scattering albedo lies in the range of 0.87 to 0.94 (mean value 0.90 $\pm$ 0.03), indicating significant aerosol absorption. The estimated aerosol radiative forcing was as low as 4.2 W m^(-2) at the surface, +0.7 W m^(-2) at the top of the atmosphere, implying an atmospheric forcing of +4.9 W m^(-2). Though absolute value of the atmospheric forcing is quite small, which arises primarily from the very low AOD (or the column abundance of aerosols), the forcing efficiency (forcing per unit optical depth) was $\sim$88 W m^(-2), which is attributed to the high BC mass fraction.Comment: 32 Pages, Accepted in JGR (Atmosphere

Comparative analysis of COVID-19 vaccine responses and third booster dose-induced neutralizing antibodies against Delta and Omicron variants

Vaccination shows efficacy in protecting from COVID-19, but regime and dosing optimization is still ongoing. Here the authors show that BNT162b2, mRNA-1273, or their combination with ChAdOx1 induces similar antibody responses, and those receiving three doses of BNT162b2 induce neutralizing antibodies against the Omicron variant. Two COVID-19 mRNA (of BNT162b2, mRNA-1273) and two adenovirus vector vaccines (ChAdOx1 and Janssen) are licensed in Europe, but optimization of regime and dosing is still ongoing. Here we show in health care workers (n = 328) that two doses of BNT162b2, mRNA-1273, or a combination of ChAdOx1 adenovirus vector and mRNA vaccines administrated with a long 12-week dose interval induce equally high levels of anti-SARS-CoV-2 spike antibodies and neutralizing antibodies against D614 and Delta variant. By contrast, two doses of BNT162b2 with a short 3-week interval induce 2-3-fold lower titers of neutralizing antibodies than those from the 12-week interval, yet a third BNT162b2 or mRNA-1273 booster dose increases the antibody levels 4-fold compared to the levels after the second dose, as well as induces neutralizing antibody against Omicron BA.1 variant. Our data thus indicates that a third COVID-19 mRNA vaccine may induce cross-protective neutralizing antibodies against multiple variants.Peer reviewe

COVID-19 mRNA vaccine induced antibody responses against three SARS-CoV-2 variants

As SARS-CoV-2 has been circulating for over a year, dozens of vaccine candidates are under development or in clinical use. The BNT162b2 mRNA COVID-19 vaccine induces spike protein-specific neutralizing antibodies associated with protective immunity. The emergence of the B.1.1.7 and B.1.351 variants has raised concerns of reduced vaccine efficacy and increased re-infection rates. Here we show, that after the second dose, the sera of BNT162b2-vaccinated health care workers (n=180) effectively neutralize the SARS-CoV-2 variant with the D614G substitution and the B.1.1.7 variant, whereas the neutralization of the B.1.351 variant is five-fold reduced. Despite the reduction, 92% of the seronegative vaccinees have a neutralization titre of >20 for the B.1.351 variant indicating some protection. The vaccinees' neutralization titres exceeded those of recovered non-hospitalized COVID-19 patients. Our work provides evidence that the second dose of the BNT162b2 vaccine induces cross-neutralization of at least some of the circulating SARS-CoV-2 variants. Emerging SARS-CoV-2 variants contain mutations in the spike protein that may affect vaccine efficacy. Here, Jalkanen et al. show, using sera from 180 BNT162b2-vaccinated health care workers, that neutralization of SARS-CoV2 variant B.1.1.7 is not affected, while neutralization of B.1.351 variant is five-fold reduced.Peer reviewe

COVID-19 mRNA vaccine induced antibody responses against three SARS-CoV-2 variants

As SARS-CoV-2 has been circulating for over a year, dozens of vaccine candidates are under development or in clinical use. The BNT162b2 mRNA COVID-19 vaccine induces spike protein-specific neutralizing antibodies associated with protective immunity. The emergence of the B.1.1.7 and B.1.351 variants has raised concerns of reduced vaccine efficacy and increased re-infection rates. Here we show, that after the second dose, the sera of BNT162b2-vaccinated health care workers (n = 180) effectively neutralize the SARS-CoV-2 variant with the D614G substitution and the B.1.1.7 variant, whereas the neutralization of the B.1.351 variant is five-fold reduced. Despite the reduction, 92% of the seronegative vaccinees have a neutralization titre of >20 for the B.1.351 variant indicating some protection. The vaccinees’ neutralization titres exceeded those of recovered non-hospitalized COVID-19 patients. Our work provides evidence that the second dose of the BNT162b2 vaccine induces cross-neutralization of at least some of the circulating SARS-CoV-2 variants

Triglyceride Blisters in Lipid Bilayers: Implications for Lipid Droplet Biogenesis and the Mobile Lipid Signal in Cancer Cell Membranes

Triglycerides have a limited solubility, around 3%, in phosphatidylcholine lipid bilayers. Using millisecond-scale course grained molecular dynamics simulations, we show that the model lipid bilayer can accommodate a higher concentration of triolein (TO) than earlier anticipated, by sequestering triolein molecules to the bilayer center in the form of a disordered, isotropic, mobile neutral lipid aggregate, at least 17 nm in diameter, which forms spontaneously, and remains stable on at least the microsecond time scale. The results give credence to the hotly debated existence of mobile neutral lipid aggregates of unknown function present in malignant cells, and to the early biogenesis of lipid droplets accommodated between the two leaflets of the endoplasmic reticulum membrane. The TO aggregates give the bilayer a blister-like appearance, and will hinder the formation of multi-lamellar phases in model, and possibly living membranes. The blisters will result in anomalous membrane probe partitioning, which should be accounted for in the interpretation of probe-related measurements