Aims
Staphylococcus aureus
bloodstream infection is one of the most common serious bacterial infections worldwide. It represents a heterogenous clinical entity with a high risk of metastatic ...complications and a high in-hospital mortality ranging between 20 and 30%. The outcome can be improved by optimised diagnostic and therapeutic management. Thus, our minireview should provide important and often missed pieces of information in the management of
S. aureus
bloodstream infection.
Methods
We describe the essentials in the management of
S. aureus
bloodstream infection.
Results
Five essentials were identified: 1)
S. aureus
bacteremia should always be considered clinically significant. 2) Length of bacteremia and fever is relevant for diagnostic workup, duration of therapy and prognosis. 3) Prompt identification and eradication of portal of entry and infective/metastatic foci are essential. 4) Infective endocarditis should be excluded. 5) Intravenous treatment for at least two weeks up to 4–6 weeks with antistaphylococcal penicillins for MSSA and vancomycin or daptomycin for MRSA bloodstream infection is indicated.
Conclusion
Further efforts should be undertaken to increase the adherence to the essentials in the management of
S. aureus
bloodstream infection.
Electrocatalytic activities and stabilities of Pt supported on Sb-doped SnO2 (ATO) were examined for methanol (MOR) and ethanol (EOR) oxidation reactions. Pt colloidal particles were deposited on ATO ...nanoparticles (Pt/ATO) with various amounts of Pt loading. The prepared electrocatalysts were characterized by X-ray diffraction, transmission electron microscopy (TEM), X-ray photoelectron spectroscopy, thermogravimetric analysis, and cyclic voltammetry. Electrochemical activities of the Pt/ATO for CO oxidation, MOR, and EOR were compared with those of Pt supported on carbon (Pt/C). The MOR and EOR activities of the Pt/ATO were enhanced over those of the Pt/C with decreasing amounts of Pt loaded on ATO. The Pt/ATO exhibited much higher electrochemical and thermal stabilities than the Pt/C. According to TEM, the growth rate of Pt particles was lower in the Pt/ATO than in the Pt/C. The ATO nanoparticles appear to be promising support materials that promote electrochemical reactions and stabilize catalyst particles in direct alcohol fuel cells. PUBLICATION ABSTRACT
Background and purpose
Recent studies have demonstrated that Alzheimer's disease (AD) and subcortical vascular dementia (SVaD) have white matter (WM) microstructural changes. However, previous ...studies on AD and SVaD rarely eliminated the confounding effects of patients with mixed Alzheimer's and cerebrovascular disease pathologies. Therefore, our aim was to evaluate the divergent topography of WM microstructural changes in patients with pure AD and SVaD.
Methods
Patients who were clinically diagnosed with AD and SVaD were prospectively recruited. Forty AD patients who were Pittsburgh compound B (PiB) positive PiB(+) AD without WM hyperintensities and 32 SVaD patients who were PiB negative PiB(−) SVaD were chosen. Fifty‐six cognitively normal individuals were also recruited (NC). Tract‐based spatial statistics of diffuse tensor imaging were used to compare patterns of fractional anisotropy (FA) and mean diffusivity (MD).
Results
Compared with the NC group, the PiB(+) AD group showed decreased FA in the bilateral frontal, temporal and parietal WM regions and the genu and splenium of the corpus callosum as well as increased MD in the left frontal and temporal WM region. PiB(−) SVaD patients showed decreased FA and increased MD in all WM regions. Direct comparison between PiB(+) AD and PiB(−) SVaD groups showed that the PiB(−) SVaD group had decreased FA across all WM regions and increased MD in all WM regions except occipital regions.
Conclusion
Our findings suggest that pure AD and pure SVaD have divergent topography of WM microstructural changes including normal appearing WM.
Geologic carbon capture and storage (CCS) is an option for reducing CO2 emissions, but leakage to the surface is a risk factor. Natural CO2 reservoirs that erupt from abandoned oil and gas holes leak ...to the surface as spectacular cold geysers in the Colorado Plateau, United States. A better understanding of the mechanisms of CO2‐driven cold‐water geysers will provide valuable insight about the potential modes of leakage from engineered CCS sites. A notable example of a CO2‐driven cold‐water geyser is Crystal Geyser in central Utah. We investigated the fluid mechanics of this regularly erupting geyser by instrumenting its conduit with sensors and measuring pressure and temperature every 20 sec over a period of 17 days. Analyses of these measurements suggest that the timescale of a single‐eruption cycle is composed of four successive eruption types with two recharge periods ranging from 30 to 40 h. Current eruption patterns exhibit a bimodal distribution, but these patterns evolved during past 80 years. The field observation suggests that the geyser's eruptions are regular and predictable and reflect pressure and temperature changes resulting from Joule–Thomson cooling and endothermic CO2 exsolution. The eruption interval between multiple small‐scale eruptions is a direct indicator of the subsequent large‐scale eruption.
Aims
Due to the increase of severely immunocompromised patients, of invasive procedures including central intravascular catheters, and of the use of broad-spectrum antibiotics, the incidence of
...Candida
bloodstream infections has risen intensely in the last decades.
Candida
bloodstream infection is a serious disease with high mortality. Optimized diagnostic and therapeutic management can improve outcome. Thus, the aim of our mini-review is to highlight important and often missed opportunities in the management of
Candida
bloodstream infection.
Methods
We searched the published literature and describe the essentials in the management of
Candida
bloodstream infection.
Results
Four essentials were identified: (1) isolation of
Candida
spp. from a blood culture should always be considered relevant and requires treatment. Daily blood cultures should be drawn to determine cessation of candidemia. (2) Central venous catheter (CVC) and/or other indwelling devices should be removed. (3) Echinocandins are the first choice. Antifungal treatment should be continued for at least 14 days after cessation of fungemia. Susceptibility testing should be performed to identify resistance and to facilitate transition to oral treatment. (4) In persistent candidemia, echocardiography is an important investigation; ophthalmoscopy should be considered.
Conclusion
Further efforts should be undertaken to increase the adherence to the essentials in the management of
Candia
bloodstream infection.
Background and purpose
Smoking is a major risk factor for cognitive decline and dementia. However, the exact pathobiology of smoking remains unknown. The effects of smoking on cortical thickness as a ...biomarker of neurodegeneration or white matter hyperintensities and lacunes as biomarkers of cerebrovascular burden were concurrently evaluated.
Methods
Our study included 977 cognitively normal men who visited a health promotion centre and underwent medical check‐ups, including 3.0 T magnetic resonance imaging. Participants were categorized into never smoker, past smoker or current smoker groups and pack‐years and the years of smoking cessation were used as continuous variables.
Results
The current smoker group exhibited cortical thinning in frontal and temporo‐parietal regions compared with the never smoker group. These effects were particularly prominent in smokers with a high cumulative exposure to smoking in the current smoker group. However, there was no association between smoking and the severity of white matter hyperintensity or number of lacunes.
Conclusion
Our findings indicate that smoking might impact on neurodegeneration rather than cerebrovascular burdens in cognitively normal men, suggesting that smoking might be an important modifiable risk factor for the development of Alzheimer's disease.
, in the family Malvaceae, is a biennial plant native to China and is grown typically for gardening in Korea (Lee 2003). Seven microcyclic
species have been reported on
(Demers et al. 2015; Aime and ...Abbasi 2018). In early May 2022, characteristic symptoms of rust were observed on four of ten seedlings of
purchased at a wholesale nursery (36°50'19.8″N, 128°55'28.7″E) in Bonghwa, Korea. Rust spots were present on almost 90% of the 1,000 seedlings of
in that nursery during our survey in late May. Through a distribution survey from June to July 2022, similar symptomatic leaves were additionally collected from the leaves of
grown in gardens at five sites in Gimcheon (two sites), Gumi (one), Seongju (one), and Busan (one). Spots were yellow-orange the center surrounded by chlorotic haloes on the adaxial leaf surface, and reddish-brown or dark brown pustules on the abaxial leaf surface. Over time, the spots enlarged and coalesced, causing the decay of large sections of the leaves, and heavily infected leaves fell early. Spermogonia, produced at the center of the chlorotic spot on the adaxial leaf surface, were subepidermal, obovoid, and 113.2-164.5 × 97.6-153.3 μm in size. Telia were reddish-brown to dark brown, round, mostly grouped, 0.28-0.61 mm in diameter, and mainly formed on the abaxial leaf surface but sometimes on the adaxial leaf surface also. Teliospores were two-celled, but rarely one- or three-celled, and were fusoid and 37. 6-110 × 12.4-21.5 μm in size; the wall was yellowish or almost colorless, smooth, 1.2-2.6 μm thick at the sides, and up to 7.4 μm thick at the apex. The morphological characteristics were similar to those of P. modiolae, although the teliospores in our study were longer than those observed by Aime and Abbasi (2018). For phylogenetic analysis, genomic DNA was extracted from the teliospores of each regional specimen. Partial 18S, internal transcribed spacer (ITS), and partial 28S sequences were amplified using primers NS1, ITS4, ITS5, and LR11. The PCR products were sequenced (Celemics, Seoul, Korea) and deposited in GenBank. The ITS-partial large subunit (LSU) sequence and 28S sequences had 100% homology with other
sequences deposited in GenBank (accession numbers are shown in Fig. 2). In the phylogenetic trees of the ITS and LSU sequences, the isolates collected in this study were grouped with the reference sequences of
, including the Korean isolate (ON631218) recently reported on
by Lee et al. (2022). For the pathogenicity test, the teliospores with germinating basidiospores were suspended in sterile distilled water and smeared on the upper surface of asymptomatic
leaves in August. The inoculated plants were sprayed with distilled water and kept in the dark with saturated moisture for 24 h in an isolated glass house of the Animal & Plant Quarantine Agent. After 2 weeks, typical rust spots and telia of
were observed on the leaves of the inoculated plants, but not in the control plants, which were only sprayed with distilled, sterilized water and otherwise treated similarly to the inoculated plants. The results of this study show that the casual fungus is
, which has been commonly found in
in Korea. To the best of our knowledge, this is the first report of
in
in Korea.
Somatic cell nuclear transfer and transcription-factor-based reprogramming revert adult cells to an embryonic state, and yield pluripotent stem cells that can generate all tissues. Through different ...mechanisms and kinetics, these two reprogramming methods reset genomic methylation, an epigenetic modification of DNA that influences gene expression, leading us to hypothesize that the resulting pluripotent stem cells might have different properties. Here we observe that low-passage induced pluripotent stem cells (iPSCs) derived by factor-based reprogramming of adult murine tissues harbour residual DNA methylation signatures characteristic of their somatic tissue of origin, which favours their differentiation along lineages related to the donor cell, while restricting alternative cell fates. Such an 'epigenetic memory' of the donor tissue could be reset by differentiation and serial reprogramming, or by treatment of iPSCs with chromatin-modifying drugs. In contrast, the differentiation and methylation of nuclear-transfer-derived pluripotent stem cells were more similar to classical embryonic stem cells than were iPSCs. Our data indicate that nuclear transfer is more effective at establishing the ground state of pluripotency than factor-based reprogramming, which can leave an epigenetic memory of the tissue of origin that may influence efforts at directed differentiation for applications in disease modelling or treatment.
Celotno besedilo
Dostopno za:
DOBA, IJS, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Abstract Purpose To develop a toolkit of test methods for characterizing potentially critical quality attributes (CQAs) of topical semisolid products and to evaluate how CQAs influence the rate and ...extent of active ingredient bioavailability (BA) by monitoring cutaneous pharmacokinetics (PK) using an In Vitro Permeation Test (IVPT). Methods Product attributes representing the physicochemical and structural (Q3) arrangement of matter, such as attributes of particles and globules, were assessed for a set of test acyclovir creams (Aciclostad® and Acyclovir 1A Pharma) and compared to a set of reference acyclovir creams (Zovirax® US, Zovirax® UK and Zovirax® Australia). IVPT studies were performed with all these creams using heat-separated human epidermis, evaluated with both, static Franz-type diffusion cells and a flow through diffusion cell system. Results A toolkit developed to characterize quality and performance attributes of these acyclovir topical cream products identified certain differences in the Q3 attributes and the cutaneous PK of acyclovir between the test and reference sets of products. The cutaneous BA of acyclovir from the set of reference creams was substantially higher than from the set of test creams. Conclusions This research elucidates how differences in the composition or manufacturing of product formulations can alter Q3 attributes that modulate myriad aspects of topical product performance. The results demonstrate the importance of understanding the Q3 attributes of topical semisolid drug products, and of developing appropriate product characterization tests. The toolkit developed here can be utilized to guide topical product development, and to mitigate the risk of differences in product performance, thereby supporting a demonstration of bioequivalence (BE) for prospective topical generic products and reducing the reliance on comparative clinical endpoint BE studies.
Impact of P-glycoprotein on clopidogrel absorption Taubert, Dirk; Beckerath, Nicolas; Grimberg, Gundula ...
Clinical pharmacology and therapeutics,
November 2006, Letnik:
80, Številka:
5
Journal Article
Recenzirano
Objective
The antiplatelet activity of clopidogrel is characterized by considerable interindividual differences. Variable intestinal absorption is suggested to contribute to the inconsistencies in ...response. We tested the hypothesis that the intestinal efflux transporter P‐glycoprotein (P‐gp) limits the oral bioavailability of clopidogrel and that variance in the MDR1 gene encoding P‐gp predicts absorption variability.
Methods and Results
P‐gp‐mediated transport of clopidogrel was assessed by transflux, influx, and efflux experiments by use of Caco‐2 cells. Inhibition of P‐gp activity by different modulators increased the absorptive clopidogrel flux across Caco‐2 monolayers from 0.51 ± 0.19 pmol/cm2 (mean ± SD) at baseline by a maximum of 5‐ to 9‐fold (P < .001) and the intracellular accumulation from 0.99 ± 0.11 pmol/mg protein by a maximum of 2.5‐fold (P < .001) in response to 1‐μmol/L clopidogrel and decreased clopidogrel efflux to the level of passive diffusion. In 60 patients with coronary artery disease who underwent percutaneous coronary intervention, the peak plasma concentration (Cmax) and the total area under the plasma concentration‐time curve (AUC) of clopidogrel and its active metabolite after a single oral loading dose of 300, 600, or 900 mg were tested for correlation with the MDR1 genotype. In the 300‐mg and 600‐mg groups (but not in the 900‐mg group) Cmax and AUC values were lower in subjects homozygous for the MDR1 3435T variant compared with subjects with the 3435C/T and 3435C/C genotypes. After the 600‐mg loading dose, Cmax values (mean ± SD) of clopidogrel and its active metabolite in 3435T/T carriers were 13.3 ± 5.2 ng/mL and 2.5 ± 1.2 ng/mL, respectively, compared with 49.7 ± 41.6 ng/mL (P = .001) and 6.6 ± 3.6 ng/mL (P = .011), respectively, in 3435C/T and 3435C/C carriers; AUC values were 1502 ± 463 ng/mL × min for clopidogrel and 209 ± 99 ng/mL × min for its active metabolite in 3435T/T carriers compared with 7057 ± 5443 ng/mL × min (P = .0006) and 744 ± 541 ng/mL × min (P = .011), respectively, in 3435C/T and 3435C/C carriers.
Conclusions
Clopidogrel absorption and thereby active metabolite formation are diminished by P‐gp‐mediated efflux and are influenced by the MDR1 C3435T genotype.
Clinical Pharmacology & Therapeutics (2006) 80, 486–501; doi: 10.1016/j.clpt.2006.07.007
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