Differential Mitochondrial Adaptation in Primary Vascular Smooth Muscle Cells from a Diabetic Rat Model

Diabetes affects more than 330 million people worldwide and causes elevated cardiovascular disease risk. Mitochondria are critical for vascular function, generate cellular reactive oxygen species (ROS), and are perturbed by diabetes, representing a novel target for therapeutics. We hypothesized that adaptive mitochondrial plasticity in response to nutrient stress would be impaired in diabetes cellular physiology via a nitric oxide synthase- (NOS-) mediated decrease in mitochondrial function. Primary smooth muscle cells (SMCs) from aorta of the nonobese, insulin resistant rat diabetes model Goto-Kakizaki (GK) and the Wistar control rat were exposed to high glucose (25 mM). At baseline, significantly greater nitric oxide evolution, ROS production, and respiratory control ratio (RCR) were observed in GK SMCs. Upon exposure to high glucose, expression of phosphorylated eNOS, uncoupled respiration, and expression of mitochondrial complexes I, II, III, and V were significantly decreased in GK SMCs (p<0.05). Mitochondrial superoxide increased with high glucose in Wistar SMCs (p<0.05) with no change in the GK beyond elevated baseline concentrations. Baseline comparisons show persistent metabolic perturbations in a diabetes phenotype. Overall, nutrient stress in GK SMCs caused a persistent decline in eNOS and mitochondrial function and disrupted mitochondrial plasticity, illustrating eNOS and mitochondria as potential therapeutic targets

Women and ARVâ based prevention: opportunities and challenges

Peer Reviewedhttps://deepblue.lib.umich.edu/bitstream/2027.42/138349/1/jia29419.pd

2017 Research & Innovation Day Program

A one day showcase of applied research, social innovation, scholarship projects and activities.https://first.fanshawec.ca/cri_cripublications/1004/thumbnail.jp

Within- and cross-language contributions of morphological awareness to word reading development in Chinese-English bilingual children

A growing body of cross-linguistic research has suggested that morphological awareness plays a key role in both L1 and L2 word reading among bilingual readers. However, little is known about the interaction and development of L1 and L2 morphological awareness in relation to word reading. We addressed this issue by evaluating the unique contributions of L1 Chinese and L2 English morphological awareness to word reading in both Chinese and English across Grades 2 (N = 150), 5 (N = 158), and 8 (N = 159) Hong Kong Chinese–English bilingual children. Children completed five tasks of Chinese morphological awareness which tapped for compounding awareness, homophone awareness, homographic awareness, semantic radical awareness, and affix awareness, and six English morphological judgment and analogy tasks that assessed morphological awareness at three levels: inflection, derivation, and compounding. English phonological awareness, Chinese and English vocabulary, and nonverbal ability were measured as controls. Word reading was assessed in both languages. Within-language analyses revealed that Chinese morphological awareness accounted for 27, 22, and 12% of unique variances in Chinese word reading above the control measures in Grades 2, 5, and 8 respectively. In contrast, English morphological awareness explained small but significant unique variances in English word reading, i.e., 4, 8, and 2%, across Grades 2, 5, and 8 respectively. Critically, there were cross-language influences: Chinese morphological awareness explained 4% of unique variance in English word reading in Grade 2 after controlling for IQ, English vocabulary, English phonological awareness, and English morphological awareness; English morphological awareness explained significant variances in Chinese word reading, i.e., 4, 3, and 4% in Grades 2, 5, and 8 respectively, after the relevant controls. These findings suggest a bi-directional cross-language transfer of morphological awareness to word reading in L1 Chinese and L2 English. However, the direction of its transfer may be constrained by some language-specific morphological features

GWAS meta-analysis of intrahepatic cholestasis of pregnancy implicates multiple hepatic genes and regulatory elements

Intrahepatic cholestasis of pregnancy (ICP) is a pregnancy-specific liver disorder affecting 0.5–2% of pregnancies. The majority of cases present in the third trimester with pruritus, elevated serum bile acids and abnormal serum liver tests. ICP is associated with an increased risk of adverse outcomes, including spontaneous preterm birth and stillbirth. Whilst rare mutations affecting hepatobiliary transporters contribute to the aetiology of ICP, the role of common genetic variation in ICP has not been systematically characterised to date. Here, we perform genome-wide association studies (GWAS) and meta-analyses for ICP across three studies including 1138 cases and 153,642 controls. Eleven loci achieve genome-wide significance and have been further investigated and fine-mapped using functional genomics approaches. Our results pinpoint common sequence variation in liver-enriched genes and liver-specific cis-regulatory elements as contributing mechanisms to ICP susceptibility

Effectiveness of a national quality improvement programme to improve survival after emergency abdominal surgery (EPOCH): a stepped-wedge cluster-randomised trial

Background: Emergency abdominal surgery is associated with poor patient outcomes. We studied the effectiveness of a national quality improvement (QI) programme to implement a care pathway to improve survival for these patients. Methods: We did a stepped-wedge cluster-randomised trial of patients aged 40 years or older undergoing emergency open major abdominal surgery. Eligible UK National Health Service (NHS) hospitals (those that had an emergency general surgical service, a substantial volume of emergency abdominal surgery cases, and contributed data to the National Emergency Laparotomy Audit) were organised into 15 geographical clusters and commenced the QI programme in a random order, based on a computer-generated random sequence, over an 85-week period with one geographical cluster commencing the intervention every 5 weeks from the second to the 16th time period. Patients were masked to the study group, but it was not possible to mask hospital staff or investigators. The primary outcome measure was mortality within 90 days of surgery. Analyses were done on an intention-to-treat basis. This study is registered with the ISRCTN registry, number ISRCTN80682973. Findings: Treatment took place between March 3, 2014, and Oct 19, 2015. 22 754 patients were assessed for elegibility. Of 15 873 eligible patients from 93 NHS hospitals, primary outcome data were analysed for 8482 patients in the usual care group and 7374 in the QI group. Eight patients in the usual care group and nine patients in the QI group were not included in the analysis because of missing primary outcome data. The primary outcome of 90-day mortality occurred in 1210 (16%) patients in the QI group compared with 1393 (16%) patients in the usual care group (HR 1·11, 0·96–1·28). Interpretation: No survival benefit was observed from this QI programme to implement a care pathway for patients undergoing emergency abdominal surgery. Future QI programmes should ensure that teams have both the time and resources needed to improve patient care. Funding: National Institute for Health Research Health Services and Delivery Research Programme

Effectiveness of a national quality improvement programme to improve survival after emergency abdominal surgery (EPOCH): a stepped-wedge cluster-randomised trial

BACKGROUND: Emergency abdominal surgery is associated with poor patient outcomes. We studied the effectiveness of a national quality improvement (QI) programme to implement a care pathway to improve survival for these patients. METHODS: We did a stepped-wedge cluster-randomised trial of patients aged 40 years or older undergoing emergency open major abdominal surgery. Eligible UK National Health Service (NHS) hospitals (those that had an emergency general surgical service, a substantial volume of emergency abdominal surgery cases, and contributed data to the National Emergency Laparotomy Audit) were organised into 15 geographical clusters and commenced the QI programme in a random order, based on a computer-generated random sequence, over an 85-week period with one geographical cluster commencing the intervention every 5 weeks from the second to the 16th time period. Patients were masked to the study group, but it was not possible to mask hospital staff or investigators. The primary outcome measure was mortality within 90 days of surgery. Analyses were done on an intention-to-treat basis. This study is registered with the ISRCTN registry, number ISRCTN80682973. FINDINGS: Treatment took place between March 3, 2014, and Oct 19, 2015. 22 754 patients were assessed for elegibility. Of 15 873 eligible patients from 93 NHS hospitals, primary outcome data were analysed for 8482 patients in the usual care group and 7374 in the QI group. Eight patients in the usual care group and nine patients in the QI group were not included in the analysis because of missing primary outcome data. The primary outcome of 90-day mortality occurred in 1210 (16%) patients in the QI group compared with 1393 (16%) patients in the usual care group (HR 1·11, 0·96-1·28). INTERPRETATION: No survival benefit was observed from this QI programme to implement a care pathway for patients undergoing emergency abdominal surgery. Future QI programmes should ensure that teams have both the time and resources needed to improve patient care. FUNDING: National Institute for Health Research Health Services and Delivery Research Programme

The Suffering of Others: The human cost of the International Finance Corporation's lending through financial intermediaries

Increasingly, development money is being channelled through third parties such as banks or private equity funds. The world's leading proponent of this financing model, the International Finance Corporation, spent $36bn this way in just the four years leading up to June 2013. But what does this 'hands-off' form of development financing mean for people? Are the risks to communities and their livelihoods just too high given the weaker social and environmental protections entailed? This report tells the human story behind the high finance and statistics, and asks whether reforms to this model of lending have gone far enough to protect communities

'Our Land, Our Lives': Time out on the global land rush

Land eight times the size of the UK was sold off globally in the last decade, enough to grow food for a billion people, equivalent to the number of people who go hungry in the world each night. More than 60 per cent of investments in agricultural land by foreign investors between 2000 and 2010 were in developing countries with serious hunger problems. However, two-thirds of those investors plan to export everything they produce on that land. Oxfam supports greater investment in agriculture and to small-scale producers; however, the unprecedented rush for land has not been adequately regulated or policed to prevent land grabs. This means that poor people continue to be evicted, often violently, without consultation or compensation. Many lose their homes and are left destitute, without access to the land they rely on. The World Bank must act now to temporarily freeze investments involving large-scale land deals so it can review its advice to developing countries, help set standards for investors, and introduce more robust policies to stop land grabs

Now or Never: Climate change: time to get down to business

Climate change affects poor people first and worst. It is a major obstacle to development and poverty alleviation, as well as a serious threat to business supply chains and markets in developing countries. Oxfam believes that companies can help to determine whether the world wins or loses the fight against climate changes. It cannot be a case of continuing development or adapting to climate change - without both, neither will happen. Climate change is a global problem, requiring a global solution. Oxfam has seen first-hand the impacts that climate change can have on poor people and action is urgent. We must keep the rise in global temperatures below 2 degrees. This means that emissions must peak and start to decline in the next decade; so we must act now to set the world on a low-carbon path. Coordinated international action is essential. Every business must join the fight against climate change. Companies large and small can take steps to ensure that they reduce their own contribution to climate change and encourage