This review deals with the adaptive mechanisms that plants can implement to cope with the challenge of salt stress. Plants tolerant to NaCl implement a series of adaptations to acclimate to salinity, ...including morphological, physiological and biochemical changes. These changes include increases in the root/canopy ratio and in the chlorophyll content in addition to changes in the leaf anatomy that ultimately lead to preventing leaf ion toxicity, thus maintaining the water status in order to limit water loss and protect the photosynthesis process. Furthermore, we deal with the effect of salt stress on photosynthesis and chlorophyll fluorescence and some of the mechanisms thought to protect the photosynthetic machinery, including the xanthophyll cycle, photorespiration pathway, and water-water cycle. Finally, we also provide an updated discussion on salt-induced oxidative stress at the subcellular level and its effect on the antioxidant machinery in both salt-tolerant and salt-sensitive plants. The aim is to extend our understanding of how salinity may affect the physiological characteristics of plants.
The aim of this study was to analyze the mortality and predictors of 30-day mortality among hospitalized patients with Pseudomonas aeruginosa urinary tract infection (PAUTI) and the impact of ...antibiotic treatment on survival.
Patients admitted to our hospital with PAUTI or those diagnosed of PAUTI during hospitalization for other disease between September 2012 and September 2014 were included. Repeated episodes from the same patient were excluded. Database with demographic, clinical and laboratory ítems was created. Empirical and definitive antibiotic therapy, antimicrobial resistance and all-cause mortality at 30 and 90 days were included.
62 patients were included, with a mean age of 75 years. 51% were male. Mortality was 17.7% at 30 days and 33.9% at 90 days. Factors associated with reduced survival at 30 days were chronic liver disease with portal hypertension (P<0,01), diabetes mellitus (P = 0,04) chronic renal failure (P = 0,02), severe sepsis or septic shock (P<0,01), Charlson index > 3 (P = 0.02) and inadequated definitive antibiotic treatment (P<0,01). Independent risk factors for mortality in multivariate analysis were advanced chronic liver disease (HR 77,4; P<0,01), diabetes mellitus (HR 3,6; P = 0,04), chronic renal failure (HR 4,1; P = 0,03) and inadequated definitive antimicrobial treatment (HR 6,8; P = 0,01).
PAUTI are associated with high mortality in hospitalized patients, which increases significantly in those with severe comorbidity such as chronic renal failure, advanced liver disease or diabetes mellitus. Inadequated antibiotic treatment is associated with poor outcome, which remarks the importance of adjusting empirical antibiotic treatment based on the microbiological susceptibility results.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Motivation: Dynamic simulations of systems with biologically relevant sizes and time scales are critical for understanding macromolecular functioning. Coarse-grained representations combined with ...normal mode analysis (NMA) have been established as an alternative to atomistic simulations. The versatility and efficiency of current approaches normally based on Cartesian coordinates can be greatly enhanced with internal coordinates (IC).
Results: Here, we present a new versatile tool chest to explore conformational flexibility of both protein and nucleic acid structures using NMA in IC. Consideration of dihedral angles as variables reduces the computational cost and non-physical distortions of classical Cartesian NMA methods. Our proposed framework operates at different coarse-grained levels and offers an efficient framework to conduct NMA-based conformational studies, including standard vibrational analysis, Monte-Carlo simulations or pathway exploration. Examples of these approaches are shown to demonstrate its applicability, robustness and efficiency.
Contact:
pablo@chaconlab.org
Supplementary Information:
Supplementary data are available at Bioinformatics online.
Abstract Background Malnutrition is common in hospitalized heart failure (HF) patients and predicts adverse outcomes. The relationship between nutritional status and outcomes in HF has been partially ...studied. Our aim was to determine the relationship between the nutritional status and the long-term prognosis in patients hospitalized for acute HF. Methods We analyzed 145 patients admitted consecutively to a cardiology department for acute HF. Nutritional status was measured with the CONUT method, a validated scale based on laboratory testing (albumin; cholesterol; lymphocytes) during hospitalization. Patients were classified as normal, mildly, moderately or severely malnourished, and followed in a HF clinic. Results The mean aged of the population was 69.6 years and 61% of patients were men, 54 had previous HF hospitalization (37%), 112 had hypertension (77%), 67 were diabetic (46%) and 135 had class III or IV NYHA (93%). Forty eight patients (33%) had normal nutritional status, 75 were mildly malnourished (52%), and 22 were moderately or severely malnourished (15%). Age, sex, hypertension, diabetes mellitus, or NYHA class among the three groups were not statistically different. ProBNP was directly correlated with the nutritional status. After a mean follow-up of 326 days, 27 had a HF hospitalization (19%) and 61 (42.1%) had a hospitalization not related to HF. The analysis by Kaplan-Meier curves and log rank test showed that these differences were statistically significant. Conclusion Malnutrition is common in patients hospitalized for HF. It seems to be a mediator of disease progression and determines a poor prognosis especially in advanced stages.
Background
During COVID‐19 pandemic in Spain, elective procedures were canceled or postponed, mainly due to health care systems overwhelming.
Objective
The objective of this study was to evaluate the ...consequences of interrupting invasive procedures in patients with chronic cardiac diseases due to the COVID‐19 outbreak in Spain.
Methods
The study population is comprised of 2,158 patients that were pending on elective cardiac invasive procedures in 37 hospitals in Spain on the 14th of March 2020, when a state of alarm and subsequent lockdown was declared in Spain due to the COVID‐19 pandemic. These patients were followed‐up until April 31th.
Results
Out of the 2,158 patients, 36 (1.7%) died. Mortality was significantly higher in patients pending on structural procedures (4.5% vs. 0.8%, respectively; p < .001), in those >80 year‐old (5.1% vs. 0.7%, p < .001), and in presence of diabetes (2.7% vs. 0.9%, p = .001), hypertension (2.0% vs. 0.6%, p = .014), hypercholesterolemia (2.0% vs. 0.9%, p = .026) Correction added on December 23, 2020, after first online publication: as per Dr. Moreno's request changes in p‐values were made after original publication in ., chronic renal failure (6.0% vs. 1.2%, p < .001), NYHA > II (3.8% vs. 1.2%, p = .001), and CCS > II (4.2% vs. 1.4%, p = .013), whereas was it was significantly lower in smokers (0.5% vs. 1.9%, p = .013). Multivariable analysis identified age > 80, diabetes, renal failure and CCS > II as independent predictors for mortality.
Conclusion
Mortality at 45 days during COVID‐19 outbreak in patients with chronic cardiovascular diseases included in a waiting list due to cancellation of invasive elective procedures was 1.7%. Some clinical characteristics may be of help in patient selection for being promptly treated when similar situations happen in the future.
Human milk is the biological fluid with the highest exosome amount and is rich in microRNAs (miRNAs). These are key regulators of gene expression networks in both normal physiologic and disease ...contexts, miRNAs can influence many biological processes and have also shown promise as biomarkers for disease. One of the key aspects in the regeneration of the nervous system is that there are practically no molecules that can be used as potential drugs. In the first weeks of lactation, we know that human breast milk must contain the mechanisms to transmit molecular and biological information for brain development. For this reason, our objective is to identify new modulators of the nervous system that can be used to investigate neurodevelopmental functions based on miRNAs. To do this, we collected human breast milk samples according to the time of delivery and milk states: mature milk and colostrum at term; moderate and very preterm mature milk and colostrum; and late preterm mature milk. We extracted exosomes and miRNAs and realized the miRNA functional assays and target prediction. Our results demonstrate that miRNAs are abundant in human milk and likely play significant roles in neurodevelopment and normal function. We found 132 different miRNAs were identified across all samples. Sixty-nine miRNAs had significant differential expression after paired group comparison. These miRNAs are implicated in gene regulation of dopaminergic/glutamatergic synapses and neurotransmitter secretion and are related to the biological process that regulates neuron projection morphogenesis and synaptic vesicle transport. We observed differences according to the delivery time and with less clarity according to the milk type. Our data demonstrate that miRNAs are abundant in human milk and likely play significant roles in neurodevelopment and normal function.
Cellular senescence and low-grade inflammation favor the acceleration of aging. The liver is an essential metabolic organ because changes related to its function are related to age-related diseases. ...The objective of this study was to evaluate the effects of maraviroc (MVC) and/or rapamycin (RAPA) on liver tissue in an experimental model of frailty syndrome in mice, since MVC and RAPA are two molecules able to decrease CCR5 expression, which is overexpressed in patients with frailty. Methods: Eighty male homozygous IL10KO mice were randomly assigned to one of 4 groups (n = 20): i) IL10KO group; ii) MVC group, iii) RAPA group, and iv) MVC-RAPA group. Liver samples were analyzed. Gene expression quantification and western blotting were also performed. The proinflammatory cytokines IL-6 and IL-18 were decreased in MVC and MVC/RAPA groups, IL-12 was decreased in RAPA and MVC/RAPA groups and TNF-α was decreased in all therapeutic groups. P21 was decreased in RAPA and MVC/RAPA groups, Galactosidase beta-1, was also significantly reduced in all therapeutic groups, as were NF-kB1, NF-kB2 and STAT3. In all groups, mTOR and CCL5 were significantly reduced. CCR5 expression was decreased in the MVC and MVC/RAPA groups. Conclusion: MVC and RAPA may protect against some factors involved in liver aging. More studies will be necessary to verify their clinical applications.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
The general transcription factor IID (TFIID) plays a central role in the initiation of RNA polymerase II (Pol II)-dependent transcription by nucleating pre-initiation complex (PIC) assembly at the ...core promoter. TFIID comprises the TATA-binding protein (TBP) and 13 TBP-associated factors (TAF1-13), which specifically interact with a variety of core promoter DNA sequences. Here we present the structure of human TFIID in complex with TFIIA and core promoter DNA, determined by single-particle cryo-electron microscopy at sub-nanometre resolution. All core promoter elements are contacted by subunits of TFIID, with TAF1 and TAF2 mediating major interactions with the downstream promoter. TFIIA bridges the TBP-TATA complex with lobe B of TFIID. We also present the cryo-electron microscopy reconstruction of a fully assembled human TAF-less PIC. Superposition of common elements between the two structures provides novel insights into the general role of TFIID in promoter recognition, PIC assembly, and transcription initiation.
Normal mode analysis (NMA) in internal (dihedral) coordinates naturally reproduces the collective functional motions of biological macromolecules. iMODS facilitates the exploration of such modes and ...generates feasible transition pathways between two homologous structures, even with large macromolecules. The distinctive internal coordinate formulation improves the efficiency of NMA and extends its applicability while implicitly maintaining stereochemistry. Vibrational analysis, motion animations and morphing trajectories can be easily carried out at different resolution scales almost interactively. The server is versatile; non-specialists can rapidly characterize potential conformational changes, whereas advanced users can customize the model resolution with multiple coarse-grained atomic representations and elastic network potentials. iMODS supports advanced visualization capabilities for illustrating collective motions, including an improved affine-model-based arrow representation of domain dynamics. The generated all-heavy-atoms conformations can be used to introduce flexibility for more advanced modeling or sampling strategies. The server is free and open to all users with no login requirement at http://imods.chaconlab.org.
Therapeutic interventions to improve the efficacy of whole-body cooling for hypoxic-ischemic encephalopathy (HIE) are desirable. Topiramate has been effective in reducing brain damage in experimental ...studies. However, in the clinical setting information is limited to a small number of feasibility trials. We launched a randomized controlled double-blinded topiramate/placebo multicenter trial with the primary objective being to reduce the antiepileptic activity in cooled neonates with HIE and assess if brain damage would be reduced as a consequence.
Neonates were randomly assigned to topiramate or placebo at the initiation of hypothermia. Topiramate was administered via a nasogastric tube. Brain electric activity was continuously monitored. Topiramate pharmacokinetics, energy-related and Krebs' cycle intermediates, and lipid peroxidation biomarkers were determined using liquid chromatography-mass spectrometry and MRI for assessing brain damage.
Out of 180 eligible patients 110 were randomized, 57 (51.8%) to topiramate and 53 (48.2%) to placebo. No differences in the perinatal or postnatal variables were found. The topiramate group exhibited less seizure burden in the first 24 h of hypothermia (topiramate, n = 14 25.9% vs. placebo, n = 22 42%); needed less additional medication, and had lower mortality (topiramate, n = 5 9.2% vs. placebo, n = 10 19.2%); however, these results did not achieve statistical significance. Topiramate achieved a therapeutic range in 37.5 and 75.5% of the patients at 24 and 48 h, respectively. A significant association between serum topiramate levels and seizure activity (p < 0.016) was established. No differences for oxidative stress, energy-related metabolites, or MRI were found.
Topiramate reduced seizures in patients achieving therapeutic levels in the first hours after treatment initiation; however, they represented only a part of the study population. Our results warrant further studies with higher loading and maintenance dosing of topiramate.
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