How do BMI-restrictive policies impact women seeking NHS-funded IVF in the United Kingdom? A qualitative analysis of online forum discussions.

BACKGROUND: Across the United Kingdom's National Health Service (NHS), women with a Body Mass Index (BMI) of > 30 face restrictions accessing In Vitro Fertilisation (IVF) treatment. This study asks: what are the (un)expected and (un)intended harms and consequences experienced by women restricted from accessing NHS-funded IVF due to BMI threshold criteria? METHODS: Posts from a popular infertility online forum were collected and reflexively thematically analysed. RESULTS: On the forum, users discussed how they struggled to lose weight, how they faced time pressures to meet BMI thresholds, and they shared knowledge on how to comply or appear compliant with BMI cut-offs. Our study found widespread moral discourses around body weight were reproduced in the forum, particularly commonplace narratives that body weight is under personal control, that people with a high BMI should 'work' to change their bodies, and that this work helps demonstrate deservingness for IVF treatment. Moralising discourses around weight were linked to the responsibilities of a hoped-for future of motherhood, as users performed deservingness through emphasising their commitment to meeting the BMI threshold. CONCLUSION: We conclude that NHS-IVF policies in the United Kingdom do not consider the burdensome emotional and moral work placed on people seeking treatment due to inflexible upper-limit BMI criteria.

In the United Kingdom, people can access public funding for In Vitro Fertilisation (IVF) treatment if certain criteria are met. Funding restrictions differ between geographical areas, but most areas restrict treatment to women with a Body Mass Index (BMI) below 30. This study explores the unexpected and unintended harms experienced by women restricted from NHS-funded IVF due to these BMI criteria. Posts from a popular infertility online forum were collected and thematically analysed. The study found moralising discourses around body weight which emphasized that women had personal control over their bodies and needed to 'work' to change their bodies to show deservingness for treatment. We conclude that NHS-IVF policies in the UK overlook the emotional and moral burdens placed on individuals due to rigid BMI criteria. As the impact of BMI limits on healthcare access is an under-researched topic, we believe this work is important for demonstrating the harms of BMI-restrictive policies.

Genetic copy number variants, cognition and psychosis: a meta-analysis and a family study.

The burden of large and rare copy number genetic variants (CNVs) as well as certain specific CNVs increase the risk of developing schizophrenia. Several cognitive measures are purported schizophrenia endophenotypes and may represent an intermediate point between genetics and the illness. This paper investigates the influence of CNVs on cognition. We conducted a systematic review and meta-analysis of the literature exploring the effect of CNV burden on general intelligence. We included ten primary studies with a total of 18,847 participants and found no evidence of association. In a new psychosis family study, we investigated the effects of CNVs on specific cognitive abilities. We examined the burden of large and rare CNVs (>200 kb, <1% MAF) as well as known schizophrenia-associated CNVs in patients with psychotic disorders, their unaffected relatives and controls (N = 3428) from the Psychosis Endophenotypes International Consortium (PEIC). The carriers of specific schizophrenia-associated CNVs showed poorer performance than non-carriers in immediate (P = 0.0036) and delayed (P = 0.0115) verbal recall. We found suggestive evidence that carriers of schizophrenia-associated CNVs had poorer block design performance (P = 0.0307). We do not find any association between CNV burden and cognition. Our findings show that the known high-risk CNVs are not only associated with schizophrenia and other neurodevelopmental disorders, but are also a contributing factor to impairment in cognitive domains such as memory and perceptual reasoning, and act as intermediate biomarkers of disease risk.

Mitochondrial content is central to nuclear gene expression: Profound implications for human health.

We review a recent paper in Genome Research by Guantes et al. showing that nuclear gene expression is influenced by the bioenergetic status of the mitochondria. The amount of energy that mitochondria make available for gene expression varies considerably. It depends on: the energetic demands of the tissue; the mitochondrial DNA (mtDNA) mutant load; the number of mitochondria; stressors present in the cell. Hence, when failing mitochondria place the cell in energy crisis there are major effects on gene expression affecting the risk of degenerative diseases, cancer and ageing. In 2015 the UK parliament approved a change in the regulation of IVF techniques, allowing "Mitochondrial replacement therapy" to become a reproductive choice for women at risk of transmitting mitochondrial disease to their children. This is the first time that this technique will be available. Therefore understanding the interaction between mitochondria and the nucleus has never been more important.

A novel quantitative assay of mitophagy: Combining high content fluorescence microscopy and mitochondrial DNA load to quantify mitophagy and identify novel pharmacological tools against pathogenic heteroplasmic mtDNA.

Mitophagy is a cellular mechanism for the recycling of mitochondrial fragments. This process is able to improve mitochondrial DNA (mtDNA) quality in heteroplasmic mtDNA disease, in which mutant mtDNA co-exists with normal mtDNA. In disorders where the load of mutant mtDNA determines disease severity it is likely to be an important determinant of disease progression. Measuring mitophagy is technically demanding. We used pharmacological modulators of autophagy to validate two techniques for quantifying mitophagy. First we used the IN Cell 1000 analyzer to quantify mitochondrial co-localisation with LC3-II positive autophagosomes. Unlike conventional fluorescence and electron microscopy, this high-throughput system is sufficiently sensitive to detect transient low frequency autophagosomes. Secondly, because mitophagy preferentially removes pathogenic heteroplasmic mtDNA mutants, we developed a heteroplasmy assay based on loss of m.3243A>G mtDNA, during culture conditions requiring oxidative metabolism ("energetic stress"). The effects of the pharmacological modulators on these two measures were consistent, confirming that the high throughput imaging output (autophagosomes co-localising with mitochondria) reflects mitochondrial quality control. To further validate these methods, we performed a more detailed study using metformin, the most commonly prescribed antidiabetic drug that is still sometimes used in Maternally Inherited Diabetes and Deafness (MIDD). This confirmed our initial findings and revealed that metformin inhibits mitophagy at clinically relevant concentrations, suggesting that it may have novel therapeutic uses.

Transcriptome-wide association study reveals two genes that influence mismatch negativity.

Mismatch negativity (MMN) is a differential electrophysiological response measuring cortical adaptability to unpredictable stimuli. MMN is consistently attenuated in patients with psychosis. However, the genetics of MMN are uncharted, limiting the validation of MMN as a psychosis endophenotype. Here, we perform a transcriptome-wide association study of 728 individuals, which reveals 2 genes (FAM89A and ENGASE) whose expression in cortical tissues is associated with MMN. Enrichment analyses of neurodevelopmental expression signatures show that genes associated with MMN tend to be overexpressed in the frontal cortex during prenatal development but are significantly downregulated in adulthood. Endophenotype ranking value calculations comparing MMN and three other candidate psychosis endophenotypes (lateral ventricular volume and two auditory-verbal learning measures) find MMN to be considerably superior. These results yield promising insights into sensory processing in the cortex and endorse the notion of MMN as a psychosis endophenotype.

Mobile primary health care clinics for Indigenous populations in Australia, Canada, New Zealand and the United States: a scoping review protocol.

OBJECTIVE: The objective of this review is to explore and examine the available evidence on mobile primary health care clinics for Indigenous populations in Australia, Canada, New Zealand and the United States. INTRODUCTION: Despite the evidence for the effectiveness of primary health care in improving health outcomes, accessing primary care services is often problematic for Indigenous populations in Australia, Canada, New Zealand and the United States. Improving the accessibility of primary health care services for Indigenous populations is considered essential to alleviating the burden of disease and improving well-being. INCLUSION CRITERIA: The review will consider literature that discusses the implementation of a mobile primary health clinic for Indigenous populations. Mobile primary health care clinics targeting Indigenous populations of all ages will be included in this review. Transportable clinics (e.g. van, truck or bus) fitted with health care equipment that deliver health services in a defined geographical area will be included. Only literature published in English from 1 January 2006 will be included. METHODS: Ovid MEDLINE, CINAHL, Embase, Cochrane Database of Systematic Reviews and SocINDEX will be searched, as well as gray literature sources. The full-text of selected literature will be retrieved and assessed in detail against the inclusion criteria by two independent reviewers. Data will be extracted by two independent reviewers, and a narrative summary will be provided on the objectives, concepts and results of the review question.