One step forward, two steps back – requiring ministerial approval for all ‘non-therapeutic\' health research involving minors

The new National Health Act has clarified that children may take part in ‘non-therapeutic\' research (NTR) and the age at which they may provide independent consent to such research, viz. at legal majority. However, the Act will require consent from the Minister of Health for all research classed as NTR and involving minors regardless of the level of risk. This requirement is overly broad. It will require that low-risk research without direct benefits, which might be adequately reviewed by an accredited research ethics committee (REC), must also be reviewed by the Minister. As it currently stands this requirement serves no plausible ethical purpose, will cause delays and discourage essential research on the needs of children, and may inspire researchers and RECs alike to ‘foil the system\'. We argue that in the long term there should be comprehensive law reform for child research. However, in the short term, amendments should be made to the Act to narrow the scope of this provision. The amendment should require ministerial consent for research that is currently not approvable by an REC in terms of national ethical guidelines, namely, research that does not hold out direct benefit but presents more than a minor increase over minimal risk. If our law reform recommendations are rejected, we favour the delegation of this task to RECs because, if they receive appropriate training, they should be competent to conduct it. We accept the disadvantages, namely that the same body will review protocols twice from slightly different perspectives and that certain categories of research will remain unapprovable.South African Medical Journal Vol. 97 (2) 2007: pp.200-202

General Protocol for Constructing Molecular Models of Nanodiscs

Nanodisc technology is increasingly being applied for structural and biophysical studies of membrane proteins. In this work, we present a general protocol for constructing molecular models of nanodiscs for molecular dynamics simulations. The protocol is written in python and based on geometric equations, making it fast and easy to modify, enabling automation and customization of nanodiscs in silico. The novelty being the ability to construct any membrane scaffold protein (MSP) variant fast and easy given only an input sequence. We validated and tested the protocol by simulating seven different nanodiscs of various sizes and with different membrane scaffold proteins, both circularized and noncircularized. The structural and biophysical properties were analyzed and shown to be in good agreement with previously reported experimental data and simulation studies

LION/web:a web-based ontology enrichment tool for lipidomic data analysis

Background: A major challenge for lipidomic analyses is the handling of the large amounts of data and the translation of results to interpret the involvement of lipids in biological systems. Results: We built a new lipid ontology (LION) that associates &gt; 50,000 lipid species to biophysical, chemical, and cell biological features. By making use of enrichment algorithms, we used LION to develop a web-based interface (LION/web, www.lipidontology.com) that allows identification of lipid-associated terms in lipidomes. LION/web was validated by analyzing a lipidomic dataset derived from well-characterized sub-cellular fractions of RAW 264.7 macrophages. Comparison of isolated plasma membranes with the microsomal fraction showed a significant enrichment of relevant LION-terms including "plasma membrane", "headgroup with negative charge", "glycerophosphoserines", "above average bilayer thickness", and "below average lateral diffusion". A second validation was performed by analyzing the membrane fluidity of Chinese hamster ovary cells incubated with arachidonic acid. An increase in membrane fluidity was observed both experimentally by using pyrene decanoic acid and by using LION/web, showing significant enrichment of terms associated with high membrane fluidity ("above average", "very high", and "high lateral diffusion" and "below average transition temperature"). Conclusions: The results demonstrate the functionality of LION/web, which is freely accessible in a platform-independent way.</p

Insights from Comparative Genomics of the Genus Salmonella

Comparative genomics have become a standard approach to gain insights into the interrelationships of microorganisms. Here, we have applied variable bioinformatic techniques to compare over 200 Salmonella genomes. First, we present a tree of all sequenced different members of the Enterobacteriaceae family, based on comparison of average amino acid identities. This technique was also applied to zoom in on the genomes of the genus Salmonella. The pan and core genomes of this genus were established and compared to experimental data available on the literature that identified essential genes. Difficulties and shortcomings of both approaches are discussed. Metabolic pathways unique for Salmonella were identified. Finally, we present an analysis of genes coding for small RNAs, an important part of the genetic repertoire of bacteria that is often ignored. The findings reported here are discussed and compared with available literature

Research ethics committees in a tight spot: Approving consent strategies for child research that are prima facie illegal but are ethical in terms of national guidelines

It is an internationally accepted principle that ethics norms should be applied and enforced in research with humans through ethics review by research ethics committees (RECs). This places RECs at the very heart of the system for protecting participants and enforcing their rights. In the South African ethical-legal framework for child research, there are divergent approaches to consent. That is, section 71 of the National Health Act (No. 61 of 2003) (NHA) requires mandatory parental consent for child research, and limits the authority for proxy consent to parents and legal guardians. However, national ethics guidelines authorised by section 72 of the NHA and issued by the National Health Research Ethics Council (NHREC) acting in terms of its mandate (National Department of Health, 2015) allow a more nuanced approach – i.e. self-consent by older adolescents, provided certain conditions are met, and consent by a range of parental substitutes where there are no available parents or legal guardians. We have argued elsewhere that the consent approach in section 71 is inappropriately restrictive and are of the view that the consent approach endorsed in national ethics guidelines is more defensible. An REC that elects to approve a consent strategy allowable in ethics guidelines is effectively electing to not follow section 71, which raises the question of what the consequences might be for that REC. This article examines the legal liability of RECs through three ‘threads’ of accountability: the NHREC, the institutions hosting RECs, and the courts. We conclude that: (i) if an REC approves a child protocol with consent strategies allowable in terms of national ethics guidelinesbut not in terms of section 71, it is unlikely that the NHREC would discipline the REC in the face of a complaint – provided the REC acted within national ethics guidelines issued by the NHREC in terms of the latter’s section 72 mandate to set national norms and standards; (ii) if an REC approves a consent approach allowed for in ethics guidance, it is also unlikely that the host institution would discipline the REC in the face of a complaint – especially if the institution is aware of the REC’s explicit decision to follow national ethics guidelines that are authorised by section 72 of the NHA; and (iii) an REC could only be sued by a participant in terms of the law of delict (and be liable for damages) if several demanding components are proven, such as that the harm suffered by the participant resulted directly from the REC’s actions in approving a particular consent strategy for that research. Furthermore, the court may well look to national ethics guidelines in making determinations about whether an REC’s conduct was wrongful for the purposes of liability in civil law. RECs are protected from being collectively liable by insurance taken out by their host institutions. We make a series of recommendations to address this issue.

Stable isotope analysis of soft tissues from mummified human remains

Mummies are faunal remains that include the preservation of soft tissues, such as skin, muscle, nails and hair as well as bone. These soft tissues are generally rich in collagen or keratin proteins and thus provide potentially suitable material for stable isotope studies. When preserved, such tissues can provide high-resolution information about the diet and migration of humans in the weeks and months before death. Hair, nails and soft tissue provide short-term (months) dietary information in contrast to bone which will represent 5–20 years of dietary history prior to death, depending on the bone analysed. Such high-resolution data can answer questions on the season of death, seasonality of food resources and the movement and relocation of people. This review begins with a summary of the most common isotope techniques (13C/12C, 15N/14N) and the tissues concerned, followed by an analysis of the key questions that have been addressed using these methods. Until relatively recently work has focused on bulk protein isotope analysis, but in the last 10 years this has been expanded to on-line compound-specific amino acid analysis and to a wider variety of isotopes (18O/16O, 2H/1H and 34S/32S) and these applications are also discussed

Differential expression and sex chromosome association of CHD3/4 and CHD5 during spermatogenesis

ATP-dependent nucleosome remodelers of the CHD family play important roles in chromatin regulation during development and differentiation. The ubiquitously expressed CHD3 and CHD4 proteins are essential for stem cell function and serve to orchestrate gene expression in different developmental settings. By contrast, the closely related CHD5 is predominantly expressed in neural tissue and its role is believed to be restricted to neural differentiation. Indeed, loss of CHD5 contributes to neuroblastoma. In this study, we first demonstrate that CHD5 is a nucleosome-stimulated ATPase. We then compare CHD3/4 and CHD5 expression in mouse brain and show that CHD5 expression is restricted to a subset of cortical and hippocampal neurons whereas CHD3/4 expression is more widespread. We also uncover high levels of CHD5 expression in testis. CHD5 is transiently expressed in differentiating germ cells. Expression is first detected in nuclei of postmeiotic round spermatids, reaches a maximum in stage VIII spermatids and then falls to undetectable levels in stage IX spermatids. Surprisingly, CHD3/4 and CHD5 show complementary expression patterns during spermatogenesis with CHD3/ 4 levels progressively decreasing as CHD5 expression increases. In spermatocytes, CHD3/4 localizes to the pseudoautosomal region, the X centromeric region and then spreads into the XY body chromatin. In postmeiotic cells, CHD5 colocalises with macroH2A1.2 in association with centromeres and part of the Y chromosome. The subnuclear localisations of CHD4 and CHD5 suggest specif

Gendered endings: Narratives of male and female suicides in the South African Lowveld

This is the author's accepted manuscript. The final publication is available at Springer via http://dx.doi.org/10.1007/s11013-012-9258-y. Copyright @ Springer Science+Business Media, LLC 2012.Durkheim’s classical theory of suicide rates being a negative index of social solidarity downplays the salience of gendered concerns in suicide. But gendered inequalities have had a negative impact: worldwide significantly more men than women perpetrate fatal suicides. Drawing on narratives of 52 fatal suicides in Bushbuckridge, South Africa, this article suggests that Bourdieu’s concepts of ‘symbolic violence’ and ‘masculine domination’ provide a more appropriate framework for understanding this paradox. I show that the thwarting of investments in dominant masculine positions have been the major precursor to suicides by men. Men tended to take their own lives as a means of escape. By contrast, women perpetrated suicide to protest against the miserable consequences of being dominated by men. However, contra the assumption of Bourdieu’s concept of ‘habitus’, the narrators of suicide stories did reflect critically upon gender constructs

Oral Nutrition as a Form of Pre-Operative Enhancement in Patients Undergoing Surgery for Colorectal Cancer:A Systematic Review

Background: Nutritional status has major impacts on the outcome of surgery, in particular in patients with cancer. The aim of this review was to assess the merit of oral pre-operative nutritional support as a part of prehabilitation in patients undergoing surgery for colorectal cancer. Methods: A systematic literature search and meta-analysis was performed according to the Preferred Reporting of Systematic Reviews and Meta-Analyses (PRISMA) recommendations in order to review all trials investigating the effect of oral pre-operative nutritional support in patients undergoing colorectal surgery. The primary outcome was overall complication rate. Secondary outcomes were incision infection rate, anastomotic leakage rate, and length of hospital stay. Results: Five randomized controlled trials and one controlled trial were included. The studies contained a total of 583 patients with an average age of 63y (range 23-88y), of whom 87% had colorectal cancer. Malnourishment rates ranged from 8%-68%. All investigators provided an oral protein supplement. Overall patient compliance rates ranged from 72%-100%. There was no significant reduction in the overall complication rate in the interventional groups (odds ratio 0.82; 95% confidence interval 0.52-1.25). Conclusion: Current studies are too heterogeneous to conclude that pre-operative oral nutritional support could enhance the condition of patients undergoing colorectal surgery. Patients at risk have a relatively lean body mass deficit (sarcopenia) rather than an absolute malnourished status. Compliance is an important element of prehabilitation. Targeting patients at risk, combining protein supplements with strength training, and defining standardized patient-related outcomes will be essential to obtain satisfactory result