Metabolomic analysis of human disease and its application to the eye

Metabolomics, the analysis of the metabolite profile in body fluids or tissues, is being applied to the analysis of a number of different diseases as well as being used in following responses to therapy. While genomics involves the study of gene expression and proteomics the expression of proteins, metabolomics investigates the consequences of the activity of these genes and proteins. There is good reason to think that metabolomics will find particular utility in the investigation of inflammation, given the multi-layered responses to infection and damage that are seen. This may be particularly relevant to eye disease, which may have tissue specific and systemic components. Metabolomic analysis can inform us about ocular or other body fluids and can therefore provide new information on pathways and processes involved in these responses. In this review, we explore the metabolic consequences of disease, in particular ocular conditions, and why the data may be usefully and uniquely assessed using the multiplexed analysis inherent in the metabolomic approach

Causes of molecular convergence and parallelism in protein evolution

To what extent is the convergent evolution of protein function attributable to convergent or parallel changes at the amino acid level? The mutations that contribute to adaptive protein evolution may represent a biased subset of all possible beneficial mutations owing to mutation bias and/or variation in the magnitude of deleterious pleiotropy. A key finding is that the fitness effects of amino acid mutations are often conditional on genetic background. This context dependence (epistasis) can reduce the probability of convergence and parallelism because it reduces the number of possible mutations that are unconditionally acceptable in divergent genetic backgrounds. Here, I review factors that influence the probability of replicated evolution at the molecular level

Organically modified clays for pollutant uptake and environmental protection

Because of their natural abundance and widespread occurrence, clays have been used 'in the service of man' (Konta 1995) since antiquity, notably as the raw materials in pottery and ceramics. Similarly, the use of fuller's earth (a calcium-rich montmorillonite) as a scouring and cleaning agent of raw wool dates back to before 2000 BC (Robertson 1986). Clays have also long served as medicinal and therapeutic agents, among which Bolus Armenus (a red clay from Cappadocia) and terra sigillata (a kaolinite-rich material from the island of Lemnos) are well known for their efficacy in curing festering wounds, skin afflictions, and snake bites (Robertson 1986, Carretero et al. 2006, Droy-Lefaix and Tateo 2006). Likwise, Sudanese villagers along the Nile have traditionally used a local bentonite clay to rid river water of viruses and bacteria (Lund and Nissen 1986, Madsen and Schlundt 1989). For a description of the modern-day uses of clays and clay materials in various industries the reader is referred to the reviews by Murray (2003) and Harvey and Lagaly (2006). Clay therapy and many practical applications of clays rely on the ability of these minerals to sorb and retain harmful and undesirable substances from their immediate environment. The sorptive capacity of clays is related to their small particle size, extensive surface area, layer structure, and charge characteristics. The vast literature on the interactions of clay minerals, especially smectites, with small and polymeric organic molecules has periodically been reviewed (Mortland 1970, Theng 1974, 1979, Huang and Schnitzer 1986, Yariv and Cross 2002, Lagaly et al. 2006). Although the reactivity of these minerals might be expected to extend to anthropogenic and industrial pollutants, the use of smectites for environmental protection is a relatively recent development. Its emergence is prompted by a growing awareness that industrial pollutants pose a threat to environmental and human health, and the need to find inexpensive and environmentally friendly materials for pollution control (Kowalska et al. 1994, Xu et al. 1997, Prost and Yaron 2001). Here we assess the literature that has accumulated over the past two decades on the use of smectites and their organically modified forms as sorbents of non-ionic organic compounds and pollutants. As far as is possible, we will refer to key papers and reviews, rather than cite individual authors.B.K.G. Theng, G.J. Churchman, W.P. Gates & F. Yua

The impact of surgical delay on resectability of colorectal cancer: An international prospective cohort study

AimThe SARS-CoV-2 pandemic has provided a unique opportunity to explore the impact of surgical delays on cancer resectability. This study aimed to compare resectability for colorectal cancer patients undergoing delayed versus non-delayed surgery.MethodsThis was an international prospective cohort study of consecutive colorectal cancer patients with a decision for curative surgery (January-April 2020). Surgical delay was defined as an operation taking place more than 4 weeks after treatment decision, in a patient who did not receive neoadjuvant therapy. A subgroup analysis explored the effects of delay in elective patients only. The impact of longer delays was explored in a sensitivity analysis. The primary outcome was complete resection, defined as curative resection with an R0 margin.ResultsOverall, 5453 patients from 304 hospitals in 47 countries were included, of whom 6.6% (358/5453) did not receive their planned operation. Of the 4304 operated patients without neoadjuvant therapy, 40.5% (1744/4304) were delayed beyond 4 weeks. Delayed patients were more likely to be older, men, more comorbid, have higher body mass index and have rectal cancer and early stage disease. Delayed patients had higher unadjusted rates of complete resection (93.7% vs. 91.9%, P = 0.032) and lower rates of emergency surgery (4.5% vs. 22.5%, P ConclusionOne in 15 colorectal cancer patients did not receive their planned operation during the first wave of COVID-19. Surgical delay did not appear to compromise resectability, raising the hypothesis that any reduction in long-term survival attributable to delays is likely to be due to micro-metastatic disease