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"Ramsay, Morgan"
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Nutrition and Frailty: Opportunities for Prevention and Treatment
Frailty is a syndrome of growing importance given the global ageing population. While frailty is a multifactorial process, poor nutritional status is considered a key contributor to its pathophysiology. As nutrition is a modifiable risk factor for frailty, strategies to prevent and treat frailty should consider dietary change. Observational evidence linking nutrition with frailty appears most robust for dietary quality: for example, dietary patterns such as the Mediterranean diet appear to be protective. In addition, research on specific foods, such as a higher consumption of fruit and vegetables and lower consumption of ultra-processed foods are consistent, with healthier profiles linked to lower frailty risk. Few dietary intervention studies have been conducted to date, although a growing number of trials that combine supplementation with exercise training suggest a multi-domain approach may be more effective. This review is based on an interdisciplinary workshop, held in November 2020, and synthesises current understanding of dietary influences on frailty, focusing on opportunities for prevention and treatment. Longer term prospective studies and well-designed trials are needed to determine the causal effects of nutrition on frailty risk and progression and how dietary change can be used to prevent and/or treat frailty in the future.
Journal Article
Psoriasin (S100A7) associates with integrin β6 subunit and is required for αvβ6-dependent carcinoma cell invasion
Expression of the integrin αvβ6 is upregulated in a variety of carcinomas where it appears to be involved in malignant progression, although the biology of this integrin is not fully explored. We have generated oral carcinoma cells that express αvβ6 composed of wild-type αv and a mutant β6 that lacks the unique C-terminal 11 amino acids (aa). We found that these residues, although not required for αvβ6-dependent adhesion or migration, are essential for αvβ6-dependent invasive activity. We have used a proteomic approach to identify novel binding partners for the β6 subunit cytoplasmic tail and report that psoriasin (Psor) (S100A7) bound preferentially to the recombinant β6 cytoplasmic domain, though not in the absence of the unique C-terminal 11aa. Endogenous cellular Psor co-precipitated with endogenous β6 and colocalised with αvβ6 at the cell membrane and intracellular vesicles. Knockdown of Psor, with small interfering RNA, had no effect on αvβ6-dependent adhesion or migration but abrogated αvβ6-mediated oral carcinoma cell invasion both in Transwell and, the more physiologically relevant, organotypic invasion assays, recapitulating the behaviour of the β6-mutant cell line. Membrane-permeant Tat-peptides encoding the unique C-terminal residues of β6, bound directly to recombinant Psor and inhibited cellular Psor binding to β6; this blocked αvβ6-dependent, but not αvβ6-independent, invasion. These data identify a novel interaction between Psor and β6 and demonstrate that it is required for αvβ6-dependent invasion by carcinoma cells. Inhibition of this interaction may represent a novel therapeutic strategy to target carcinoma invasion.
Journal Article
Exploring the role of quality of life in surgical decision making for patients undergoing pancreatectomy
The influence of baseline health-related quality of life (HRQoL) on peri-operative outcomes in pancreatobiliary (PB) patients is not well established. This study investigated the impact of baseline HRQoL on peri-operative outcomes and the effect of surgery on HRQoL.
A secondary post-hoc analysis of a multicenter trial (2011–2016) assessed PB patients undergoing pancreatectomy. Pre-operative and 30-day post-operative FACT-G surveys were analyzed. Logistic regressions determined associations between baseline HRQoL scores and 60-day major complications. Subgroup analysis evaluated change in HRQoL (pre-operative to 30-day scores).
Among 391 patients, higher baseline HRQoL (FACT-G overall OR 0.54,p = 0.04) was associated with decreased likelihood of developing major complications. Surgery resulted in improvement in HRQoL for patients with chronic pancreatitis (10.2 points) compared to other pathologies (−7 to 3.9 points).
Baseline HRQoL was associated with post-operative complications and HRQoL significantly improved for patients with chronic pancreatitis, highlighting the importance of HRQoL on patient-centered outcomes.
•Lower quality of life predicts major complications after pancreatobiliary surgery.•Patients with chronic pancreatitis had greatest improvement in QoL after surgery.•Baseline quality of life assessments may aid in pre-operative risk stratification.
Journal Article
Improved calibration procedures for the EM27/SUN spectrometers of the COllaborative Carbon Column Observing Network (COCCON)
In this study, an extension on the previously reported status of the COllaborative Carbon Column Observing Network's (COCCON) calibration procedures incorporating refined methods is presented. COCCON is a global network of portable Bruker EM27/SUN FTIR spectrometers for deriving column-averaged atmospheric abundances of greenhouse gases. The original laboratory open-path lamp measurements for deriving the instrumental line shape (ILS) of the spectrometer from water vapour lines have been refined and extended to the secondary detector channel incorporated in the EM27/SUN spectrometer for detection of carbon monoxide (CO). The refinements encompass improved spectroscopic line lists for the relevant water lines and a revision of the laboratory pressure measurements used for the analysis of the spectra. The new results are found to be in good agreement with those reported by Frey et al. (2019) and discussed in detail. In addition, a new calibration cell for ILS measurements was designed, constructed and put into service. Spectrometers calibrated since January 2020 were tested using both methods for ILS characterization, open-path (OP) and cell measurements. We demonstrate that both methods can detect the small variations in ILS characteristics between different spectrometers, but the results of the cell method indicate a systematic bias of the OP method. Finally, a revision and extension of the COCCON network instrument-to-instrument calibration factors for XCO2, XCO and XCH4 is presented, incorporating 47 new spectrometers (of 83 in total by now). This calibration is based on the reference EM27/SUN spectrometer operated by the Karlsruhe Institute of Technology (KIT) and spectra collected by the collocated TCCON station Karlsruhe. Variations in the instrumental characteristics of the reference EM27/SUN from 2014 to 2017 were detected, probably arising from realignment and the dual-channel upgrade performed in early 2018. These variations are considered in the evaluation of the instrument-specific calibration factors in order to keep all tabulated calibration results consistent.
Journal Article
Not the story you want? Assessing the fit of a conceptual framework characterising mental health recovery narratives
PurposeNarratives of recovery have been central to the development of the recovery approach in mental health. However, there has been a lack of clarity around definitions. A recent conceptual framework characterised recovery narratives based on a systematic review and narrative synthesis of existing literature, but was based on a limited sample. The aims of this study were to assess the relevance of the framework to the narratives of more diverse populations, and to develop a refined typology intended to inform narrative-based research, practice and intervention development.Method77 narrative interviews were conducted with respondents from four under-researched mental health sub-populations across England. Deductive and inductive analysis was used to assess the relevance of the dimensions and types of the preliminary typology to the interview narratives.ResultsFive or more dimensions were identifiable within 97% of narratives. The preliminary typology was refined to include new definitions and types. The typology was found not to be relevant to two narratives, whose narrators expressed a preference for non-verbal communication. These are presented as case studies to define the limits of the typology.ConclusionThe refined typology, based on the largest study to date of recovery narratives, provides a defensible theoretical base for clinical and research use with a range of clinical populations. Implications for practice include ensuring a heterogeneous selection of narratives as resources to support recovery, and developing new approaches to supporting non-verbal narrative construction.
Journal Article
Biopsy decision for intermediate–high-risk lung nodules is significantly changed when guided by prior positron emission tomography/CT (PET/CT) results: results of the prospective PET-FIRST study
IntroductionPositron emission tomography/CT (PET/CT) may have an important role in guiding decisions regarding biopsy of high-risk lung nodules suspicious for lung cancer. The PET-FIRST study aimed to assess the role of PET/CT prior to any biopsy of a high-risk lung nodule.MethodsA prospective study was performed in two tertiary hospitals. A study multidisciplinary team (MDT) was established (independent of the hospital Tumour Board) to review referrals of lung nodules with an intermediate–high (≥10%) risk of malignancy by Brock score. A two-stage consensus assessment was undertaken by the MDT regarding choice of biopsy: (1) based on the referral CT alone and then (2) after unblinding the results of PET/CT. The primary study outcome was change in biopsy decision.Results168 patients were included in the study; of these, 53% of nodules were malignant, 44% were benign and 3% cases refused follow-up. In 59 of the 168 patients (35%), the initial recommended biopsy decision was changed based on PET/CT findings. Regarding whether to biopsy the nodule or not, in 42 cases (25%), the initial management decision was changed after PET/CT (p<0.01). Sensitivity analysis showed that the benefit of having PET/CT before nodule biopsy was observed across all ranges of Brock scores. There was an estimated total cost reduction by procedure avoidance of $AA60 796 ($AA362 per patient).ConclusionsIn patients with lung nodules of intermediate–high risk for lung cancer, fluorodeoxyglucose PET/CT performed prior to any biopsy of the nodule has a significant effect in determining biopsy choice.
Journal Article
Vaccine-mediated protection of pigs against infection with pandemic H1N1 2009 swine influenza A virus requires a close antigenic match between the vaccine antigen and challenge virus
Swine influenza A virus (SwIV) infection has considerable economic and animal welfare consequences and, because of the zoonotic potential, can also have public health implications. The 2009 pandemic H1N1 ‘swine-origin’ infection is now endemic in both pigs and humans. In Europe, avian-like H1avN1, human-like H1huN2, human-like swine H3N2 and, since 2009, pandemic H1N1 (pH1N1) lineage viruses and reassortants, constitute the dominant subtypes. In this study, we used a swine pH1N1 challenge virus to investigate the efficacy of whole inactivated virus vaccines homologous or heterologous to the challenge virus as well as a commercial vaccine. We found that vaccine-mediated protection was most effective when vaccine antigen and challenge virus were homologous and correlated with the specific production of neutralising antibodies and a cellular response to the challenge virus. We conclude that a conventional whole inactivated SwIV vaccine must be antigenically matched to the challenge strain to be an effective control measure.
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