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1.
Tutulan-Cunita AC Mikoshi M Mizunuma M Hirata D Miyakawa T 《Genes to cells : devoted to molecular & cellular mechanisms》2005,10(5):409-420
Multidrug resistance ABC transporter Pdr5p of Saccharomyces cerevisiae is particularly important due to its ability to export a wide range of unrelated substrates. To clarify its function, we generated Pdr5p mutants by random mutagenesis and screened for mutants with altered drug specificity in vivo by using 5 drug compounds. Nine point mutations that caused significant changes in drug specificity distributed throughout the length of Pdr5p, namely, in the extracellular, transmembrane or cytoplasmic regions of the transporter. We then investigated their effects upon drug resistance, using 36 chemically related or distinct substrates. From this study, overall geometry of the Pdr5p was suggested to contribute in acquiring the enormous range of drug specificity. Based on their ability to inhibit the growth of the mutant strains, the 36 tested drugs were classified into: drugs to which the mutants responded differently (Group 1), drugs to which all the mutants showed sensitivity (Group 2), and drugs to which all the mutants exhibited resistance (Group 3). The ability of the compounds to be partitioned to the plasma membrane seemed an important factor for recognition by Pdr5p. 相似文献
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Iulia Raiu Raluca Lupuoru Alina Popescu Ioan Sporea Adrian Goldi Mirela Dnil Bogdan Miuescu Tudor Moga Andreea Barbulescu Roxana irli 《Medicine》2022,101(45)
Acute upper gastrointestinal bleeding (UGIB) is a typical medical emergency, with an incidence of 84 to 160 cases per 100,000 individuals and a mortality rate of approximately 10%. This study aimed to identify all cases of UGIB hospitalized in a tertiary gastroenterology department, to identify possible predictive factors involved in rebleeding and mortality, potential associations between different elements and the severity of bleeding, and the differences between the upper digestive hemorrhage due to nonvariceal and variceal bleeding. This was an observational, retrospective study of patients with UGIB admitted to the tertiary Department of Gastroenterology between January 2013 and December 2020. A total of 1499 patients were enrolled in the study. One thousand four hundred and ninety-nine patients were hospitalized for 7 years with active upper digestive hemorrhage, 504 variceal bleeding, and 995 nonvariceal bleeding. When comparing variceal with nonvariceal bleeding, in nonvariceal bleeding, the mean age was higher, similar sex, higher mortality rate, higher rebleeding rate, and higher hemorrhagic shock rate. Endoscopy treatment was also performed more frequently in variceal bleeding than in nonvariceal bleeding. Severe anemia was found more frequently in patients with variceal bleeding. The mortality rate was 10% in the entire study group, which was not significantly different between the 2 batches. However, the rebleeding rate is higher in patients with variceal gastrointestinal bleeding. 相似文献
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Dina Almaatani Andreea Zurbau Farnaz Khoshnevisan Robert H. J. Bandsma Tauseef A. Khan John L. Sievenpiper Meta Van Den Heuvel 《Maternal & child nutrition》2023,19(1)
In the extended UNICEF framework of early childhood nutrition, parents'' stress is associated with parental feeding style. However, no comprehensive review has examined the association between parents'' stress and feeding styles and practices. The objective of our review was to synthesise the current literature examining the association between parents'' stress and their feeding practices and/or styles, among parents of children ≤ 5 years old. We searched; MEDLINE, EMBASE, PSYCHINFO and CINAHL from 2019 to 2021. Two investigators independently extracted relevant data and assessed the study quality and the certainty of evidence. Data were pooled using generic inverse variance with fixed effects (<5 comparisons) or random effects (≥5 comparisons) and expressed as correlation coefficients with 95% confidence intervals (CI). Between study heterogeneity was assessed using Cochran''s Q and quantified with I 2. We identified 6 longitudinal and 11 cross‐sectional studies, of which 4 studies provided sufficient data to be pooled. A very small correlation between general stress and restrictive feeding practices was observed (r = 0.06 [95% CI: 0.01−0.12]; no substantial heterogeneity (I 2 = 0.00%, P Q < 0.85, very low certainty). No correlation between general stress and feeding pressure was identified (r = 0.06 [95% CI: −0.02 to 0.15]). Results showed that both general and parenting stress were associated with suboptimal breastfeeding practices and unresponsive feeding styles. Conclusion: This study demonstrated a low‐to‐moderate quality of literature for the inclusion of parents'' stress in the extended UNICEF care model of child nutrition. Future research needs to explore this relationship longitudinally and in ethnic diverse populations to inform tailored interventions that promote responsive feeding practices. 相似文献
4.
Relu Coco Beatrice Mahler Adina Turcu-Stiolica Alexandru Stoichi Andreea Ghinet Elena-Silvia Shelby Laureniu Camil Bohîlea 《Viruses》2022,14(6)
Our study objective was to construct models using 20 routine laboratory parameters on admission to predict disease severity and mortality risk in a group of 254 hospitalized COVID-19 patients. Considering the influence of confounding factors in this single-center study, we also retrospectively assessed the correlations between the risk of death and the routine laboratory parameters within individual comorbidity subgroups. In multivariate regression models and by ROC curve analysis, a model of three routine laboratory parameters (AUC 0.85; 95% CI: 0.79–0.91) and a model of six laboratory factors (AUC 0.86; 95% CI: 0.81–0.91) were able to predict severity and mortality of COVID-19, respectively, compared with any other individual parameter. Hierarchical cluster analysis showed that inflammatory laboratory markers grouped together in three distinct clusters including positive correlations: WBC with NEU, NEU with neutrophil-to-lymphocyte ratio (NLR), NEU with systemic immune-inflammation index (SII), NLR with SII and platelet-to-lymphocyte ratio (PLR) with SII. When analyzing the routine laboratory parameters in the subgroups of comorbidities, the risk of death was associated with a common set of laboratory markers of systemic inflammation. Our results have shown that a panel of several routine laboratory parameters recorded on admission could be helpful for early evaluation of the risk of disease severity and mortality in COVID-19 patients. Inflammatory markers for mortality risk were similar in the subgroups of comorbidities, suggesting the limited effect of confounding factors in predicting COVID-19 mortality at admission. 相似文献
5.
Ionela Andreea Neacsu Sorina-Alexandra Leau Stefania Marin Alina Maria Holban Bogdan-Stefan Vasile Adrian-Ionut Nicoara Vladimir Lucian Ene Coralia Bleotu Mdlina Georgiana Albu Kaya Anton Ficai 《Materials》2021,14(5)
Microbial infections associated with skin diseases are frequently investigated since they impact on the progress of pathology and healing. The present work proposes the development of freeze-dried, glutaraldehyde cross-linked, and non-cross-linked biocomposite dressings with a porous structure, which may assist the reepithelization process through the presence of collagen and carboxymethylcellulose, along with a therapeutic antimicrobial effect, due to silver nanoparticles (AgNPs) addition. Phisyco-chemical characterization revealed the porous morphology of the obtained freeze-dried composites, the presence of high crystalline silver nanoparticles with truncated triangular and polyhedral morphologies, as well as the characteristic absorption bands of collagen, silver, and carboxymethylcellulose. In vitro tests also assessed the stability, functionality, and the degradability rate of the obtained wound-dressings. Antimicrobial assay performed on Gram-negative (Escherichia coli), Gram-positive (Staphyloccocus aureus) bacteria, and yeast (Candida albicans) models demonstrated that composite wound dressings based on collagen, carboxymethylcellulose, and AgNPs are suitable for skin lesions because they prevent the risk of infection and have prospective wound healing capacity. Moreover, the cell toxicity studies proved that the obtained materials can be used in long time treatments, with no cytotoxic effects. 相似文献
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Fluid shear stress generated by blood flowing over the endothelium is a major determinant of arterial tone, vascular remodeling, and atherogenesis. Nitric oxide (NO) produced by endothelial NO synthase (eNOS) plays an essential role in regulation of vascular function and structure by blood flow, but the molecular mechanisms that transduce mechanical force to eNOS activation are not well understood. In this study, we found that laminar flow (shear stress=12 dyne/cm2) rapidly activates vascular endothelial growth factor receptor 2 (VEGFR2) in a ligand-independent manner and leads to eNOS activation in cultured endothelial cells. Flow-stimulated VEGFR2 recruits phosphoinositide 3-kinase and mediates activation of Akt and eNOS. Inhibiting VEGFR2 kinase with selective inhibitors blocks flow-induced activation of Akt and eNOS and production of NO. Decreasing VEGFR2 expression with antisense VEGFR2 oligonucleotides significantly attenuates activation of Akt and eNOS. Furthermore, Src kinases are involved in flow-stimulated VEGFR2 because inhibiting Src kinases by PP2, a selective inhibitor for Src kinases, abolishes flow-induced VEGFR2 tyrosine phosphorylation and downstream signaling. Finally, we show that inhibiting VEGFR2 kinase significantly reduces flow-mediated NO-dependent arteriolar dilation in vivo. These data identify VEGFR2 as a key mechanotransducer that activates eNOS in response to blood flow. 相似文献
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