Relating Dispositional Mindfulness and Long-Term Mindfulness Training with Executive Functioning, Emotion Regulation, and Well-Being in Pre-adolescents

The present study examined whether both dispositional mindfulness without mindfulness training and mindfulness resulting from longer-term mindfulness training are positively associated with pre-adolescents’ well-being, via enhanced executive functioning (EF) and emotion regulation. EF was assessed in a GoNoGo task via behavioral performance and event-related potentials. Study 1 (N = 62) investigated associations of dispositional mindfulness without mindfulness training with EF, well-being and emotion regulation; longitudinal Study 2 with an active control group compared the effects of long-term mindfulness training (N = 28) with a positive psychology intervention (N = 15). Dispositional mindfulness without training was associated with lower EF, unrelated to emotion regulation and the relationship with well-being was mixed. Long-term mindfulness training was positively related to EF and well-being (reduced negative affect), but was uncorrelated with emotion regulation and mindfulness scores. Taken together, long-term mindfulness training was found to have mixed effects. Further research is required in this area

A Narrative Review of the Applications of Ex-vivo Human Liver Perfusion

Ex-vivo perfusion describes the extra-corporeal delivery of fluid to an organ or tissue. Although it has been widely studied in the context of organ preservation and transplantation, it has also proven to be an invaluable tool in the development of novel models for translational pre-clinical research. Here, we review the literature reporting ex-vivo human liver perfusion experiments to further understand current perfusion techniques and protocols together with their applications. A computerised search was made of Ovid, MEDLINE, and Embase using the search words “ex-vivo liver or hepatic perfusion”. All relevant studies in English describing experiments using ex-vivo perfusion of human livers between 2016 and 2021, inclusive, were included. Of 21 reviewed studies, 19 used ex-vivo human liver perfusion in the context of allogeneic liver transplantation. The quality and size of the studies varied considerably. Human liver perfusion was almost exclusively limited to whole organs and “split” livers, although one study did describe the successful perfusion of tissue sections following a partial hepatectomy. This review of recent literature involving ex vivo human liver perfusion demonstrates that the technique is not limited to whole liver perfusion. Split liver perfusion is extremely valuable allowing one lobe to act as a control and increasing the number available for research. This review also highlights the present lack of any reports of segmental liver perfusion. The discarded donor liver is a scarce resource, and the successful use of segmental perfusion has the potential to expand the available experimental models to facilitate pre-clinical experimentation

Multicomponent analysis of the tumour microenvironment reveals low CD8 T cell number, low stromal caveolin-1 and high tenascin-C and their combination as significant prognostic markers in non-small cell lung cancer

The complex interplay of the tumour microenvironment (TME) and its role in disease progression and response to therapy is poorly understood. The majority of studies to date focus on individual components or molecules within the TME and so lack the power correlative analysis. Here we have performed a multi-parameter analysis of the TME in 62 resectable non-small cell lung cancer (NSCLC) specimens detailing number and location of immune infiltrate, assessing markers of cancer-associated fibroblasts, caveolin-1 and tenascin-C, and correlating with clinicopathological details, as well as markers of disease progression such as epithelial-to-mesenchymal transition (EMT). The influence of individual parameters on overall survival was determined in univariate and multivariate analysis and the combination of risk factors and interplay between components analysed. Low numbers of CD8 T cells, low stromal levels of caveolin-1 or high levels of tenascin-C were significant prognostic markers of decreased overall survival in both univariate and multivariate analysis. Patients with two or more risk factors had dramatically reduced overall survival and those with all three a median survival of just 7.5 months. In addition, low levels of tumour E-cadherin correlated with reduced immune infiltrate into the tumour nests, possibly linking EMT to the avoidance of CD8 T cell control. The multicomponent approach has allowed identification of the dominant influences on overall survival, and exploration of the interplay between different components of the TME in NSCLC

A tunable amorphous p-type ternary oxide system:the highly mismatched alloy of copper tin oxide

The approach of combining two mismatched materials to form an amorphous alloy was used to synthesise ternary oxides of CuO and SnO2. These materials were analysed across a range of compositions, and the electronic structure was modelled using density functional theory. In contrast to the gradual reduction in optical band gap, the films show a sharp reduction in both transparency and electrical resistivity with copper contents greater than 50%. Simulations indicate that this change is caused by a transition from a dominant Sn 5s to Cu 3d contribution to the upper valence band. A corresponding decrease in energetic disorder results in increased charge percolation pathways: a “compositional mobility edge.” Contributions from Cu(II) sub band-gap states are responsible for the reduction in optical transparency

NAFLD exacerbates the effect of dietary sugar on liver fat and development of an atherogenic lipoprotein phenotype

This is the author accepted manuscript. It is currently under an indefinite embargo pending publication by Springer.${\bf Aims/hypothesis:}$ We aimed to test the hypothesis that the effects of dietary sugar on lipoprotein metabolism are influenced by non-alcoholic fatty liver disease (NAFLD). ${\bf Methods:}$ The effect of two 12 week, iso-energetic diets, high and low in non-milk extrinsic sugars (26% and 6% total energy), matched for macronutrient content, was examined in a randomised, cross-over study in men with NAFLD (n=11) and controls (n= 14). Lipoprotein kinetics and the sources of fatty acids for triacylglycerol (TAG) production were measured using stable isotope tracers. ${\bf Results:}$ Liver fat was higher after the high versus low-sugar diet in both groups (p<0.02), but men with NAFLD showed a relatively greater response than controls (p<0.05). After the high versus low-sugar diet, VLDL1-TAG production rate was higher in the controls (p <0.002) due to a greater contribution from splanchnic fatty acids (p<0.02) and de novo lipogenesis (p <0.002), whereas in NAFLD, VLDL2-TAG production rate was higher (p <0.05), due to a greater contribution from splanchnic fatty acids (p<0.02). There was no difference in the contribution of systemic NEFA to VLDL1 and VLDL2-TAG production rate between diets in either group. Intermediate density lipoprotein (IDL), LDL2 and LDL3-apolipoprotein B production rates and post-heparin hepatic lipase activity were all higher (p<0.05) on the high-sugar diet in NAFLD. ${\bf Conclusions:}$ A high sugar intake promoted a greater accumulation of liver fat in NAFLD than controls and increased VLDL-TAG production in both groups, due mainly to an increased contribution of fatty acids from splanchnic sources, which includes hepatic TAG storage pools. These effects may drive the formation of atherogenic lipoproteins.The work was supported by a UK government grant from the Biological Biotechnology Scientific Research Council (Grant no. BB/G009899/1); University of Surrey PhD scholarship for AM; Medical Research Council (body composition measurements) and infrastructure support from the National Institute of Health Research at the Cambridge Biomedical Research Centre

Genome Sequencing Shows that European Isolates of Francisella tularensis Subspecies tularensis Are Almost Identical to US Laboratory Strain Schu S4

BACKGROUND: Francisella tularensis causes tularaemia, a life-threatening zoonosis, and has potential as a biowarfare agent. F. tularensis subsp. tularensis, which causes the most severe form of tularaemia, is usually confined to North America. However, a handful of isolates from this subspecies was obtained in the 1980s from ticks and mites from Slovakia and Austria. Our aim was to uncover the origins of these enigmatic European isolates. METHODOLOGY/PRINCIPAL FINDINGS: We determined the complete genome sequence of FSC198, a European isolate of F. tularensis subsp. tularensis, by whole-genome shotgun sequencing and compared it to that of the North American laboratory strain Schu S4. Apparent differences between the two genomes were resolved by re-sequencing discrepant loci in both strains. We found that the genome of FSC198 is almost identical to that of Schu S4, with only eight SNPs and three VNTR differences between the two sequences. Sequencing of these loci in two other European isolates of F. tularensis subsp. tularensis confirmed that all three European isolates are also closely related to, but distinct from Schu S4. CONCLUSIONS/SIGNIFICANCE: The data presented here suggest that the Schu S4 laboratory strain is the most likely source of the European isolates of F. tularensis subsp. tularensis and indicate that anthropogenic activities, such as movement of strains or animal vectors, account for the presence of these isolates in Europe. Given the highly pathogenic nature of this subspecies, the possibility that it has become established wild in the heartland of Europe carries significant public health implications

The impact of immediate breast reconstruction on the time to delivery of adjuvant therapy: the iBRA-2 study

Background: Immediate breast reconstruction (IBR) is routinely offered to improve quality-of-life for women requiring mastectomy, but there are concerns that more complex surgery may delay adjuvant oncological treatments and compromise long-term outcomes. High-quality evidence is lacking. The iBRA-2 study aimed to investigate the impact of IBR on time to adjuvant therapy. Methods: Consecutive women undergoing mastectomy ± IBR for breast cancer July–December, 2016 were included. Patient demographics, operative, oncological and complication data were collected. Time from last definitive cancer surgery to first adjuvant treatment for patients undergoing mastectomy ± IBR were compared and risk factors associated with delays explored. Results: A total of 2540 patients were recruited from 76 centres; 1008 (39.7%) underwent IBR (implant-only [n = 675, 26.6%]; pedicled flaps [n = 105,4.1%] and free-flaps [n = 228, 8.9%]). Complications requiring re-admission or re-operation were significantly more common in patients undergoing IBR than those receiving mastectomy. Adjuvant chemotherapy or radiotherapy was required by 1235 (48.6%) patients. No clinically significant differences were seen in time to adjuvant therapy between patient groups but major complications irrespective of surgery received were significantly associated with treatment delays. Conclusions: IBR does not result in clinically significant delays to adjuvant therapy, but post-operative complications are associated with treatment delays. Strategies to minimise complications, including careful patient selection, are required to improve outcomes for patients

Finishing the euchromatic sequence of the human genome

The sequence of the human genome encodes the genetic instructions for human physiology, as well as rich information about human evolution. In 2001, the International Human Genome Sequencing Consortium reported a draft sequence of the euchromatic portion of the human genome. Since then, the international collaboration has worked to convert this draft into a genome sequence with high accuracy and nearly complete coverage. Here, we report the result of this finishing process. The current genome sequence (Build 35) contains 2.85 billion nucleotides interrupted by only 341 gaps. It covers ∼99% of the euchromatic genome and is accurate to an error rate of ∼1 event per 100,000 bases. Many of the remaining euchromatic gaps are associated with segmental duplications and will require focused work with new methods. The near-complete sequence, the first for a vertebrate, greatly improves the precision of biological analyses of the human genome including studies of gene number, birth and death. Notably, the human enome seems to encode only 20,000-25,000 protein-coding genes. The genome sequence reported here should serve as a firm foundation for biomedical research in the decades ahead