Ethyl pyruvate (EP) is protective in experimental models of many illnesses. This study investigates whether EP can protect against neonatal hypoxic-ischemic (H-I) brain injury. Pre-treatment with EP significantly reduced brain damage at 7 days post-H-I, with 50 mg/kg EP achieving over 50% recovery in tissue loss compared to vehicle-treated animals. Delayed treatment with EP until 30 min after H-I was still neuroprotective. EP-afforded brain protection, together with neurological function improvement, was observed up to 2 months after H-I. We further demonstrated an inhibitory effect of EP on cell death, both in an in vivo model of H-I and in in vitro neuronal cultures subjected to OGD, by reducing calpain activation and calcium dysregulation. Moreover, EP exerted an antiinflammatory effect in microglia by inhibiting NF-κB activation and subsequent release of inflammatory mediators. Taken together, our results suggest that EP confers potent neuroprotection against neonatal H-I brain injury via its anti-cell death and anti-inflammatory actions. EP is a potential novel therapeutic agent for neonatal H-I brain injury.

BackgroundChronic kidney disease (CKD) poses a major challenge to public health. In CKD patients, adequate disease self-management has been shown to improve both proximal and distal outcomes. Currently, electronic health (eHealth) interventions are increasingly used to optimize patients’ self-management skills.ObjectiveThis study aimed to systematically review the existing evidence regarding the implementation and effectiveness of eHealth self-management interventions for patients with CKD.MethodsFollowing a search in 8 databases (up to November 2017), quantitative and qualitative data on process and effect outcomes were extracted from relevant studies. Quality was appraised using the Crowe Critical Appraisal Tool; narrative synthesis was performed to analyze the data extracted.ResultsOf the 3307 articles retrieved, 24 (comprising 23 studies) were included in this review; of these, almost half were appraised to be of low to moderate quality. There was considerable heterogeneity in the types of interventions used and the outcomes measured. A total of 10 effect and 9 process outcome indicators were identified. The most frequently reported effect outcome indicators were specific laboratory tests and blood pressure (BP), whereas satisfaction was the most frequently reported process outcome indicator. Positive effects were found for proximal outcomes (eg, BP control and medication adherence), and mixed effects were found for more distal outcomes (eg, quality of life). High feasibility, usability, and acceptability of and satisfaction with eHealth self-management interventions were reported. The determinant ability of health care professionals to monitor and, if necessary, anticipate on patient measurements online was mostly cited to influence patients’ adherence to interventions.ConclusionseHealth self-management interventions have the potential to improve disease management and health outcomes. To broaden the evidence base and facilitate intervention upscaling, more detailed descriptions and thorough analysis of the intervention components used are required. In addition, our review reveals that outcomes closely related to the scope and duration of the intervention implemented are most likely to be impacted. For instance, if a 4-week Web-based training to optimize disease management skills is implemented, the outcome perceived control would more likely be affected than kidney function. Although this seems obvious, most studies evaluate only distal outcomes and thereby fail to capture intervention effects that might contribute to long-term health improvement. We advise future researchers to carefully consider their choice of outcomes based on their sensitivity for change. In this way, we ensure that relevant effects are captured and legitimate conclusions are drawn.

BackgroundDiabetes mellitus is associated with many kinds of complications. Recent studies have shown that oxidative stress and inflammatory reactions have critical roles in the pathogenesis of diabetic gastroparesis. Curcumin is known to have antioxidant and anti-inflammatory properties. In the present study, we investigated the effect of curcumin on diabetic gastric motility in a Sprague Dawley rat model of type 1 diabetes mellitus.MethodsMale SD rats were divided into a control group, a control group receiving curcumin, a diabetic group, and a diabetic group receiving curcumin. Diabetes was induced by intraperitoneal injection of streptozotocin. Curcumin (150 mg/kg) was given intragastrically for 6 weeks, and blood glucose levels and body weights were measured. Stomachs were excised for analysis of gastric emptying rates, and levels of oxidative stress. NF-κB, I-κB, and stem cell factor (SCF)/c-kit protein levels were assessed by western blot analysis, while the apoptosis of interstitial cells of Cajal (ICCs) was assessed by TUNEL staining.ResultsCurcumin-treated diabetic rats showed significantly improved gastric emptying rates [(59.4 ± 7.5)%] compared with diabetic rats [(44.3 ± 5.7)%], as well as decreased levels of MDA [21.4 ± 1.8 (nmol/mg) vs 27.9 ± 2.1 (nmol/mg)], and increased SOD activity [126.2 ± 8.8 (units/mg) vs 107.9 ± 7.5 (units/mg)]. On the other hand, the gastric emptying level in the control group was not significantly different from that in the control group receiving curcumin treatment. In addition, curcumin-treated diabetic rats showed significantly increased levels of SCF/c-kit protein in stomach tissues, inhibited I-κB degradation and NF-κB activation, and reduced ICC apoptosis index [(26.2 ± 4.1)% vs (47.5 ± 6.2)%], compared with the diabetic group.ConclusionCurcumin treatment improved gastric emptying by blocking the production of oxidative stress, abolishing NF-κB signal transduction and enhancing expression of SCF/c-kit in rats with diabetic gastroparesis.

Background Chronic obstructive pulmonary disease (COPD) and asthma have a high prevalence and disease burden. Blended self-management interventions, which combine eHealth with face-to-face interventions, can help reduce the disease burden. Objective This systematic review and meta-analysis aims to examine the effectiveness of blended self-management interventions on health-related effectiveness and process outcomes for people with COPD or asthma. Methods PubMed, Web of Science, COCHRANE Library, Emcare, and Embase were searched in December 2018 and updated in November 2020. Study quality was assessed using the Cochrane risk of bias (ROB) 2 tool and the Grading of Recommendations, Assessment, Development, and Evaluation. Results A total of 15 COPD and 7 asthma randomized controlled trials were included in this study. The meta-analysis of COPD studies found that the blended intervention showed a small improvement in exercise capacity (standardized mean difference [SMD] 0.48; 95% CI 0.10-0.85) and a significant improvement in the quality of life (QoL; SMD 0.81; 95% CI 0.11-1.51). Blended intervention also reduced the admission rate (relative ratio [RR] 0.61; 95% CI 0.38-0.97). In the COPD systematic review, regarding the exacerbation frequency, both studies found that the intervention reduced exacerbation frequency (RR 0.38; 95% CI 0.26-0.56). A large effect was found on BMI (d=0.81; 95% CI 0.25-1.34); however, the effect was inconclusive because only 1 study was included. Regarding medication adherence, 2 of 3 studies found a moderate effect (d=0.73; 95% CI 0.50-0.96), and 1 study reported a mixed effect. Regarding self-management ability, 1 study reported a large effect (d=1.15; 95% CI 0.66-1.62), and no effect was reported in that study. No effect was found on other process outcomes. The meta-analysis of asthma studies found that blended intervention had a small improvement in lung function (SMD 0.40; 95% CI 0.18-0.62) and QoL (SMD 0.36; 95% CI 0.21-0.50) and a moderate improvement in asthma control (SMD 0.67; 95% CI 0.40-0.93). A large effect was found on BMI (d=1.42; 95% CI 0.28-2.42) and exercise capacity (d=1.50; 95% CI 0.35-2.50); however, 1 study was included per outcome. There was no effect on other outcomes. Furthermore, the majority of the 22 studies showed some concerns about the ROB, and the quality of evidence varied. Conclusions In patients with COPD, the blended self-management interventions had mixed effects on health-related outcomes, with the strongest evidence found for exercise capacity, QoL, and admission rate. Furthermore, the review suggested that the interventions resulted in small effects on lung function and QoL and a moderate effect on asthma control in patients with asthma. There is some evidence for the effectiveness of blended self-management interventions for patients with COPD and asthma; however, more research is needed. Trial Registration PROSPERO International Prospective Register of Systematic Reviews CRD42019119894; https://www.crd.york.ac.uk/prospero/display_record.php?RecordID=119894

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