Health Sciences Research News SEPTEMBER 2016

Congratulations

to

Professor Maureen Coetzee, Co-

Director of the Wits Research Institute for Malaria, for being one of the finalists for the Top Woman in Science Award. The Standard Bank Top Women Awards have been held annually for the past 12 years to recognise women in business. In its 13th year, the collaborative platform was expanded to celebrate outstanding leadership, inspiration,

Inside this issue Leading Research News 1

vision and innovation in both the public and private sectors that

support

and

shape

women’s

roles

in

various

organisations. The award categories reflected a wide spectrum of work, from organisations in engineering, retail, pharmaceuticals,

Researcher Profile

3

Research Findings

4

construction, transport and energy, to government departments, and individual awards in categories such as young achiever, aviation, agriculture, property and science, and finally, top business woman and lifetime achiever awards.

Professor Frederick Raal, Director of the Carbohydrate and Lipid Metabolism Research Unit received a Gold Scientific Achievement Award from the Medical Research Council in recognition of his research excellence and for raising the profile of science in South Africa. His main focus of research has been the epidemiological, clinical and biochemical aspects of common diseases affecting lipid and glucose metabolism in the different ethnic groups of Southern Africa. Professor Raal is well recognized both nationally and internationally for his work on familial hypercholesterolaemia (FH), the most common inherited condition in humans. South Africa has one of the highest incidences of this disorder in the world

Research News and Events 7

SEPTEMBER 2016|RESEARCH NEWS |2 with over 200000 people affected. If untreated, FH often results in death from cardiovascular disease in the prime of one’s life, so it is essential that this condition be identified and treated. Professor Raal has researched novel therapies such as antisense apo B-100 and PCSK9-inhibitor therapy in FH subjects. These therapies now under development and soon to be made available in South Africa will allow FH patients to lead normal, healthy lives in the future.

Congratulations to Associate Professor Cheryl Cohen from the School of Public Health who was recently awarded an MRC Silver Medal. Her research emphasis is in the field of respiratory diseases which focus on the burden of disease and risk groups for severe illness, as well as assessment of the impact and effectiveness of interventions to reduce respiratory disease burden.

The Faculty Research Committee recently recognized a new research programme entitled “Project for Improving Neonatal Care (PRINCE)” which will be led by Professor Daynia Ballot from the Department of Paediatrics & Child Health. The programme will focus on quality improvement in three areas of neonatal care – perinatal asphyxia, extreme prematurity and prevention of infection. The Perinatal Asphyxia Project will include training in neonatal resuscitation, therapeutic hypothermia for asphyxiated babies and long term follow up of these babies, including developmental outcome. The project for extreme prematurity will include provision of continuous positive airways pressure for all neonates below 1000 grams birth weight and long term follow up of these babies. The prevention of infection will include infection control bundles and antibiotic stewardship measures. The rates of infection and patterns of antimicrobial resistance will be determined. All data for the project will be managed using REDCap™ software hosted by the University.

The annual National Research Foundation (NRF) Awards ceremony was held on 1 September 2016. The purpose of the awards is to recognize and celebrate South African research excellence. Although we have previously featured articles on NRF ratings, the Faculty again congratulates Professor Charles Feldman, Director of the Pulmonary Infection Research Unit, Professor Lenore Manderson from the School of Public Health and Professor Lynn Morris, Head of HIV virology laboratory at National Institute for Communicable Diseases for being announced as 2016 A-rated researchers.

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SEPTEMBER 2016|RESEARCH NEWS |3

Professor Gavin Norton completed a BSc Honours degree in Physiology, an MBBCh and a PhD in Physiology at Wits. His training as a scientist started when he was completing his Physiology Honours degree, which was the inspiration for his research career. He continued as part of the MRC Circulation Research Unit while completing his MBBCh and later Postdoctoral Fellowship at the University of Massachusetts (USA). Professor Norton has been awarded the Wits Vice-Chancellor’s Research Award, the Young Researcher’s Special Award and recently the MRC Gold Scientific Achievement Award. His research mainly focuses on improving cardiovascular risk and risk prediction as applied to resource-limited settings, such as in South Africa. Presently, cardiovascular events are the main cause of death world-wide and are equal in impact to infectious diseases in Africa. In this regard, standard cardiovascular risk assessment and prediction is suboptimal not only because there is limited awareness and application of currently accepted approaches, but also because in many circumstances researchers are only able to detect 50% of risk with standard risk calculators. Significant mentors during his early training included Professors Duncan Mitchell, Helen Laburn, Graham Mitchell, Clive Rosendorff, Geoff Rogers and Dr Izzy Katzeff (Wits). Major role models in his early career include Professors Phillip Tobias, Jack Allan, Beverley Kramer and Trefor Jenkins (Wits). During his later years, major role models and sometimes co-workers include Professors Lionel Opie (UCT), Pinhas Sareli (Wits), Theo Meyer (Wits and University of Massachusetts), John Milne (Wits), Yusuf Veriava (Wits), YK. Seed at (UKZ) and Jan Staessen (Leuven, Belgium). The most important inspiration for his research has been working closely with Professor Angela Woodiwiss (co-Director of Cardiovascular Pathophysiology and Genomics Research Unit). Professor Norton loves painting, sculpting, gardening and walking. He particularly loves to walk through the countryside and through small villages in Italy. He also loves to spend time with his wife and their three cats. Read one of Professor Norton’s articles: Booysen HL, Woodiwiss AJ, Sibiya MJ, Hodson B, Raymond A, Libhaber E, Sareli P, Norton GR. (2015). Indexes of aortic pressure augmentation markedly underestimate the contribution of reflected waves toward variations in aortic pressure and left ventricular mass. Hypertension. 65:540-546.

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SEPTEMBER 2016|RESEARCH NEWS |4

Hepatitis B virus (HBV) is hyperendemic in Southern Africa, with subgenotype A1 prevailing. Infection with this subgenotype is associated with rapid disease development and a high frequency of progression to hepatocellular carcinoma (HCC) compared to subgenotype A2 and D3. Subgenotype A2 is the genotype of A circulating outside Africa, whereas subgenotype D3 is the genotype of D circulating in southern Africa. The precore/core (PreC/C) region of subgenotype A1 has unique sequence characteristics, differentiating it from subgenotypes A2 and D3. This region encodes for hepatitis B e antigen (HBeAg), which acts as a tolerogen against HBV because it shares epitopes with HBcAg, the viral capsid protein. The aim of the study was to follow the expression of HBeAg in cells transfected with subgenotype A1 relative to subgenotypes A2 and D3, in order to explain the mechanisms for the higher hepatocarcinogenic potential of subgenotype A1. Huh7 cells were transfected with replication competent plasmids of HBV belonging to subgenotypes A1, A2 and D3. The subcellular localization of HBeAg in the secretory pathway, activation of the unfolded protein response (UPR) and subsequent activation of apoptosis was determined. Dr Nimisha Bhoola and Professor Anna Kramvis from the Hepatitis Virus Diversity Research Unit found that following transfection, subgenotype D3 HBeAg passes through the secretory pathway earlier than genotype A HBeAg. Subgenotype A1 showed a lower expression of HBeAg in the secretory pathway and a higher co-localization in the nucleus. This reduced secretion of HBeAg and its intracellular retention was accompanied by greater ER stress and an earlier and prolonged activation of the UPR. Cells transfected with subgenotype A1 had increased apoptosis. In the presence of reduced HBeAg, HBcAg, may be targeted directly by both the cellular or humoral immune responses in vivo.

Considering that HBcAg elicits a

significantly more vigorous antibody response than HBeAg in vivo, this canlead to necrosis of hepatocytes and liver damage. Liver damage is an important contributing factor in the development of HBV-related HCC. This study therefore suggests a mechanism by which liver damage many be induced and contribute to the higher hepatocarcinogenic potential of subgenotype A1. Negative (Mock)

Subgenotype D3

Day 3

Day 3

Day 5

Day 5

Subgenotype A2 Day 3

Day 5

Subgenotype A1 Day 3

Day 5

Bhoola NH, Kramvis A (2016) Hepatitis B e Antigen Expression by Hepatitis B Virus Subgenotype A1 Relative to Subgenotypes A2 and D3 in Cultured Hepatocellular Carcinoma (Huh7) Cells. Intervirology 59 (1):48-59

ER

ERGIC Figure 1: Subcellular localization of HBeAg in the ER and ER Golgi-intermediate compartment (ERGIC) of the Secretory Pathway

WITS|HEALTHSCIENCES

SEPTEMBER 2016|RESEARCH NEWS |5 (structure);

sub-optimal

(process);

rigid

(process);

and

clinic HIV

defaulter-tracing

appointment stigmatisation

system in

the

community due to defaulter-tracing activities of home-based carers. These findings could have implications for the The Integrated Chronic Disease Management

nationwide scale up of the ICDM model in South

(ICDM) model was introduced as a response to

Africa.

the

dual

burden

of

HIV/AIDS

and

non-

communicable diseases in South Africa. Dr Soter Ameh from the Rural Public Health and Health

Ameh S, Klipstein-Grobusch K, D'ambruoso L, Kahn K, Tollman

SM,

Gómez-Olivé

FX

(2016)

“Quality

of

integrated chronic disease care in rural South Africa: user

Transitions Research Unit (Agincourt) and co-

and provider perspectives”. Health Policy Plan.pii: czw118.

authors described the viewpoints of operational

[Epub ahead of print]

managers and patients regarding quality of care in the ICDM model. In 2013, the authors conducted a case study of the seven PHC facilities in the rural Agincourt sub-district in northeast South Africa. Focus group discussions were used to obtain data from 56 purposively selected patients older than 18 years. In-depth interviews were conducted with operational managers of each facility and the sub-

Antimicrobial resistance is a global problem with

district health manager. Donabedian’s structure,

micro-organisms

process and outcome theory for service quality

considerably faster than the rate at which new

evaluation underpinned the conceptual framework

antibiotics are developed. Essential oils, one of

in this study.

the most widely used natural products to date,

The manager and patient narratives showed the inadequacies in structure (malfunctioning blood pressure machines and staff shortage); process (irregular prepacking of drugs); and outcome (long waiting times). There was discordance between

managers

and

patients

regarding

reasons for long patient waiting time which managers attributed to staff shortage and missed appointments, while patients ascribed it to late arrival of managers to the clinics. Patients reported

anti-hypertension

drug

stock-outs

developing

resistance

have been used since antiquity to treat infections, even before the discovery of penicillin. In a recently published study, 59 different commercial essential oils were investigated against 13 skin pathogens, including micro-organisms such as methicillin

and

gentamicin

resistant

Staphylococcus aureus as well as Pseudomonas aeruginosa, two pathogens that are globally responsible for severe nosocomial infections and high morbidity rates. Excellent broad-spectrum activity was observed for lemongrass, bay, patchouli, clove and vetiver oils. The chemical

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SEPTEMBER 2016|RESEARCH NEWS |6 profiles for all the essential oils were identified using gas chromatography coupled to mass spectrometry. This data was interlaced with the antimicrobial activity using chemometric analysis. From

this

compounds

it was

possible to

responsible

for

the

predict the noteworthy

antimicrobial activity which included amongst others eugenol, geranial and geraniol. Mrs Ane Orchard and co-authors from the Department of Pharmacy

carried

out

further

analysis

to

determine the antimicrobial activity individually as well as other compound combinations, with the

over human evolution, blood flow rate to the brain has increased by an impressive 600%. According to Dr Snelling, blood flow is a much better indicator of brain metabolism and cognition than simple estimates of brain size. Dr Snelling said: “The disproportionate increase in blood supply to the brain over human evolution appears to be closely linked to the progression of human intelligence whereby the human brain has evolved to become not only larger, but more energetically costly than previously believed.”

aim to develop new synthetic antimicrobial oil with advanced antimicrobial efficacy.

Human skull. Arrows point to the internal carotid foramina which allow passage for the internal carotid arteries that supply blood to the brain. Photo credit: Edward Snelling. Sourced from the Raymond Dart Collection of Human Skeletons, School of Anatomical Sciences, Faculty of Health Sciences, University of the Witwatersrand.

Orchard A, Sandasi M, Kamatou G, Viljoen A, van Vuuren S.

(2016).

Thein

vitro

antimicrobial

activity

and

chemometric modelling of 59 commercial essential oils against pathogens of dermatological relevance. Chemistry and Biodiversity.doi: 10.1002/cbdv.201600218.

Dr Edward Snelling from the Brain Function Research Group and co-authors have found a way to calculate the change in the blood flow rate to the brain across 3 million years of human evolution. The authors used the dimensions of the holes at the base of the skull, termed the internal carotid foramina, to calculate the blood flow rate of the arteries that passed through these holes and supplied the brain with blood in our human ancestors. Their findings, published in Royal Society Open Science, unseat previous theories that the progression of human intelligence is simply related to the increase in the size of the brain. Their research shows that while brain size has increased by about 350%

Hominin skull casts. Photo credit: Roger Seymour. Sourced from the South Australian Museum, Adelaide, Australia Seymour RS, Bosiocic V, Snelling EP. (2016). Fossil skulls reveal that blood flow rate to the brain increased faster than brain volume during human evolution. Royal Society Open Science 3: 160305.

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SEPTEMBER 2016|RESEARCH NEWS |7

Congratulations to Mrs Estelle Watson from the Centre for Exercise Science and Sports Medicine on being nominated for the Biokinetics Association of South Africa (BASA) award. BASA is a professional body that represents Biokineticists in South Africa. Every two years the association presents awards to their members under various categories. The researcher award (B3 Scientific award) is aimed at recognizing a significant research contribution in the field of Biokinetics, as well as being involved with community research projects.

The Discovery Foundation Awards ceremony took place on the 25th August 2016. Congratulations to the following researchers who received the Discovery Foundation grants for 2016: Dr Gladness Nethathe from the Department of Anaesthesiology, Dr Ntabozuko Dwane from the Department of Paediatrics & Child Health, Dr Eitzaz Sadiq from the Department of Neurology, Dr John Thomson from the Department of Surgery, Dr Tanya Schickerling from the Department of Paediatrics & Child Health, Dr Glen Tshakhuma from the Department of Nephrology and Dr Claire van Deventer from the Department of Family Medicine. The grants are awarded to doctors in the public sector and aim to address shortage of healthcare resources through training specialists for rural areas and to help build capacity in rural healthcare institutions.

The Faculty Research Day and Postgraduate Expo 2016 took place over two days. On the 31 August 2016, Dr Paul Harris, Director of Research Informatics at Vanderbilt University and inventor of the REDCap™ software presented a plenary lecture entitled “Advancing health informatics by enabling and nurturing local talent”. His presentation was based on the technical and administrative aspects of the REDCap™ system. Photograph (left to right): Dr Paul Harris and Dr Michael Klipin

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SEPTEMBER 2016|RESEARCH NEWS |8 On the morning of the 1st September 2016, Professor Keith Klugman, Director of Pneumonia at the Bill and Melinda Gates Foundation, delivered the second Phillip V Tobias Plenary Lecture entitled “Research to prevent pneumonia deaths in children”.

Photograph (left to right): Professors Witness Mudzi, Zeblon Vilakazi, Keith Klugman, Beverley Kramer and Martin Veller

The Research Day covered five thematic areas namely, Clinical Sciences and Therapeutics for Health; Diseases of Lifestyle; Education Policy and Systems; Infectious Diseases and Molecular and Comparative Biosciences. Inside Wits Medical School rows of poster boards displayed the work of staff and students. In total, more than 250 researchers and postgraduate students presented their work at this year’s Faculty Research Day and Postgraduate Expo. The event was well attended with 1000 attendees across the Faculty. Roundtable discussions included topics such as: “targeting behaviour change in diseases of lifestyle”; “are we winning/losing the fight in managing mental health issues in the country”? and “conflict between research and health sciences education in 2016”.

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SEPTEMBER 2016|RESEARCH NEWS |9

Research Day prize winners: Clinical Sciences and Therapeutics for Health Best oral - Nasreen Mahomed Best poster - Deirdre Kruger Best student oral – Johannes van Aartsen Best student poster - Ruchika Meel Diseases of Lifestyle Best oral - Eugene Kelly Best poster - Pascaline Fonteh

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S E P T E M B E R 2 0 1 6 | R E S E A R C H N E W S | 10 Best student oral – Nyasha Mukonowenzou Best student poster - Mercy Manyame Education Policy and Systems Best oral - Linda Hlabangana Best poster - Lesley Robertson Best student oral – Felix Limbani Best student poster - Kaamil Alli Infectious Diseases Best oral - Lawrence Long Best poster - Letitia Greener Best student oral – Sibusiso Senzani Best student poster - Courtney Olwagen Molecular and Comparative Biosciences Best oral - Susan Williams Best poster - Sharon Moeno Best student oral – Nicole Narrandes Best student poster - Dale Liebenberg

The Health Sciences Research Office was delighted to welcome

back

Carnegie-Wits

Alumni

Diaspora

Fellow

Professor Roy Zent of Vanderbilt University, who was hosted by Professor Beverley Kramer, Assistant Dean: Research and Postgraduate Support. Professor Zent is the Vice Chair of Research in the Department of Medicine at the Vanderbilt Photograph (left to right): Professor Roy Zent, Dr Abdullahi Mudi, Dr Salome Maswine and Dr Coceka Mnyani

University, School of Medicine. This year marks Professor Zent’s sixth visit to the University as part of the CarnegieWits Alumni Diaspora Programme. During his visit, in July

2016, Professor Zent met with researchers and academics involved in collaborative initiatives between Wits

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S E P T E M B E R 2 0 1 6 | R E S E A R C H N E W S | 11 and Vanderbilt, once again hosted the scientific and grant writing workshops for the Faculty of Health Sciences and delivered a lecture on scientific writing. The writing workshops were particularly successful, with participants gaining key insight into developing a publishable paper as well as drafting a successful grant application. Professor Zent was joined by Professor Sten Vermund, Director of the Institute for Global Health at Vanderbilt University.

In September 2016 Dr Robert Jacobson visited the Faculty of Health Sciences. Dr Jacobson is an Associate Professor of Clinical Biomedical Science at Florida Atlantic University College of Medicine, teaching medical students and residents haematology and oncology. He was hosted by Professor Johnny Mahlangu the Head of School of Pathology. Dr Jacobson presented a Faculty Lecture entitled “Old Hats and New Genes” where he gave the audience a snapshot of blood disease pathology and treatment through the years, and looking forward to the future. Dr Jacobson’s research focus has centred on a wide range of benign and malignant blood diseases. Photograph (left to right): Professor Martin Veller and Dr Robert Jacobson His visit to the Faculty was an opportunity to reconnect with colleagues, explore collaborative research, and impart knowledge to young researchers.

Thank you to all who contributed to this issue. Do you have any significant research news you would like us to include, or comments you would like to make? Please contact [email protected] (news items to reach us by 12 October 2016) The newsletter is edited by Professor Bev Kramer, Professor Andrea Fuller, Nomfundo Sibiya and Boipelo Kgosinkwe

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