Investigating the nutritional advice and support given to colorectal cancer survivors in the UK: is it fit for purpose and does it address their needs?

BACKGROUND: The present study assessed the quantity and quality of nutritional advice and support given to colorectal cancer survivors in the UK. METHODS: A descriptive cross-sectional survey was completed by 75 colorectal cancer survivors recruited through social media and bowel cancer support groups in the UK. The survey consisted of open-ended and closed questions that aimed to explore the nutritional needs, nutritional advice given and other sources of information accessed by colorectal cancer survivors. RESULTS: Sixty-nine percent of respondents reported that they did not receive any nutritional advice or support from their healthcare team throughout diagnosis, treatment and post-treatment. Colorectal cancer survivors accessed nutritional advice from a variety of sources, mainly cancer charity websites. Respondents expressed their desire for individualised advice relating to their nutritional problems. CONCLUSIONS: The results obtained in the present study indicate that a high proportion of colorectal cancer patients are not receiving the nutritional support that they need to overcome nutritional difficulties. There is an urgent need to improve clinical practice to ensure colorectal patients receive nutritional advice that is both consistent between healthcare professionals and personalised throughout each stage of diagnosis, treatment and post-treatment.

Riboflavin in development and cell fate.

Riboflavin (7,8-dimethyl-10-ribitylisoalloxazine; vitamin B2) is a water-soluble vitamin, cofactor derivatives of which (FAD, FMN) act as electron acceptors in the oxidative metabolism of carbohydrate, amino acids and fatty acids and which in the reduced state can donate electrons to complex II of the electron transport chain. This means that riboflavin is essential for energy generation in the aerobic cell, through oxidative phosphorylation. The classic effects of riboflavin deficiency on growth and development have generally been explained in terms of these functions. However, research also suggests that riboflavin may have specific functions associated with cell fate determination, which would have implications for growth and development. In particular, riboflavin depletion interferes with the normal progression of the cell cycle, probably through effects on the expression of regulatory genes, exerted at both the transcriptional and proteomic level.

Comparison of Dietary Intake in UK Adults Aged 50 to 75 Years During the 2020 UK Covid-19 Lockdown Compared to their 2019 Intakes.

The lockdown restrictions imposed as a result of COVID-19 impacted on many areas of daily life including dietary behaviours. A cohort of middle-older age adults (n=17), who had previously provided 3-day food diaries in May 2019 were asked to record their 3 day dietary intake in May 2020 when the UK was under lockdown restrictions. Mean (SD) energy intakes were significantly higher by ~750kilojoules in 2020 (8587kJ (1466.9)) compared to 2019 (7837 kJ (1388.9)). This energy increase is equivalent to ~170kcal; approximately 2 slices of bread. Furthermore, recorded meat/meat products, riboflavin, vitamin B6/B12 and iron intakes were all greater in 2020. No other dietary differences were observed between the two timepoints. This was a small, homogenous but well controlled sample, who exhibited a relatively stable diet during lockdown compared with pre-pandemic intakes 12 months earlier. It can be concluded that there was little evidence of food insecurity in this cohort.

Cell damage-induced conformational changes of the pro-apoptotic protein Bak in vivo precede the onset of apoptosis.

Investigation of events committing cells to death revealed that a concealed NH2-terminal epitope of the pro-apoptotic protein Bak became exposed in vivo before apoptosis. This occurred after treatment of human Jurkat or CEM-C7A T-lymphoma cells with the mechanistically disparate agents staurosporine, etoposide or dexamethasone. The rapid, up to 10-fold increase in Bak-associated immunofluorescence was measured with epitope-specific monoclonal antibodies using flow cytometry and microscopy. In contrast, using a polyclonal antibody to Bak, immunofluorescence was detected both before and after treatment. There were no differences in Bak protein content nor in subcellular location before or after treatment. Immunofluorescence showed Bcl-xL and Bak were largely associated with mitochondria and in untreated cells they coimmunoprecipitated in the presence of nonioinic detergent. This association was significantly decreased after cell perturbation suggesting that Bcl-xL dissociation from Bak occurred on exposure of Bak's NH2 terminus. Multiple forms of Bak protein were observed by two dimensional electrophoresis but these were unchanged by inducers of apoptosis. This indicated that integration of cellular damage signals did not take place directly on the Bak protein. Release of proteins, including Bcl-xL, from Bak is suggested to be an important event in commitment to death.

Post-translational control of sp-family transcription factors.

Sp-family transcription factors are widely expressed in human tissues and involved in the regulation of many cellular processes and response to cellular microenvironment. These responses appear to be mediated by alterations in transcription factor affinity for DNA rather than altered protein level. How might such changes be effected? This review will identify the range of known post-translational modifications (PTMs) of Sp-factors and the sometimes conflicting literature about the roles of PTMs in regulating activity. We will speculate on the interaction between cell environment, chromatin microenvironment and the role of PTM in governing functionality of the proteins and the complexes to which they belong.

Protein for Life: Towards a focussed dietary framework for healthy ageing.

'Ageing well' has been highlighted as an important research area by the World Health Organization. In the UK, healthy ageing has been identified as a priority research area by multiple Research Councils and is a key NHS priority. Sarcopaenia, the decline of muscle mass/strength and a key component of healthy ageing, can have a major impact on quality of life and is associated with premature mortality. Increasing protein intake at all stages of the life course may help to reduce the rate of muscle decline and the onset of associated health conditions. However, there is a lack of understanding of the social, demographic and psychological drivers of food choices surrounding protein intake. This report describes the multidisciplinary approach that has been adopted by the Protein for Life project to create a framework for the development of palatable, cost-effective higher-protein foods suitable for an ageing population.

Upregulation of BAK by butyrate in the colon is associated with increased Sp3 binding.

Butyrate is a key bioactive product of dietary fibre fermentation thought to play a key role in cancer prevention. One contributory mechanism in this role is the regulation of apoptosis by butyrate. As butyrate shows low levels of toxicity, the mechanisms by which it triggers or regulates apoptosis are of great interest. We and others have shown that the proapoptotic protein BAK is upregulated by butyrate. We show here that this observation is conserved across multiple cell lines, that it occurs in all cells in a population and is at the transcriptional level. We have used a promoter-reporter construct to identify the regulatory regions of the BAK promoter and found that much of the transcriptional activity occurs via a single Sp1/Sp3 binding site. We have shown that both Sp1 and Sp3 bind, but upon butyrate treatment Sp1 binding decreases in favour of Sp3 binding. We speculate that this may be an acetylation-mediated event.

Systematic review: psychological morbidity in young people with inflammatory bowel disease - risk factors and impacts.

BACKGROUND: Psychological morbidity in young people aged 10-24 years, with inflammatory bowel disease (IBD) is increased, but risk factors for and impacts of this are unclear. AIM: To undertake a systematic literature review of the risk factors for and impact of psychological morbidity in young people with IBD. METHODS: Electronic searches for English-language articles were performed with keywords relating to psychological morbidity according to DSM-IV and subsequent criteria; young people; and IBD in the MEDLINE, PsychInfo, Web of Science and CINAHL databases for studies published from 1994 to September 2014. RESULTS: One thousand four hundred and forty-four studies were identified, of which 30 met the inclusion criteria. The majority measured depression and anxiety symptoms, with a small proportion examining externalising behaviours. Identifiable risk factors for psychological morbidity included: increased disease severity (r(2) = 0.152, P < 0.001), lower socioeconomic status (r(2) = 0.046, P < 0.001), corticosteroids (P ≤ 0.001), parental stress (r = 0.35, P < 0.001) and older age at diagnosis (r = 0.28, P = 0.0006). Impacts of psychological morbidity in young people with IBD were wide-ranging and included abdominal pain (r = 0.33; P < 0.001), sleep dysfunction (P < 0.05), psychotropic drug use (HR 4.16, 95% CI 2.76-6.27), non-adherence to medication (12.6% reduction) and negative illness perceptions (r = -0.43). CONCLUSIONS: Psychological morbidity affects young people with IBD in a range of ways, highlighting the need for psychological interventions to improve outcomes. Identified risk factors provide an opportunity to develop targeted therapies for a vulnerable group. Further research is required to examine groups under-represented in this review, such as those with severe IBD and those from ethnic minorities.

Cellular damage signals promote sequential changes at the N-terminus and BH-1 domain of the pro-apoptotic protein Bak.

The pro-apoptotic protein Bak is converted from a latent to an active form by damage-induced signals. This process involves an early exposure of an occluded N-terminal epitope of Bak in intact cells. Here we report a subsequent damage-induced change in Bak, detected using an antibody to the central BH-1 domain. Bak co-immunoprecipitated with Bc1-x(L) both in undamaged cells and early after damage, when the N-terminal epitope was exposed but the BH-1 epitope remained occluded. A subsequent decrease in binding of Bak to Bc1-x(L) correlated with exposure of an epitope in the Bak BH-1 domain. Overexpression of Bc1-x(L) did not affect the kinetics of exposure of the Bak N-terminal epitope but delayed exposure of the BH-1 domain. Cytochrome c release from mitochondria facilitates the activation of apoptotic caspases. The majority of cells with exposed Bak BH-1 domains contained cytosolic cytochrome c. However, a small proportion of cells exhibited exposed Bak BH-1 domains that co-localized with mitochondrial cytochrome c. The data are consistent with a two-step model for the activation of Bak by drug-induced damage signals where dissociation of Bc1-x(L) from the BH-1 domain of Bak occurs immediately prior to or concomitantly with cytochrome c release.

Molecular genetical and phenotypical analysis of the gerM spore germination gene of Bacillus subtilis 168.

The gerM gene, encoding a single product of 22.5 kDa, has been identified by subcloning and sequencing of DNA recovered from adjacent to a Tn917 insertion. The gene product has a potential lipoprotein signal sequence, but otherwise has no homology to known sequences. Spores of the gerM mutant were more heat sensitive than wild-type, but their dipicolinic acid content was normal. The level of cortical peptidoglycan in mutant spores is also normal but release at germination of hexosamine-containing fragments, the breakdown products of cortex degradation, is less complete than wild-type. The sporulation, resistance and germination phenotypes of the gerM mutant would be consistent with the gene product having a role, either directly or indirectly, in peptidoglycan synthesis during sporulation.

Clinical trial: a multistrain probiotic preparation significantly reduces symptoms of irritable bowel syndrome in a double-blind placebo-controlled study.

BACKGROUND: The efficacy of probiotics in alleviating the symptoms of irritable bowel syndrome (IBS) appears to be both strain- and dose-related. AIM: To investigate the effect of LAB4, a multistrain probiotic preparation on symptoms of IBS. This probiotic preparation has not previously been assessed in IBS. METHODS: Fifty-two participants with IBS, as defined by the Rome II criteria, participated in this double blind, randomized, placebo-controlled study. Participants were randomized to receive either a probiotic preparation comprising two strains of Lactobacillus acidophilus CUL60 (NCIMB 30157) and CUL21 (NCIMB 30156), Bifidobacterium lactis CUL34 (NCIMB 30172) and Bifidobacterium bifidum CUL20 (NCIMB 30153) at a total of 2.5 × 10(10) cfu/capsule or a placebo for 8 weeks. Participants reported their IBS symptoms using a questionnaire fortnightly during the intervention and at 2 weeks post-intervention. RESULTS: A significantly greater improvement in the Symptom Severity Score of IBS and in scores for quality of life, days with pain and satisfaction with bowel habit was observed over the 8-week intervention period in the volunteers receiving the probiotic preparation than in the placebo group. CONCLUSION: LAB4 multistrain probiotic supplement may benefit subjects with IBS.

Daily ingestion of alginate reduces energy intake in free-living subjects.

Sodium alginate is a seaweed-derived fibre that has previously been shown to moderate appetite in models of acute feeding. The mechanisms underlying this effect may include slowed gastric clearance and attenuated uptake from the small intestine. In order to assess whether alginate could be effective as a means of appetite control in free-living adults, 68 males and females (BMI range: 18.50-32.81 kg/m(2)) completed this randomised, controlled two-way crossover intervention to compare the effects of 7 day daily ingestion of a strong-gelling sodium alginate formulation against a control. A sodium alginate with a high-guluronate content was chosen because, upon ingestion, it forms a strong gel in the presence of calcium ions. Daily preprandial ingestion of the sodium alginate formulation produced a significant 134.8 kcal (7%) reduction in mean daily energy intake. This reduced energy intake was underwritten by significant reductions in mean daily carbohydrate, sugar, fat, saturated fat and protein intakes. The absence of any significant interaction effects between the main effect of preload type and those of gender, BMI classification and/or timing of preload delivery indicates the efficacy of this treatment for individuals in different settings. These findings suggest a possible role for a strong-gelling sodium alginate formulation in the future management of overweight and obesity.

Analysis of the expression and regulation of the gerB spore germination operon of Bacillus subtilis 168.

The gerB spore germination operon of Bacillus subtilis 168 is a homologue of the gerA spore germination operon. The expression and regulation of the gerB operon has been examined using a lacZ transcriptional fusion and the transcriptional start defined. The gerB operon is expressed during sporulation under the control of RNA polymerase containing the forespore-specific sigma factor, delta G. This is a further homology to the gerA operon, which is similarly regulated. It is predicted from the localization of expression and the encoded primary sequences that the GerB proteins are located at the inner spore membrane.

Spore germination.

Despite being relatively insensitive to environmental insult, the spore is responsive to low concentrations of chemical germinants, which induce germination. The process of bacterial spore germination involves membrane permeability changes, ion fluxes and the activation of enzymes that degrade the outer layers of the spore. A number of components in the spore that are required for the germination response have been identified, including a spore-specific family of receptor proteins (the GerA family), an ion transporter and cortex lytic enzymes. The germinant traverses the outer layers of the spore and interacts with its receptor in the inner membrane to initiate the cascade of germination events, but the molecular details of this signal transduction process remain to be identified.

The gerB region of the Bacillus subtilis 168 chromosome encodes a homologue of the gerA spore germination operon.

Spores of gerB spore germination mutants of Bacillus subtilis 168 are defective in response to the germinative mixture of L-asparagine, glucose, fructose and potassium ions (AGFK), but are normal in the L-alanine (ALA) triggered germination response. A lambda clone of 15 kbp carrying the gerB region has been identified. Sequencing of the gerB region of the clone revealed a cluster of three ORFs encoding putative proteins of 53.3, 41.3 and 42.4 kDa (GerBA, GerBB and GerBC, respectively). The first two of these proteins have substantial hydrophobic regions and the third is a possible lipoprotein. At least two, and probably all three products are required for normal germination in AGFK. The three proteins form a set of homologues of the products of the gerA operon, mutations in which cause a defect in the ALA germination pathway, but cause no defect in AGFK. The GerB proteins show 42%, 31% and 35% identity at the amino-acid level to the corresponding GerA proteins, and the homologues occur in the same order in both operons.

Alanine germination receptors of Bacillus subtilis.

The alanine-stimulated spore germination responses of Bacillus subtilis 168 have been dissected by combining physiological and genetical approaches. From the analyses the authors infer that there are three classes of alanine response. Two of the responses are mediated via the GerA proteins, with and without germinal adjuncts, the third is mediated via the GerB proteins and obligately requires adjuncts.

Damage-induced Bax N-terminal change, translocation to mitochondria and formation of Bax dimers/complexes occur regardless of cell fate.

Sequential steps in the activation of the pro-apoptotic protein Bax are described for cells with different sensitivity to cytotoxins. SH-EP1 and SH-SY5Y human neuroblastoma cells, derived from a single precursor cell line, differed in their sensitivity to taxol but showed the same sensitivity to cisplatin. Both drugs, in both cell lines, induced exposure of a constitutively occluded N-terminal epitope of Bax. This was reversible and occurred before the translocation of cytosolic Bax to mitochondria. The N-terminal change in Bax, its subsequent movement to mitochondria and its dimerization/complex formation were insufficient for commitment to death, occurring in the same proportion of cells that either maintained (SH-SY5Y) or lost (SH-EP1) clonogenic survival after taxol treatment. Suppression of taxol-induced apoptosis occurred upstream of cytochrome c release from mitochondria in SH-SY5Y cells. The data suggest that a further drug damage-induced event occurs after Bax dimerization/complex formation but prior to cytochrome c release. This event was absent in the taxol-resistant cells.

Localization of GerAA and GerAC germination proteins in the Bacillus subtilis spore.

The GerAA, -AB, and -AC proteins of the Bacillus subtilis spore are required for the germination response to L-alanine as the sole germinant. They are likely to encode the components of the germination apparatus that respond directly to this germinant, mediating the spore's response; multiple homologues of the gerA genes are found in every spore former so far examined. The gerA operon is expressed in the forespore, and the level of expression of the operon appears to be low. The GerA proteins are predicted to be membrane associated. In an attempt to localize GerA proteins, spores of B. subtilis were broken and fractionated to give integument, membrane, and soluble fractions. Using antibodies that detect Ger proteins specifically, as confirmed by the analysis of strains lacking GerA and the related GerB proteins, the GerAA protein and the GerAC+GerBC protein homologues were localized to the membrane fraction of fragmented spores. The spore-specific penicillin-binding protein PBP5*, a marker for the outer forespore membrane, was absent from this fraction. Extraction of spores to remove coat layers did not release the GerAC or AA protein from the spores. Both experimental approaches suggest that GerAA and GerAC proteins are located in the inner spore membrane, which forms a boundary around the cellular compartment of the spore. The results provide support for a model of germination in which, in order to initiate germination, germinant has to permeate the coat and cortex of the spore and bind to a germination receptor located in the inner membrane.