Retained capacity for perceptual learning of degraded speech in primary progressive aphasia and Alzheimer's disease

This work was supported by the Alzheimer’s Society (AS-PG-16-007), the National Institute for Health Research University College London Hospitals Biomedical Research Centre, the UCL Leonard Wolfson Experimental Neurology Centre (PR/ylr/18575) and the Economic and Social Research Council (ES/K006711/1). Individual authors were supported by the Medical Research Council (PhD Studentship to CJDH and RLB; MRC Clinician Scientist Fellowship to JDR), the Wolfson Foundation (Clinical Research Fellowship to CRM), Alzheimer’s Research UK (ART-SRF2010-3 to SJC) and the Wellcome Trust (091673/Z/10/Z to JDW)

Lipoprotein lipase activity and mass, apolipoprotein C-II mass and polymorphisms of apolipoproteins E and A5 in subjects with prior acute hypertriglyceridaemic pancreatitis

Journal Article; Research Support, Non-U.S. Gov't;BACKGROUND Severe hypertriglyceridaemia due to chylomicronemia may trigger an acute pancreatitis. However, the basic underlying mechanism is usually not well understood. We decided to analyze some proteins involved in the catabolism of triglyceride-rich lipoproteins in patients with severe hypertriglyceridaemia. METHODS Twenty-four survivors of acute hypertriglyceridaemic pancreatitis (cases) and 31 patients with severe hypertriglyceridaemia (controls) were included. Clinical and anthropometrical data, chylomicronaemia, lipoprotein profile, postheparin lipoprotein lipase mass and activity, hepatic lipase activity, apolipoprotein C II and CIII mass, apo E and A5 polymorphisms were assessed. RESULTS Only five cases were found to have LPL mass and activity deficiency, all of them thin and having the first episode in childhood. No cases had apolipoprotein CII deficiency. No significant differences were found between the non-deficient LPL cases and the controls in terms of obesity, diabetes, alcohol consumption, drug therapy, gender distribution, evidence of fasting chylomicronaemia, lipid levels, LPL activity and mass, hepatic lipase activity, CII and CIII mass or apo E polymorphisms. However, the SNP S19W of apo A5 tended to be more prevalent in cases than controls (40% vs. 23%, NS). CONCLUSION Primary defects in LPL and C-II are rare in survivors of acute hypertriglyceridaemic pancreatitis; lipase activity measurements should be restricted to those having their first episode during childhood.Part of the studies were financed by grants from the Swedish Research Council and from the King Gustaf V and Queen Victoria Research Fund and by grants from Grupos de Investigacion y Desarrollo Tecnologico de la Junta de Andalucia (Grupo consolidado CTS- 159).Ye

The emerging era of pharmacogenomics: current successes, future potential, and challenges

10.1111/cge.12392CLINICAL GENETICS86121-2

CYP2D6 Polymorphisms and Codeine Analgesia in Postpartum Pain Management: A Pilot Study

Background: Codeine, a common opiate prescribed for pain postcesarean section (c-section), is biotransformed by the highly polymorphic Cytochrome P450 enzyme 2D6 (CYP2D6). Ultrarapid metabolizers (UMs), individuals with multiple active copies of CYP2D6, can biotranform up to 50% more codeine into morphine than normal individuals can. In contrast, poor metabolizers (PMs), individuals who have no active CYP2D6 genes, convert almost no codeine into morphine and as a result may take multiple doses of codeine without attaining analgesia. Objective: The aim was to study the relationship between CYP2D6 genotype and codeine analgesia among women recovering from c-section. Methods: Forty-five mothers prescribed codeine provided a blood sample for CYP2D6 genotyping and recorded their pain level 4 times a day for 3 days immediately after a c-section. Codeine was used on an as-needed basis; doses and times were recorded. The relationship between CYP2D6 genotype, pain scores, need for codeine, and adverse events was studied. Theoretical morphine dose, based on CYP2D6 genotype, was estimated. Results: Women at the genotypic extremes reported codeine effects consistent with their genotype: the 2 PMs of codeine reported no analgesia as a result of taking codeine, whereas 2 of the 3 UMs reported immediate pain relief from codeine but stopped taking it due to dizziness and constipation. Much larger numbers are needed to study similar correlations among extensive and intermediate metabolizers. Conclusions: In this pilot study, the extreme CYP2D6 genotypes (PMs and UMs) seemed to predict pain response and adverse events. Larger sample sizes are needed to correlate the range of genotypes with pain response

Pharmacogenomic diversity in Singaporean populations and Europeans

10.1038/tpj.2014.22PHARMACOGENOMICS JOURNAL146555-563United State

Output from the CIHR Canadian HIV Trials Network international postdoctoral fellowship for capacity building in HIV clinical trials

Lawrence Mbuagbaw,1–3 Amy L Slogrove,4,5 Jacqueline Sas,6 John Lengwe Kunda,7 Frederick Morfaw,8 Jackson K Mukonzo,9 Wei Cao,10–12 Gisele Ngomba-Kadima,13 Moleen Zunza,14,15 Pierre Ongolo-Zogo,3 Philip N Nana,8 Anne Cockcroft,16,17 Neil Andersson,16,18,19 Nelson Sewankambo,9 Mark F Cotton,4 Taisheng Li,12 Taryn Young,14 Joel Singer,5,6 Jean-Pierre Routy,6,10,11,20 Colin JD Ross,21 Kyaw Thin,22 Lehana Thabane,1,2,6,23–25 Aslam H Anis5,6 1Department of Health Research Methods, Evidence and Impact, McMaster University, 2Biostatistics Unit, Father Sean O’Sullivan Research Centre, St Joseph’s Healthcare Hamilton, Hamilton, ON, Canada; 3Centre for Development of Best Practices in Health, Yaoundé Central Hospital, Yaoundé, Cameroon; 4Department of Paediatrics and Child Health, Family Clinical Research Unit (FAM-CRU), Stellenbosch University, Tygerberg, South Africa; 5UBC School of Population and Public Health, Vancouver, BC, 6CIHR Canadian HIV Trials Network, UBC, Canada; 7Community Information and Epidemiological Technologies (CIET), Lusaka, Zambia; 8Department of Obstetrics and Gynaecology, Faculty of Medicines and Biomedical Sciences, University of Yaoundé 1, Yaoundé, Cameroon; 9School of Biomedical Sciences, College of Health Sciences, University of Makerere, Kampala, Uganda; 10Chronic Viral Illness Service, McGill University Health Centre, 11Research Institute of the McGill University Health Centre, Montreal, QC, Canada; 12Department of Infectious Diseases, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences, Beijing, China; 13Queen Mamahato Memorial Hospital, Maseru, Lesotho; 14Centre for Evidence-based Health Care, Faculty of Health Sciences, Stellenbosch University, Tygerberg, South Africa; 15Research Institute, McGill University Health Centre, Montreal, QC, Canada; 16Community Information and Epidemiological Technologies (CIET) Trust Botswana, Gaborone, Botswana; 17Community Information and Epidemiological Technologies – Participatory Research at McGill (CIET-PRAM), Department of Family Medicine, McGill University, 18Centro de Investigación de Enfermedades Tropicales, Universidad Autónoma de Guerrero, Chilpancingo, Mexico; 19Department of Family Medicine, McGill University, Montreal, Canada; 20Division of Hematology, McGill University Health Centre, Montreal, QC, Canada; 21Faculty of Pharmaceutical Sciences, University of British Columbia, Vancouver, BC, Canada; 22Research Coordination Unit, Ministry of Health and Social Welfare, Maseru, Lesotho; 23Departments of Paediatrics and Anaesthesia, McMaster University, Hamilton, ON, Canada; 24Centre for Evaluation of Medicine, St Joseph’s Healthcare—Hamilton, ON, Canada; 25Population Health Research Institute, Hamilton Health Sciences, Hamilton, ON, Canada Abstract: As a response to the human immunodeficiency virus (HIV) epidemic and part of ­Canadian Institutes for Health Research’s mandate to support international health research capacity building, the Canadian Institutes for Health Research Canadian HIV Trial Network (CTN) developed an international postdoctoral fellowship award under the CTN’s Postdoctoral Fellowship Awards Program to support and train young HIV researchers in resource-limited settings. Since 2010, the fellowship has been awarded to eight fellows in Cameroon, China, Lesotho, South Africa, Uganda and Zambia. These fellows have conducted research on a wide variety of topics and have built a strong network of collaboration and scientific productivity, with 40 peer-reviewed publications produced by six fellows during their fellowships. They delivered two workshops at international conferences and have continued to secure funding for their research, using the fellowship as a stepping stone. The CTN has been successful in building local HIV research capacity and forming a strong network of like-minded junior low- and middle-income country researchers with high levels of research productivity. They have developed into mentors, supervisors and faculty members, who, in turn, build local capacity. The sustainability of this international fellowship award relies on the recognition of its strengths and the involvement of other stakeholders for additional resources. Keywords: CTN, postdoctoral fellowship, capacity building, clinical trials, networkin

Differential effect of the rs4149056 variant in SLCO1B1 on myopathy associated with simvastatin and atorvastatin

Statins reduce cardiovascular morbidity and mortality in appropriately selected patients. However, statin-associated myopathy is a significant risk associated with these agents. Recently, variation in the SLCO1B1 gene was reported to predict simvastatin-associated myopathy. The aim of this study was to replicate association of the rs4149056 variant in SLCO1B1 with severe statin-associated myopathy in a cohort of patients using a variety of statin medications and to investigate the association with specific statin types. We identified 25 cases of severe statin-associated myopathy and 84 controls matched for age, gender, statin type and dose. The rs4149056 variant in SLCO1B1 was not significantly associated with myopathy in this group as a whole. However, when subjects were stratified by statin type, the SLCO1B1 rs4149056 genotype was significantly associated with myopathy in patients who received simvastatin, but not in patients who received atorvastatin. Our findings provide further support for a role for SLCO1B1 genotype in simvastatin-associated myopathy, and suggest that this association may be stronger for simvastatin compared with atorvastatin. The Pharmacogenomics Journal (2012) 12, 233-237; doi: 10.1038/tpj.2010.92; published online 18 January 201