It is estimated that more than one-tenth of adults aged ≥60 years are now classified as having sarcopenic obesity (SO), a clinical condition characterized by the concurrent presence of sarcopenia (low muscle mass and weakness) and obesity (excessive fat mass). Independently, sarcopenia and obesity are associated with a high risk of numerous adverse health outcomes including cardiovascular diseases (CVDs) and neurological conditions (e.g. dementia), but SO may confer a greater risk, exceeding either condition alone. This imposes a substantial burden on individuals, healthcare systems and society. In recent years, an increasing number of observational studies have explored the association between SO and the risk of CVDs; however, results are mixed. Moreover, the pathophysiology of SO is governed by a complex interplay of multiple mechanisms including insulin resistance, inflammation, oxidative stress, hormonal shifts and alteration of energy balance, which may also play a role in the occurrence of various CVDs. Yet, the exact mechanisms underlying the pathological connection between these two complex conditions remain largely unexplored. The aim of this review is to examine the association between SO and CVDs. Specifically, we seek to: (1) discuss the definition, epidemiology and diagnosis of SO; (2) reconcile previously inconsistent findings by synthesizing evidence from longitudinal studies on the epidemiological link between SO and CVDs; and (3) discuss critical mechanisms that may elucidate the complex and potentially bidirectional relationships between SO and CVDs.

The interplay between genetic and environmental factors plays a significant role in interindividual variation in immune and inflammatory responses. The availability of high-throughput low-cost genotyping and next-generation sequencing has revolutionized our ability to identify human genetic variation and understand how this varies within and between populations, and the relationship with disease. In this review, we explore the potential of genomics for patient benefit, specifically in the diagnosis, prognosis and treatment of inflammatory and immune-related diseases. We summarize the knowledge arising from genetic and functional genomic approaches, and the opportunity for personalized medicine. The review covers applications in infectious diseases, rare immunodeficiencies and autoimmune diseases, illustrating advances in diagnosis and understanding risk including use of polygenic risk scores. We further explore the application for patient stratification and drug target prioritization. The review highlights a key challenge to the field arising from the lack of sufficient representation of genetically diverse populations in genomic studies. This currently limits the clinical utility of genetic-based diagnostic and risk-based applications in non-Caucasian populations. We highlight current genome projects, initiatives and biobanks from diverse populations and how this is being used to improve healthcare globally by improving our understanding of genetic susceptibility to diseases and regional pathogens such as malaria and tuberculosis. Future directions and opportunities for personalized medicine and wider application of genomics in health care are described, for the benefit of individual patients and populations worldwide.

Animal mass mortality events (MMEs) will increase with weather and climate extremes. MMEs can add significant stress to ecosystems through extraordinary nutrient pulses or contribute to potential disease transmission risks. Given their efficient removal of carrion biomass from landscapes, we argue here for the potential of scavenger guilds to be a key nature-based solution to mitigating MME effects. However, we caution that scavenger guilds alone will not be a silver bullet. It is critical for further research to identify how the composition of scavenger guilds and the magnitude of MMEs will determine when scavengers will buffer the impacts of such events on ecosystems and when intervention might be required. Some MMEs are too large for scavengers to remove efficiently, and there is a risk of MMEs subsidizing pest species, altering nutrient cycling or leading to disease spread. Prioritizing native scavenger taxa in conservation management policies may help to boost ecosystem resilience through preserving their key ecological services. This should be part of a multi-pronged approach to MME mitigation that combines scavenger conservation with practices such as carcass dispersal or removal when exceeding a threshold quantity. Policymakers are urged to identify such thresholds and to recognize both the insects and the vertebrate scavengers that could act as allies for mitigating the emerging problem of climate-driven MMEs.

In many human populations, especially those living in regions with pronounced climatic differences between seasons, the most sensitive (prenatal and neonatal) developmental stages occur in contrasting conditions depending on the season of conception. The difference in prenatal and postnatal environments may be a factor significantly affecting human development and risk for later life chronic diseases. Factors potentially contributing to this kind of developmental programming include nutrition, outdoor temperature, infectious exposures, duration of sunlight, vitamin D synthesis, etc. Month of birth is commonly used as a proxy for exposures which vary seasonally around the perinatal period. Season-of-birth patterns have been identified for many chronic health outcomes. In this review, the research evidence for the seasonality of birth in adult-life disorders is provided and potential mechanisms underlying the phenomenon of early life seasonal programming of chronic disease and longevity are discussed.

Maternal folic acid (FA) supplementation is well recognised to protect against neural tube defects. Folate is a critical cofactor in one-carbon metabolism involved in the epigenetic regulation of transcription that underpins development. Thus, it is possible that maternal FA supplementation may have additional, unforeseen persistent effects in the offspring. This is supported by the modification by maternal supplementation with one-carbon donors and FA of the epigenetic regulation of offspring phenotype in mutant mice. The present article reviews studies in human subjects and experimental animals of the effect of maternal FA intake and phenotypic outcomes in the offspring. Maternal FA intake was associated with a short-term increased incidence of allergy-related respiratory impairment in children and multigenerational respiratory impairment in rats. Higher maternal folate status during pregnancy was associated positively with insulin resistance in 6-year-olds. In rats, maternal FA supplementation modified hepatic metabolism and vascular function through altered transcription, in some cases underpinned by epigenetic changes. FA supplementation in pregnant rats increased mammary tumorigenesis, but decreased colorectal cancer in the offspring. Maternal FA supplementation decreased a range of congenital cardiac defects in children. These findings support the view that maternal FA supplementation induces persistent changes in a number of phenotypic outcomes in the offspring. However, the number of studies is limited and insufficient to indicate a need to change current recommendations for FA intake in pregnancy. Nevertheless, such effects should be investigated thoroughly in order to support firm conclusions about the risk of unanticipated long-term negative effects of maternal FA supplementation in humans.

The twin concepts of zooprophylaxis and the dilution effect originated with vector-borne diseases (malaria), were driven forward by studies on Lyme borreliosis and have now developed into the mantra “biodiversity protects against disease”. The basic idea is that by diluting the assemblage of transmission-competent hosts with non-competent hosts, the probability of vectors feeding on transmission-competent hosts is reduced and so the abundance of infected vectors is lowered. The same principle has recently been applied to other infectious disease systems – tick-borne, insect-borne, indirectly transmitted via intermediate hosts, directly transmitted. It is claimed that the presence of extra species of various sorts, acting through a variety of distinct mechanisms, causes the prevalence of infectious agents to decrease. Examination of the theoretical and empirical evidence for this hypothesis reveals that it applies only in certain circumstances even amongst tick-borne diseases, and even less often if considering the correct metric – abundance rather than prevalence of infected vectors. Whether dilution or amplification occurs depends more on specific community composition than on biodiversity per se. We warn against raising a straw man, an untenable argument easily dismantled and dismissed. The intrinsic value of protecting biodiversity and ecosystem function outweighs this questionable utilitarian justification.

Variations in human DNA, most frequently single-nucleotide polymorphisms (SNPs), can have functional consequences ranging from severe to none. Variations in outcome (phenotype) can be compared, from cystic fibrosis through haemochromatosis to general familial risks in, for example, colo-rectal cancer (CRC). Cystic fibrosis and haemochromatosis have severe phenotypes with high penetrance, with signs and symptoms always or mostly present; thus, they have been easy to identify from family studies. However, the familial risks that are known to contribute markedly to CRC are unknown. The sequencing of the human genome has now made possible the identification of these and other disease variants. Knowing the DNA sequence in an idealised individual adds little unless variants that increase (or decrease) disease risk from the norm can be identified. Such variants can be expected to be very common in the general population, but have low penetrance and only change risk to a limited extent. Many patients will not have the risk variant and many ‘normal’ patients will have the risk variant. Thus, very large case–control cohorts are essential. These case–control cohorts can be analysed at three different levels: (1) individual SNPs; (2) individual genes; (3) genome-wide analysis (GWA). Level 1 looks for case–control differences for specific SNPs. Alternatively, new technology can be applied to examine a range of SNPs within a gene to track differences in its regulation as well as in function. Finally, the whole genome with ≥0·5×106 SNPs could be marked. The first two approaches involve selecting ‘candidate’ SNPs or genes, while GWA looks for any variation in the genome that is enriched in the cases. All three approaches carry the certainty that significant associations will be found by statistical chance, for which correction must be made. This latter issue is helped by large numbers and by independent replication cohorts.

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.

There is an increasing body of evidence, including that from prospective population studies and epidemiological observational studies, suggesting a strong inverse relationship between increased consumption of wholegrain foods and reduced risk of CVD. This evidence has translated into specific dietary recommendations in the USA to consume at least three servings of whole grain per d, and has informed the development of specific health claims for wholegrain foods both in the USA and in Europe. Wholegrain foods are rich sources of many nutrients and phytochemicals, including complex carbohydrates, dietary fibre, minerals, vitamins, antioxidants and phyto-oestrogens such as lignans. Many of these components are lost from the grain during processing and although some may be replaced (such as in the mandatory fortification of white flour), this practice ignores the possible synergistic effects of the ‘natural’ constituents. The notion that wholegrain foods are simply a source of dietary fibre has been dispelled, although the additional components that contribute to the health benefits have not been clearly identified. In addition, the mechanisms by which wholegrain foods may have their effect are poorly understood. At present there are few strictly-controlled intervention studies that have confirmed a beneficial effect of increased consumption of wholegrain foods, demonstrated the level of consumption required to elicit a beneficial effect or provided evidence of modes of action. Although wholegrain foods are considered amongst the healthiest food choices available, their consumption falls well below current recommendations, which have been based mainly on epidemiological evidence. Well-controlled intervention studies are needed to provide more detailed mechanistic evidence to support the health claims and findings which can be used to develop effective public health strategies to promote whole-grain consumption.