Highlights of the BMC Series – September 2020

Considerations for CRISPR human germline editing • A unified tool to assess the risk of research bias • Dietary supplementation and its effects on human gut microbiota • Pregnancy and the risks of e-cigarettes • Uncertainty in interpreting COVID-19 evidence • Uganda's responses to the COVID-19 pandemic • Qualitative experiences of unpaid carers before and during COVID-19

BMC Medical Ethics
Human germline editing in the era of CRISPR-Cas: risk and uncertainty, inter-generational responsibility, therapeutic legitimacy

Credit: Alexander Heinel/Picture Alliance/DPA

History was made this year when two women, Jennifer Doudna and Emmanuelle Charpentier, won the Nobel Prize in Chemistry for the development of a genome editing method using CRISPR-Cas9, which has numerous applications in the editing of plant and animal genomes. However, even before the discovery of CRISPR-Cas’ use in DNA editing, the use of genome editing techniques in humans has long been considered unethical, with many countries making it illegal to edit human embryos. In 2018, the highly-controversial birth of the ‘CRISPR babies’ – twin girls allegedly born with CRISPR-edited genomes – shocked the world and renewed discussions about the ethics and legality of such practices.

Using cystic fibrosis scenarios as functional examples, Schleidgen et al. explore three consistently-debated issues of human germline therapies in relation to CRISPR-Cas: the risks of using the tool in human germline editing, what responsibilities future generations bear and whether the treatment is legitimate.

The authors argue that categorically prohibiting the use of CRISPR-Cas ‘one-generation germline therapies’ – which would theoretically phenotypically cure the developing embryo, but ensure that the changes are not passed onto offspring – would not be legally or ethically justifiable, provided that concepts surrounding human germline editing are clarified.


BMC Medical Research Methodology
Assessing risk of bias: a proposal for a unified framework for observational studies and randomized trials

There are currently no unified guidelines to help individual healthcare professionals (and medical students) assess bias across different study types, an essential skill in the practice of evidence-based medicine. Study type-specific tools do currently exist, such as those that aid in the assessment of bias in observational studies, but can’t be reliably applied to other study types, such as randomized trials.

Luijendijk et al. have identified this gap and also argue that current frameworks are limited in requiring only methodological knowledge to detect bias, as some study aspects may only be appraised using subject-matter knowledge. In order to generate a unified framework, they applied a popular conceptual framework typically used only in observational studies to randomized trials, by defining the research question in terms of study population, intervention and outcome, and using causal diagrams to illustrate how each source of bias can lead to over- or under-estimations of treatment effects. The developed framework allows for the identification of three sources of bias independent of study design: bias due to a common cause, bias due to systematic measurement error, and bias due to a common effect.


BMC Microbiology
Relative abundance of the Prevotella genus within the human gut microbiota of elderly volunteers determines the inter-individual responses to dietary supplementation with wheat bran arabinoxylan-oligosaccharides

Koli Bacteria, Escherichia Coli, Bacteria, Disease

The human gut is colonized by many commensal and pathogenic bacteria, which constitute part of the gut microbiome. Since it was established that the composition of the human gut microbiome can have major impacts on our health, the field of research has rapidly grown; in the last 40 years, 80% of human gut microbiome research was published between 2013 and 2017. Bifidobacteria are relatively abundant in the human gut, and attract particular interest due to their potential for use as probiotics (live bacteria that are considered to be good for health) and as targets of prebiotics (substances that increase the abundance or activity of existing bacteria).

In their study, Chung et al. investigated the effect of dietary supplementation of AXOS (arabinoxylan oligosaccharides, which have been demonstrated to promote the abundance of Bifidobacteria) on gut microbiota. They carried out a crossover, randomised, double-blind trial whereby the diets of elderly volunteers were supplemented with AXOS or maltodextrin, and their effects on faecal bacteria and blood serum parameters were measured.

The faecal samples analysed revealed an increase in Bifidobacteria observed across the entire cohort in response to AXOS supplementation, independent of the observed inter-individual variation in gut microbiota. However, variation in the levels of baseline Prevotella species of gut bacteria did determine how responsive each patient was to AXOS supplementation. The authors conclude that AXOS supplementation is bifidogenic, suggesting that AXOS may be considered a viable prebiotic option in the elderly, and due to the influence of existing gut bacteria on the bifidogenic response, call for the consideration of microbiota profiling when testing the efficacy of prebiotics.


BMC Pregnancy and Childbirth
Electronic cigarettes may not be a “safer alternative” of conventional cigarettes during pregnancy: evidence from the nationally representative PRAMS data

Gray scale Photo of a Pregnant Woman

Conventional cigarette smoking during pregnancy is linked to adverse effects on both mother and baby health, and is amongst one of the leading preventable causes of adverse birth outcomes. The difficulties of quitting smoking during pregnancy have led many to consider alternatives to conventional cigarettes, such as electronic or ‘e’ cigarettes. As they contain fewer toxic chemicals than conventional cigarettes, e-cigarettes are largely believed to have fewer adverse health effects compared to traditional cigarettes, but there is little evidence to support this.

Authors Sooyong Kim and Sanda Cristina Oancea sought to determine whether e-cigarettes are safer in pregnancy than conventional cigarettes, by extracting and analysing data from the PRAMS (Pregnancy Risk Assessment Monitoring System) study cohort, a large study that included data on 55,000 pregnancies. Participants were classified into three groups: complete tobacco abstinence, exclusive conventional cigarette use, and exclusive e-cigarette use, and adverse birth outcomes were defined as low birth weight, preterm birth and ‘small for gestational age’. They found that, when compared to conventional cigarette users, the risk of each adverse birth outcome was not significantly reduced, and e-cigarettes cannot be considered to be safer than conventional cigarettes. Following this, the authors encourage the complete abstinence from all tobacco products during pregnancy.


Top COVID-19 Research

BMC Infectious Diseases
COVID-19: interpreting scientific evidence – uncertainty, confusion and delays

In an Editorial, Julian W Tang, a virologist at the University of Leicester, UK, who contributed to a commentary that urges the medical community and public-health authorities to acknowledge the potential for airborne transmission of SARS-CoV-2, discusses expert consensus on emerging pathogens such as SARS-CoV-2, and its effects on public health policy.


BMC Medical Ethics
Ethical and human rights considerations in public health in low and middle-income countries: an assessment using the case of Uganda’s responses to COVID-19 pandemic

In this Debate article, authors Barugahare et al. form criteria to appraise emergency public health measures adopted by the Ugandan government from an ethical and human rights perspective, and argue that measures must be ‘effective, strictly necessary, proportionate to the magnitude of the threat, reasonable in the circumstances, equitable, and least restrictive.’


BMC Geriatrics
Decision-making for receiving paid home care for dementia in the time of COVID-19: a qualitative study

Giebel et al. have presented the first study which provides insights into the experiences of UK-based unpaid carers receiving paid home care for dementia, both before and during the pandemic.

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