Oxidative stress via hydrogen peroxide and menadione does not induce the secretion of IGFBP-5 in primary rat hepatocytes

Conference abstract describing how oxidative stress via hydrogen peroxide and menadione does not induce the secretion of IGFBP-5 in primary rat hepatocytes. Presented at the 2010 annual congress of the british toxicology societ

Insulin-like growth factor binding protein-5 as a biomarker for detection of early liver disease

Study identifying an Insulin-like growth factor binding protein-5 as a biomarker for detection of early liver disease presented at the annual congress of the british toxicology societ

Describing return to work after stroke : a feasibility trial of 12-month outcomes

Objective: Stroke is the greatest cause of disability in adults. A quarter of strokes in the UK affect people of working age, yet under half of them return to work after stroke. There has been little investigation into what constitutes “return to work” following stroke. The aim of this study is to describe the work metrics of stroke survivor participants in a feasibility randomized controlled trial of an early stroke specific vocational rehabilitation intervention. Methods: Retrospective analysis of trial data. Metrics on work status, working hours, workplace accommodations and costs were extracted from trial out - comes gathered by postal questionnaire at 3, 6, and 12 months’ post-randomization for 46 stroke participants in a feasibility randomized controlled trial. Participants were randomized to receive vocational rehabilitation (intervention) or usual care (control). Results: Two-thirds ( n = 29; 63%) of participants re - turned to work at some point in the 12 months following stroke. Participants took a mean of 90 days to return to work. Most returned to the same role with an existing employer. Only one-third of participants who were employed full-time at stroke onset were working full-time at 12 months post-stroke. Most participants experienced a reduction in pre-stroke earnings. Workplace accommodations were more common among intervention group participants. More intervention participants than control participants reported satisfaction with work at both 6 and 12 months post-randomization. Conclusion: This study illustrates the heterogeneous nature of return to work and the dramatic impact of stroke on work status, working hours and income. Longitudinal research should explore the socioeconomic legacy of stroke and include clear definitions of work and accurate measures of working hours and income from all sources

ELF3 controls thermoresponsive growth in Arabidopsis

Plant development is highly responsive to ambient temperature, and this trait has been linked to the ability of plants to adapt to climate change [1]. The mechanisms by which natural populations modulate their thermoresponsiveness are not known [2]. To address this, we surveyed Arabidopsis accessions for variation in thermal responsiveness of elongation growth and mapped the corresponding loci. We find that the transcriptional regulator EARLY FLOWERING3 (ELF3) controls elongation growth in response to temperature. Through a combination of modeling and experiments, we show that high temperature relieves the gating of growth at night, highlighting the importance of temperature-dependent repressors of growth. ELF3 gating of transcriptional targets responds rapidly and reversibly to changes in temperature. We show that the binding of ELF3 to target promoters is temperature dependent, suggesting a mechanism where temperature directly controls ELF3 activity

Genetic bias, diversity indices, physiochemical properties and CDR3 motifs divide auto-reactive from allo-reactive T-Cell repertoires

The distinct properties of allo-reactive T-cell repertoires are not well understood. To investigate whether auto-reactive and allo-reactive T-cell repertoires encoded distinct properties, we used dextramer enumeration, enrichment, single-cell T-cell receptor (TCR) sequencing and multiparameter analysis. We found auto-reactive and allo-reactive T-cells differed in mean ex vivo frequency which was antigen dependent. Allo-reactive T-cells showed clear differences in TCR architecture, with enriched usage of specific T-cell receptor variable (TRBJ) genes and broader use of T-cell receptor variable joining (TRBJ) genes. Auto-reactive T-cell repertoires exhibited complementary determining regions three (CDR3) lengths using a Gaussian distribution whereas allo-reactive T-cell repertoires exhibited distorted patterns in CDR3 length. CDR3 loops from allo-reactive T-cells showed distinct physical-chemical properties, tending to encode loops that were more acidic in charge. Allo-reactive T-cell repertoires differed in diversity metrics, tending to show increased overall diversity and increased homogeneity between repertoires. Motif analysis of CDR3 loops showed allo-reactive T-cell repertoires differed in motif preference which included broader motif use. Collectively, these data conclude that allo-reactive T-cell repertoires are indeed different to auto-reactive repertoires and provide tangible metrics for further investigations and validation. Given that the antigens studied here are overexpressed on multiple cancers and that allo-reactive TCRs often show increased ligand affinity, this new TCR bank also has translational potential for adoptive cell therapy, soluble TCR-based therapy and rational TCR design

Factor influencing women with learning disabilities deciding to, and accessing, cervical and breast cancer screening: Findings from a Q methodology study of women with learning disabilities, family and paid carers

Objectives: To understand knowledge of, attitudes towards, and decision making around cervical and breast cancer screening in women with learning disabilities, family carers and paid carers. Methods: A Q methodology study involving 13 women with learning disabilities, three family carers and five paid care workers, from the North-East of England. A Q-sort, of 28 statements was completed with all participants completing a post-Q-sort interview to understand the reason behind the card placements. Factor analysis was completed using PQMethod and interpreted using framework analysis. Results: Factor one, named ‘Personal choice and ownership’, explores how women with learning disabilities want to be supported to make their own decision to attend cancer screening and explored their preferred support needs. Factor two, named ‘Protecting vs enablement’, portrayed the battle family carers and paid care workers felt to protect women with learning disabilities from harm, whilst feeling that they were supporting women with learning disabilities to decide to attend cancer screening. Eight consensus statements were identified indicating a shared perspective. Conclusions: Cancer screening services should ensure that women with learning disabilities are supported to make informed decisions to attend cancer screening and then be further supported throughout the cancer pathway

Acupuncture and reflexology for patients undergoing chemotherapy : a cohort study

Purpose: Around three quarters of individuals undergoing chemotherapy self-report multiple symptoms. There is clinical trial evidence of effectiveness for acupuncture for commonly experienced symptoms, and emerging evidence for reflexology, but little is known about the effects of these therapies on multiple symptoms when implemented in a real world setting during active chemotherapy treatment. Methods: This was a cohort study of participants receiving reflexology and/or acupuncture while attending chemotherapy. Participants received a 20 minute reflexology treatment or a 20 minute acupuncture treatment or a combination of both. Patient reported outcome measures were administered before and after the treatment using the Edmonton Symptom Assessment Scale (ESAS). Results: During the study period, 330 unique patients received a total of 809 acupuncture and/or reflexology treatments. Participants had, on average, 5.3 symptoms each which they reported as moderate to severe (≥4/10) using the ESAS at baseline. Following treatment, participants reported 3.2 symptoms as moderate to severe. The symptom change for all participant encounters receiving any therapy was statistically significant for all symptoms, and clinically significant (a reduction of more than 1) for all symptoms except financial distress, appetite, and memory. Clinically significant levels of global distress (<3) were reduced in 72% of all participants receiving either therapy. No adverse events were recorded. Conclusions: The results indicate that acupuncture and reflexology administered alongside chemotherapy may reduce patient reported symptom burden and patient global symptom related distress. Future research would include an active control group, and consider confounding factors such as chemotherapy stage and medication

Acupuncture for treatment of erectile dysfunction : a systematic review and meta-analysis

Purpose: To assess the effectiveness and safety of acupuncture for erectile dysfunction (ED). Materials and Methods: We searched six major English and Chinese databases included randomized controlled trials (RCTs) testing acupuncture alone or in combination for ED. Dichotomous data were presented as risk ratio (RR) and continuous data were presented as mean difference (MD) both with 95% confidence interval (CI). The Revman (v.5.3) was used for data analyses. Quality of evidence across studies was assessed by the online GRADEpro tool. Results: We identified 22 RCTs, fourteen of them involving psychogenic ED. Most of the included RCTs had high or unclear risk of bias. There was no difference between electro-acupuncture and sham acupuncture with electrical stimulation on the rate of satisfaction and self-assessment (RR, 1.50; 95% CI, 0.71-3.16; 1 trial). Acupuncture combined with tadalafil appeared to have better effect on increasing cure rate (RR, 1.31; 95% CI, 1.00-1.71; 2 trials), and International Index of Erectile Function-5 scores (MD, 5.38; 95% CI, 4.46-6.29; 2 trials). When acupuncture plus herbal medicine compared with herbal medicine alone, the combination therapy showed significant better improvement in erectile function (RR, 1.68; 95% CI, 1.31-2.15; 7 trials). Only two trials reported facial red and dizziness cases, and needle sticking and pruritus cases in acupuncture group. Conclusions: Low quality evidence shows beneficial effect of acupuncture as adjunctive treatment for people mainly with psychogenic ED. Safety of acupuncture was insufficiently reported. The findings should be confirmed in large, rigorously designed and well-reported trials

ENSO-driven extreme oscillations in mean sea level destabilise critical shoreline mangroves—An emerging threat

Recent ENSO-related, extreme low oscillations in mean sea level, referred to as ‘Taimasa’ in Samoa, have destabilised shoreline mangroves of tropical northern Australia, and possibly elsewhere. In 1982 and 2015, two catastrophic Taimasa each resulted in widespread mass dieback of ~76 km2 of shoreline mangroves along 2,000 km of Australia’s Gulf of Carpentaria. For the 2015 event, we determined that a temporary drop in sea level of ~0.4 metres for up to six months duration caused upper zone shoreline mangroves across the region to die from severe moisture deficit and desiccation. The two dramatic collapse events revealed a previously unrecognised vulnerability of semi-arid tidal wetland habitats to more extreme ENSO influences on sea level. In addition, we also observed a relationship between annual sea level oscillations and mangrove forest productivity where seasonal oscillations in mean sea level were co-incident with regular annual mangrove leaf growth during months of higher sea levels (March-May), and leaf shedding during lower sea levels (September-November). The combination of these periodic fluctuations in sea level defined a mangrove ‘Goldilocks’ zone of seasonal productivity during median-scale oscillations, bracketed by critical threshold events when sea levels became unusually low, or high. On the two occasions reported here when sea levels were extremely low, upper zone mangrove vegetation died en masse in synchrony across northern Australia. Such extreme pulse impacts combined with localised stressors profoundly threaten the longer-term survival of mangrove ecosystems and their benefits, like minimisation of shoreline erosion with rising sea levels. These new insights into such critical influences of climate and sea level on mangrove forests offer further affirmation of the urgency for implementing well-considered mitigation efforts for the protection of shoreline mangroves at risk, especially given predictions of future re-occurrences of extreme events affecting sea levels, combined with on-going pressure of rapidly rising sea levels

Decadal shift in foraging strategy of a migratory southern ocean predator

Rapid anthropogenic environmental change is expected to impact a host of ecological parameters in Southern Ocean ecosystems. Of critical concern are the consequences of these changes on the range of species that show fidelity to migratory destinations, as philopatry is hypothesized to help or hinder adaptation to climate change depending on the circumstances. Many baleen whales show philopatry to feeding grounds and are also capital breeders that meet migratory and reproductive costs through seasonal energy intake. Southern right whales (Eubalaena australis, SRWs) are capital breeders that have a strong relationship between reproductive output and foraging success. The population dynamics of South Africa's population of SRWs are characterized by two distinct periods: the 1990s, a period of high calving rates; and the late 2010s, a period associated with lowered calving rates. Here we use analyses of stable carbon (δ13C) and nitrogen (δ15N) isotope values from SRW biopsy samples (n = 122) collected during these two distinct periods to investigate foraging ecology of the South African population of SRWs over a time period coincident with the demographic shift. We show that South African SRWs underwent a dramatic northward shift, and diversification, in foraging strategy from 1990s to 2010s. Bayesian mixing model results suggest that during the 1990s, South African SRWs foraged on prey isotopically similar to South Georgia/Islas Georgias del Sur krill. In contrast, in the 2010s, South African SRWs foraged on prey isotopically consistent with the waters of the Subtropical Convergence, Polar Front and Marion Island. We hypothesize that this shift represents a response to changes in preferred habitat or prey, for example, the decrease in abundance and southward range contraction of Antarctic krill. By linking reproductive decline to changing foraging strategies for the first time in SRWs, we show that altering foraging strategies may not be sufficient to adapt to a changing ocean