The relationship between systemic inflammation and stoma formation following anterior resection for rectal cancer: a cross-sectional study

Introduction: There is evidence that temporary defunctioning stoma formation in patients undergoing anterior resection reduces the risk of anastomotic leakage. The aim of the present study was to investigate the relationship between stoma formation, the postoperative systemic inflammatory response and complications following anterior resection for rectal cancer. Methods: Data was recorded prospectively for patients who underwent anterior resection for histologically proven rectal cancer, from 2008 to 2015 at a single centre, n = 167. Patients had routine preoperative and postoperative blood sampling including serum C-reactive protein (CRP). Postoperative complications including anastomotic leakage were recorded. Results: Of the 167 patients, the majority were male (61%) and over 65 years old (56%) with node negative disease (60%). 36 patients (22%) underwent preoperative neoadjuvant treatment. 100 patients (60%) had a stoma formed at the time of surgery. Stoma formation was significantly associated with male sex (69% vs. 50%, p = 0.017), neoadjuvant chemoradiotherapy (30% vs 9%, p = 0.001) and open surgery (71% vs. 55%, p = 0.040). Of those 100 patients who had a stoma formed, 80 had it reversed. Permanent stoma was significantly associated with increasing age (p = 0.011), exceeding the established CRP threshold of 150 mg/L on postoperative day 4 (67% vs 37%, p = 0.039), higher incidence of postoperative complications (76% vs 47%, p = 0.035), anastomotic leakage (24% vs 2%, p = 0.003) and higher Clavien Dindo score (p = 0.036). Conclusions: There was no significant association between stoma formation during anterior resection and the postoperative systemic inflammatory response. However, in these patients both the postoperative systemic inflammatory response and complications were associated with permanent stoma

MTHFR C677T polymorphism, homocysteine and B vitamins status in a sample of Chinese and Malay subjects in Universiti Putra Malaysia.

INTRODUCTION: Methylenetetrahydrofolate reductase (MTHFR) C677T is involved in folate and homocysteine metabolism. Disruption in the activity of this enzyme will alter their levels in the body. METHODOLOGY: This study assessed MTHFR C677T polymorphism and its relationship with serum homocysteine and B-vitamins levels in a sample of Chinese and Malays subjects in UPM, Serdang. One hundred subjects were randomly selected from among the university population. Folate, vitamin B12, B6, and homocysteine levels were determined using MBA, ECLIA, and HPLC, respectively. PCR coupled with HinfI digestion was used for detection of MTHFR C677T polymorphism. RESULTS: The frequency of T allele was higher in the Chinese subjects (0.40) compared to the Malay (0.14). Folate, vitamin B12 and B6 levels were highest in the wild genotype in both ethnic groups. Subjects with heterozygous and homozygous genotype showed the highest homocysteine levels. The serum folate and homocysteine were mainly affected by homozygous genotype. CONCLUSION: MTHFR C677T polymorphism plays an important role in influencing the folate and homocysteine metabolism

Morphology, carbohydrate distribution, gene expression, and enzymatic activities related to cell wall hydrolysis in four barley varieties during simulated malting

Many biological processes, such as cell wall hydrolysis and the mobilisation of nutrient reserves from the starchy endosperm, require stringent regulation to successfully malt barley (Hordeum vulgare) grain in an industrial context. Much of the accumulated knowledge defining these events has been collected from individual, unrelated experiments, and data have often been extrapolated from Petri dish germination, rather than malting, experiments. Here, we present comprehensive morphological, biochemical, and transcript data from a simulated malt batch of the three elite malting cultivars Admiral, Navigator, and Flagship, and the feed cultivar Keel. Activities of lytic enzymes implicated in cell wall and starch depolymerisation in germinated grain have been measured, and transcript data for published cell wall hydrolytic genes have been provided. It was notable that Flagship and Keel exhibited generally similar patterns of enzyme and transcript expression, but exhibited a few key differences that may partially explain Flagship's superior malting qualities. Admiral and Navigator also showed matching expression patterns for these genes and enzymes, but the patterns differed from those of Flagship and Keel, despite Admiral and Navigator having Keel as a common ancestor. Overall (1,3;1,4)-β-glucanase activity differed between cultivars, with lower enzyme levels and concomitantly higher amounts of (1,3;1,4)-β-glucan in the feed variety, Keel, at the end of malting. Transcript levels of the gene encoding (1,3;1,4)-β-glucanase isoenzyme EI were almost three times higher than those encoding isoenzyme EII, suggesting a previously unrecognised importance for isoenzyme EI during malting. Careful morphological examination showed that scutellum epithelial cells in mature dry grain are elongated but expand no further as malting progresses, in contrast to equivalent cells in other cereals, perhaps demonstrating a morphological change in this critical organ over generations of breeding selection. Fluorescent immuno-histochemical labelling revealed the presence of pectin in the nucellus and, for the first time, significant amounts of callose throughout the starchy endosperm of mature grain.Natalie S. Betts, Laura G. Wilkinson, Shi F. Khor, Neil J. Shirley, Finn Lok, Birgitte Skadhauge, Rachel A. Burton, Geoffrey B. Fincher and Helen M. Collin

Protein-energy wasting and nutritional supplementation in patients with end-stage renal disease on hemodialysis

© 2016 Elsevier Ltd and European Society for Clinical Nutrition and Metabolism Background & aims Protein-Energy Wasting (PEW) is the depletion of protein/energy stores observed in the most advanced stages of Chronic Kidney Disease (CKD). PEW is highly prevalent among patients on chronic dialysis, and is associated with adverse clinical outcomes, high morbidity/mortality rates and increased healthcare costs. This narrative review was aimed at exploring the pathophysiology of PEW in end-stage renal disease (ESRD) on hemodialysis. The main aspects of nutritional status evaluation, intervention and monitoring in this clinical setting were described, as well as the current approaches for the prevention and treatment of ESRD-related PEW. Methods An exhaustive literature search was performed, in order to identify the relevant studies describing the epidemiology, pathogenesis, nutritional intervention and outcome of PEW in ESRD on hemodialysis. Results and conclusion The pathogenesis of PEW is multifactorial. Loss of appetite, reduced intake of nutrients and altered lean body mass anabolism/catabolism play a key role. Nutritional approach to PEW should be based on a careful and periodic assessment of nutritional status and on timely dietary counseling. When protein and energy intakes are reduced, nutritional supplementation by means of specific oral formulations administered during the hemodialysis session may be the first-step intervention, and represents a valid nutritional approach to PEW prevention and treatment since it is easy, effective and safe. Omega-3 fatty acids and fibers, now included in commercially available preparations for renal patients, could lend relevant added value to macronutrient supplementation. When oral supplementation fails, intradialytic parenteral nutrition can be implemented in selected patients

Revealing the potential of squid chitosan-based structures for biomedical applications

In recent years, much attention has been given to different marine organisms, namely as potential sources of valuable materials with a vast range of properties and characteristics. In this work, β-chitin was isolated from the endoskeleton of the giant squid Dosidicus gigas and further deacetylated to produce chitosan. Then, the squid chitosan was processed into membranes and scaffolds using solvent casting and freeze-drying, respectively, to assess their potential biomedical application. The developed membranes have shown to be stiffer and less hydrophobic than those obtained with commercial chitosan. On the other hand, the morphological characterization of the developed scaffolds, by SEM and micro-computed tomography, revealed that the matrices were formed with a lamellar structure. The findings also indicated that the treatment with ethanol prior to neutralization with sodium hydroxide caused the formation of larger pores and loss of some lamellar features. The in vitro cell culture study has shown that all chitosan scaffolds exhibited a non-cytotoxic effect over the mouse fibroblast-like cell line, L929 cells. Thus, chitosan produced from the endoskeletons of the giant squid Dosidicus gigas has proven to be a valuable alternative to existing commercial materials when considering its use as biomaterial.This work was partially funded by FEDER through INTERREG III A Project Proteus and POCTEP Project IBEROMARE. The Portuguese Foundation for Science and Technology is gratefully acknowledged for post-doctoral grants of THS, JMO and SSS. The authors would also like to acknowledge to Dr Julio Maroto from the Fundacion CETMAR and Roi Vilela from PESCANOVA S.A, Spain, for the kind offer of squid pens and to Dr Ramon Novoa, Professor Ricardo Riguera and Professor Mariana Landin from the University of Santiago of Compostela for the SEC-MALLS measurements

A metabolite-derived protein modification integrates glycolysis with KEAP1-NRF2 signalling.

Mechanisms that integrate the metabolic state of a cell with regulatory pathways are necessary to maintain cellular homeostasis. Endogenous, intrinsically reactive metabolites can form functional, covalent modifications on proteins without the aid of enzymes1,2, and regulate cellular functions such as metabolism3-5 and transcription6. An important 'sensor' protein that captures specific metabolic information and transforms it into an appropriate response is KEAP1, which contains reactive cysteine residues that collectively act as an electrophile sensor tuned to respond to reactive species resulting from endogenous and xenobiotic molecules. Covalent modification of KEAP1 results in reduced ubiquitination and the accumulation of NRF27,8, which then initiates the transcription of cytoprotective genes at antioxidant-response element loci. Here we identify a small-molecule inhibitor of the glycolytic enzyme PGK1, and reveal a direct link between glycolysis and NRF2 signalling. Inhibition of PGK1 results in accumulation of the reactive metabolite methylglyoxal, which selectively modifies KEAP1 to form a methylimidazole crosslink between proximal cysteine and arginine residues (MICA). This posttranslational modification results in the dimerization of KEAP1, the accumulation of NRF2 and activation of the NRF2 transcriptional program. These results demonstrate the existence of direct inter-pathway communication between glycolysis and the KEAP1-NRF2 transcriptional axis, provide insight into the metabolic regulation of the cellular stress response, and suggest a therapeutic strategy for controlling the cytoprotective antioxidant response in several human diseases

The prevalence of hypertension among Malaysian adults and its associated risk factors: data from Malaysian Community Salt Study (MyCoSS)

Background Hypertension is one of the most common risk factors for cardiovascular disease and leading cause of mortality globally. The aims of this study were to assess the prevalence of hypertension and its associated risk factors among Malaysian population using data from the Malaysian Community Salt Study (MyCoSS). Methods This study was a cross-sectional study using multi-stage stratified sampling method. Data collection was carried out via face-to-face interview at the respondent’s home from October 2017 until March 2018. A total of 1047 respondents aged 18 years and above completed the questionnaires and blood pressure measurement. A person who reported diagnosis of hypertension by a physician and had systolic blood pressure ≥140 mmHg and/or diastolic blood pressure ≥90 mmHg on three readings was categorised as hypertensive. Risk factors of hypertension were analysed using multiple logistic regression. Results The prevalence of hypertension in the present study was 49.39% (95% CI 44.27–54.51). There was no statistically significant difference in gender. Age, household income, BMI, and diabetes were significantly associated with hypertension. Hypertension found had inverse association with the level of education. Age was the strongest predictor of hypertension (35–44 years old; OR=2.39, 95% CI=1.39–4.09, 45–54 years old; OR=5.50, 95% CI=3.23–9.38, 55–64 years old OR=13.56, 95% CI=7.77–23.64 and 65 years old and above; OR=25.28, 95% CI=13.33–48.66). Those who had higher BMI more likely to be hypertensive as compared to respondents with normal weight (overweight, OR=1.84; 95% CI=1.18–2.86; obese, OR=4.29% CI=2.56–7.29). Conclusion The findings showed that hypertension is prevalent among adults in Malaysia. Those with older age, higher BMI, and diabetes are more likely to have hypertension. Efforts regarding lifestyle modification and education could be important in hypertension management and prevention

Reformism, Economic Liberalisation and Popular Mobilisation in Iran

Whereas in other MENA countries the impact of neo-liberal policies has been the subject of intense debate, there are at present few voices that directly analyse or critique its social and political consequences in Iran. This article seeks to address this lacuna by analysing the dynamics of reformism, economic liberalisation and popular mobilisation in Iran. It charts the country’s move from a post-revolutionary populism to a liberalised yet increasingly exclusivist model of politics and compares this to trajectories of economic liberalisation in Egypt. Two distinct outcomes of economic reform are analysed in the first part of the article: Socio-economic exclusion; and the contraction of political rights. In the second half, I investigate the ways successive post-war governments in Iran have packaged neo-liberal reforms, and how their re-imagining of the role of the state has led to differing levels of popular resistance. Finally I argue that under the present administration, political elites increasingly are oriented toward strengthening the state and seeking to limit opposition to their policies. However, the absence of neo-liberal hegemony in Iran means that growing mobilization on socio-economic issues is challenging these policies. The Right in Iranian politics is utilizing this mobilisation to present a populist challenge to the reformists in power

Health state utilities of a population of Nigerian hypertensive patients

<p>Abstract</p> <p>Background</p> <p>Establishment of the health impact of hypertension on quality of life of Nigerians is a step towards controlling the disease. The study aimed to provide a Nigerian specific reference list of utility scores of hypertensive patients with various interacting conditions.</p> <p>Findings</p> <p>An interviewer-based, cross-sectional study was conducted using hypertensive patients in two purposively selected tertiary hospitals located in South-Eastern Nigeria. Health Utility Index Mark 3 (HUI3) was used.</p> <p>A total of 384 participants with either hypertension alone or with hypertension-associated complications were interviewed in the two tertiary hospitals.</p> <p>The overall mean utility score was 0.35 +/- 0.42. Patients with hypertension alone had the highest overall mean utility score (0.57 +/- 0.29) while hypertensive patients with stroke had the lowest overall mean score (0.04 +/- 0.36). Being a male, increase in age and mean arterial blood pressure, emergency visit and loss of work due to illness were associated with significant decrease in overall utility scores.</p> <p>Conclusions</p> <p>This study presented a reference for health state utilities of a population of Nigerian hypertensive patients.</p