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.

Operationalizing outcome measures of human papillomavirus vaccination among adolescents.

OBJECTIVES: When examining vaccination coverage, researchers must make decisions about how to define outcome measures based on many factors, including the timing of doses. Different operationalizations of the same outcome can often lead to different findings and can affect the ability to make comparisons across studies. This methodological article aimed to illustrate the implications of two options for operationalizing human papillomavirus (HPV) vaccination based on timing: initiation of the first dose at any age vs before the 13th birthday (on time). STUDY DESIGN: Cross-sectional observational design. METHODS: The 2014 National Immunization Survey for Teens (N = 16,439 adolescents aged 13-17 years) was analyzed using multivariate logistic regression for each outcome measure and effect modification by gender. RESULTS: Age was positively associated with initiation at any age but negatively associated with on-time initiation. Gender modified the effect of race/ethnicity for both measures of initiation, but the pattern across groups was different for the two outcomes. Gender modified the effect of provider recommendation for initiation at any age, while gender modified the effects of age and region for on-time initiation. CONCLUSION: Decisions of how to operationalize outcomes of HPV vaccine initiation among adolescents can lead to different conclusions about the role of age and gender differences for several predictive variables. To inform the development of public health efforts that promote on-time HPV vaccination among male and female adolescents, researchers should consider the importance of dose timing when operationalizing outcome measures. We recommend including on-time receipt of the HPV vaccine as an outcome measure.

Kinetic theory and Vlasov simulation of nonlinear ion-acoustic waves in multi-ion species plasmas.

The theory of damping and nonlinear frequency shifts from particles resonant with ion-acoustic waves (IAWs) is presented for multi-ion species plasma and compared to driven wave Vlasov simulations. Two distinct IAW modes may be supported in multi-ion species plasmas, broadly classified as fast and slow by their phase velocity relative to the constituent ion thermal velocities. In current fusion-relevant long pulse experiments, the ion to electron temperature ratio, T(i)/T(e), is expected to reach a level such that the least damped and thus more readily driven mode is the slow mode, with both linear and nonlinear properties that are shown to differ significantly from the fast mode. The lighter ion species of the slow mode is found to make no significant contribution to the IAW frequency shift despite typically being the dominant contributor to the Landau damping.

Raman backscatter as a remote laser power sensor in high-energy-density plasmas.

Stimulated Raman backscatter is used as a remote sensor to quantify the instantaneous laser power after transfer from outer to inner cones that cross in a National Ignition Facility (NIF) gas-filled hohlraum plasma. By matching stimulated Raman backscatter between a shot reducing outer versus a shot reducing inner power we infer that about half of the incident outer-cone power is transferred to inner cones, for the specific time and wavelength configuration studied. This is the first instantaneous nondisruptive measure of power transfer in an indirect drive NIF experiment using optical measurements.

X-chromosome inactivation occurs at different times in different tissues of the post-implantation mouse embryo.

During mammalian development, one of the two X chromosomes in female embryos is randomly inactivated in the somatic cell in order to achieve gene dosage compensation. But is X inactivation established simultaneously or is it accomplished over time in a lineage-dependent fashion? We have examined this question in mouse embryos carrying an X-linked lacZ transgene. This transgene is subject to inactivation and the loss of beta-galactosidase activity provides a direct indication of X inactivation in individual cells. We find that X inactivation proceeds with different schedules in different somatic tissues, and the notochord, the heart, cranial mesoderm and the hindgut are among the last tissues to undergo X inactivation.

Plasma and rectal mucosal oxylipin levels during aspirin and eicosapentaenoic acid treatment in the seAFOod polyp prevention trial.

BACKGROUND: Aspirin and eicosapentaenoic acid (EPA) have colorectal polyp prevention activity, alone and in combination. This study measured levels of plasma and rectal mucosal oxylipins in participants of the seAFOod 2 × 2 factorial, randomised, placebo-controlled trial, who received aspirin 300 mg daily and EPA 2000 mg free fatty acid, alone and in combination, for 12 months. METHODS: Resolvin (Rv) E1, 15-epi-lipoxin (LX) A4 and respective precursors 18-HEPE and 15-HETE (with chiral separation) were measured by ultra-high performance liquid chromatography-tandem mass spectrometry in plasma taken at baseline, 6 months and 12 months, as well as rectal mucosa obtained at trial exit colonoscopy at 12 months, in 401 trial participants. RESULTS: Despite detection of S- and R- enantiomers of 18-HEPE and 15-HETE in ng/ml concentrations, RvE1 or 15­epi-LXA4 were not detected above a limit of detection of 20 pg/ml in plasma or rectal mucosa, even in individuals randomised to both aspirin and EPA. We have confirmed in a large clinical trial cohort that prolonged (12 months) treatment with EPA is associated with increased plasma 18-HEPE concentrations (median [inter-quartile range] total 18-HEPE 0.51 [0.21-1.95] ng/ml at baseline versus 0.95 [0.46-4.06] ng/ml at 6 months [P<0.0001] in those randomised to EPA alone), which correlate strongly with respective rectal mucosal 18-HEPE levels (r = 0.82; P<0.001), but which do not predict polyp prevention efficacy by EPA or aspirin. CONCLUSION: Analysis of seAFOod trial plasma and rectal mucosal samples has not provided evidence of synthesis of the EPA-derived specialised pro-resolving mediator RvE1 or aspirin-trigged lipoxin 15­epi-LXA4. We cannot rule out degradation of individual oxylipins during sample collection and storage but readily measurable precursor oxylipins argues against widespread degradation.

Stochastic ion heating from many overlapping laser beams in fusion plasmas.

In this Letter, we show through numerical simulations and analytical results that overlapping multiple (N) laser beams in plasmas can lead to strong stochastic ion heating from many (~N(2)) electrostatic perturbations driven by beat waves between pairs of laser beams. For conditions typical of inertial-confinement-fusion experiment conditions, hundreds of such beat waves are driven in mm(3)-scale plasmas, leading to ion heating rates of several keV/ns. This mechanism saturates cross-beam energy transfer, with a reduction of linear gains by a factor ~4-5 and can strongly modify the overall hydrodynamics evolution of such laser-plasma systems.

Observation of high soft x-ray drive in large-scale hohlraums at the National Ignition Facility.

The first soft x-ray radiation flux measurements from hohlraums using both a 96 and a 192 beam configuration at the National Ignition Facility have shown high x-ray conversion efficiencies of ∼85%-90%. These experiments employed gold vacuum hohlraums, 6.4 mm long and 3.55 mm in diameter, heated with laser energies between 150-635 kJ. The hohlraums reached radiation temperatures of up to 340 eV. These hohlraums for the first time reached coronal plasma conditions sufficient for two-electron processes and coronal heat conduction to be important for determining the radiation drive.

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.

Characterizing the optical response of ultra-low-noise far-infrared 60-110 µm transition edge sensors.

Far-infrared Transition Edge Sensors (TESs) are being developed for the SAFARI grating spectrometer on the cooled-aperture space telescope SPICA. In support of this work, we have devised a cryogenic (90 mK) test facility for carrying out precision optical measurements on ultra-low-noise TESs. Although our facility is suitable for the whole of the SAFARI wavelength range, 34 µm-230 µm, we focus on a representative set of measurements at 60 µm-110 µm using a device having a noise equivalent power of 0.32 aW Hz-1/2. The system is able to perform a range of measurements: (i) dark electrical characterization, (ii) optical efficiency with respect to a partially coherent beam having a modal composition identical to that of an ideal imaging telescope, (iii) optical saturation and dynamic range, (iv) fast optical transient response to a modulated thermal source, and (v) optical transient response in the presence of high-level background loading. We describe dark measurements to determine the operating characteristics of a TES and then compare the predicted optical behavior with the measured optical behavior. By comparing electrical and optical transient responses, we were able to observe thermalization in the device. We comment on the challenge of eliminating stray light.

Fucosyltransferase gene expression in goat endometrium during the estrous cycle and early pregnancy.

Regulation of the expression of the alpha(1,2)fucosyltransferase (FUT) genes and their enzymatic products, including the H-type 1 antigen (HT1), on the luminal surface of the uterus is believed to be critical for establishment of pregnancy in mammals. The FUT1 gene is a marker for conception rates in dairy cows and HT1 is a marker for uterine receptivity in rodents. To determine the spatiotemporal expression patterns of FUT1 and FUT2 genes in goats, endometrial tissues were obtained on six days spanning the estrous cycle (Days 5, 11, 13, 15, 17 and 19) and seven days spanning early pregnancy (Days 5, 11, 13, 15, 17, 19 and 25). In all data, we found no effect of status (cyclic or pregnant; P > 0.1) and pooled data where appropriate. We cloned FUT1 cDNA from goat endometrium and made probes from it for Northern and slot blot analyses. The analyses indicated that FUT1 gene expression was high until Day 13, and then declined. In situ hybridization revealed a change in the cell-specificity of FUT1 gene expression over the estrous cycle and early pregnancy. In situ hybridization signal intensity scores indicated that FUT1 expression by uterine epithelium was high on Day 5, moderate on Day 11, and minimal on subsequent days. In situ hybridization signals in uterine glandular epithelial cells remained high from Day 5 to Day 13, with weaker signals thereafter. Quantitative reverse transcription-PCR (RT-qPCR) assays were used for quantitation of FUT1 and FUT2 mRNAs. Quantitative RT-qPCR data were generated from endometrium collected from cyclic and pregnant animals on Days 5, 11 and 17. Relative levels of FUT1 mRNA were high on Days 5 and 11, but then fell 5-fold by Day 17 (P < 0.01). FUT2 mRNA concentrations were below the accurate detectable limit of the assay. High levels of HT1 were observed on the apical surface of uterine luminal epithelia on Days 5, 15, 17 and 19, with much lower levels on Days 11 and 13. Thus, data suggests that FUT1 is the primary enzyme responsible for the high levels of HT1 antigen present on the uterine luminal epithelium between Days 5 and 11 of the estrous cycle and early pregnancy. But changes in the expression of the FUT1 gene does not directly correlate to HT1 staining, which increased from Day 13-15. Future studies are required to understand the regulation of the HT1 antigen on the luminal surface of endometrium.

A Comparison of Food Portion Size Estimation by Older Adults, Young Adults and Nutritionists.

OBJECTIVES: To investigate the ability of older adults, younger adults and nutritionists to assess portion size using traditional methods versus a computer-based method. This was to inform the development of a novel dietary assessment method for older adults "The NANA system". DESIGN: Older and younger adults assessed the portion size of self-served portions of foods from a buffet style set up using traditional and computerised portion size assessment aids. Nutritionists assessed the portion size of foods from digital photographs using computerised portion size aids. These estimates were compared to known weights of foods using univariate analyses of covariance (ANCOVA). SETTING: The University of Sheffield, United Kingdom. SUBJECTS: Forty older adults (aged 65 years and over), 41 younger adults (aged between 18 and 40 years) and 25 nutritionists. RESULTS: There was little difference in the abilities of older and younger adults to assess portion size using both assessment aids with the exception of small pieces morphology. Even though the methods were not directly comparable among the test groups, there was less variability in portion size estimates made by the nutritionists. CONCLUSION: Older adults and younger adults are similar in their ability to assess food portion size and demonstrate wide variability of estimation compared to the ability of nutritionists to estimate portion size from photographs. The results suggest that the use of photographs of meals consumed for portion size assessment by a nutritionist may improve the accuracy of dietary assessment. Improved portion size assessment aids are required for all age groups.

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.

Using the NANA toolkit at home to predict older adults' future depression.

BACKGROUND: Depression is currently underdiagnosed among older adults. As part of the Novel Assessment of Nutrition and Aging (NANA) validation study, 40 older adults self-reported their mood using a touchscreen computer over three, one-week periods. Here, we demonstrate the potential of these data to predict future depression status. METHODS: We analysed data from the NANA validation study using a machine learning approach. We applied the least absolute shrinkage and selection operator with a logistic model to averages of six measures of mood, with depression status according to the Geriatric Depression Scale 10 weeks later as the outcome variable. We tested multiple values of the selection parameter in order to produce a model with low deviance. We used a cross-validation framework to avoid overspecialisation, and receiver operating characteristic (ROC) curve analysis to determine the quality of the fitted model. RESULTS: The model we report contained coefficients for two variables: sadness and tiredness, as well as a constant. The cross-validated area under the ROC curve for this model was 0.88 (CI: 0.69-0.97). LIMITATIONS: While results are based on a small sample, the methodology for the selection of variables appears suitable for the problem at hand, suggesting promise for a wider study and ultimate deployment with older adults at increased risk of depression. CONCLUSIONS: We have identified self-reported scales of sadness and tiredness as sensitive measures which have the potential to predict future depression status in older adults, partially addressing the problem of underdiagnosis.

Characterization of tightly bound substrates in pure preparations of dihydrofolate reductase: implications for studies on enzymes.

Investigations have been made to determine the identity and binding characteristics of the pterins that are bound tightly to dihydrofolate reductases which are isolated from vertebrate sources by a well established procedure. This procedure involves the binding of enzyme to a Sepharose-methotrexate column, elution with dihydrofolate and removal of free dihydrofolate by dialysis or by size-exclusion chromatography. Addition to such preparations of NADPH results in oxidation of the nucleotide and from the progress curves so obtained, it is possible to identify the bound pterin and to calculate the stoichiometry of binding. The data indicated that stoichiometric amounts of dihydrofolate or folate plus dihydrofolate were bound to the dihydrofolate reductases. It can also be concluded that binding occurs at the active sites of the enzymes. Enzyme preparations from which bound pterin had been removed by isoelectric focussing reacted with folate or dihydrofolate to form 1:1 enzyme-pterin complexes from which the pterin could not be removed by dialysis or by size-exclusion chromatography. From the magnitude of the dissociation constants for the enzyme-pterin complexes and the concentration of enzyme present in fractions after the step involving affinity chromatography on Sepharose-methotrexate, it could be concluded that the presence of bound folate and/or dihydrofolate in pure preparations of dihydrofolate reductase is simply a consequence of an association-dissociation reaction. Preparations of the enzyme from bacterial sources were also found to contain bound pterins. The findings have implications with respect to kinetic and thermodynamic studies on dihydrofolate reductase and other enzymes which are isolated by affinity chromatography techniques.

Perforin-dependent nuclear entry of granzyme B precedes apoptosis, and is not a consequence of nuclear membrane dysfunction.

Killer lymphocytes utilize the synergy of a membranolytic protein, perforin, and the serine protease granzyme B (grB) to induce target cell apoptosis, however the mechanism of this synergy remains incompletely defined. We have previously shown that perforin specifically induces the redistribution of cytoplasmic grB into the nucleus of dying cells, however a causal role for nuclear targeting of grB in cell death has not been demonstrated. In the present study, we used confocal laser scanning microscopy (CLSM) to determine whether the nuclear accumulation of fluoresceinated (FITC-) grB precedes or is a consequence of apoptosis. Two distinct and mutually exclusive cellular responses were observed in FDC-P1 cells: (i) up to 50% of the cells rapidly accumulated FITC-grB in the nucleus (maximal at 7 min; t1/2 of 2 min) and underwent apoptosis; (ii) the remaining cells took up FITC-grB only into the cytoplasm, and escaped apoptosis. Under these conditions, DNA fragmentation was not observed for at least 13 min, indicating nuclear accumulation of grB preceded the execution phase of apoptosis. Furthermore, nuclear import of grB proceeded through an intact nuclear membrane, as the nuclei of cells whose cytoplasm was pre-loaded with 70 kDa FITC-dextran excluded dextran for up to 90 min while still undergoing apoptosis in response to perforin and grB. These findings indicated that perforin-induced nuclear accumulation of grB precedes apoptosis, and is not a by-product of caspase-induced nuclear membrane degradation. The cell membrane lesions formed by perforin in these experiments were not large enough to permit a 13 kDa protein (yeast cdk p13suc) access into the cytoplasm, but an 8 kDa protein (bacterial azurin) was able to equilibrate between the cytosol and the exterior. Therefore, transmembrane pores large enough to allow passive diffusion of grB (32 kDa) into the cell are not necessary for apoptosis. Rather, a perforin-dependent signal results in a redistribution of grB from the cytoplasm to the nucleus, where it may contribute to the nuclear changes associated with apoptosis.

The acute and chronic effect of 5-methoxytryptamine on selected members of a primate social colony.

The acute and chronic effect of 5-methoxytryptamine (5-MeOT), a structural analogue of known tryptamine hallucinogens and a substance found in mammalian brain, on nonhuman primate behavior was studied in a social colony of four Stumptail macaques. In the first study, dose-dependent behavioral changes induced by 5-MeOT were determined with the administration of seven acute doses to each animal. At higher doses, 10-20 mg/kg, 5-MeOT induced two abnormal or "emergent" behaviors, body shakes and limb jerks. 5-MeOT also induced a dose-dependent reduction in normal social and solitary behavior of treated animals suggesting that this drug has sedative properties. The second study examined the effect of once daily administration of 5-MeOT, 10 mg/kg, for 5 days. During this time, tolerance developed to both 5-MeOT-induced body shakes and limb jerks, but failed to develop to the reduction in social and solitary behaviors. Since body shakes and limb jerks are behaviors characteristically induced in this species by hallucinogens, these results suggest that 5-MeOT may possess hallucinogenic properties. However, this effect may be weak and may only occur after large doses since large doses of 5-MeOT were required to induce a relatively small number of body shakes and limb jerks in monkeys when compared to potent hallucinogens such as LSD and 5-MeODMT.

Ventral mesopontine projections of the caudomedial shell of the nucleus accumbens and extended amygdala in the rat: double dissociation by organization and development.

The shell of the nucleus accumbens and central division of the extended amygdala are telencephalic structures that influence motor activity and lately have been regarded by some as components of a single functional-anatomic continuum. Each has a highly differentiated internal organization and output system and distinct pharmacologic responses however, and it is thus likely that each subserves distinct contributions to behavior. In this investigation, nucleus accumbens and extended amygdala outputs were compared by using retrograde tracing in adult and postnatal rats. Fluoro-Gold, when injected into the ventral tegmental area, produced substantial retrograde labeling in the adult nucleus accumbens shell, but only trivial amounts in the central division of the extended amygdala. Injection sites in the lateral mesopontine tegmentum produced robust labeling in the central extended amygdala but little in the nucleus accumbens. The projections of extended amygdala were substantially developed by postnatal day 1, whereas those of the caudomedial shell of the nucleus accumbens only reached the ventral tegmental area by approximately postnatal day 6. Few neurons projecting from the caudomedial shell of the accumbens to the ventral tegmental area were observed even at postnatal day 21. In consideration of the reported importance of the nucleus accumbens, particularly the caudomedial shell, in neural processing related to reward and motivation and the central nervous system response to antipsychotic drugs, it may be important to determine whether processes occurring during the protracted postnatal development of the caudomedial shell are vulnerable to destructive circumstances, such as drug intoxication, maternal separation, or social isolation.

T cell-specific activity in rabbit anti-human thymocyte globulin. Correlation with immunosuppresive activity in nonhuman primates.

Spotaneous E rosette-forming (T) lymphocytes were monitored in the peripheral blood of rhesus monkeys receiving a 5-day course of rabbit anti-human thymocyte globulin (RATG) after skin allotransplantation. Mean graft survival in RATG-treated recipients was 32.3 +/- 7.6 (SD) days compared with 8.2 +/- 1.7 (SD) days in controls. The percentage and total number of circulating T cells fell precipitously after RATG treatment and recovered slowly. Linear regression analysis showed that the recovery pattern of the total number of circulating T cells, but not the percentage of T cells, was significantly correlated with rejection. Specific antihuman T cell antibody was detected in RATG preparations after extensive absorption with human erythrocytes, platelets, and B lymphoblastoid cells. The cytotoxic titers of B cell-absorbed RATG preparations to human peripheral blood lymphocytes showed a significant correlation with the mean skin allograft survival times obtained in RATG-treated primates. Overall the data suggest that the immunosuppressive potency of RATG in the primate skin graft assay is related in large part to its anti-T cell activity.

Differential distribution of parvalbumin immunoreactive neurons in the striatum of cocaine sensitized rats.

Intermittent administration of psychostimulants such as cocaine and amphetamine can result in behavioral sensitization, which is believed to model the onset of drug addiction, as well as possible neural adaptations that lead to addictive behaviors. The dorsal striatum and the nucleus accumbens (NAc) have been shown to play an integral role in this phenomenon. However, these structures comprise a complex neuroanatomical organization, and few studies have correlated anatomical differentiation within these brain regions with functional (i.e. behavioral) outcome, particularly after psychostimulant exposure. Parvalbumin (PV)-containing GABAergic interneurons are a key neuronal cell population that can significantly regulate input-output functions in these brain regions. The present study quantified parvalbumin-immunoreactive cells in subterritories of the striatum and NAc in animals behaviorally sensitized to cocaine. Rats received a sensitization-inducing regimen of cocaine (twice-daily injections of 15 mg/kg i.p. for 5 consecutive days). Two or 14 days following the last injection, rats were given a challenge injection of cocaine (15 mg/kg i.p.), and killed 2 h later. Sections through the striatum (including the NAc) were processed for parvalbumin immunoreactivity, and the number of immunoreactive neurons was quantified. Repeated cocaine administration resulted in robust sensitization that correlated with transient increases in the number of PV immunoreactive neurons in the ventrolateral, dorsolateral and dorsomedial striatum. After a 2-week withdrawal period, sensitized animals showed a significant decrease in the number of PV+ neurons in the ventrolateral shell of the NAc and dorsomedial striatum, and no significant difference in any other area examined. These data suggest a dichotomous role for PV interneurons in different subterritories of the striatum and NAc during the short-term (induction) vs. long-term (expression) phases of cocaine sensitization.