Thalassaemia (part 2)

No abstract

The evolution of life cycle assessment in the food and beverage industry: A review

Life cycle assessment (LCA) has been progressively used as an tool to quantify and compare environmental impacts in the food and beverage industry. This paper reviews LCAs on single-use food and beverage plastic products from January 2000 to June 2022. Studies are also analysed in the context of marine plastic pollution which is a global concern. A total of 91 studies were reviewed with 44% conducted for the European region. Findings suggest that most studies follow the traditional approach and structure of LCA with some studies focusing on global warming potential and others incorporating aspects such as life cycle costs and mass-based indicators. A total of 62% of reviewed studies had a cradle-to-grave scope. LCA studies can be influenced by public discourse, for example, the rising concern surrounding plastic marine pollution. From 2019, additional environmental indicators have been included in LCAs wherein the product is a major contributor to pollution. To date, six studies have proposed marine litter indicators. In future years, we can expect further development of life cycle impact assessment methods to reflect concerns in the public discourse. This includes methodologies for assessing circularity or plastic pollution. Furthermore, product foci will continue to follow popular trends

Multiple breast cancer risk variants are associated with differential transcript isoform expression in tumors.

Genome-wide association studies have identified over 70 single-nucleotide polymorphisms (SNPs) associated with breast cancer. A subset of these SNPs are associated with quantitative expression of nearby genes, but the functional effects of the majority remain unknown. We hypothesized that some risk SNPs may regulate alternative splicing. Using RNA-sequencing data from breast tumors and germline genotypes from The Cancer Genome Atlas, we tested the association between each risk SNP genotype and exon-, exon-exon junction- or transcript-specific expression of nearby genes. Six SNPs were associated with differential transcript expression of seven nearby genes at FDR < 0.05 (BABAM1, DCLRE1B/PHTF1, PEX14, RAD51L1, SRGAP2D and STXBP4). We next developed a Bayesian approach to evaluate, for each SNP, the overlap between the signal of association with breast cancer and the signal of association with alternative splicing. At one locus (SRGAP2D), this method eliminated the possibility that the breast cancer risk and the alternate splicing event were due to the same causal SNP. Lastly, at two loci, we identified the likely causal SNP for the alternative splicing event, and at one, functionally validated the effect of that SNP on alternative splicing using a minigene reporter assay. Our results suggest that the regulation of differential transcript isoform expression is the functional mechanism of some breast cancer risk SNPs and that we can use these associations to identify causal SNPs, target genes and the specific transcripts that may mediate breast cancer risk

Inhibition of fatty acid oxidation as a therapy for MYC-overexpressing triple-negative breast cancer.

Expression of the oncogenic transcription factor MYC is disproportionately elevated in triple-negative breast cancer (TNBC), as compared to estrogen receptor-, progesterone receptor- or human epidermal growth factor 2 receptor-positive (RP) breast cancer. We and others have shown that MYC alters metabolism during tumorigenesis. However, the role of MYC in TNBC metabolism remains mostly unexplored. We hypothesized that MYC-dependent metabolic dysregulation is essential for the growth of MYC-overexpressing TNBC cells and may identify new therapeutic targets for this clinically challenging subset of breast cancer. Using a targeted metabolomics approach, we identified fatty acid oxidation (FAO) intermediates as being dramatically upregulated in a MYC-driven model of TNBC. We also identified a lipid metabolism gene signature in patients with TNBC that were identified from The Cancer Genome Atlas database and from multiple other clinical data sets, implicating FAO as a dysregulated pathway that is critical for TNBC cell metabolism. We found that pharmacologic inhibition of FAO catastrophically decreased energy metabolism in MYC-overexpressing TNBC cells and blocked tumor growth in a MYC-driven transgenic TNBC model and in a MYC-overexpressing TNBC patient-derived xenograft. These findings demonstrate that MYC-overexpressing TNBC shows an increased bioenergetic reliance on FAO and identify the inhibition of FAO as a potential therapeutic strategy for this subset of breast cancer

Electrocortical therapy for motion sickness

Given a sufficiently provocative stimulus, almost everyone can be made motion sick, with approximately one-third experiencing significant symptoms on long bus trips, on ships, or in light aircraft.1–4 Current countermeasures are either behavioral or pharmacologic. Behavioral measures include habituation/desensitization treatment protocols5 as well as positioning the head in alignment with the direction of the gravito-inertial force and maintaining a stable horizontal reference frame.5 Pharmacologic measures include antimuscarinics, H1 antihistamines, and sympathomimetics, which all detrimentally impact upon cognitive function, rendering them inappropriate for occupational use.5 All current therapies are only partially effective

Thalassaemia (part 2): Management

The management of thalassaemia with a severe phenotype includes blood transfusion, iron chelation, bone marrow transplantation, prenatal diagnosis and national programmes to co-ordinate these in countries with a high prevalence. If blood transfusion and iron chelation therapy are not administered regularly, as was the case historically and as is still the case in many poorer regions, progressive deterioration occurs, viz. impaired growth and development, hepatosplenomegaly, bony abnormalities, cardiac failure, increased susceptibility to infections and premature mortality. Remarkable progress has been made in the past few decades, which has led to much-improved survival rates. Transfusion therapy has evolved to a hyper-transfusion regimen designed to maintain a physiological haemoglobin level and achieve a post-transfusion haemoglobin of 14 g/dL, which, as a matter of course, necessitated intensification of iron chelation. The development of effective oral iron chelators has led to improved compliance. Exploration of novel therapeutic approaches continues, with several agents under study. The prospect of gene therapy is particularly exciting as it has potential to provide cure on a large scale. Currently, regular blood transfusion and iron chelation therapy remain the cornerstone of management of thalassaemia major

Role of handedness-related vestibular cortical dominance upon the vestibular–ocular reflex

Letter to the Editor

Role of handedness-related vestibular cortical dominance upon the vestibular–ocular reflex

© 2015 The Authors. Published by Springer. This is an open access article available under a Creative Commons licence. The published version can be accessed at the following link on the publisher’s website: https://doi.org/10.1007/s00415-015-7690-yDear Sirs, Cortical influences over low-order vestibular function such as the vestibular–ocular reflex (VOR) are widely accepted [1–3]. Hallpike and colleagues originally demonstrated that patients with temporal lobe lesions, exhibit a strong asymmetry (i.e. “directional preponderance”), in the vestibular nystagmus elicited during caloric stimulation” [3]. Recent work to establish the neural correlates of human vestibular cortical processing have implemented three main approaches. Functional imaging [4–6], clinical lesion studies [2, 7, 8] and brain stimulation data [9–11] have all implicated tempo-parietal areas, usually with right hemisphere dominance. However, it was not until the seminal paper by Dieterich et al. [4] that the concept of handedness-related vestibular hemispheric dominance took shape, showing that the right hemisphere is vestibular dominant in right-handed individuals and vice versa in left handers