Metabolic alterations in the critically ill have been studied for more than a century, but the heterogeneity of the critically ill patient population, the varying duration and severity of the acute ...phase of illness, and the many confounding factors have hindered progress in the field. These factors may explain why management of metabolic alterations and related conditions in critically ill patients has for many years been guided by recommendations based essentially on expert opinion. Over the last decade, a number of randomized controlled trials have been conducted, providing us with important population-level evidence that refutes several longstanding paradigms. However, between-patient variation means there is still substantial uncertainty when translating population-level evidence to individuals. A cornerstone of metabolic care is nutrition, for which there is a multifold of published guidelines that agree on many issues but disagree on others. Using a series of nine questions, we provide a review of the latest data in this field and a background to promote efforts to address the need for international consistency in recommendations related to the metabolic care of the critically ill patient. Our purpose is not to replace existing guidelines, but to comment on differences and add perspective.
Background
The addition of calcium to resuscitation fluids is a common practice in horses, but studies evaluating the effects of calcium supplementation are limited. In healthy horses, decreases in ...heart rate and changes in serum electrolyte concentrations have been reported.
Hypothesis
Calcium gluconate administration at a rate of 0.4 mg/kg/min to eliminated endurance horses with metabolic problems will affect heart rate, gastrointestinal sounds, and serum electrolyte concentrations.
Animals
Endurance horses eliminated from the Tevis Cup 100‐mile (160 km) endurance ride for metabolic problems and requiring IV fluid therapy were eligible.
Methods
Sixteen horses were randomly assigned to receive 0.4 mg/kg/min of calcium (23% calcium gluconate solution) over 1 hour diluted in 10 L of a non‐calcium containing isotonic crystalloid (CAL group) or 10 L of a non‐calcium containing isotonic crystalloid (CON group). Staff members administering the fluids were blinded to treatment group. Blood samples were collected and physical examinations performed before and after treatment. Heart rates were recorded every 15 min during fluid administration. Data were compared using 2‐way analysis of variance (ANOVA) with repeated measures for continuous variables and Fisher's exact test for categorical variables.
Results
Calcium was associated with lower heart rates 45 min after starting the infusion (P = .002). Gastrointestinal sounds were less likely to improve in the calcium group compared with the control group (P = .005). An increase in plasma phosphorus concentration (P = .03) was associated with calcium administration.
Conclusions
Intravenous calcium supplementation to endurance horses eliminated from competition after development of metabolic problems may decrease heart rate but impairs improvement in gastrointestinal sounds.
Objective
To develop updated guidelines for the pharmacologic management of rheumatoid arthritis.
Methods
We developed clinically relevant population, intervention, comparator, and outcomes (PICO) ...questions. After conducting a systematic literature review, the Grading of Recommendations Assessment, Development and Evaluation (GRADE) approach was used to rate the certainty of evidence. A voting panel comprising clinicians and patients achieved consensus on the direction (for or against) and strength (strong or conditional) of recommendations.
Results
The guideline addresses treatment with disease‐modifying antirheumatic drugs (DMARDs), including conventional synthetic DMARDs, biologic DMARDs, and targeted synthetic DMARDs, use of glucocorticoids, and use of DMARDs in certain high‐risk populations (i.e., those with liver disease, heart failure, lymphoproliferative disorders, previous serious infections, and nontuberculous mycobacterial lung disease). The guideline includes 44 recommendations (7 strong and 37 conditional).
Conclusion
This clinical practice guideline is intended to serve as a tool to support clinician and patient decision‐making. Recommendations are not prescriptive, and individual treatment decisions should be made through a shared decision‐making process based on patients’ values, goals, preferences, and comorbidities.
A new model which comprehensively explains the working principles of contact-mode triboelectric nanogenerators (TENGs) based on Maxwell's equations is presented. Unlike previous models which are ...restricted to known simple geometries and derived using the parallel plate capacitor model, this model is generic and can be modified to a wide range of geometries and surface topographies. We introduce the concept of a distance-dependent electric field, a factor not taken into account in previous models, to calculate the current, voltage, charge, and power output under different experimental conditions. The versatility of the model is demonstrated for non-planar geometry consisting of a convex–concave surface. The theoretical results show excellent agreement with experimental TENGs. Our model provides a complete understanding of the working principles of TENGs, and accurately predicts the output trends, which enables the design of more efficient TENG structures.
BACKGROUND
Male factor and idiopathic infertility contribute significantly to global infertility, with abnormal testicular gene expression considered to be a major cause. Certain types of male ...infertility are caused by failure of the sperm to activate the oocyte, a process normally regulated by calcium oscillations, thought to be induced by a sperm-specific phospholipase C, PLCzeta (PLCζ). Previously, we identified a point mutation in an infertile male resulting in the substitution of histidine for proline at position 398 of the protein sequence (PLCζH398P), leading to abnormal PLCζ function and infertility.
METHODS AND RESULTS
Here, using a combination of direct-sequencing and mini-sequencing of the PLCζ gene from the patient and his family, we report the identification of a second PLCζ mutation in the same patient resulting in a histidine to leucine substitution at position 233 (PLCζH233L), which is predicted to disrupt local protein interactions in a manner similar to PLCζH398P and was shown to exhibit abnormal calcium oscillatory ability following predictive 3D modelling and cRNA injection in mouse oocytes respectively. We show that PLCζH233L and PLCζH398P exist on distinct parental chromosomes, the former inherited from the patient's mother and the latter from his father. Neither mutation was detected utilizing custom-made single-nucleotide polymorphism assays in 100 fertile males and females, or 8 infertile males with characterized oocyte activation deficiency.
CONCLUSIONS
Collectively, our findings provide further evidence regarding the importance of PLCζ at oocyte activation and forms of male infertility where this is deficient. Additionally, we show that the inheritance patterns underlying male infertility are more complex than previously thought and may involve maternal mechanisms.
High-throughput sequencing has enabled detailed insights into complex microbial environments, including the human gut microbiota. The accuracy of the sequencing data however, is reliant upon ...appropriate storage of the samples prior to DNA extraction. The aim of this study was to conduct the first MiSeq sequencing investigation into the effects of faecal storage on the microbiota, compared to fresh samples. Culture-based analysis was also completed.
Seven faecal samples were collected from healthy adults. Samples were separated into fresh (DNA extracted immediately), snap frozen on dry ice and frozen for 7 days at -80°C prior to DNA extraction or samples frozen at -80°C for 7 days before DNA extraction. Sequencing was completed on the Illumina MiSeq platform. Culturing of total aerobes, anaerobes and bifidobacteria was also completed.
No significant differences at phylum or family levels between the treatment groups occurred. At genus level only Faecalibacterium and Leuconostoc were significantly different in the fresh samples compared to the snap frozen group (p = 0.0298; p = 0.0330 respectively). Diversity analysis indicated that samples clustered based on the individual donor, rather than by storage group. No significant differences occurred in the culture-based analysis between the fresh, snap or -80°C frozen samples.
Using the MiSeq platform coupled with culture-based analysis, this study highlighted that limited significant changes in microbiota occur following rapid freezing of faecal samples prior to DNA extraction. Thus, rapid freezing of samples prior to DNA extraction and culturing, preserves the integrity of the microbiota.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Renal blood flow is reduced in patients with chronic respiratory failure caused by chronic obstructive pulmonary disease (COPD), and changes in renal hemodynamics are likely to be important in the ...pathogenesis of the edematous state of cor pulmonale. We therefore examined the hypothesis that this renal vasoconstriction is reversible by comparing the effects of oxygen therapy and the renal vasodilator dopamine on renal hemodynamics in both hypoxemic patients with COPD and those who were also hypercapnic. We assessed renal hemodynamics noninvasively with color-flow Doppler ultrasound. In order to validate the technique we recorded renal hemodynamics in a group of healthy volunteers before and during a dopamine infusion, and in a subgroup we simultaneously measured effective renal plasma flow (ERPF) with para-aminohippurate clearance. In the healthy volunteers there was a 22.5% rise in time-adjusted mean arterial velocity (Tamx) measured by Doppler compared with a 22% rise in ERPF with dopamine. This rise was significant (p < 0.05). In hypoxemic, normocapnic subjects Tamx rose by 25% with oxygen (p < 0.005), 20% with dopamine (p < 0.005), and 24% with both therapies. There was no significant change in aortic flow whether the subjects received air, oxygen, or dopamine (p = 0.77). In the hypercapnic patients there was no significant change in aortic or renal velocities while receiving oxygen or dopamine (p = 0.85 and 0.86). We conclude that color-flow Doppler velocity measurements can accurately detect changes in renal blood flow. Oxygen and dopamine are equipotent renal vasodilators in hypoxic COPD, but the effect is not additive.
Understanding the kinematics and triggers of a landslide is central to assessing the risk of a landslide. This understanding can be achieved through a robust instrumentation plan that addresses key ...factors such as meteorological conditions, groundwater conditions, and deformation trends and velocity. High-frequency landslide displacement measurements at multiple locations across a sliding mass allow for the evaluation of the impact of meteorological events in the short and long terms. Installation of a monitoring system that provides reliable and accurate high-frequency displacement data from multiple locations can be expensive, and thus, this approach is not commonly used. Single-frequency differential GNSS (dGNSS) provides a relatively low-cost alternative to achieve long-term monitoring goals at multiple locations within a landslide. Networks of single-frequency Geocube™ dGNSS units were installed at test sites at two slow-moving Canadian landslides: the Ten-mile landslide near Lillooet, BC, and the Chin Coulee landslide near Taber, AB. The Geocube system monitored surficial deformation every 60 s for the duration of the monitoring program (> 500 day) and achieved a precision in direct measurements characterized by a standard deviation of 10.5 mm or less. The quality of the collected data was compared to data provided by a high-end multi-frequency GMX 910 Leica GPS, installed at the Ripley landslide near Ashcroft, BC. The data collected from the Geocube systems revealed that displacement orientations and rates varied within each of the sliding masses. The application of multiple monitoring points provided a relatively low-cost method to evaluate the shape of the sliding shear surface and the causal factors driving movement at each site. A practical evaluation of cost-effective dGNSS systems that provide reliable information as required for enhanced understanding of landslide kinematics and the development of early warning systems is presented in this paper.
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