Healthy and sustainable diets that meet greenhouse gas emission reduction targets and are affordable for different income groups in the UK

We thank Amandine Perrin and Hubert Ehlert for their help writing some of the early linear programming code. Financial Support: This study was funded by the Scottish Government's Rural and Environment Science and Analytical Services Division (RESAS)Peer reviewedPublisher PD

Modelling population responses to workplace minimum dietary standards introduced as workers return after social lockdowns

Funding This work was funded by the Scottish Government’s Rural and Environment Science Analytical Services Strategic Research Programme.Peer reviewedPublisher PD

Cardiomyopathy in Offspring of Pregestational Diabetic Mouse Pregnancy

Purpose. To investigate cardiomyopathy in offspring in a mouse model of pregestational type 1 diabetic pregnancy. Methods. Pregestational diabetes was induced with STZ administration in female C57BL6/J mice that were subsequently mated with healthy C57BL6/J males. Offspring were sacrificed at embryonic day 18.5 and 6-week adolescent and 12-week adult stages. The size and number of cardiomyocyte nuclei and also the extent of collagen deposition within the hearts of diabetic and control offspring were assessed following cardiac tissue staining with either haematoxylin and eosin or Picrosirius red and subsequently quantified using automated digital image analysis. Results. Offspring from diabetic mice at embryonic day 18.5 had a significantly higher number of cardiomyocyte nuclei present compared to controls. These nuclei were also significantly smaller than controls. Collagen deposition was shown to be significantly increased in the hearts of diabetic offspring at the same age. No significant differences were found between the groups at 6 and 12 weeks. Conclusions. Our results from offspring of type 1 diabetic mice show increased myocardial collagen deposition in late gestation and have increased myocardial nuclear counts (hyperplasia) as opposed to increased myocardial nuclear size (hypertrophy) in late gestation. These changes normalize postpartum after removal from the maternal intrauterine environment

The relationship between anaesthetic technique, clinicopathological characteristics and the magnitude of the postoperative systemic inflammatory response in patients undergoing elective surgery for colon cancer

Background/aim: The magnitude of the postoperative systemic inflammatory response (SIR) is now recognised to be associated with both short and long-term outcomes in patients undergoing surgery for colon cancer. During such surgery, it is unclear whether the anaesthetic regimens influence the magnitude of the postoperative SIR, independent of other factors. The aim of the present study was to examine the association between anaesthetic agents, clinicopathological characteristics and the magnitude of the postoperative SIR in patients undergoing elective surgery for colon cancer. Methods: Patients with colon cancer who underwent elective open or laparoscopic surgery between 2008 and 2016 (n = 409) were studied at a single center. The relationship between type of anaesthesia, surgical technique; open (n = 241) versus laparoscopic (n = 168) and clinicopathological characteristics was examined by using chi-square testing. The chi-square test was used to determine which anaesthetic group influences the POD 2 CRP for only patients undergoing elective open colon surgery. Results: The majority of patients were <75 years old, male, normal weight or obese, underwent open surgery and had regional anaesthesia, in particular an epidural approach. There was a significant association between type of anaesthesia and post-operative CRP on day 2 (p <0.001) in patients undergoing open surgery but not laparoscopic surgery. Other factors associated with type of anaesthesia included; year of operation (p <0.01), surgical technique (p <0.001), and preoperative dexamethasone (p <0.01). Conclusion: In patients undergoing surgery for elective colon cancer, the type of anaesthesia varied over time. The type of anaesthesia appears to influence the magnitude of the postoperative SIR on post-operative day 2 in open surgery but not laparoscopic surgery. Future work using prospective study design is required to better define this relationship

Attitudes towards the use of perioperative steroids in resectional colorectal cancer surgery in the UK: a qualitative study

Introduction: Resectional surgery remains the mainstay of treatment for colorectal cancer. A heightened postoperative systemic inflammatory response has been shown to correlate negatively with short/long-term outcomes. Perioperative steroid administration may help to alleviate this systemic inflammatory response. This survey has been carried out to assess current attitudes towards perioperative steroid use and to gauge interest in a randomised control trial in this area. Method: An internet-based survey consisting of 9 questions was circulated via email. Those responses from outside the United Kingdom were excluded. Result: 74 doctors from the United Kingdom, predominantly Consultant Anaesthetists (54%) responded to this survey. 77% gave some or all of their patients steroids, in 75% of cases at the discretion of the anaesthetist. The main perceived benefit was to reduce postoperative nausea and vomiting. Diabetics and those deemed at high risk of wound infection were the group in whom most respondents would be reluctant to give steroids. 32% of respondents had no concerns. 87% of respondents felt that that a randomised trial in this field would be of clinical interest with most respondents (58%) preferring a three-armed trial – no steroids vs low dose steroids vs high dose steroids. Conclusion: – This survey indicated that perioperative steroid use is currently widespread. Sufficient equipoise exists for a trial in this area with regard to examining the impact of dexamethasone on postoperative complications and the postoperative systemic inflammatory response. Respondents favoured a 3-armed trial – no steroids vs low-dose steroids vs high-dose steroids

Possible dose dependent effect of perioperative dexamethasone and laparoscopic surgery on the postoperative systemic inflammatory response and complications following surgery for colon cancer

Background: Perioperative dexamethasone is associated with attenuation of the postoperative systemic inflammatory response and fewer postoperative complications following elective surgery for colorectal cancer. This study examined the impact of different doses of dexamethasone, given to reduce postoperative nausea and vomiting (PONV) after elective colonic resection for cancer, on the postoperative Glasgow Prognostic Score (poGPS) and morbidity. Methods: Patients from a single centre were included if they underwent potentially curative resection of colonic cancer from 2008 to 2017 (n = 480). Patients received no dexamethasone (209, 44%), or either 4 mg (166, 35%), or 8 mg (105, 21%), intravenously during anaesthesia, at the discretion of the anaesthetist. The postoperative Glasgow Prognostic Score (poGPS) on day 3 and 4, and complication rate at discharge were recorded. Results: When patients were grouped by surgical approach (open or laparoscopic) and dexamethasone dose (0 mg, 4 mg or 8 mg), there was a statistically significant linear trend toward a lower postoperative systemic inflammatory response (day 3 poGPS) with the use of minimally invasive surgery and higher doses of dexamethasone (p < 0.001). Furthermore, this combination of laparoscopic surgery and higher doses of dexamethasone was significantly associated with a lower proportion of postoperative complications (p < 0.001). At multivariate Cox regression, dexamethasone was not significantly associated with either improved or poorer cancer specific or overall survival. Conclusions: Higher doses of perioperative dexamethasone are associated with greater reduction in postoperative systemic inflammation and complications following surgery for colonic cancer without negative impact on survival

The pre treatment systemic inflammatory response is an important determinant of poor pathologic response for patients undergoing neoadjuvant therapy for rectal cancer

Background Not all patients respond equally to neoadjuvant chemoradiotherapy (nCRT), with subsequent effects on survival. The systemic inflammatory response has been shown to predict long-term outcomes in colorectal cancer. The current study examined the association between systemic inflammation and nCRT in patients with rectal cancer. Methods Between 1999 and 2010, patients who underwent nCRT were identified. Serum measurements of hemoglobin, C-reactive protein, albumin, modified Glasgow prognostic score (mGPS), and differential white cell counts were obtained before and after nCRT. The Rödel scoring system measured pathologic tumor regression, and magnetic resonance imaging and computed tomography determined radiologic staging. Results The study included 79 patients. Of these patients, 37% were radiologically downstaged, and 44% were categorized as showing a good pathologic response (Rödel scores 3 and 4). As a validated measure of the systemic inflammatory response, mGPS (P = 0.022) was associated with a poor pathologic response to nCRT. A radiologic response was associated with a good pathologic response to treatment (P = 0.003). A binary logistic regression model identified mGPS (odds ratio [OR] 0.27; 95% confidence interval [CI] 0.07–0.96; P = 0.043) and radiologic response (OR 0.43; 95% CI 0.18–0.99; P = 0.048) as strong independent predictors of a pathologic response to treatment. Conclusion The current study showed that a systemic inflammatory response before nCRT is associated with a poor pathologic response. Further study in a prospective controlled trial setting is warranted. Stephan B. Dreyer and Arfon G. M. T. Powell—contributed equally. Colorectal cancer (CRC) is the third most common cancer and the second highest cause of cancer death in the United Kingdom.1 The 5-year survival rate for CRC still is less than 60% with surgery alone, offering the only chance of cure. Rectal cancers comprise about one third of surgical resections for colorectal cancer.2 The widely adapted surgical technique of total mesorectal excision (TME), increased centralization, specialization of rectal surgery, and earlier disease detection have led to improved survival in the last 30 years.3,4 Preoperative neoadjuvant radiotherapy with or without chemotherapy currently is accepted as a standard of care for patients with margin-threatening rectal cancer. This increases disease-free survival (DFS) and sphincter preservation rates and improves circumferential resection margins and local recurrence rates.5–8 Current management of CRC in the United Kingdom involves evaluating patients using magnetic resonance imaging (MRI) and computed tomography (CT) before treatment to identify those with margin-threatening disease (T3 or T4).9 These patients are offered neoadjuvant chemoradiotherapy (nCRT) before surgical resection.10 Not all patients respond to nCRT, and there is a need to identify biomarkers of response because treatment is associated with significant morbidity. Rödel et al.11 have shown that the presence of spontaneous apoptosis in the resected specimen is a good marker of tumor regression and improved prognosis. The prognostic value of the systemic inflammatory response (SIR) has been widely studied in gastrointestinal cancers, particularly in the operative setting, using measurements of circulating markers including C-reactive protein (CRP), albumin, the modified Glasgow prognostic score (mGPS), the neutrophil lympocyte ratio (NLR), the platelet-to-lymphocyte ratio (PLR), and more recently, the neutrophil-platelet score (NPS) and the derived neutrophil-to-lymphocyte ratio (dNLR).12–16 This study investigated the association between markers of the systemic inflammatory response and the pathologic response to nCRT in patients with rectal cancer

Effect of increasing fruit and vegetable intake by dietary intervention on nutritional biomarkers and attitudes to dietary change : a randomised trial

This work was funded by The Scottish Government Rural and Environmental Science and Analytical Sciences Division (RESAS) and supported by the Rank Prize Funds.Peer reviewedPublisher PD

Nanopore-based kinetics analysis of individual antibody-channel and antibody-antigen interactions

<p>Abstract</p> <p>Background</p> <p>The UNO/RIC Nanopore Detector provides a new way to study the binding and conformational changes of individual antibodies. Many critical questions regarding antibody function are still unresolved, questions that can be approached in a new way with the nanopore detector.</p> <p>Results</p> <p>We present evidence that different forms of channel blockade can be associated with the same antibody, we associate these different blockades with different orientations of "capture" of an antibody in the detector's nanometer-scale channel. We directly detect the presence of antibodies via reductions in channel current. Changes to blockade patterns upon addition of antigen suggest indirect detection of antibody/antigen binding. Similarly, DNA-hairpin anchored antibodies have been studied, where the DNA linkage is to the carboxy-terminus at the base of the antibody's Fc region, with significantly fewer types of (lengthy) capture blockades than was observed for free (un-bound) IgG antibody. The introduction of chaotropic agents and its effects on protein-protein interactions have also been observed.</p> <p>Conclusion</p> <p>Nanopore-based approaches may eventually provide a direct analysis of the complex conformational "negotiations" that occur upon binding between proteins.</p