Hyponatremia in cirrhosis is defined as a serum sodium level ≤130 mEq/L and occurs in approximately 22% of patients with cirrhosis. The appearance of hyponatremia in patients with cirrhosis portends ...a poor prognosis before liver transplantation (LT), independent of the Model for End‐Stage Liver Disease (MELD) score. With the development of the MELD‐sodium score, the management of hyponatremia has become more relevant than ever before. Overcorrection of hyponatremia before LT or perioperatively can lead to the devastating neurologic condition known as osmotic demyelination syndrome, which is often irreversible and fatal. Therefore, the most important tenet of hyponatremia is to avoid correcting the serum sodium by ≥8 mEq/L in a 24‐hour period. Treatment of hyponatremia is highly challenging. The vast majority of patients with cirrhosis have chronic hypervolemic hyponatremia. Fluid restriction increases serum sodium levels, but tolerance and compliance are significant barriers. Diuretic withdrawal is helpful but contributes to worsening fluid overload. There are limited data to support use of intravenous concentrated albumin solutions. The use of the arginine vasopressin antagonists (“vaptans”) is contentious; however, they may have a limited role. Risk factors for intraoperative overcorrection of serum sodium include increased utilization of packed red blood cell and fresh frozen plasma transfusions, which are often unavoidable. Intraoperative management is evolving, and more data are needed in regard to the use of sodium‐reduced continuous venovenous hemofiltration and the use of trishydroxymethylaminomethane (Tris) to avoid excess sodium rebound. A thorough discussion of the current treatment options before and during LT is given in this review.
This article studies the spatial evolution of mergers and acquisitions (M&A) in Canada to investigate the path dependence process of corporate control geography. The analysis is based on network ...analysis and quadratic assignment procedure (QAP) regression models for transactions of more than C$5 million between 1994 and 2016. The results indicate that the geography of economic decision-making is highly path-dependent, and that Toronto, Montreal, Vancouver, and Calgary are the main destinations of M&As. However, Winnipeg and Guelph have emerged as new power centers.
In principle, evolutionary outcomes could be largely predicted if all of the relevant physicochemical variants of a particular protein function under selection were known and integrated into an ...appropriate physiological model. We have tested this principle by generating a family of variants of the tetracycline resistance protein TetX2 and identified the physicochemical properties most correlated with organismal fitness. Surprisingly, small changes in the K ₘ₍MCN₎, less than twofold, were sufficient to produce highly successful adaptive mutants over clinically relevant drug concentrations. We then built a quantitative model directly relating the in vitro physicochemical properties of the mutant enzymes to the growth rates of bacteria carrying a single chromosomal copy of the tet(X2) variants over a wide range of minocycline (MCN) concentrations. Importantly, this model allows the prediction of enzymatic properties directly from cellular growth rates as well as the physicochemical-fitness landscape of TetX2. Using experimental evolution and deep sequencing to monitor the allelic frequencies of the seven most biochemically efficient TetX2 mutants in 10 independently evolving populations, we showed that the model correctly predicted the success of the two most beneficial variants tet(X2) T₂₈₀A and tet(X2) N₃₇₁I. The structure of the most efficient variant, TetX2 T₂₈₀A, in complex with MCN at 2.7 Å resolution suggests an indirect effect on enzyme kinetics. Taken together, these findings support an important role for readily accessible small steps in protein evolution that can, in turn, greatly increase the fitness of an organism during natural selection.
Hepatorenal syndrome (HRS)-acute kidney injury (HRS-AKI) is a specific type of kidney injury seen in patients with cirrhosis and ascites and is associated with high mortality and morbidity. It is ...characterized by rapid deterioration of renal function due to reduced renal blood flow secondary to portal hypertensive splanchnic and systemic vasodilation. Early diagnosis and treatment of HRS-AKI are associated with greater likelihood of improvement in renal function, lower need for dialysis, and better post-transplant outcomes.
This review discusses the diagnostic criteria for HRS-AKI, which has undergone several key changes over the last decade, with an aim to secure an early diagnosis and aid swift treatment initiation. Additionally, this review outlines the current treatment paradigms for HRS-AKI.
In the last 20 years, there have been several advances in understanding the pathophysiology and natural course of HRS-AKI. These have led to critical changes in its definition and diagnostic algorithm. However, prognosis of HRS-AKI remains dismal with no significant improvement in HRS-AKI reversal or HRS-related mortality over this time. We discuss several gaps in the current understanding and management of HRS-AKI that will benefit from further research.
DNA methylation (DNAm) is one of the most studied epigenetic modifications. DNAm has emerged as a key biological mechanism and biomarkers to test associations between environmental exposure and ...outcomes in epidemiological studies. Although previous studies have focused on associations between DNAm and either exposure/outcomes, it is useful to test for mediation of the association between exposure and outcome by DNAm. The purpose of this scoping review is to introduce the methodological essence of statistical mediation analysis and to examine emerging epidemiological research applying mediation analyses. We conducted this scoping review for published peer-reviewed journals on this topic using online databases (PubMed, Scopus, Cochrane, and CINAHL) ending in December 2020. We extracted a total of 219 articles by initial screening. After reviewing titles, abstracts, and full texts, a total of 69 articles were eligible for this review. The breakdown of studies assigned to each category was 13 for smoking (18.8%), 8 for dietary intake and famine (11.6%), 6 for other lifestyle factors (8.7%), 8 for clinical endpoints (11.6%), 22 for environmental chemical exposures (31.9%), 2 for socioeconomic status (SES) (2.9%), and 10 for genetic factors and race (14.5%). In this review, we provide an exposure-wide summary for the mediation analysis using DNAm levels. However, we found heterogenous methods and interpretations in mediation analysis with typical issues such as different cell compositions and tissue-specificity. Further accumulation of evidence with diverse exposures, populations and with rigorous methodology will be expected to provide further insight in the role of DNAm in disease susceptibility.
Objective
This study aims to evaluate the effects of exposure time and irradiance on the dentin bonding properties (microtensile bond strength (μTBS) and nanoleakage (NL)) of the Clearfil Universal ...Bond Quick (CUQ) adhesive and Scotchbond Universal Adhesive (SBU) immediately and after 2 years of water storage.
Material and methods
Hence, 128 human molars were randomly assigned to 16 groups based on adhesive strategy, irradiance/exposure times, and storage time for each universal adhesive tested. The adhesives were applied using the etch-and-rinse and self-etch strategies and were light-cured using four different irradiance/exposure times: 1400 mW/cm
2
for 5 s (1400 × 5), 1400 mW/cm
2
for 10 s (1400 × 10), 3200 mW/cm
2
for 5 s (3200 × 5), and 3200 mW/cm
2
for 10 s (3200 × 10). Then, each sample was restored and sectioned into a resin-dentin bonded stick to be tested for μTBS and NL (immediately and after 2 years of water storage). The mean μTBS and NL of all resin-dentin bonded sticks from the same hemi-tooth (factor time) were statistically analyzed using a three-way ANOVA and Tukey’s test (
a
= 0.05).
Results
Despite a significant decrease in the μTBS values for all groups after 2 years of water storage, the 3200 × 5 group showed higher μTBS values, whereas the 3200 × 10 group showed lower μTBS values for both universal adhesives tested. Although a significant increase in the NL values was observed for all groups after 2 years of water storage, the 3200 × 10 group showed higher NL values than the other groups (
p
< 0.001).
Conclusion
Results indicate that light-curing the adhesive layer with 14–16 J/cm
2
led to an improvement in the stability of the resin-dentin adhesive interface. A longer exposure time (10 s) coupled with a higher irradiance (3200 mW/cm
2
) resulted in a greater degree of degradation of the adhesive interface.
Clinical significance
To guarantee better stability of the adhesive interface, clinicians could be preferred a light-cured universal adhesive layer with 14–16 J/cm
2
. Higher irradiances should be avoided.
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