Hypoxia-induced regulation of the very low density lipoprotein receptor

The very low density lipoprotein receptor (VLDLr) is highly upregulated during hypoxia in mouse cardiomyocytes and in human and mouse ischemic hearts causing a detrimental lipid accumulation. To know how the gene is regulated is important for future studies. In this study, we have thoroughly mapped the 5 '-flanking region of the mouse VLDLr promoter and show that the hypoxia-mediated increase in VLDLr expression is dependent on Hif-1 alpha, binding to a hypoxia responsive element (HRE) located at -162 to-158 bp 5 ' of translation start. We show that classical HRE sites and the previously described PPAR gamma and Sp1 binding are not involved in the hypoxia-induced regulation of the VLDLr promoter. Using a chromatin immunoprecipitation (ChIP) assay, we show that Hif-1 alpha t specifically binds and activates the mouse VLDLr promoter at the previously described non-classical HRE in HL-1 cells. We also show that the same HRE is present and active in response to hypoxia in human cardiomyocytes, however at a different location (-812 bp from translation start). These results conclude that in the hypoxic hearts of mice and men, the VLDLr gene is regulated by a direct binding of Hif-1 alpha to the VLDLr promoter. (C) 2013 Elsevier Inc. All rights reserved

Long-term outcomes of vagus nerve stimulation paired with upper extremity rehabilitation after stroke

BACKGROUND: Persistent upper extremity (UE) impairment is common after stroke. Durable treatment benefits for chronic ischemic stroke are needed. The purpose of this report is to determine the long-term effects of vagus nerve stimulation paired with rehabilitation on impairment, activity, and participation in people with UE impairment after ischemic stroke. METHODS: This is a post hoc analysis of data from the VNS-REHAB (A Pivotal Randomized Study Assessing Vagus Nerve Stimulation [VNS] During Rehabilitation for Improved Upper Limb Motor Function After Stroke) randomized clinical trial. Here, we report unblinded, partial crossover, and pooled 1-year outcomes. Initially, 108 participants across 19 sites with chronic ischemic stroke and moderate-to-severe UE impairment were enrolled in VNS-REHAB. Participants received 18 sessions of in-clinic intensive task-specific rehabilitation and 3 months of self-initiated home-based exercise with either real (active) or sham (control) vagus nerve stimulation. Thereafter, Control participants crossed over to receive in-clinic therapy paired with active stimulation. All participants performed home-based exercises paired with self-initiated active stimulation for 1 year. The Fugl-Meyer Assessment UE, Wolf Motor Function Test, and participation outcomes were assessed through 12 months. RESULTS: Seventy-four participants (69%; 51 male; age, mean±SD, 59.6±8.9) completed 1-year follow-up and provided pooled data through 1 year. At 1 year, compared with baseline, there were improvements in impairment (Fugl-Meyer Assessment UE, 5.23 [95% CI, 4.08–6.39]; P <0.001) activity (Wolf Motor Function Test, 0.50 [95% CI, 0.41–0.59]; P <0.001) and patient-reported outcomes (Motor Activity Log–Quality of Movement: 0.64 [95% CI, 0.46–0.82], P <0.001; Motor Activity Log–Amount of Use: 0.64 [95% CI, 0.46–0.82], P <0.001; Stroke Impact Scale–Activities of Daily Living: 7.43 [95% CI, 5.09–9.77], P <0.001; Stroke Impact Scale–Hand: 17.89 [95% CI, 14.16–21.63], P <0.001; EQ-5D: 5.76 [95% CI, 2.08–9.45], P <0.05; and Stroke Specific–Quality of Life: 0.29 [95% CI, 0.19–0.39], P <0.001) compared with baseline. CONCLUSIONS: People treated with paired vagus nerve stimulation maintained improvements in UE impairment, activity, participation, and quality-of-life measures at 1 year. Paired vagus nerve stimulation is a Food and Drug Administration–approved, beneficial treatment option for long-term benefit in individuals with chronic UE limitations after ischemic stroke

Uniting the global gastroenterology community to meet the challenge of climate change and non-recyclable waste

Climate change has been described as the biggest global health threat of the 21st century1 and has significant implications for gastrointestinal (GI) health and disease,2 which is the focus of this consensus commentary provided by the World Gastroenterology Organisation (WGO) Climate Change Working Group (CCWG). The CCWG has members from 18 countries representing high-income, medium-income and low-income populations. The WGO includes gastroenterology societies from 108 countries, which represent more than 60 000 medical practitioner members. The CCWG members, who have coauthored this consensus commentary, aim to review the scientific literature on climate and GI health, to encourage education and the undertaking of actionable measures including advocacy, and to further research and collaborations within the global GI community. The CCWG’s objective is to assist GI health providers worldwide to adapt to, and mitigate, the effects of climate change on health. The CCWG has partnered with three major GI journals, which are copublishing this commentary, given the timeliness and importance of the topic.Versión publicad