Selecting an appropriate target population is essential to maximize survival benefits of anticoagulant therapy against sepsis. Our meta-analysis of three populations with sepsis and nationwide ...observational study in Japan showed that anticoagulants improved mortality only in sepsis-induced disseminated intravascular coagulation (DIC) but not in non-DIC. This divergent effect was physiologically explained by host-protective immune responses of local thrombosis, which are mandatory in the early stage of sepsis. Meanwhile, the lack of definitive evidence for survival benefit provided by several trials of sepsis-induced DIC indicated that this condition was probably not the best target of anticoagulants. Our multicenter cohort study including only patients with sepsis-induced DIC showed a survival benefit from recombinant thrombomodulin only in patients with high disease severity. Thus, we believe that the population with sepsis and DIC and high disease severity is the optimal target for anticoagulant therapy. Anticoagulant therapy without appropriate target selection should be avoided because of the increased risk of bleeding with no survival benefit.
ESSENTIALS: Most anticoagulant therapy has failed to demonstrate a survival benefit in the overall sepsis population. We conducted separate meta-analyses of anticoagulant therapy in three different ...populations. Survival benefit was observed only in the septic disseminated intravascular coagulation (DIC) population. Further randomized controlled trials should focus on specific populations with septic DIC.
Although many preclinical trials have indicated the effectiveness and safety of anticoagulant therapy as an adjuvant therapy against sepsis, there is little evidence to support its effectiveness to reduce mortality in the overall population with sepsis in clinical situations. However, several studies suggested that specific anticoagulant therapy may potentially reduce mortality in patients with sepsis-induced disseminated intravascular coagulation (DIC).
We investigated whether the survival benefit of anticoagulant therapy might pertain to the coagulopathic population with sepsis.
We conducted separate meta-analyses of randomized controlled trials for anticoagulant therapy in three different populations: (i) overall population with sepsis, (ii) population with sepsis-induced coagulopathy, and (iii) population with sepsis-induced DIC. We searched MEDLINE, Scopus, and the Cochrane Central Register of Controlled Trials comparing anticoagulant therapy with placebo or no intervention in sepsis patients. We measured all-cause mortality as the primary outcome and bleeding complications as the secondary outcome.
We analyzed 24 trials enrolling 14 767 patients. There were no significant reductions in mortality in the overall sepsis population and the population with sepsis-induced coagulopathy. Otherwise, we observed significant reductions in mortality (risk ratio 0.72, 95% confidence interval 0.62-0.85) in the population with sepsis-induced DIC. As adverse events, bleeding complications tended to increase similarly with anticoagulant therapy in all three populations.
Although associated with an increased risk of bleeding, anticoagulant therapy resulted in no survival benefits in the overall sepsis population and even the population with sepsis-induced coagulopathy; beneficial effects on mortality were observed only in the population with sepsis-induced DIC.
The purpose of this study was to clarify the time course of the viscoelasticity of gastrocnemius medialis muscle and tendon after stretching. In 11 male participants, displacement of the myotendinous ...junction on the gastrocnemius medialis muscle was measured ultrasonographically during the passive dorsiflexion test, in which the ankle was passively dorsiflexed at a speed of 1°/s to the end of the range of motion (ROM). Passive torque, representing resistance to stretch, was also measured using an isokinetic dynamometer. On five different days, passive dorsiflexion tests were performed before and 0, 15, 30, 60 or 90 min after stretching, which consisted of dorsiflexion to end ROM and holding that position for 1 min, five times. As a result, end ROM was significantly increased at 0, 15 and 30 min (P<0.05 each) after stretching as compared with each previous value. Passive torque at end ROM was also significantly increased after stretching. Although the stiffness of the muscle–tendon unit was significantly decreased immediately after stretching (P<0.05), this shift recovered within 15 min. These results showed that the retention time of the effect of stretching on viscoelasticity of the muscle–tendon unit was shorter than the retention time of the effect of stretching on end ROM.
The mechanisms by which the diffusion rate in the plasma membrane (PM) is regulated remain unresolved, despite their importance in spatially regulating the reaction rates in the PM. Proposed models ...include entrapment in nanoscale noncontiguous domains found in PtK2 cells, slow diffusion due to crowding, and actin-induced compartmentalization. Here, by applying single-particle tracking at high time resolutions, mainly to the PtK2-cell PM, we found confined diffusion plus hop movements (termed "hop diffusion") for both a nonraft phospholipid and a transmembrane protein, transferrin receptor, and equal compartment sizes for these two molecules in all five of the cell lines used here (actual sizes were cell dependent), even after treatment with actin-modulating drugs. The cross-section size and the cytoplasmic domain size both affected the hop frequency. Electron tomography identified the actin-based membrane skeleton (MSK) located within 8.8 nm from the PM cytoplasmic surface of PtK2 cells and demonstrated that the MSK mesh size was the same as the compartment size for PM molecular diffusion. The extracellular matrix and extracellular domains of membrane proteins were not involved in hop diffusion. These results support a model of anchored TM-protein pickets lining actin-based MSK as a major mechanism for regulating diffusion.
The purpose of this study was to clarify the temporal course of stiffness in the muscle-tendon unit after stretching. In 11 male participants, displacement of the myotendinous junction on the ...gastrocnemius medialis muscle was measured ultrasonographically during the passive-dorsiflexion test, with the ankle was passively dorsiflexed at 1 °/s to the end of the range of motion. Passive torque, representing resistance to stretch, was also measured using an isokinetic dynamometer. On 4 different days, passive-dorsiflexion tests were performed before and immediately, 5, 10 or 15 min after stretching, which comprised dorsiflexion to end range of motion and holding that position for 1 min, 5 times. As a result, end range of motion and passive torque at end range of motion were significantly increased after stretching (P<0.05) as compared with each previous value. Although stiffness of the muscle-tendon unit was significantly decreased immediately and 5 min after stretching (P<0.05), this change recovered within 10 min. These results suggest that static stretching for 5 min results in significantly increased range of motion over 30 min, but significant decreases in stiffness of the muscle-tendon unit returned to baseline levels within 5-10 min.
The purpose of this study was to identify changes in ankle range of motion and passive mechanical properties of the muscle-tendon unit after dynamic stretching. 12 healthy subjects participated in ...this study. Displacement of the muscle-tendon junction was measured using ultrasonography while the ankle was passively dorsiflexed at 1°/sec to its maximal dorsiflexion angle. Passive torque was also measured using an isokinetic dynamometer. Measurements were conducted pre-intervention, immediately after the intervention and 5, 10, 15 and 30 min post-intervention. The dynamic stretching consisted of four 30-s periods of ankle dorsiflexion and plantarflexion. Ankle range of motion was significantly increased immediately (from 18.3±1.8° to 21.4±1.7°) and 10 min (20.9±1.9°) after dynamic stretching, but this change disappeared within 15 min. However, stiffness of the muscle-tendon unit and displacement of the muscle-tendon junction at the submaximal dorsiflexion angle did not differ between the experimental conditions. These results demonstrate that dynamic stretching by contracting an antagonist muscle group increases ankle range of motion temporarily without changing the passive mechanical properties of the muscle-tendon unit. The increased range of motion of the ankle after dynamic stretching might be caused by enhanced stretch tolerance.
Summary
The associations between mid-femoral cross-sectional geometry and exercise characteristics were investigated in female athletes. The effects on bone geometry for weight-bearing sports with ...low-to-high-impact were greater than those for non-impact weight-bearing sports, whereas low-impact or high-strain-magnitude/low-strain-rate sports had less of an effect on bone geometry compared with higher-impact sports.
Introduction
Many previous studies have investigated tibial geometry in athletes; however, few studies have examined the associations between femoral cross-sectional geometry and exercise characteristics. The aim of this study was to investigate these relationships using magnetic resonance imaging (MRI) at the femoral mid-shaft.
Methods
One hundred and fifty-three female elite athletes, aged 18–34 years, were classified into five groups based on the characteristics of their sports. Sports were considered non-impact (
n
= 27), low- or moderate-impact (
n
= 39), odd-impact (
n
= 38), high-strain-magnitude/low-strain-rate (
n
= 10), or high-impact (
n
= 39). Bone geometrical parameters, including cortical area, periosteal perimeter, and moment of inertia (bone strength index), were determined using MRI images.
Results
Higher-impact groups displayed bone expansion, with significantly greater periosteal perimeters, cortical areas (~37.3 %), and minimum moments of inertia (
I
min
, ~92.3 %) at the mid-femur than non- and low-impact groups. After adjusting for age, height, and weight, the cortical area and
I
min
of the low-impact and high-strain-magnitude/low-strain-rate groups were also significantly greater than those of the non-impact group.
Conclusions
Higher-impact sports with high strain rates stimulated periosteal bone formation and improved bone geometry and strength indices at the femoral mid-shaft. Although our results indicate that weight-bearing sports are beneficial even if they are low impact, the effects of lower-impact or high-strain-magnitude/low-strain-rate sports on bone geometry were less pronounced than the effects of higher-impact sports at the femoral mid-shaft.
Cassava is an important crop that provides food security and income generation in many tropical countries and is known for its adaptability to various environmental conditions. Despite its global ...importance, the development of cassava microarray tools has not been well established. Here, we describe the development of a 60-mer oligonucleotide Agilent microarray representing ∼20,000 cassava genes and how it can be applied to expression profiling under drought stress using three cassava genotypes (MTAI16, MECU72 and MPER417-003). Our results identified about 1300 drought stress up-regulated genes in cassava and indicated that cassava has similar mechanisms for drought stress response and tolerance as other plant species. These results demonstrate that our microarray is a useful tool for analysing the cassava transcriptome and that it is applicable for various cassava genotypes.
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