Commentary: not just genes - reclaiming a role for environmental influences on aetiology and outcome in autism. A commentary on Mandy and Lai (2016)

Mandy and Lai (2015) do the field a service in 'reclaiming' the role of pre- and postnatal environmental influences on the aetiology and course of autism spectrum conditions (ASC). This follows several decades where now discredited theories about putative psychogenic and biological disease models held sway, not least in the public mind. We discuss issues that arise from their review; including the need to identify how large the environmental influences on ASC are likely to be; the specificity of these environmental influences to ASC as opposed to a broader range of neurodevelopmental conditions and outcomes; how best to study complex interactions between genetic and environmental influences; and the promise of novel insights into their mechanisms of action. The review highlights current research that aims to better our understanding of the role of environmental factors in the aetiology and course of ASC and, in the near future, may offer the potential for personalised medicine approaches to intervention based on these discoveries.

Students’ perception of the safety and value of a herbal vs. a conventional medicine for treating insomnia

University students suffer from variable sleep patterns including insomnia;[1] furthermore, the highest incidence of herbal use appears to be among college graduates.[2] Our objective was to test the perception of safety and value of herbal against conventional medicine for the treatment of insomnia in a non-pharmacy student population. We used an experimental design and bespoke vignettes that relayed the same effectiveness information to test our hypothesis that students would give higher ratings of safety and value to herbal product compared to conventional medicine. We tested another hypothesis that the addition of side-effect information would lower people’s perception of the safety and value of the herbal product to a greater extent than it would with the conventional medicine.

The imminent availability of a potent weight-loss medicine in pharmacies: public perception of effectiveness

Orlistat is an effective weight-loss medicine, which will soon be available for purchase in pharmacies. We used a factorial experiment and found that informing people about the availability for purchase of this medicinal product previously only available on prescription resulted in higher ratings of perceived value and effectiveness compared to a natural health supplement even though we used the same statement about effectiveness. This positive perception of orlistat was not impaired by the provision of side-effect information. Orlistat will soon be available in pharmacies. Health professionals must act to prevent its misuse by those not overweight.

Copper complexes of new benzodioxotetraaza macrocycles with potential applications in nuclear medicine

Two novel benzodioxotetraaza macrocycles [2,9-dioxo-1,4,7,10-tetraazabicyclo[10.4.0]1,11-hexadeca-1(11),13,15-triene (H(2)L1) and 2,10-dioxo-1,4,8,11-tetraazabicyclo[11.4.0]1,12-heptadeca-1(12),14,16-triene (H(2)L2)] were synthesized by a [1 + 1] crablike cyclization. The protonation constants of both ligands were determined by H-1 NMR titration and by potentiometry at 25.0 degrees C in 0.10 M ionic strength in KNO3. The latter method was also used to ascertain the stability constants of their copper(II) complexes. These studies showed that the CuL1 complex has a much lower thermodynamic stability than the CuL2, and the H(2)L2 displays an excellent affinity for copper(II), due to the good fit of copper(II) into its cavity. The copper complexes of the novel ligands were characterized by electronic spectroscopy in solution and by crystal X-ray diffraction. These studies indicated that the copper center in the CuL1 complex adopts a square-pyramidal geometry with the four nitrogen atoms of the macrocycle forming the equatorial plane and a water molecule at axial position, and the copper in the CuL2 complex is square-planar. Several labeling conditions were tested, and only H(2)L2 could be labeled with Cu-67 efficiently (> 98%) in mild conditions (39 degrees C, 15 min) to provide a slightly hydrophilic radioligand (log D = -0.19 +/- 0.03 at pH 7.4). The in vitro stability was studied in the presence of different buffers or with an excess of diethylenetriamine-pentaethanoic acid. Very high stability was shown under these conditions for over 5 days. The incubation of the radiocopper complex in human serum showed 6% protein binding.

Herbal medicine: the science of the art

In the last 50 years science has provided new perspectives on the ancient art of herbal medicine. The present article discusses ways in which the evidence base for the professional use of 'Western' herbal medicine, as therapy to treat disease, known as phytotherapy, can be strengthened and developed. The evidence base for phytotherapy is small and lags behind that for the nutritional sciences, mainly because phytochemicals are ingested as complex mixtures that are incompletely characterised and have only relatively recently been subject to scientific scrutiny. While some methodologies developed for the nutritional sciences can inform phytotherapy research, opportunities for observational studies are more limited, although greater use could be made of patient case notes. Randomised clinical trials of single-herb interventions are relatively easy to undertake and increasing numbers of such studies are being published. Indeed, enough data are available on three herbs (ginkgo (Ginkgo biloba), St John's wort (Hypericum perforatum) and saw palmetto (Serenoa repens)) for meta-analyses to have been undertaken. However, phytotherapy is holistic therapy, using lifestyle advice, nutrition and individually-prescribed mixtures of herbs aimed at reinstating homeostasis. While clinical experience shows that this approach is applicable to a wide range of conditions, including chronic disease, evidence of its efficacy is scarce. Strategies for investigating the full holistic approach of phytotherapy and its main elements are discussed and illustrated through the author's studies at the University of Reading.

Nutrition Society Silver Medal Lecture Nutrigenetics and personalised nutrition: how far have we progressed and are we likely to get there?

Nutrigenetics and personalised nutrition are components of the concept that in the future genotyping will be used as a means of defining dietary recommendations to suit the individual. Over the last two decades there has been an explosion of research in this area, with often conflicting findings reported in the literature. Reviews of the literature in the area of apoE genotype and cardiovascular health, apoA5 genotype and postprandial lipaemia and perilipin and adiposity are used to demonstrate the complexities of genotype-phenotype associations and the aetiology of apparent between-study inconsistencies in the significance and size of effects. Furthermore, genetic research currently often takes a very reductionist approach, examining the interactions between individual genotypes and individual disease biomarkers and how they are modified by isolated dietary components or foods. Each individual possesses potentially hundreds of 'at-risk' gene variants and consumes a highly-complex diet. In order for nutrigenetics to become a useful public health tool, there is a great need to use mathematical and bioinformatic tools to develop strategies to examine the combined impact of multiple gene variants on a range of health outcomes and establish how these associations can be modified using combined dietary strategies.

Personalised nutrition: status and perspectives

Personalised, genotype-based nutrition is a concept that links genotyping with specific nutritional advice in order to improve the prevention of nutrition-associated, chronic diseases. This review describes the current scientific basis of the concept and discusses its problems. There is convincing evidence that variant genes may indeed determine the biological response to nutrients. The effects of single-gene variants on risk or risk factor levels of a complex disease are, however, usually small and sometimes inconsistent. Thus, information on the effects of combinations of relevant gene variants appears to be required in order to improve the predictive precision of the genetic information. Furthermore, very few associations between genotype and response have been tested for causality in human intervention studies, and little is known about potential adverse effects of a genotype-derived intervention. These issues need to be addressed before genotyping can become an acceptable method to guide nutritional recommendations.