Neutrophil extracellular traps (NETs; webs of DNA coated in antimicrobial proteins) are released into the vasculature during sepsis where they contribute to host defense, but also cause tissue damage and organ dysfunction. Various components of NETs have also been implicated as activators of coagulation. Using multicolor confocal intravital microscopy in mouse models of sepsis, we observed profound platelet aggregation, thrombin activation, and fibrin clot formation within (and downstream of) NETs in vivo. NETs were critical for the development of sepsis-induced intravascular coagulation regardless of the inciting bacterial stimulus (gram-negative, gram-positive, or bacterial products). Removal of NETs via DNase infusion, or in peptidylarginine deiminase-4-deficient mice (which have impaired NET production), resulted in significantly lower quantities of intravascular thrombin activity, reduced platelet aggregation, and improved microvascular perfusion. NET-induced intravascular coagulation was dependent on a collaborative interaction between histone H4 in NETs, platelets, and the release of inorganic polyphosphate. Real-time perfusion imaging revealed markedly improved microvascular perfusion in response to the blockade of NET-induced coagulation, which correlated with reduced markers of systemic intravascular coagulation and end-organ damage in septic mice. Together, these data demonstrate, for the first time in an in vivo model of infection, a dynamic NET-platelet-thrombin axis that promotes intravascular coagulation and microvascular dysfunction in sepsis.
Highlights d A high variability in glycemic response to exercise in subjects with prediabetes exists d Responders and non-responders exhibit differential alterations of the gut microbiota d Gut microbiota from responders confers the metabolic benefits of exercise in mice d Baseline microbiome features accurately predict personalized exercise responses
The objective of this study was to examine the effectiveness of a core endurance exercise protocol. Forty-five college-age rowers (age 21 +/- 1.0) were assigned to either a core training group [core group] (n = 25), which took part in a core endurance intervention exercise protocol, or to a control training group [control group] (n = 20), which was not given any specialized core training. Training took place 2 days per week for 8 weeks. Trunk endurance was assessed using flexion, extension, and side flexion tests, whereas a variety of functional performance measures were assessed (vertical jump, broad jump, shuttle run, 40-m sprint, overhead medicine ball throw, 2,000-m maximal rowing ergometer test). The results revealed significant improvement in the two side flexion tests for the core group (p < 0.05). Interestingly, significant differences were noted in the trunk extension test endurance times for the control group (p < 0.05), but not for the core group. No significant differences were found for any of the functional performance tests. In summary, the 8-week core endurance training program improved selected core endurance parameters in healthy young men, but the effectiveness of the core intervention on various functional performance aspects was not supported.
Impairments of attention and memory are evident in early psychosis, and are associated with functional disability. In a group of stable, medicated women patients, we aimed to determine whether participating in aerobic exercise or yoga improved cognitive impairments and clinical symptoms. A total of 140 female patients were recruited, and 124 received the allocated intervention in a randomized controlled study of 12 weeks of yoga or aerobic exercise compared with a waitlist group. The primary outcomes were cognitive functions including memory and attention. Secondary outcome measures were the severity of psychotic and depressive symptoms, and hippocampal volume. Data from 124 patients were included in the final analysis based on the intention-to-treat principle. Both yoga and aerobic exercise groups demonstrated significant improvements in working memory (P<0.01) with moderate to large effect sizes compared with the waitlist control group. The yoga group showed additional benefits in verbal acquisition (P<0.01) and attention (P=0.01). Both types of exercise improved overall and depressive symptoms (all P⩽0.01) after 12 weeks. Small increases in hippocampal volume were observed in the aerobic exercise group compared with waitlist (P=0.01). Both types of exercise improved working memory in early psychosis patients, with yoga having a larger effect on verbal acquisition and attention than aerobic exercise. The application of yoga and aerobic exercise as adjunctive treatments for early psychosis merits serious consideration. This study was supported by the Small Research Funding of the University of Hong Kong (201007176229), and RGC funding (C00240/762412) by the Authority of Research, Hong Kong.
Children with DS who have better balance ability tend to have more proficient FMS. Skill-specific training improved not only FMS sub-skills but static balance stability as well. Working memory did not play a role in the changes caused by skills training. Future research should examine the causal relationship between balance and FMS.
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