Shiga-toxigenic Escherichia coli (STEC) are important human pathogens associated with diarrhea and in some cases haemorrhagic colitis. Contaminated food derived from cattle and wildlife species are ...often associated with disease outbreaks. In this study, we report the prevalence, serogroup diversity and virulence profiles of STEC strains derived from cattle, rusa deer and pig. Of the 422 samples analyzed, STEC were detected in 40% (80/200) of cattle, 27.0% (33/122) of deer and 13.0% (13/100) of pigs. STEC isolates belonged to 38 O-serogroups whereby 5.2% (24/462) of the isolates belonged to clinically important EHEC-7 serogroups: O26 (n = 2), O103 (n = 1), O145 (n = 3) and O157 (n = 18). Fourteen serogroups (O26, O51, O84, O91, O100, O104, O110, O117, O145, O146, O156, O157, O177 and ONT) displayed multiple virulence profiles. We also identified two serovars (O117 and O119) in deer which are not well-documented in epidemiological surveys. 73.7% (28/38) of recovered O-serogroups are known to be associated with serious human illnesses including haemolytic uremic syndrome (HUS) and bloody diarrhea. STEC isolates harboring single genotypes stx1, stx2, eae and hlyA accounted for 3.0% (14/462), 9.1% (42/462), 47.6% (220/462) and 1.7% (8/462) of all STEC isolates screened, respectively. Virulence combinations stx1 and stx2 were harboured by 1.3% of isolates while strains with genetic profiles eae/hlyA were the second most prevalent amongst STEC isolates. The full known virulent genotypes (stx2/eae, stx1/stx2/eae, stx1/stx2/hlyA and stx2/eae/hlyA) were present in 22 of the 462 STEC strains. A total of 10 different virulence patterns were recovered amongst animal species. Phylogeny of the gnd gene showed that amongst STEC strains, serovar O100 outlined the main cluster. Fourteen (n = 14) different sequence types (STs) were identified from a panel of twenty (n = 20) STEC isolates. One of the isolate (PG007B) possessed a unique ST (adk 10, fumC 693, gyrB 4, icd 1, mdh 8, purA 8, recA 2) that could not be assigned using MLST databases. None of the ST's recovered in deer were observed in domestic species. Our findings shows that food associated animals found on the tropical island of Mauritius carry a diversity of STEC strains with many serovars known to be associated with human disease. This report indicates that increased awareness, surveillance and hygienic attention at critical stages of the human food chain are warranted.
•Cattle, rusa deer and pigs are colonized by STEC, with cattle as the principal reservoir.•Retail beef accounted for over 85% of the 74 STEC-positive food samples.•73.7% (28/38) of O-serogroups were previously linked to HUS or bloody diarrhea.•Two rarely documented serovars (O117 and O119) were recovered in rusa deer.•38.5% of STEC strains had multiple toxigenic profiles involving stx2 and/or - eae.
Systemic telomere length has been associated with measures of diastolic function, vascular stiffness and left ventricular mass mainly in smaller, patient-specific settings and not in a general ...population. In this study we describe the applicability of these findings in a large, representative population.
Peripheral blood leukocyte telomere length (PBL TL) was measured using telomere restriction fragment analysis in the young to middle-aged (>2500 volunteers, ∼35 to 55 years old) Asklepios study population, free from overt cardiovascular disease. Subjects underwent extensive echocardiographic, hemodynamic and biochemical phenotyping. After adjusting for relevant confounders (age, sex, systolic blood pressure, heart rate, body mass index and use of antihypertensive drugs) we found no associations between PBL TL and left ventricular mass index (P = 0.943), ejection fraction (P = 0.933), peak systolic septal annular motion (P = 0.238), pulse wave velocity (P = 0.971) or pulse pressure (P = 0.999). In contrast, our data showed positive associations between PBL TL and parameters of LV filling: the transmitral flow early (E) to late (A) velocity ratio (E/A-ratio; P<0.001), the ratio of early (e') to late (a') mitral annular velocities (e'/a'-ratio; P = 0.012) and isovolumic relaxation time (P = 0.015). Interestingly, these associations were stronger in women than in men and were driven by associations between PBL TL and the late diastolic components (A and a').
In a generally healthy, young to middle-aged population, PBL TL is not related to LV mass or systolic function, but might be associated with an altered LV filling pattern, especially in women.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Whereas the importance of family history (FH) is widely recognized in cardiovascular risk assessment, its full potential could be underutilized, when applied with its current simple guidelines-based ...definition (cFH): presence of premature cardiovascular disease (CVD) in a first-degree relative. We tested the added value of a new, extended family history definition (eFH), also taking into account later onset of disease, second-degree relatives and number of affected relatives, on profiling cardiovascular risk and atherosclerotic burden in the general population.
Longitudinal population study.
Random, representative population sample from Erpe-Mere and Nieuwerkerken (Belgium, primary care).
2524 male/female volunteers, aged 35-55 years, free from overt CVD.
Subjects were extensively phenotyped including presence of atherosclerosis (ultrasound) and a newly developed FH questionnaire (4 generations).
Compared to cFH, eFH was superior in predicting an adverse risk profile (glycemic state, elevated blood pressure, lipid abnormalities, presence of metabolic syndrome components) and presence of atherosclerosis (all age & sex-adjusted p<0.05). Unlike cFH, eFH remained a significant predictor of subclinical atherosclerosis after adjusting for confounders. Most relations with eFH were not graded but showed clear informational breakpoints, with absence of CVD (including late onset) in any first-degree relative being a negative predictor of atherosclerosis, and a particularly interesting phenotype for further study.
A novel, extended FH definition is superior to the conventional definition in profiling cardiovascular risk and atherosclerotic burden in the general population. There remain clear opportunities to refine and increase the performance and informational content of this simple, readily-available inexpensive tool.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
To test the hypothesis that targeting the microenvironment (soil) may effectively kill cancer cells (seeds) through a small-molecular weight sequential dual-targeting theragnostic strategy, or ...dual-targeting approach.
With approval from the institutional animal care and use committee, 24 rats were implanted with 48 liver rhabdomyosarcomas (R1). First, the vascular-disrupting agent combretastatin A4 phosphate (CA4P) was injected at a dose of 10 mg/kg to cause tumor necrosis, which became a secondary target. Then, the necrosis-avid agent hypericin was radiolabeled with iodine 131 to form (131)I-hypericin, which was injected at 300 MBq/kg 24 hours after injection of CA4P. Both molecules have small molecular weight, are naturally or synthetically derivable, are intravenously injectable, and are of unique targetablities. The tumor response in the dual-targeting group was compared with that in vehicle-control and single-targeting (CA4P or (131)I-hypericin) groups with in vivo magnetic resonance imaging and scintigrams and ex vivo gamma counting, autoradiography, and histologic analysis. Tumor volumes, tumor doubling time (TDT), and radiobiodistribution were analyzed with statistical software. P values below .05 were considered to indicate a significant difference.
Eight days after treatment, the tumor volume of rhabdomyosarcoma in the vehicle-control group was double that in both single-targeting groups (P < .001) and was five times that in the dual-targeting group (P < .0001), without treatment-related animal death. The TDT was significantly longer in the dual-targeting group (P < .0001). Necrosis appeared as hot spots on scintigrams, corresponding to 3.13% of the injected dose of (131)I-hypericin per gram of tissue (interquartile range, 2.92%-3.97%) and a target-to-liver ratio of 20. The dose was estimated to be 100 times the cumulative dose of 50 Gy needed for radiotherapeutic response. Thus, accumulated (131)I-hypericin from CA4P-induced necrosis killed residual cancer cells with ionizing radiation and inhibited tumor regrowth.
This dual-targeting approach may be a simple and workable solution for cancer treatment and deserves further exploitation.
Spiroindolone KAE609 for Falciparum and Vivax Malaria White, Nicholas J; Pukrittayakamee, Sasithon; Phyo, Aung Pyae ...
New England journal of medicine/The New England journal of medicine,
07/2014, Letnik:
371, Številka:
5
Journal Article
Recenzirano
Odprti dostop
New antimalarial agents are needed, especially given the emergence of artemisinin resistance. In this study from Thailand, treatment with KAE609, the first in the new spiroindolone class, resulted in ...rapid parasite clearance in patients with
Plasmodium vivax
or
P. falciparum
malaria.
The treatment of
Plasmodium falciparum
malaria has changed considerably over the past decade, with a global change to the rapidly and reliably effective artemisinin-based combination therapies. The deployment of such therapies and insecticide-treated bed nets have been the two main contributors to the substantial recent declines in morbidity and mortality from malaria.
1
Unfortunately, artemisinin resistance has emerged in Southeast Asia, threatening these gains
2
–
5
and potentially derailing current control efforts. New medicines are needed,
6
but it has proved difficult to develop effective and safe antibacterial and antiparasitic drugs.
The new spiroindolone class of antimalarial agents was identified a few years . . .
Noble metal nanoparticles (NPs) can efficiently release heat under optical excitation. Applying this principle of photothermal heating, it is possible to locally heat membranes containing noble metal ...NPs to increase the membrane flux during the separation process by mere light irradiation, while not altering selectivities. Earlier work involved rather polar membrane polymers in which NP dispersion is quite straightforward. The concept of localized membrane heating was now proven to be applicable for hydrophobic membranes as well, for which dispersion of the NPs cannot be realized by the approach used in earlier work. The PDMS membranes containing gold nanoparticles (GNPs) were prepared by an in-situ method. TEM images showed that the GNPs were well-dispersed in the membrane matrix. Moreover, the photothermal heating improved PDMS membrane fluxes without significantly lowering their selectivity, as proven in a dead-end filtration coupled to laser irradiation with appropriate wavelength. Application feasibilities of the technique for membrane separation are discussed, including requirements for feed, potential application fields, alternatives for GNPs and scaling-up issues.
► GNPs are incorporated in hydrophobic PDMS SNRF membranes by an in-situ method. ► Photothermal heating improved fluxes of GNPs containing PDMS membranes. ► Application feasibilities of photothermal heating for filtration are discussed. ► The mechanism of photothermal heating enhanced membrane filtration is proposed.
Aim: Rotundone and 3-isobutyl-2-methoxypyrazine (IBMP) are two potent aroma compounds responsible for pepper and bell pepper notes in red wines, respectively. The aim of the study was to modulate, ...through common viticultural practices, the volatile composition in these two molecules of Fer red wines from a temperate climate wine region with very cool nights, located in the southwest of France.Methods and results: Three viticultural practices (leaf removal 10 days after berry set, removal of lateral shoots, and delayed harvest 7 days after the control) were investigated in 2015 and in 2016. Rotundone concentrations up to 69 ng/L were found in experimental wines. IBMP concentrations were below perception level in wines from 2016 and below detection level in wines from 2015, a vintage with particularly hot climatic conditions between berry set and bunch closure. Delayed harvest induced an increase in rotundone concentration while leaf removal and the removal of lateral shoots had no significant impact on rotundone concentration. Delayed harvest and the removal of lateral shoots were the most efficient practices to decrease IBMP in wines. The three techniques made it possible to increase the odour activity values (OAV) ratio of OAV rotundone to OAV IBMP, with the greatest impact observed for delayed harvest.Conclusion: According to our results, delayed harvest appears to be the best practice to modulate the volatile composition of Fer wines toward an increase in the OAV rotundone to OAV IBMP ratio.Significance and impact of the study: Our results may assist local grape growers to modulate the volatile composition of their wines.
In a randomized trial comparing the proton-pump inhibitor pantoprazole with placebo in the ICU, there was no significant difference in the rate of death at 90 days or in a combined end point of ...clinically meaningful events, which included gastrointestinal bleeding and pneumonia.
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